Technical Report Design Project 2 - IBIO 3870

Biomedical Engineering Department

Difficulty acquiring accurate and rapid information regarding the blood oxygen saturation in patients under vasoconstriction

Oxycure

Measuring beyond limits

Daniel Baron Espitia Cesar Pinzón Troncoso Sebastián Reyes Dávila

Alejandra Riveros Cortés Manuela Vargas Rojas

Mario Valderrama Manrique Universidad de los Andes

Juan Carlos Briceño

Universidad de los Andes

November 30, 2018

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Content 1 Executive Summary 4 2 Need Identification and Screening 4

2.1. Strategic Focus 4 2.2. Unmet Need Exploration 4

2.2.1. Observation 6 2.2.2. Insights 6 2.2.3. Opportunities 6 2.2.4. Core Problem 7 2.2.5. Population 7 2.2.6. Desired Outcome 7 2.2.7. Problem and Disease State Fundamentals 8 2.2.8. Existing Solutions and Current Treatments 8 2.2.9. Stakeholder Analysis 9 2.2.10. Market Analysis 10

3 Need Selection 10 3.1. Needs Statements 10 3.2. Need Selection 11

4 Need Specifications 11 4.1. Selected Need Statement 11 4.2. Need Validation 11 4.3. Need Criteria and Specifications 12

5 Concept 12 5.1. Design Constraints 12 5.2. Ideation and Concept Generation 13

5.2.1. Helmeier questions 17 5.2.2. Feasibility 18

5.3. Ideation and Concept Selection 19 5.4. Final Concept 21 5.5. Product name 23

6 Proof of concept (killer experiment) 23 7 Product 24

7.1. Product Specifications 24

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7.2. Regulatory Aspects 1 7.3. Engineering Standards 1 7.4 Testing, Design Verification and Design Validation 2

8 Product type and Canvas 6 8.1. Product type and Canvas 6

9 Implement – Strategy Development 7 9.1. Intellectual Property (IP) Strategy 7 9.2. Research and Development Strategy 7 9.3. Clinical Strategy 9 9.4. Regulatory Strategy 9 9.5. Quality Management 35 9.6. Reimbursement Strategy 35 9.7. Marketing, Stakeholders, Sales and Distribution Strategy 13 9.8. Competitive Advantage and Business Strategy 14 9.9. Operating Plan and Financial Model 15 9.10. Communication Strategy 18

10 Impacts and Considerations 19 11 Discussion and Conclusion 20 12 Acknowledgements 21 13 References 22 14 Appendices 24

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1 Executive Summary The present business model aims to solve the need statement, formulated by our research group, a need for a fast, effective and non-invasive acquisition of information about oxygen saturation levels in a patient with vasoconstriction. This need statement arose from a list of insights, after a heavy period of observation composed by interviews with specialists, video and photography obtained from field trips in ambulance and medical air transport. During this period, it was possible to interact with medical staff, from takeoff until the landing, including long conversations directly with the patient. It was observed that digital signals in real time are crucial for an appropriate medical care. If they do not have appropriate and effective information from said digital signals, in an emergency case, attendance process results harder and the patient life could be in danger. The stakeholders of the problem are the patients, the medical team and the private or public companies offering the service. Because of that, the potential market of the final device is significant and therefore, economically viable. This is since current mechanisms for determining the oxygen saturation in blood has the restriction of measuring properly in patients with vasoconstriction and other conditions related to hypothermia and hypotension. In addition, at the state of art it was found that there is just one academic approach to the need statement in issue, which implies that it is an interesting field to innovate. 2 Need Identification and Screening

2.1. Strategic Focus Mission: Identify and provide the solution for needs in air transport and land transport of patients in a state of vasoconstriction and low perfusion, to allow adequate detection of blood oxygen saturation levels. Strengths and weaknesses: As a strength, it is highlighted that members of the group have knowledge in diverse areas due to training in academic areas of biomedical engineering, electronic engineering and mechanical Engineering. As for the weaknesses, there is a lack of in-depth knowledge about the cardiovascular dynamics in patients in a state of vasoconstriction, as well as lack of deep knowledge regarding light wave behavior. However, there are numerous doctors specialized in medical attention during transportation air and land, as well as teacher’s with vast experience in cardiovascular dynamics and optics that can help us with any questions and issues that arise. Acceptance criteria: • Present a betterment on Medical results. • The required resources are available to achieve the desired results. • You have clients that should be cultivated and interested in the project’s outcome. • There is market growth that is anticipated (The need arises directly from the industry). • The project fits in with the mission of the innovators and with their abilities. 2.2. Unmet Need Exploration Pulse oximetry allows the in-vivo examination of arterial blood oxygen. This procedure is done by differentiating oxyhemoglobin from deoxyhemoglobin. Such task is achieved by emitting two

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distinct light wavelengths. One light source emits in the red region (660 nm) while another light source emits in the infra-red region (940 nm) [1]. Once these different wavelengths go through a relative thin portion of the body such as the finger or earlobe, a photoreceptor placed below the emitting light source detects the resulting radiation. It is important to mention the role pulsation plays in this procedure, since the cardiac cycle is constantly changing from a systole (contraction) to diastole (relaxation) one can determine the type of blood that is circulating at any given time. Thus, during the diastole venous blood circulates while in the systole arterial blood circulates [1]. This is important since light absorption is greater in arterial blood than in venous blood [1]. Once the oximeter can tell apart systole from diastole and correlate such with the wave lengths received, the blood oxygen saturation can be easily calculated from the ration between red wavelength and infra-red wavelength in each pulsation [1]. What was noticed during bibliographic research is that in patients in heavy states of vasoconstriction such as is caused by sever blood loss, hypothermia and cardiac shock the detection of blood saturation levels becomes cumbersome or even unachievable [2]. This was confirmed by de medical Doctor Rafael Suarez from Sismedica who mentioned during an interview (which can be read in the appendix) that measuring oxygen saturation levels in patients with grave vasoconstriction was not only difficult but also proved time consuming. Considering Sismedica is a private enterprise focused on the transport of critical patients, such time deficiency could prove costly for the patients in a moment of crisis. Especially in a situation where rapid blood oxygen saturation measurement is needed to adjust the treatment of the patient during transport. Such issue was also brought up in an interview with the medical Doctor Fabio Reyes from Ambulancias Aereas de Colombia S.A.S where he mentioned the difficulty of measuring blood oxygen saturation. Especially when the patient is having a cardiac shock. He also mentioned that sometimes the oximeter could start to give abnormal readings, in which case it is necessary to cover up said instrument with their hands in order to prevent the photoreceptors from receiving light from the environment or detecting vibrations form different sources other than the pulse of the patient. Another interesting fact that he mentioned was that during air transport temperatures can sometimes drop significantly, thus the patient's extremities such as the fingers or toes become vasoconstricted and warming up said appendixes is required to maintain an adequate measurement of blood oxygen saturation. A member of the research team was able to accompany an S.A.S mission to Inirida from Bogota in the transport of a neonatal patient. Although said patients have a special incubator capable of controlling the thermal and humid properties of the environment, we were unable to observe the effects of vasocontraction. However, it was possible to appreciate how important the monitoring of blood oxygen saturation was. This was apparent since the Doctor constantly revised the screen in which blood oxygen saturation was being shown in real time, along with ECG and respiratory patterns. With such information it became obvious to the research team that maintaining an appropriate flow of real time information from the oximeter is of great importance since the transport of patients is a difficult task in which a Doctor, alone with no help other than a nurse, must cope with a hostile environment for him and the patient and successfully manage any complications that might arise during the travel time. Another member of the research team was able to accompany Ambulancias Terrestres on an ambulance ride and was able to observe the importance of vital sings monitoring. It was determined that this sign allow the medical team to take quick decision during emergency situations. What was most apparent in this ride was that the oximeter signal is very inconsistent since it is constantly interrupted by the movement of the ambulance and the light in the environment.

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2.2.1. Observation The observations strategies used were: • Interviews to two medical specialists in air transport. These interviews can be found in the

Appendix 2. • Interview two medical experts in emergency situations. • Once the medical staff receives the patient it must rapidly connect it to its devices and vital sings

monitors to obtain accurate real time information about the state of the patient before the takeoff.

• Videos visualization and photographic content: thanks to the contact with specialists in air transport doctor, it was possible to obtain a video of the oxygen saturation measurement process, on board and some pictures of the current used devices. The YouTube link video is showed below: https://youtu.be/zZzk0BcpeRk

• Visits: One of the team members had de possibility of going to a medical air transportation process and he recorded videos and took photos (Appendix 1). YouTube links are shown below: https://youtu.be/rFirbEWq-tM, https://youtu.be/jnvKByTy9lQ

• We are also making the investigation protocol to submit to SISMÉDICA's committee and so on, to have the possibility of going inside an ambulance during a service. In addition, it is the possibility of talking with an ambulance specialist physician.

2.2.2. Insights To determine which approach was chosen, first, it was obtained a list of insights, as a result of the observation process: • There are not enough standardized methods for the enterprises to determine when it is truly

necessary to calibrate the devices in the ambulances. This implies an over cost to the companies, because, as it can be seen from the interview to Dr. Rafael Suarez, each device calibration implies $400.000 COP, and there are at least six equipment by ambulance.

• It is necessary to find a way to measure the oxygen saturation for patients with vasoconstriction because at this condition, the current used oximeter is not efficient.

• There is still a need of finding more efficient ways to stop faster bleedings, despite there are some options in market as Combat Gauze.

• There is a need of a method to determine quantitative which is the exact measure of oxygen saturation needed by a patient of cranioencephalic trauma, because a wrong oxygen supplement implies more damage to the patient.

However, after evaluating the obtained insights, the need of an efficient measurement to determine the saturation of oxygen in patients with vasoconstriction, was the chosen approach, as it is showed throughout the report. 2.2.3. Opportunities Based on the need previously chosen, it can be said that the value can be improved in the patient in the reduction of risk situations due to not knowing the exact saturation of oxygen in the blood, which can lead to erroneous diagnoses and a bad treatment On the other hand, the reduction of stress by the medical team can be achieved, since there is no power of adequate saturation value, this makes the doctor not know what to follow.

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2.2.4. Core Problem In the medical transportation context, one of the most important steps to save the life of a patient is the determination of oxygen saturation levels. That is because with the level known, it is possible to supply the correct volume of blood, avoiding hurting the patient. It is also useful to determine the quantity of ventilation that the patient requires. This level of ventilation must be well guarded since too much oxygen can cause hyperoxia which means it can intoxicate the patient with too much oxygen, this has numerous problems since it increases the risk of death or cardio vascular events. However, if the level of ventilation is too low, death to certain tissues can happen since cellular respiration cannot take place. On the other hand, when the patient has his blood volume at levels lower than healthy, one of the physiological responses is vasoconstriction. At this condition, blood level in limbs is significantly lower to be well recorder by the current used oximeter. Because of that, medical staff cannot measure appropriately oxygen saturation level, which implies loss of time, trying to obtain qualitative information but finally medical staff should approximate compensation oxygen volume, due to the current method of measurement. 2.2.5. Population The population affected by the problem described above are the patients transported in ambulance or HEMS (Helicopter Emergency Medical Service). Also, with them are their families, medical staff, hospitals and medical transportation companies. According with the World Health Organization (WHO), in a city there should be one ambulance every 25 thousand habitants [9]. With that information and knowing that in Colombia are 48,65million of people, there should be 1946 ambulances. In a more specific manner, in Bogota there were 132 ambulances in constant movement in 2016 [7]. On the other hand, the air medical service has a large network that includes commercial flights and the military service of all the countries. In Colombia, there were 3790 medical emergencies flights in 2015 [8]. Thus, the device that we want to design need to be in every medical transport for a better service to the patient, and for that, all of these transports would be the affected with the problem previously mentioned. On the other hand, intensive care units are another key population in the problem mentioned before. At this moment, in Colombia there are approximately 7874 beds in these sites, which are divided into each of the respective departments of the country [25]. 2.2.6. Desired Outcome Develop a device capable of performing an accurate measurement of oxygen saturation in patients with vasoconstriction in a medical transport environment, in a non-invasive manner and in which the time required to obtain an accurate measurement is reduced. In this way, the possibilities of the patient surviving are increase because the medical staff can know the precise state of health of the patient. It is however important to emphasize that the device is capable of obtaining saturation levels in patients that are not in vase-constriction as well as solve problems associated with the excessive movement and light contamination.

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2.2.7. Problem and Disease State Fundamentals The oximetry has a vital importance on emergencies. While a patient is being transported after he suffered a trauma, medical staff must regulate his vital levels to stabilize him. Especially since the medical staff must connect the patient to its vital sign monitor as soon as they receive said patient. The usage of a medical ventilator helps a patient who is not breathing efficiently to have an appropriate oxygen level in blood. The medical staff must know accurately the oximetry of the patient to regulate the medical ventilator. If the oxygen pressure in the ventilator is too low, the patient can suffer a hypoxic episode that can lead to neural death. Otherwise, if the oxygen pressure is too risk of hyperoxia is taken which can harm the chances of survival of the patient. Thus, a non-precise measurement of the oxygen in blood can lead to an irreversible damage on the patient's organs, or even death. The current method to measure oxygen in blood is a pulse oximeter. This device is placed on the patient's finger. The finger is an ideal part to measure due its small radius and blood flow. The oximeter sends different light waves which are absorbed by the blood and the oximeter's receiver gets the data to be analyzed and measure how much blood is oxygenated per the total blood volume. In an average situation where the patient's fingers are working with a normal blood flow the pulse oximeter is precise. Nevertheless, there are many circumstances where this device will not work properly. The simplest circumstance is when there is light interference. Since the operating principle of the device is light, refraction when an external source of light leaks through its sensors the measurement will be altered. The common method to fix this is by covering the device to make shadow over it which can prove cumbersome during a medical transport. The other requirement to have a precise measurement is to have an appropriate blood volume on the finger. This blood volume can be affected in many situations such as vasoconstriction or a traumatic injury. A patient's finger can suffer vasoconstriction due to hypothermia. In this case, the body opts to reduce the peripheral blood flow to retain core heat. Raynaud’s disease can also affect the blood volume on fingers. The blood vessels, mostly on fingers, overreact to stimuli such as low temperatures or stress, leading to vasoconstriction. In addition, when the patient suffers a serious bleeding the total blood volume will be reduced, then, the blood flow to peripheral areas will be reduced in order to keep the vital organs working. In a flight where the patient has had a finger amputation the medical staff can use the pulse oximeter on toes or even the earlobe. However, in the case of severe burns where the patient’s skin is affected the pulse oximeter will not be able to make the necessary measurement. 2.2.8. Existing Solutions and Current Treatments In the Colombian market place, the most used pulse oximeters are from Edan instruments and Mindray. This was observed in the S.A.S interaction in which it was revealed that most of the medical instruments bought by this private enterprise, especially the life monitoring systems were from said companies. It is important to note that the models these companies sell such as the H100N from Edan instruments [3] and the Pm-60 from Mindray [4] function in a similar way as previously described. Thus, two light sources emit at two different wavelengths. One source emits in the red range while a second source emits in the infra-red range. Since arterial blood (higher oxygen content) absorbs light in a more significant way than venous blood (lower oxygen content), one can calculate the difference in these values and infer its effects, as caused by blood oxygenation levels. Another important aspect of these devices is that they must be able to detect the pulse, which mean it must detect the cardiac cycle in its systole-diastole representations. This is of upmost importance because detectable plethysmography [5] pulsations are necessary for the oximeter to distinguish arterial blood light absorption from venous blood light absorption.

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These current solutions, in the Colombian transport business, offer no alternative to vasoconstricted patients other than switching from appendix to appendix in the hope of obtaining a successful read, or warming up an appendix to allow enough vasodilatation to obtain an oximetry measurement.

Figure 1. Mechanism of an oximeter. [5]

On the other hand, during the visit to the air ambulance commanded by Fabio Reyes, it was observed that the measurement of oxygen saturation was carried out by means of a pulse oximeter, which is coupled to an extremity, either superior or inferior. This oximeter is connected to a vital sign monitor, which presents information on oxygen saturation, blood pressure, heart rate and electrocardiography. This same lay out was observed in the ambulances used in Ambulancias Terrestres. 2.2.9. Stakeholder Analysis

Figure 2. Stakeholder of Oxycure.

Primary stakeholders • The directly affected people are the patients of medical transport of vasoconstriction condition.

Their interests are the preservation of their lives. • The transport specialist physicians and paramedical team are also directly affected by the need

statement at hand. Their interests are to preserve the lives of patients as well as to reduce the time to determine the appropriate supplementation of oxygen according to blood perfusion of patients. They also want to solve as fast as possible each medical case and to have less stressful procedures.

Secondary stakeholders:

Goverment (Law 1151 of 2007) or private resources

Private entity providing the service or Military

Forces

Patient

Family

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• Private entities offering the medical transportation service are secondary stakeholders because,

despite the company management will not interact with the final device, this is going to affect their interests as time and money optimization and the status of the company. If they have lower rates of mortality during the transportation service, they will be more recognized and hired.

• The Colombian State is also involved because it will not interact directly with the prototype, but it will affect their interests. The State aims to spend as efficient as possible the resources for each patient, so if the diagnosis is well realized, it will imply less expenses on the patient.

• The family is also a stakeholder because it is indirectly affected by the diagnosis made by the doctor during the transport, ground or air ambulance, since a family member must be the passenger of the transferred patient. If the measurement is not correct, the patient could die and therefore, the family could suffer from sentimental affiliations.

2.2.10. Market Analysis According to what is mentioned in the population section (section 2.2.2), it can be said that the market consists on all the users described above, like the patients, their families, medical staff and hospitals. In a more specific way, we will focus on ambulances and air medical transport. Thus, in Bogotá you can find 135 public ambulances and 527 private ambulances by 2016. In Colombia, there are 2.523 land ambulances (not including private or social security institutes), 105 fluvial ambulances and 34 seaway ambulances. On the other hand, in air transport there is 3790 national flights of medical emergencies. According to the above, it can be said that our market includes all the ambulances of the district, the country and even the continent. This is because, according to ambulance manuals, one of the basic devices that must be in each of the ambulance is the oximeter. Which means that our product must be carried in each of the ambulances in case of emergency. Because if we do not know the exact value of oxygen saturation in a patient with vasoconstriction, the possibilities of survival are minimum. In addition, these possibilities decrease more if the patient is in a medical transport, such an ambulance or a helicopter. 3 Need Selection

3.1. Needs Statements • A way to isolate light noise to the current method for measuring oxygen saturation in patients

in the emergency environment. • A way to warm extremities like fingers to achieve an optimal measure of oxygen saturation in

patients under vasoconstriction. • A way to address the inaccurate measurement of oxygen saturation in blood on patients

suffering vasoconstriction on the transport environment, which increases up to 30% the chance of death due neural damage

• A way to quickly and accurately measure the oxygen saturation of patients with vasoconstriction in emergency environments.

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3.2. Need Selection In order to select specific need three criteria were raised: The need must be an everyday situation; the solving of this need must increase the patient’s chance to survive the transport to a medical center and the need must affect the medical staff as well. Then, the research process continued by interviewing medical staff such ambulance doctors and aircraft-ambulance operators. A few needs were found on both transports, such as a way to stabilize neonates but still have them in the incubator, or clean-up a patient's skin due a sever burn. Nevertheless, a common need was expressed by every medical worker and it was a way to measure accurately and fast the oxygen saturation levels in blood (oximetry) on patients suffering vasoconstriction. The vasoconstriction can be stimulated by a loss on the total blood volume, high levels of stress, a state of shock or low temperatures. Since all of the conditions mentioned before are a daily situation on the medical transport environment, we opted to choose that need to develop our project. Also, an inaccurate measurement of oximetry can lead to a low input of oxygen pressure on the medical ventilator which will not improve the patient's treatment, and a higher oxygen pressure increases in 30% the chances of neural damage. Then, this need has a vital importance to save a patient during the transport. Finally, during the interviews with the medical staff they exposed how quickly they have to take decisions based on the patient's vital signs, so, since they cannot have the oximetry it can affect the process, they have to treat the patient. To sum up, the need of an accurate oximetry measurement on the medical transport environment is an everyday situation, it has a vital importance on improving a patient's health or even keeping his live, and it affects the medical staff work. 4 Need Specifications

4.1. Selected Need Statement A way to quickly and accurately measure the oxygen saturation of patients with vasoconstriction in emergency environments. 4.2. Need Validation To validate the need found an interview and an incursion in a transfer of a patient was made, in which videos, photos and audios were taken to corroborate the information. The interview was made to Dr. Rafael Suarez, Operative Manager of SISMÉDICA. In this interview, the doctor told us that one of the main difficulties in transferring patients in ambulances was to measure the oxygen saturation because the current methods are imprecise and are considerably affected by optical noise. Without the possibility of knowing the exact oxygen saturation, the patient cannot be provided with adequate ventilation and therefore reduces the chances of survival. On the other hand, the incursion was made to an air ambulance accompanied by the doctor Fabio Reyes who is medical director of the company Ambulancias Aereas de Colombia. In the incursion to the ambulance, it was observed that the difficulty in the measurement of oxygen saturation was true; in addition, it was possible to observe the complete procedure required to perform the measurement of oxygen saturation of the patient. With the help of the information collected with the interview and the incursion in air ambulance, it was possible to identify the need to build a device capable of making a correct measurement of oxygen saturation. It was also noticed during this air travel that light contamination is a big factor in the disruption of the signal, as the doctor often had covered the finger of the patient and wait for the signal to stabilize again.

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On another occasion it was possible to travel by ambulance with Ambulancias Terrestres. Here we observed how on several occasions the pulse oximeter was ejected from the patient’s finger during the transport. This was since ambulance travel is accompanied by a lot of movement associated with the acceleration and de-acceleration of the vehicle. This proved time consuming as the doctor, Yadine Alvarez, had to put it back on and wait 10s-15s for the vital sign to re appear on the monitor. Further investigation yielded that critical patients who are losing a lot of blood or are entering vasoconstriction have problems with the adequate detection of blood oxygen saturation levels. According to the head doctor in the ambulance this event is cumbersome and time consuming since the knowledge of the patient’s saturation levels in such critical condition is of great importance to modulate the level of ventilation said patient is receiving. Another member of our research group was able to interview a doctor in the Roosevelt institute. Alejandra Suarez, a doctor in the emergency room of said institute, told us that measuring oxygen saturation levels in critical patients was difficult since conventional devices often failed to pick up the signal or give an adequate value. This often put her in a tricky spot since her superiors pressured her to quickly give a saturation value, but the device often left her stranded waiting for an answer. Finally, to validate the need, a bibliographic search was carried out on the main drawbacks of the devices currently used to perform oxygen saturation measurement, and it was found that the main drawbacks were the imprecise measurement in extreme conditions, the uncoupling and instability of the pulse oximeters, the discomfort that the patients presented when using the device, easily disruption of signal from environmental factor, among others. In addition, information was also sought on the complications that could result from not knowing the exact value of oxygen saturation in a patient being transported in an ambulance and it was found that life expectancy was reduced if the patient was exposed to high amounts of oxygen ventilation during its stay in the emergency ward [19]. 4.3. Need Criteria and Specifications The device must be precise under severe circumstances, such as low temperatures, burns, bleedings and shocks. It should be easy to use and comfortable. It could be adapted to the traditional screens and medical equipment. It will not be expensive. 5 Concept

5.1. Design Constraints The limitations that our designs would have are: • Health and safety: the coating material of the design cannot be made of cooper or heavy metals

– like lead – because that can generate intoxication in the patient for prolonged use of the device. In addition, the device must be designed so that it does not affect the safety of the patient with a failure in the electrical circuit or with a fracture in the coating.

• Economic: It is necessary that the price of the device be between the ranges of reasonable prices for a market like Colombia. In addition, it is important that it become competitive with the other devices that can be found in the market, with this it means that the cost benefit of the design is comparable with the existing ones.

• Environmental: For the design, it is desired that the materials can be environmentally friendly, that is, that they degrade in a reasonable time, and that there are not so many solid waste

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pollutants after use that a large amount of greenhouse gases will not be generated during its manufacture and that can be reusable as many times as possible.

• Social: It has required that they do not have specific elements of the design or operation that can be considered racist or elitist.

• Ethical: the device can only go to the market when it has been corroborated in a precise and safe way that the correct measurements of oxygen saturation are given for different medical situations.

• Regulatory issues: The device must be within the framework of the current regulations of Colombia with respect to health and medical devices, among which we could find the INVIMA, the District Health Secretary, the WHO, among others.

• Manufacturability: in this aspect, it is not possible to carry out a design that requires complicated manufacturing in the sense of the use of expensive equipment, materials that are difficult to handle, among others. For the price to be reasonable within the framework of these devices, the materials and their processing must be as economical as possible. It is worth noting that it must have rechargeable batteries so that the device in question is mobile and reusable.

• Sustainability: It is ideal that the device does not require much maintenance or replacement of parts to be durable in its use in emergencies.

Now, the experiments of the device would be developed in humans. For ensure the safety of the subjects, its necessary first take all the experimentation in software like Inventor, Arduino IDE, and others. Then, after all the proofs of the device, it would be tested in vitro, it means with samples of blood with a skin layer between. Finally, it will be test in the ear of a human subject. For this part, it would be important make an informed consent for them, and with this, the subject will know all the risks and problems that can be produce with this proof of the device. 5.2. Ideation and Concept Generation To find an actual problem on the biomedical field we started interviewing medical staff. One of the first interviews was with Dr. Rafael Suarez, a doctor who works at SISMEDICA. This enterprise works with helicopters and light aircrafts to transport patients to different cities in Colombia. He expressed us some difficulties that occur during this process. The inconvenient that we focus on later on the research was the difficulty acquiring accurate and rapid information regarding the blood oxygen saturation in patients under vasoconstriction. When a patient is being transported it is supremely important to know his vital signs. Then, the medical staff can control his oxygen saturation to bring it to normal levels and avoid neural damage or death. After talking with Dr. Suarez, we talked to Dr. Fabio Reyes, who works at Ambulancias Aereas de Colombia, a company that also transports patient on helicopters and light aircrafts. On this interview we confirmed the need of a new device to measure oximetry when a patient does not have a normal blood flow on fingers. We started a research on oximetry and found that the oxygen levels on blood cannot be read when a patient is under stress or low temperatures due his low blood volume. We then talked to professor Juan Carlos Briceño, a researcher on cardiovascular dynamics. He confirmed our idea to measure oxygen levels on parts of the body that have a permanent blood flow but still are peripheral areas. Studying the literature, we found that the best area to measure oxygen is the ear canal. It has a constant blood flow and can be easily isolated from light interference. Also, is it a comfortable place to locate a device. At this point we knew the problematic and a solution, so we began to investigate how the traditional pulse oximeter can be modified to measure on the ear canal. We have been reading papers and studying optic signals to be able to measure oxygen levels in blood on a noninvasive way. We are currently working with professor Mario Valderrama, an expert on biological signal’s acquirement and processing. Simultaneously, at the same time we work on developing the sensor

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for the oximeter, we are working on the form and fit of it. We want to have an oximeter that is stable and will not move during a patient transportation. Also, we want the oximeter to be comfortable enough for the patient to use it on long periods without causing inconveniences nor pain.

Figure 3. Prototyping.

Quickly we set out to brainstorm different ideas with the insight that the on-field observation brought us along with the opinions of Juan Carlos Briceño. First, we decided to sketch a rough draft of the brainstorming process. As we can see, the idea of measuring saturation levels in the nose canal was explored but do to possible problems with sanitary maintenance the idea was eventually abandoned since reusability was an important parameter. We also explored the idea of a glove-like device that was able to heat the appendages enough to allow for vasodilatation, a phenomenon that would allow for a better reading of oxygen saturation levels since vasodilatation permits the passage of blood easily through the fingers. However, since this design only fixes vasoconstriction caused by low temperature levels it was quickly abandoned since it could not apply to a number of circumstances that are present in emergencies (hypovolemia, shock, cardiovascular events, etc.). Another idea that was explored and further developed on paper was an oximeter in the tongue since this muscle has a high perfusion rate and is relative thin, so it would allow the conventional method of transmittance. However, we quickly encountered that the reusability from patient to patient was strained since the whole device would be in contact with the body fluids of the patient, and so it was quickly scraped for other, more feasible options. Later in the brainstorming session, the idea of lab-on-a-chip saturation device was postulated since it would allow the measurement of gas levels through microliter drops of blood. However, of lab-on-a-chip devices by their nature are a onetime use, since the chemical reaction, once occurred, cannot be undone. Talking to medical experts it was established that the time-continuous signal was essential to monitor the patient in an adequate way, since the device at hand would allow the doctor to obtain information about the saturation blood levels in instants of time and not a in a continuous way the idea was scraped. Two ideas survived the brain storming process; 1: An auricular like design that would allow for the measurement of blood saturation levels in the ear canal. 2: A clip on device in the ear that would protect the sensor from light noise and vibrations, as well as provide head in the ear structure too allow for vasodilatation in the adjacent capillaries.

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The resulting ideas were extrapolated to life size prototypes made from soft polymers and where subjected to experimentation with users as well as context try outs. This would allow us to validate our designs in real world encounters.

Figure 4. Iteration Method.

To property explain our qualitative and quantitative methods used to compare the ideas employed in the brain storming process we graded the requirements compared them in each prototype.

Table 1. Requirements of the prototype. Requirement Weight

Must be comfortable 3 Must be reusable. 4

Must be noninvasive. 5 Must be stable in prolonged use. 3

Must be small 1 Must be light weight. 2

Once the device requirements were defined, it was possible to determine that our gold standard would be the auricular pulse oximetry since it meets most of the requirements, being that it is non-invasive, reusable, comfortable and stable. It is worth noting that the auricular design allows it to be reusable. This is all thanks to the fact that the earpiece (which is in direct contact with the ear canal) is made of medical grade silicon that is disposable. That is to say, the silicon portion is easily disposable and interchangeable with another clean silicon aperture.

Observation •Interviews and field observation

Reseach•Literature study and mentor assesorement.

Prototyping•Development of prototypes based on the results of the research.

Testing•Adquisition of data of the prototype perfomance.

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Table 2. Evaluation of the prototypes based on the table 1. Requirement Auricular Nasal Lab-on a Chip Heat Glove Clip-on

Must me comfortable 1 0 0 0 0

Must be reusable. 1 -1 0 1 0 Must be

noninvasive. 1 0 0 1 1

Must be stable in prolonged use. 1 1 0 1 0

Must be lightweight. 0 0 1 -1 0

Must be small 1 1 1 1 1 Rank 5 1 2 3 2

Pulse oximetry by means of reflectance in the auditory canal has a great potential when solving the various problems observed in medical transport of patients. Due to the anatomical location of the device, it allows us to implement an ergonomic ear design, which provides an exceptional grip when resisting sudden movements. This is evidenced in the tests carried out by the group, test subjects were moved from one side to another on stretchers simulating sudden and brisk movements, which yielded desired results since it was observed that the design was stable and was not destabilized when compared to the rest. On the other hand, as suggested by Dr. Yadine, the comfort of the design in question was also tested since this is an important parameter for elderly patients and patients with mental disabilities, since they can be inpatient and will readily take of the pulse oximeter. When testing the comfort of the design in question, using several test subjects the unanimously agreed that this (auricular design) was the most comfortable since the weight was not felt on the ear and did not become painful in the ear canal after an extended time of use. At the same time, they agreed that the design maintained a great stability since it allowed them to move in different ways and at different accelerations without worrying about the destabilization of the device in question. On the other hand, although it was not possible to test it, the circuit and therefore the infra-red sensor need implement said sensor’s, it has been found in literature that the auditory channel presents a natural isolation of different sources of light that can interfere in the reading of photoreceptor and therefore in the reading of pulse oximetry. This and the sudden movements are the main source of error in the reading of pulse oximetry in the transport of patients. Once we determined that, the reflectance pulse oximeter was the best fit to our requirement we quickly constructed a CAD design to bring our ideas to life.

Figure 5. First CAD design.

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However, it was brought to our attention that this design is too bulky and heavy sided to be wearable in the ear canal. It was also determined that it could interfere with the earrings of patients and since Oxycure wishes to represent all our costumers fairly we decided to reduce its bulkiness and make friendlier design. 5.2.1. Helmeier questions What are you trying to do? We are trying to improve the time that the medical staff spent in know the oxygen saturation of a patient with vasoconstriction. Why is this need important? Because if we do not know the exact number of oxygen saturation in a patient with vasoconstriction, the possibilities of survival are minimum. In addition, these possibilities decrease more if the patient is in a medical transport, such an ambulance or a helicopter. How is it done today (if at all)? The lecture of the oxygen saturation of the patient in an emergency it is done by a pulse oximeter from Edan instruments and Mindray. What are the limits of current solutions? or in what ways are current solutions inadequate? The limits of the above current solution are the imprecise measurement of oxygen saturation. That is because the interference that undergoes the device by optical noise. What is new in your approach and why do you think it will be successful? The innovation in our approach is that the device does not use the superior limbs of the patient for the measure of oxygen saturation. Instead of that, we will use a little cavity near to the source of oxygen in the body, like the ear. Who cares? The current problem cares to the medical staff in all the means of medical transport, and the hospitals. Also, the patient’s family and himself. If you are successful, what difference will it make? The main difference that we want to make is that the chance of survival of patients with vasoconstriction increase in a better way, giving them more possibilities to live. What are the risks and the payoffs? The main risks that our device can entail is do not take an accurate measurement of oxygen saturation of the patient and lead the doctor to erroneous conclusions about the diagnostic. The payoff that will give our device is the reduction of the time spent performing the procedure of measure oxygen saturation. In addition, it will be increasing the precision of the measure. How much will it cost? (This will be refined later) One hundred thousand of Colombian Pesos (100.000 COP). How long will it take? It depends of the development of the device in the investigation and experiment phase. We will expect that take about 2 years for the creation and much more for the test.

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What is the midterm and final “exams” to check for success? We will compare the actual method of measure oxygen saturation with our method in terms of time of measure, measurement accuracy and with the opinion of all the persons involve in this problem. 5.2.2. Feasibility The 7th cause of death in Colombia are Traffic accidents [20]. In Bogotá, it happens 800 traffic accidents daily, and in Colombia, “Centro de Referencia Nacional” reported that daily at least 18 people die due to traffic accidents. In 2017, 5.803 persons died in traffic accidents in Colombia [20]. Annually, the SOAT (“Seguro Obligatorio de Accidentes de Tránsito”) reported 500.000 medical attention covered by that insurance policy [20]. By another side, according to World Health Organization (WHO), it is recommended to provide 1 public ambulance for each 25 thousand people. However, in Bogotá, there is 1 ambulance for each 60 thousand people [21]. According to the medical experts we talked, as Dr. Rafael Suarez, expressed the difficulty to measure vital signs, particularly, oxygen saturation, with current devices used in ambulances and medical context, as pulse oximeters. The principal reasons of complications during measuring were attributed to hypothermia and hypovolemia (patients under vasoconstriction), problems of stability of the pulse oximeter, discomfort in patients with special conditions that caused the pulsoximeter to be removed by them and polish nails. Emergency physician as Dra. Alejandra Suarez and ambulance doctors as Dra. Yadine, also talked about the extra-time needed to correct factors of misreading but at the same time, the high stress pressure that it implies because against clock medical attention needs. Studies showed that measures of oxygen saturation done by current method of pulse oximetry present errors coming from lighting in contexts like in electro surgery or in light noisy contexts. Other factors as nail polish can cause a 6% underestimation of saturation and long nails also affect the measurement [22]. Physicians and paramedic staff corroborated those problems during their vital signs measurements protocols. Current way to analyze blood sample when the pulse oximeter reading is not accurate, or it is mistrusted is through a multiwavelength in vitro oximeter; however, this technic can be also altered by other blood components like fetal hemoglobin, bilirubin and intravenous dyes [22]. In addition, in vitro technic is not a feasible possibility in emergencies context. However, Oxycure is a viable solution because it performs the measurement of oxygen saturation based on the reflectance principle, in the auditory canal, thanks to the continuous perfusion, due to its proximity to the brain. It performs the acquisition of data by means of an adaptation to the existing module MAX30102 oximetry sensor module, the data processing by means of an Arduino NANO, and the sending of the information with a Bluetooth HC-05 communication module. Software as MATLAB and Arduino IDE are used. On the other hand, it is highly stable since it uses several support points, and an adequate weight distribution, avoiding damage to the walls of the ear canal, generated by the torque exerted by the device. By another side, at Oxycure design team is made up of students from last semester of Biomedical Engineering. The team also has Electronic and Mechanical engineering students. Design team members have experience performing extracurricular projects related to engineering problems as robotic prosthesis, 3D printing splint novel design for hips dysplasia, geothermal energy resource for Paipa cheese optimization, and other academic projects. Team members have belonged to research groups related to biomaterials and cell culture, innovation seminars and student chapters. Oxycure team members participated in innovation challenge where experience in biomedical

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engineering innovation was obtained and the possibility of continuing innovating abroad. Work team is characterized by high responsibility and commitment levels. The multidisciplinary of the group allows an excellent accomplishment of the tasks, from the area of greater knowledge of each member. Oxycure work team has close contact with transport and emergency specialized doctors as Dr. Fabio Reyes from Ambulancias Aereas de Colombia and Dr. Rafael Suarez from SISMEDICA. The company of air and ground ambulances SISMEDICA offered to Oxycure team work to perform research in real context and to consult when needed, the experts of that company. Oxycure work team also have contacts with medicine specialists from Roosevelt Institute, from Fundación Santa Fe, from Simon Bolivar Hospital and private hospitals. 5.3. Ideation and Concept Selection To determine the most appropriate sensor to be used according to size, anatomical and physiological constrictions, there were analyzed three options of pulse-oximetry modulus: MAX30100, MAX30102 and GY-MAX30102. There were also analyzed other sensors required for the performance of the device as Arduino Infrared sensor FC-51, Bluetooth module HC-05, voltage regulator and heat dissipater. The advantages of the infrared sensor FC-51 are its low cost, its easy implementation and a low power consumption. However, the FC-51 sensor has low sensibility, digital performance; it was not designed for medical uses but for sports applications and its technology is based only in infrared light. The pulse-oximetry module MAX 30100 was designed for medical applications. It has a low power consumption; it can filter the environmental noise and it has an intermediate cost. However, its size is not adequate for using it inside ear canal and it is hard to implement. The pulse-oximetry MAX30102 uses red and infrared light to measure. It has a low power consumption and an intermediate cost. However, it does not filter environmental noise, it is hard to implement, it was not designed for medical applications and its size is bigger than required for using it inside the ear canal. The pulse-oximetry module GY-MAX30100 was designed for medical applications, it filters environmental noise, it has a reduced size, it is easy to implement, it has a low power consumption and an intermediate cost. However, it is difficult to find it in the market. According to the previous parameters, the matrix showed below summarizes the decision-making process to determine the most appropriate module to be implemented, where five is the highest score and one the lowest by parameter.

Parameter MAX30100 MAX30102 GY-MAX30102 Low cost 3 3 3 Ease of

implementation 1 2 5

Low power consumption

5 5 5

Medical applications 1 1 5 Environmental noise

filtering 5 1 5

Small size 1 1 4 Ease to find in market 4 4 2

Total 20 17 29

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According to previous scores, the most appropriate pulse-oximetry module is GY-MAX30102 with the highest performance in the evaluated parameters. Once we determined the problem of obtaining blood saturation readings in emergency settings such as patient transport by land, air or emergency room visits with patients in a high state of hypovolemia or cardiac deficiency, we set out to find a better place to obtain continuous reading of blood saturation levels in a place that was not limited to peripheric structures of the body. With this in mind, we rapidly developed various ideas of oximetry in places where blood flow was relatively constant (As can be observed in figure 3 of this document). However, with the help of medical professionals we quickly discarded the tongue and nose prototypes because they can pose as health hazards and are not comfortable for the patients. Also, if the patient is using a nasal canula or requires tracheal intubation the device would be useless since it cannot interfere with other medical procedures. The glove idea was also discarded because it still obtains saturation readings from peripheric structures which is something that we don’t want to depend on, especially if the patient is in abnormal conditions. Later de LoC (Lab on a Chip) device was also discarded since it provides an instantaneous approximation of the saturation content in the blood, it does not however give the medical staff a real time continuous reading of the blood saturation levels since LoC devices require biochemical reactions like the ones carried out in laboratory settings to determine the results. Once the reaction is carried out another LoC is required to monitor the saturation level again, which would mean that several samples have to be taken in order to constantly have a new saturation level reading. Lastly, we cut down the candidates to two, the inner ear canal oximetry sensor and the outer ear structure sensor. Since we learned that no commercial oximeter obtains its readings from the inner ear canal exists in Colombia, we decided to pursue this idea further.

Figure 6. Ear canal irrigation. [10]

With the help of medical professionals, we quickly realized the potential of inner ear oximetry since it has a high blood flow that is not easily disrupted by cardiac deficiencies or hypovolemia since it is situated so close to the central nervous system. It is important to note that commercial oximetry sensors use a mechanism of transmittance to obtain data, as was explained in figure 1 of this document. However, this mechanism is only useful in peripheric structures since it requires a thin object to send the IR and NIR light through. Another drawback of such designs is that they are highly susceptible to environmental noise, such as light noise that is quite common in transport environment or vibrations caused by rapid movement which is also common in emergency transport environments. Our proposed solution discards this

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mechanism in favor of a reflectance-based solution. This means that the data is obtained by reading information from what came back with respect to the IR and NIR signals that where sent, as opposed to the common transmittance solution that requires one sensor to send out IR and NIR signals and a second one to receives de information that came through. With this reflectance-based mechanism we can move on from peripheric structures and concentrate on other structures, such as the inner ear canal, that are more adequately irrigated regardless of conditions. With this defined we want to implement said sensor in the inner ear canal because as it can be seen from figure 10 it has irrigated by a wide variety of blood vessels. The one specific structure in which we want to concentrate is the superficial temporal artery since is the one closes to the wall of the canal and has a high continuous blood flow since the external carotid artery gives rise to it. Since the auricular headphone design is intended to perform as a stable platform it will not only block light noise, consequence of its anatomical location, but also it is intended to block noise that arises from rapid movement. This is because it is expected that the stable structure will not allow displacement of the device. Such ideas were proved during prototyping of the design since we simulated ambulance-like settings in which sharp turns, rapid accelerations and de-accelerations did not affect the stability or cause it to fall off from the ear canal. All in all, the auricular design coupled with a reflectance-based sensor was chosen because it provided a variety of advantages when compared to our earlier prototype ideas. It also provides notable advantages when compared to commercial oximeters since it has the potential to limit background light noise and vibration noise that can interfere with the saturation readings. Also, we were able to determine that because of its anatomical location irrigation is constant and readings will not be burdened by patients who have arrhythmias, other cardiac anomalies or hypovolemia which can cause peripheric structures to enter vasoconstriction and consequently make saturation readings harder in said places. It's worth mentioning that although this is our vision for the future, our current sensor technology did not allow us to reduce the size enough to be able to fit it into the ear canal, because of this a patch solution was implemented. This patch solution allows the user to attach the sensor anywhere on the body to measure adequately the blood saturation levels. This is was especially useful when applied to areas where there is a large amount of blood flow such as the carotid arteries in the neck. 5.4. Final Concept

Figure 7. Process of application. [10]

Under this scheme [10], the user problems and their requirements were identified, these being the problem of obtaining an adequate reading in low perfusion, stability, comfort and protection against signal noise. Considering the success and failures of the iterative process, we redesigned the auricular device to remove much of its bulkiness.

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Figure 8. Final design.

The internal circuits were removed from the ear structure and mover to a lower structure which can be attached to the arm of the patient via an armband. It is worth noting that the battery employed is within this structure, so it has a port that allows the recharge of the device. Said feature is of upmost importance since it is essential for the device to be reusable. Since this device is not invasive, it does not present a great risk for patients. Because of this, it is considered that the materials used can be similar to the materials currently used in the construction of headphones. We consider that for the area of the device that will be in direct contact with the auditory canal, medical-grade silicones should be used since it is biocompatible with the internal tissue and should be comfortable enough to allow extended use. At the same time, we consider that this silicone component should act as a lining on the structure, that is, it can be removed or put on in order to facilitate the re-use of the device with other patients. On the other hand, the components of the device that do not come into direct contact with the ear canal can be made of PVC, PC or PE [11] since these plastics are hard and have the ability to resist the wear and tear associated with constant use. Finally, the implementation of the sensor requires an Arduino one or a Raspberry Pi, LED with two different wavelengths (Red and infra-Red) cables and an Arduino module called MAX30100. It is worth noting that to disinfect the device completely (not just the portion that is in contact with the ear canal) EO can be used since it requires no heating that could possibly damage the internal circuits. The group has many strengths since three of the five members are currently doing a double degree program. Manuela Vargas and Alejandra Riveros focus this double program on mechanics, while Daniel Baron focuses on electronics. At the same time, throughout the semester it has been evidenced that all the members of the group are highly responsible, that is, each one can carry out their assigned task. In turn, we found that if there is a case where a member needs help, each member could request it in time to avoid slowdowns group project. This demonstrates a broad communication within the group which is essential to perform jobs as complex as the construction of said device. At the same time, there is empathy between the group, which facilitates the process of brainstorming and creating or testing the device. That is, each member can adequately receive constructive criticism to push the final solution forward. On the other hand, the present contacts that the group must carry out the proposed task are Dr. Yadine, Doctor Rafael Suarez, Mario Valderrama and Juan Carlos Briceño. Dr. Yadine and Doctor Rafael guide us in the design of the

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device to maximize comfort and stability, while Mario Valderrama and Juan Carlos Briceño guide us in terms of the technological implementation of the device. Material’s: PVC o PC, medical grade silicon Arduino, LED, cables, MAX30100. Required services: 3-D printing and PCB workshop once the prototype is implemented. In case that the implementation of pulse oximetry by reflectance is not feasible, as a group we have decided to explore the option of pulse oximetry by means of transmittance while maintaining the ergonomic auricular design since this has proven to be a comfortable and stable way to maintain in place for a considerable amount of time. 5.5. Product name

Figure 9. Product Name.

6 Proof of concept (killer experiment) - Accurate measurement: The first experiment we made to test the sensor and its measurement accuracy was to read the oximetry on a finger. That process was checked with a commercial pulse oximeter to see the percentage of error that our sensor has and calibrate it. The sensor had less than 3% of error measuring the oximetry, yet, the measurement of BPM was far away from being accurate. We could not have an exact measurement of BPM since the data changed from 100 to 323 in a matter of seconds. That inaccurate data might be due the lack of isolation that the device has against the light in the ambient. - Fit: An appropriate fit in the ear would lead to a better measurement of the oximetry due the focal point of the lasers. If the focal point moves in the ear canal the signal that the sensor receives would vary not because of the oximetry but because of different properties of the blood vessels distribution. Since we need a tight fit in our device, we are using two main points of contact to fix it to the patient’s ear. First, we are using a rubber structure that goes around the ear to keep the sensor stable, and we are also using a flexible silicon earbud that fits in the ear canal to seal it. The test we made to prove the concept of the stability in our device was using a prototype and fixing it to a subject’s ear. Then, we laid him down on a hospital bed to imitate the conditions on an emergency situation and moved him around on an irregular path to test the stability in the worst scenario. As a result, we found out that the structure is stiff enough not to let the oximeter to fall while being flexible to do not hurt the patient and provide a tight fit. Future tests to proof the device will be taken on animals. We are considering testing the sensor into a horse’s ear canal since it is about 40% bigger (1cm) in diameter than the human ear canal.

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7 Product

7.1. Product Specifications Based on the proof made in the last weeks, the working group consider that the best device to achieve our need statement is the oximeter implemented in the ear cavity, using the reflectance of infrared rays and the Bluetooth module HC-05. Electronic Circuits The working group proposes some circuits that can be implemented to measure the oxygen saturation. However, it is important to specify that these circuits are not definitive, and the working group can apply or modify any of these and build the final circuit topology.

Figure 10. Circuit Topology using the module MAX30100, HC-05 Bluetooth Module, Arduino Nano and 9 V battery.

An interactive schematic of the circuit proposed is shown in the Figure 7. The real circuit depends of the real dimensions and the shape of the final device. The use of 9 V battery is in consideration yet because it has a great dimension and a high weight. However, in general the topology of the circuit is the shown in Figure 3. This schematic was created using Fritzing®. Electronic modules To build the schematic shown in the figure 7 is necessary to use two modules and one microcontroller. The specifications of the modules and the microcontroller are described below: • HC-05 Module: This module uses the Bluetooth technology to send information without using a

physical connection. This module is preconfigured like Master and Slave, it means that the HC-05 module can send and receive information of other devices. In our project, the working group decide to use this module because it is necessary and useful to avoid physical connections that can produce interference with other devices of the patient’s transport.

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Table 3. Pins of the HC-05 Module and it's descriptions [14].

Figure 11. Representation of the pins of the HC-05 Module. This image was taken from

https://alselectro.wordpress.com/tag/bluetooth-hc05/

• GY-MAX30100 Module: The MAX30100 is an integrated pulse oximetry and heartrate monitor sensor solution. It combines two LEDs, a photodetector, optimized optics, and low-noise analog signal processing to detect pulse oximetry and heart-rate signals. The MAX30100 operates from 1.8V and 3.3V power supplies and can be powered down through software with negligible standby current, permitting the power supply to remain connected at all times [15].

Figure 12. Pin Configuration of the MAX30100 Module [15].

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Table 4. Pin description of the MAX30100 Module [15].

• Arduino Nano: The Arduino Nano is a small, complete, and breadboard-friendly board based on the ATmega328P. It has almost the same functionality of the Arduino Duemilanove, but in a different package. It lacks only a DC power jack and works with a Mini-B USB cable instead of a standard one [16]. The working group decides to use this Arduino because is very small and light and it have enough pins to connect the different modules that will implement in the project.

Figure 13. Pin configuration of the Arduino Nano. This image was taken from http://zerote-

informatica.com/productos/index.php?route=product/product&product_id=75 In addition, it is necessary to use a screen to present information about oxygen saturation. The working group proposes the use of an LCD screen because it is cheap, and its use is easy. The information about the LCD is presented below. • LCD (Liquid Crystal Displays): Liquid crystal displays offer a very fast and striking way to display

information in the form of text. The most common character LCDs are 4 or 8 bits, depending on the number of wires (bits) that must be connected to the circuit to receive or send data. Each LCD model is different, so it is very important to consult your specific data sheet to be able to distinguish the different connection pins it offers and its general characteristics. However, the most common is that a standard LCD screen offers a pin to receive power and another pin to connect the screen to ground, a pin to adjust the contrast of the screen, three control pins usually marked "RS", "In" and "RW", several pins to establish parallel communication lines and, finally, two exclusive pins for the backlight circuit [17].

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Figure 14. Pin representation of a 4-bit 16x2 LCD. Image taken from http://howtomechatronics.com/wp-

content/uploads/2015/07/LCD-Display-Tutorial.png?x57244

Table 5. Description of the pins of a 4-bit 16x2 LCD. PIN Characteristic GND Ground or point of potential difference 0. VCC Power pin of the device. Vo Pin to set the contrast of the LCD.

RS Pin that serves for the microcontroller to tell the LCD if it wants to show characters or if what it wants is to send control commands.

R/W Pin to determine if the screen will provide or receive information. E Pin to warn the LCD that the microcontroller is going to send data.

D0-D7 They are used to establish the communication lines in parallel where the data and control commands of the Arduino board are transferred

to the LCD.

A Pin used to control the backlight, this pin is connected to Voltage, usually 5 V.

K Pin used to control the backlight, this pin is connected to GND. Mechanical parts To show the mechanical parts of the oximeter the working group built a CAD in Inventor. The results are presented below.

Figure 15. Oximeter CAD’s built in Inventor.

Figure 16. Oximeter case and patch.

Software Arduino IDE: The open-source Arduino Software (IDE) makes it easy to write code and upload it to the board. It runs on Windows, Mac OS X, and Linux. The environment is written in Java and based on Processing and another open-source software. This software can be used with any Arduino board.

MATLAB: MATLAB combines an improved desktop environment for iterative analysis and design processes with a programming language that expresses matrix and matrix mathematics directly. MATLAB is an interactive system whose basic data element is an

array that does not require dimensioning. This allows you to solve many technical computing problems, especially those with matrix and vector formulations, in a fraction of the time it would take to write a program in a scalar no interactive language such as C or FORTRAN. *The information above was taken from official sites of corresponding software. 7.2. Regulatory Aspects To classify our device according to the FDA requirements we made a research on similar devices. We found an oximeter that reads oxygen saturation on blood placed over the ear. According to this, our device would be on FDA Class 2 medical devices. This classifies our device as a general control or special control due its performance standards. In addition, it would be in the Part 870 (Cardiovascular device) and subpart C (Cardiovascular monitoring device) [18]. 7.3. Engineering Standards Considering the amount of contact that the device will have directly on the epithelium of the ear canal and the ear in general, it is necessary to carry out biocompatibility tests to avoid complications in the patients. However, to avoid the implementation of tests that comply with Biocompatibility testing (ISO 10993-10), it was decided to use materials that have been previously approved by regulatory entities in order to be used in medical applications. Among the plastics that we consider as strong candidates for use in design (PVC, PC, PE, medical grade silicone) all have been approved by the FDA for use in other medical devices. On the other hand, since the device in question will have electrical components, it is necessary to carry out current tests that comply with the IEC 60601-1 electrical safety tests standard. Since it is an internally powered type device, it requires several tests to check if there is a current risk that may affect the patient. This includes a visual inspection of the electronic components and the measurement of resulting currents in both the normal and the single fault states. This means that several experiments in both normal and single fault conditions must be performed to check whether the amount of current emitted can be dangerous to the patient. In turn, the possibility of 'patient leakage' should be considered, where the current flows from the patient to the device. However, it is worth noting that our device does not require 'earth bound tests' since these only apply to CALSE I equipment [12]. Lastly, a FMEA analysis [13] will be considered: Step 1. Identify possible sources of failure: Fracture in the design, short circuit, inadequate reading of blood oxygen saturation. Step 2. Determine the severity in case that the event occurs (S)

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Table 6. Rating Meaning

1 No effect 2 Low 3 Minor

4-6 Moderate 7-8 High

9-10 Very High Step 3. Determine the probability that the event occurs. (O)

Table 7. Rating Meaning

1 No effect 2 Very low 3 Low

4-6 Moderate 7-8 High

9-10 Very High Step 4. Determine the probability that it will occur during the trials. (D)

Table 8. Rating Meaning

1 Very High 2 High 3 Moderate

4-6 Minor 7-8 Low

9-10 Very low

Risk Priority number (RPN) = S·O·D Fracture = (8)(4)(1) = 32

Short circuit = (8)(3)(5) = 60 Inadequate reading = (9)(6)(7) = 378

In conclusion, it is considered that most of the organizational efforts should focus on making an adequate and appropriate reading of blood oxygen saturation in diverse context.

7.4 Testing, Design Verification and Design Validation Methods used to evaluate and its justification: • Functionality: Because the prototypes were used just to evaluate stability, comfortability and setting time performance, it was not still possible to determine if the device can measure effectively the oxygen saturation levels in the patients. However, according to the test made with current pulse-oximeters, it was corroborated that the evaluated model has limitations measuring under low blood perfusion conditions, as video one can corroborate (Appendix 3).

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The test was performed first bye measuring the subject’s oxygen saturation without interventions. Then, the design team set a rubber in the finger of the test subject, and the same oximeter measured the saturation level. As the video 1 shows, the device cannot measure oxygen levels because of the obstruction in blood flow in the finger. That test allowed the design team to understand better the analyzed problematic. The justification of the test was to validate one of the scenarios where the current oximeter fails that is under low perfusion. • Performance: To evaluate performance, the design team made in cold porcelain the exterior design of two finalist prototypes. These were determined after evaluating the advantages and disadvantages of proposed prototypes in brainstorming step (figures 5 and 6 shows results). After that, it was quantified the time required to set the proposed prototypes in test subjects. In the table 3, it is exposed the time required to set the finalist prototypes, and its difficulty, according to the videos found in the links in appendix 3.

Figure 17. Prototype wireless-

Figure 18. Prototype concave.

Table 9. Performance tests summary.

Prototype Time to set Difficulty Wireless prototype 5 seconds Easy Concave prototype 14 seconds Medium

According to results, it can be concluded that the Wireless prototype has a better performance according to Time to set and Difficulty, compared with Concave prototype; it was required just 35,71% of Concave prototype total time to set the first prototype. However, when Time to set is compared with current pulse oximeters models, it is evident that current models are faster to set in patients because of the easier accessibility of fingers than ear canal. Nevertheless, an important factor to consider is the experience of paramedic staff to measure oxygen saturation levels with current models; with an appropriate training, paramedic staff could spend less time setting the Wireless prototype. To demonstrate the performance of the device, a validation test was performed. In this test, the Wireless prototype was coupled to the cavity of a patient's ear, and the patient transport environment was simulated. It is important to note that in the patient transport environment there are constant movements and vibrations that cause the oximeter to be decoupled and the data collection interrupted. During the validation test the device showed great stability and a continuous

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sensing was observed thanks to the support that prevented the oximeter from undocking from its measurement site. As a conclusion to this test, it was observed that the wireless prototype presents great stability in situations where sudden movements and strong vibrations are present, which can guarantee a continuous sensing. The justification of the test was to evaluate the most appropriate exterior model according to set parameters as time and difficulty. So on, the design team was able to decide about the most accurate model according to weight and dimensions. • Usability To evaluate product usability, the design team asked to 3 test subjects about their perception of finalist prototypes, according to stability and comfortability. The results are showed in appendix 4 and these are summarized in table 4.

Table 10. Usability tests summary. Test subject Prototype Stability Comfortability

Subject 1 Wireless prototype High High Concave prototype Low Low

Subject 2 Wireless prototype High High Concave prototype Low Low

Subject 3 Wireless prototype Medium |High Concave prototype Low Low

According to results showed in table 4, the Wireless prototype is more stable than the Concave prototype, and the first one is more comfortable than second. This allowed design team to determine that the wireless options fits better with user perception, so its external design is a better option than the second one. The justification of the test was to acquire feedback from users about their perception of models. According to the recollected information, it was easier to the design team determine constrains of final model about fitting method, technique to acquire signals, weight and shape. Now, the users of these devices are all kind of people, from a newborn to an older adult. That is because any person can be found in a situation of health emergency, and for that everybody is susceptible to need an oximeter that works in different situations. For the other hand, the client of this company would be hospitals, private and public ambulance, the state and person who want to buy their own oximeter. This product can be adapted according with the needs of the patient in matter of functionality in different situation of emergency that the subject can be found. Finally, the final prototypes selected for the design team can be tested in the user simply putted in their ear or finger, depending of the device tested. Conclusion of the design specification: According with the prototypes tested, the solution selected to keep working is the wireless prototype. This is because it accomplishes with all the specification we wanted to have in our design. Among the specifications, it can be found stability, comfortability and safety. These 3 concepts were evaluated for the design team in the wireless prototype and we conclude that it can be a device

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comfortable for the user – small, lightweight, and easy to place –. In addition, it is stable considering that it is designed to be able to stay in place while in a moving car, and this is proof with the test showed in the video No. 3 of the Appendix 3. Finally, it is safe considering that it would be completely cover in the electronic part of the design, and it would not have parts in the device that can represent a danger to the patient. Future experiments to demonstrate: • Functionality and efficiency: To demonstrate functionality the design team will evaluate: 1. Accuracy: measuring oxygen saturation levels and comparing with current models. 2. Time to set the device: Since turning on the device until fitting it in the ear. It will be compared

with current models. 3. Time to obtain the saturation levels: Since device is set in patient until it is obtained and stable

value of oxygen saturation level.

• Safety: To demonstrate the safety of the product, the design team will evaluate the ranges of the device in voltage, current and impedance. It will be evaluated that the results are under healthy value limits that are 1 mA as the body perception threshold. To evaluate the materials used, design team will choose materials that are previously accepted by regulatory organizations referred to biocompatibility. Initial and current specifications

Table 11. Initial and current specifications. Initial specifications Current specifications

Non-invasive Non-invasive Accurate under emergency scenarios Accurate under emergency scenarios

Weight was not explicitly specified Light-weight

Small size Small size components to fit inside ear canal

Comfortable Comfortable Easy to fit in patients Easy to fit to fit in patients

Not specified Wireless

Not specified Stable under turbulence or continuous movement

It should not affect avionics It should not affect avionics Less time to obtain oxygen saturation

levels Less time to obtain oxygen saturation

levels Competitive in market Competitive in market

The implementation of PatchOne uses the same principles that where laid out by the dream of an auricular device that uses the reflectance phenomenon to obtain an oxygen saturation level value.

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It is also noninvasive way of getting an exact value that is not encumbered by the vasoconstriction levels of a patient. It also prevents noise that is common in-patient transportation because the patch sticks to the skin and blocks environmental light. However, this method varies with the Wight of each person because the content of fat in the body alters the reading of reflectance from skin. Because of this the next workable prototype is the reduction of the oximeter sensor in order to be able to apply it to the human ear canal. 8 Product type and Canvas

8.1. Product type and Canvas Oxycure offers a device that measure the oxygen saturation in blood based on the reflectance phenomenon. Also, the device is focused on the measurement of this vital sign in conditions of vasoconstriction. For that reason, it will be placed inside the ear cavity. This medical equipment is reusable after proper sterilization, as it will be in contact with body fluid like ear wax. Finally, Oxycure seeks the reduction of white noise, discomfort of the patient, costs, weight and size of the device and instability. In the Figure 18, it can be seen a summarize of the business model in a canvas form.

Figure 19. Canvas model.

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9 Implement – Strategy Development

9.1. Intellectual Property (IP) Strategy The strategy to protect the Intellectual Property of PatchOne by Oxycure will apply for a patent by industrial design through which it is intended to protect the box-like structure where the electronic components are housed as well as the patch that is located in the different parts of the body. However, it is expected that for the final prototype which will be set inside the ear canal, the device we will fill the provisional patent application. Since PatchOne fits as a class II device, we will ask for a patent through a De novo pathway for finally obtain a patent over the device. The main claim for the patent of the device will be based on:

1. A method and device for measuring blood oxygen saturation of a patient even under vasoconstriction condition through a reflectance technique and a patch that can be set in non-peripheral zones as the front, the neck, the chest and other non-low blood perfused body parts.

According to the status of IP landscape and the required action, the relative level of IP risk of PatchOne can be related with Medium since there are “other patents in field but claims are broad enough to potentially be invalidated”. For this, the required action will be a comprehensive claims analysis detailing the limitations of every relevant claim and development of careful risk mitigation strategies. 9.2. Research and Development Strategy First, it is important to recognize what is the main risks that the patient would suffer while use PatchOne. The main risks presented while the patients use PatchOne are listed below: RISKS:

• Decoupling of the device. • Exposure to temperatures higher than body temperature. • Exposure to dissipated powers of around 6 mW. • Incorrect measurement of oxygen saturation and, therefore, lead medical staff to erroneous

diagnoses about the patient's condition. The next key milestones were intended to sequentially retire the most significant risks in the project and develop the final device, which will be introduced in the Colombian market. Key Milestones

• Evaluate the stability of the different proposed prototypes in environments with a lot of movement.

• Evaluate the comfort of the different proposed prototypes in humans. • Design the prototype of the functional circuit on a prototyping platform. • Evaluate the accuracy in the measurement of oxygen saturation provided by the designed

circuit and compare it with a commercial device. • Design the structure of the device. • Measure the power dissipated by the circuit in order to make a diagnosis of the electrical

risk that the user may suffer.

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• Measure the maximum temperature at which the device can reach to assess the thermal risk that the user may suffer.

• Connect the functional circuit and structure, and then evaluate the functionality and comfort of the device in different test users.

Based on the key Milestones presented before, Oxycure propose the following technical challenges. Technical Challenges:

1. Create a device that measures in a quick and accurate way the oxygen saturation of a patient in any physiological condition.

2. Ensure there are no current leaks that may affect the user. 3. Ensure the stability and comfort of the device. 4. Find a sensor that measures the oxygen saturation of a patient using the reflectance

method. 5. Find a module to send the oximetry information in a wireless way. 6. Find a processor capable of receiving information from the sensor and send it through the

wireless module. 7. Find a power supply that is small, rechargeable and easy to use. 8. Ensure that the device does not suffer from overheating that may affect the user.

All technical challenges can be solved using different test, resources and engineering activities. The first technical challenge is the general challenge that Oxycure must overcome to demonstrate the value of the project. To solve this challenge, Oxycure needs to evaluate the measurement speed and the accuracy of the final device and compare PatchOne with other commercial devices used to measure oxygen saturation. In addition, Oxycure needs a protocol that describes the steps performed during the evaluation because the protocol is useful to validate the conclusions reached after performing the accuracy test and speed of measurement of the oxygen saturation of the device. The protocol consists in perform five measurements in different test users using PatchOne, the current pulse oximeter and the gasometry. After of this test, compare the measurements and obtain the experimental error in PatchOne compared with other commercial devices. The second challenge is avoiding the leakage currents in the device. To solve this, it is necessary to measure the high supply current used by the device. The resources needed to perform this test is an ammeter and safety implements. First, it is necessary to measure the current dissipated in each branch of the circuit and use physical laws to calculate the leakage currents in the device. After, Oxycure must compare the leakage current calculated before with the maximum current supported by the body, if the leakage current of the device is greater than the maximum current supported by the body it is necessary that Oxycure isolates electrically the device to ensure the safety of the user. The third challenge is guaranteeing the comfortability and the stability of the device. The above is important because if the device uncouple the measure stops and the medical staff does not know the health state of the patient. In addition, the patient has to feel comfortable with the use of the device. To evaluate stability, tests will be carried out in which an environment with high movement is simulated. In addition, to simulate the comfort of the device, different test users will be used, and a survey will be carried out to assess the comfort of the device. The resources needed to carry out these tests are a stretcher and several test users.

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Challenges 4, 5, 6 and 7 consist in the search of different devices that meet the necessary requirements of the device. The necessary resources are a computer with internet access or advice from people who have contacts with the electronic industry. The eight challenge consists in avoid the increase in the temperature in the device. To solve this challenge is necessary to measure the maximum temperature that is presented in the device and assess if this temperature affects the physiology of the user. If the increase in the temperature is considerable, Oxycure must isolate thermally the device to ensure the safety of the user. The resources needed to do this assessment is a thermocouple and safety implements. 9.3. Clinical Strategy Preclinical studies will be done on the device to guarantee its precise measurement. This will be done by measuring the voltage it provides while passing through different materials with different light absorption rates. Then, the device will be calibrated by doing tests on 200 people. The test will be measuring oximetry with PatchOne along the traditional pulseoximeter. Then, a calibration curve will be made to make the device precise and be sure that the data it provides is according to the patient’s oximetry. Clinical studies might be done to try out the efficacy of the device. Therefore, once the sensor has passed through a calibration curve to ensure that it is responding to an accurate quantification of light, it can be taken to a hospital to collect data of its measurements. The study will be done at an emergency room since the purpose is to measure oximetry on patients who are suffering peripheral vasoconstriction due stress, blood loss or low temperatures. Then, for a period of six months PatchOne will be used on every patient along the traditional pulseoximeter and arterial gasometry if needed. Two PatchOne units will be used, one on the forehead and one in the neck. After the six months we will analyze the data to decide how accurate is our device on emergency environments and where is the best zone in the body to take the measurement. Additionally, on the same period of six months 100 PatchOne units will be taken to an intensive care unit (ICU) to be used on patients while on observation and while using the traditional pulseoximeter used on ICU. The data that will be gotten from that study will be the accuracy of the measurement, the stability of the device (if it stops measuring due movement or vibrations) and the level of comfort that it gives to the patient. Those data will let the company know the efficacy and accuracy of the device on different medical environments. 9.4. Regulatory Strategy The process to follow for obtaining INVIMA clearance of PatchOne by Oxycure must fulfil the Requirements for obtaining a sanitary registration or permit of commercialization of medical devices. In the case of a medical device of Class IIA, the main technical requirements according to “Artículo 18 Decreto 4725 de 2005” are:

1. Technical studies and analytical checks. • Design verification and validation. • Certificate of analysis of the finished product

2. Sterilization method 3. Disposal method or final disposal 4. Studies of biocompatibility, stability, cytotoxicity, electrical safety. 5. Risk analysis 6. Description of security measures

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The figure shows a summary of the process according to the information provided by INVIMA in the document “ABC de Dispositivos Médicos” [21].

Figure 20. Summary of Regulatory Strategy process for INVIMA.

In addition, when asking for market expansion for United States, the pathway to get FDA clearance for PatchOne by Oxycure will be to follow the 510(k) premarket notification. This is possible since PatchOne by Oxycure can be defined as a Class II device. To determine the appropriate devices that are substantially equivalent to PatchOne and are legally marketed devices, we will search on the patents data bases UPSO databases and Free Patents Online. For example, there is a reported device for measuring oxygen saturation in vasoconstriction condition called Oximeter sensor with perfusion enhancing (US5267563A) [22]. This kind of devices, which the claims are similar to the main claim of PatchOne by Oxycure, can be used as substantially equivalent to apply for a 510(k) premarket notification. 9.5. Quality Management Quality management is regulated by two important processes, quality assurance and quality control. This two differ in the emphasis each process has, since quality assurance is process oriented and is intended to be highly prospective and preventive. While quality control is more product oriented and intended to confirm the status of the product, it is a retrospective process. It’s important to note that said quality management systems are further sub-divided into other processes that allow the precise management and control of activities that are essential to the quality of the product [10].

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Figure 21. Activities involved in quality management systems [10].

For these activities to be properly implemented in a way that makes the quality management system useful it must have documentation of every and all product system requirements. Employees of the startup must be well trained and be taught to follow documented requirements. Records must be generated in order to have an easy way to track that said requirements are followed accordingly by the employees. And lastly a proactive system must be put in place so that the identification and resolution of encountered problems is swift and efficient [10]. Management Controls: This activity gives management specific duties to allow for the allocation of resources so that effective designs, manufacturing m distribution and installation can take place. All this must take place within a rigorous plan–do–check–adjust (PDCA) cycle so that management can continuously improve its defended quality objectives, polices and plans [24]. Our startup has taken sis activity by heart in every reiteration of its prototypes in order to assure that each of its prototypes is the most qualified. Design Controls: This activity is essential from an engineering perspective since it is the first approximation that allows the start up to review design verification and designs validation. These validations are important since any design will need to be validated before its implemented in a production system and verified before the product is delivered to a costumer. Especially since designs verification confirms the requirements established by the development team while design validations confirm that said requirements meet the requirements of the consumer. Our start up team in Oxycure made sure that design verification and design validation was implemented in every prototype since we would not be able to test out the results in a patient with our checking if the constructed prototype fit all our initial requirements. Once a prototype did check all out requirements it was tested on patients or in simulated emergency situations to test if it was adequate for commercial use. Again, if it was found that a prototype did not fit either the design verification or design validation a PDCA cycle was implemented to review the possible errors and improve on the initial design [10].

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Production and process controls: These activities differ from design verification and design validation since they don’t verify the results rather, they check if processes themselves and the operation of equipment is adequate [10]. Since this activity is carried out during commercial production it has not been thoroughly implemented in the construction of each of our prototypes. Corrective and preventive actions: This activity is made up of the documentation of production process deviations, costumer complaints and non-conforming raw materials. This documentation is then fed into policies that take appropriate actions that correct and prevent the eventual recurrence of these problems [10]. Although these product and quality problems usually arise further downstream in the product development cycle Oxycure is fully aware that it is important to stablish a strong general framework in order to put the corrective and preventive subsystem into work. With this in mind Oxycure has investigated Colombia’s regulatory agency in order to see the type of medical device reporting that must be met. It was found that Oxycure will have to comply with Invima’s techno vigilance program that was established in 2008 under de resolution 4816 that establishes the need for the reporting of customer complaints and production deviations. As well as specific process that correct the problems specified in the reports [23]. Equipment and facility controls: These activities are carried out once the startup has the equipment and installations required for mass production of its products. Although Oxycure currently lacks the infrastructure required it is aware of the need preemptive measures to assure the longevity of its future infrastructure. It is especially important that these preemptive systems are applied to equipment and facilities involved in productions, designs and post production/ post-sale activities [10]. This is important since preventive and predictive maintenance reduces the cost and the risk of failure in equipment, while caring out corrective maintenance is merely a reactive policy that could lead to high costs of reparation or reposition of expensive equipment. Material Controls: Since Oxycure has developed PatchOne, a medical device capable of obtaining the blood oxygen saturation levels anywhere in the body it must consider the bio-compability of materials that will be in direct contact with the skin. Because of this we were inspired by the low irritability that electrodes have after prolonged use on the skin. And so, a rigorous screening of the materials must be established before the productions of every PatchOne. Since similar materials for human applications have already been used in the market, it will allow us to save time on the cost and timelines of regulatory processes and product qualification [10]. Also, to follow regulations of electric safety and engineering standards Oxycure is sure to implement commercial batteries and electrical components that have already been tested and approved for human use. Since it is an ‘internally powered type device’, the device needs several tests to check if there exists some sort of current risk that may harm the patient. This includes but is not limited to, visual inspection of the electronic components, the measurement of resulting currents in the normal state and in the single fault state. Also, the possibility of 'patient leakage' should be considered, this means that the possibility of detecting a flow of current from the patient to the device must be considered. However, it is worth noting that our device does not require 'earth bound tests' since these only apply to CALSE I equipment [12]. For PatchOne by Oxycure to gain regulatory clearance in Colombia it must go through the regulatory agency INVIMA. In the case of a medical device of Class IIA, the main technical requirements according to “Artículo 18 Decreto 4725 de 2005” which specify a design verification and validation

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process where there is a certificate of analysis on the finished product. Sterilization methods must also be stipulated as well as final disposal method. Patch one must also pass electrical safety and BioComp ability tests as well as present a through risk analysis with a description of security measures. Records, documents, and change controls: This activity is important during the early development activities since it creates a healthy culture of organization and accountability. Once the startup grows these systems can effectively control the policies and protocols that are in place, as well as the Maintenance of a historical record so that past protocols and policies can be reviewed. 9.6. Reimbursement Strategy In order to get PatchOne out into the marketplace Oxycure is exploring different alternatives. First Oxycure will stablish an online website where the sale of our medical device is easy to obtain. Oxycure plans to make available nationwide delivery in order to facilitate the implementation in different IPS. Since our target market varies from emergency units, intensive care units, to medical transport ambulances. Oxycure market is reasonably large and will first focus in Bogota DC to then eventually cover different departments of Colombia. This slow but steady expansion assures that Oxycure can prepare itself to offer quality post sale services that will allow us to retain customers in the long run. Oxycure also plans to make its first official entry into the market using its support from SISMEDICA since it was a key ally that allowed the development team to interview medical professionals and observe problems that could be solved during a medical transport. 9.7. Marketing, Stakeholders, Sales and Distribution Strategy Oxycure offers a reflectance pulse oximeter. This device can replace the traditional pulse oximeter. The price for our device is 150.000 COP, which is about 167% of the production cost (89,430 COP). It is important to position the company and its brand in a way where the most important needs of each stake holder are smartly targeted and isolated in order to bring our value proposal. For our primary stake holders (doctors and patients) we hope to emphasize the impact our product will have in reducing stressful situations and assuring maximum comfort. We know this can be impactful in said populations since doctors often suffer stressful encounters with pulse oximeter readings in patients that are in critical conditions because accurate and fast readings are hard to come by in these situations, thus making fast decision even tougher to make. It was also prevalent to us in our field work that patients in ambulance rides or emergency departments are often uncomfortable and feel encumbered by additional medical devices that impede their already restricted movement capabilities, since our device will be wireless and ´headset-like´ said encumberment will be heavily reduced. We hope to socialize these potential benefits with our primary stakeholders through our website, social media and in pamphlets where distributers allow us to promote the launch of our new product. Our secondary stake holders (private IPS´s and Colombian government) are more likely to respond to positioning along benefits and price lines. Because of this we will expose the problems that current conventional pulse oximeters have when dealing with emergency situations. We will then emphasize the failure rate that conventional devices have in these situations and how our novel product can solve this problem. We will also emphasize our competitive price when compared to other products that are not all purpose and will fail in emergency situations. As we know that costumer experience is an important factor when it comes to retaining clients and gaining new ones, we also will pledge full after sale service to our numerous clients in order to gain a foothold in the

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market. To emphasize this positional strategy, we will initially offer a commodatum contract with our direct link to the IPS market in Colombia. We hope this will allow us to gain initial practical exposure in the market that will lead to word of mouth and sales. These potential benefits will also be thoroughly exposed in medical device fairs and symposiums, along with our website and selective commercials to influence potential IPS buyers. Our target customer to begin with will be Colombian IPS. This is because the IPS control the hospitals and ambulance services. We will segment this customer group by starting on ambulances. The market size is estimated to be about 2000 ambulances to start with. Also, we will offer our device on medical conferences where doctors are looking for new technologies. Our main way to offer our device will be by contacting companies such as Sismedica. Oxycure will have a webpage that will work to show our device characteristics and benefits, and as a way for our clients to contact us. 9.8. Competitive Advantage and Business Strategy The primary competitors of Oxycure are the business in charge of selling and distributing pulse oximeters to different IPS in Colombia such as Philips, siemens, Mindray and Edan. These brands are known because distributers such as Quirurgil, Jmedics and Novamedica (which are the preferred distributers for IPS´s in Colombia) sell traditional pulse oximeters between $100000 COP and $500000 COP. It´s is worth mentioning that the pulse oximeters that are offered by this companies are traditional oximeters that obtain the blood saturation levels using a transmittance method, and as it has been previously mentioned thought out this document such methods present have real problems when emergency situations are involved. According to the Porter forces the entry barriers that established companies can use against new businesses are large scale economies, cost of change, capital requirements, learning curves, unequal access to communication channels and restrictive government laws. For Oxycure the most important barriers of entry that must be considered are large scale economies since large companies will be able to mass produce their products at a lower cost than our initial products. Capital requirement is another barrier of entry that will impact the initial venture since an initial influx of capital will be needed to create the product, distribute it, market it and pay all the nominal salaries. Oxycure will develop a novel pulse oximeter that is capable of accurately detecting saturation levels in different settings. It is not only capable of detecting saturation levels quickly and accurately in stable patients, but it will also work efficiently in patients who are in extreme emergency settings and because of signal noise, low cardiac output, environmental factors or low blood volume, conventional pulse oximeters will fail to give an accurate reading. Oxycure knows that in order to differentiate itself from its competitors it must present to its numerous potential costumers' substantial benefits in order keep the price difference from being an important factor. Because of this Oxycure will dedicate itself to bringing quality customer service in order to assure a great costumer experience. It is also worth noting that our all-purpose pulse oximeter can be bought for a price of $150000 COP which makes it highly competitive with the alternatives in the Colombian market considering the value proposal and innovation that is intrinsic to the design. Since our business will be focused on a niche market, IPS´s in Colombia, the distribution channels and client relation are tailor made for our clients in mind.

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Our client relations will try to be as fast and personalized as possible. We hope to have online automatic service so that our clients can quickly resolve questions about their products. In any case where additional assistance is necessary, we will have a fast response personalized service where a company technician will resolve the issue with the pulse oximeter. The communications channels and supply network are of the upmost importance since it allows the clients to know the company´s products and services. It allows the clients to evaluate our value proposal and to receive the appropriate costumer service support after it acquire our service or product. Oxycure will initially be known in the industry through our connections with IPS´s, especially with the support of Ambulancias Terrestres de Colombia and Sismedica. After this initial exposure we hope to attend various seminars and conventions of medical devices in Colombia in order to expand the brand throughout the country. We hope to have a vibrant community in our website that evaluates our products in a scale of 1-5 and leaves reviews not only about the physical product but also about our customer service in order to grow as a company and to show potential customers that we are a serious and dedicated enterprise that always goes the extra mile for our clients. We will be selling our products through an online model where we will cover shipping throughout the country, Colombia. We also hope to be able to sell and gain clients in the seminars and conventions of medical devices where we will show off our products. Our products will be delivered to the place of choice of our clients or they can buy them directly from one of our members in the seminars or conventions. Finally, as we have talked about previously costumer service will be an important pillar of our company since it will be an important factor that differentiates us from the competition, apart from the novel proposal of an all-purpose pulse oximeter. We will have automatic service so that our clients can get rapid answers to their issues. If the issue persists, we will have exclusive personalized service where the issue at hand will be resolved. We also hope to construct a community where not only will they be able to rate our service and product, but they can also leave constructive comments on how to appropriately manage the product. 9.9. Operating Plan and Financial Model In the Figure 22, it can be seen the specific timeline for our operating and the manufacturing plan. There are 4 main activities from the realization of the first prototype to the final commercialization of it. In the first stage, it would be done a proof of concept. For this, it will be necessary to carry out 2 key activities: the first one will be the production of instrumentation and structural prototypes, followed by an appropriate validation of it through in vitro tests. In the second stage, it would be done the security verification of the prototype. For this, 4 activities will be carried out, which consist of: authorization of tests for the device through ethics committees, carrying out pilot tests of functionality, testing in an animal model and, finally, obtaining a clinical evaluation of the idea. In the third stage, it would be obtained the licenses, that is, the regulation of the project. For this, it is necessary to carry out two key activities: first, it is necessary to apply for the licenses for manufacturing and commercialization of the product through INVIMA, and to carry out the respective documentation in order to obtain a possible patent.

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Finally, the last stage consists of the marketing of the previously approved product. For that, 3 key activities will be carried out, which are: to carry out a massive distribution of the device, where in the first year the marketing of approximately 10% of the market will take place; Then, the advertising and marketing costs must be taken into account in order to obtain greater recognition and, finally, a maintenance and technical service system must be implemented. All the activities of the 4 stages would be carried out by the group of 5 engineering of Oxycure. Now, for each of the stages an approximate cost for each one of them has been preselected, as shown in Figure 22. The money needed for each of these must be obtained through an initial investment made by potential investors or through bank loans. With these costs in mind, a business model was made in order to have an idea of what the projected business would look like 5 years from today.

Figure 22. Timeline for operating and manufacturing plan.

A 5-year projection was made taking into account inflation, the number of ICU’s beds and ambulances. As for the financial needs of the company, the costs linked to the production of the device must be met, that is, related to the income that is going to be had. To achieve this, an increase in the price of approximately 100% to sell price, will be made in order to cover the costs involved and generate a profit. Revenues are expected to arise from the sale of the devices primarily. According to the free cash flow, it can be seen that in year 1 the return on the initial investment starts to be obtained. Based on the data obtained, the viability of the project is confirmed, since an increase in the values in the net margin is confirmed in the free cash flow (figure 23). It is highlighted that in the 5th year, the company continue increase the net margin instead of reducing it, which is achieved through after-sales services such as maintenance, spare parts, cleaning, among others. It is observed that the gross margin also increases because the incomes not only depends on the sale of device, but also takes into account the sale of spare parts every two years on a mandatory basis, since this time is the useful life of the sensor used.

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Figure 23. Free cash flow.

Figure 24. Gross margin.

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9.10. Communication Strategy Measuring oxygen saturation in the blood is one of the procedures which you may have seen a least once in your life or to which you may have been subjected sometime when receiving medical attention. The nurse or paramedic had set a “pulse oximeter” or a device with clamp-shape in one of your fingers to check a number on it. This apparently not very complicated procedure is a vital step in determining the patient's vital signs and allows the physician to make decisions of great impact on the conservation of the individual's life. However, did you know that the device that is currently used for measuring oxygen saturation is not fast enough and accurate during a condition called vasoconstriction? Vasoconstriction is the response of the body of decreasing blood perfusion to peripheral areas of the body, such as the fingers, where the pulse oximeter is set, to preserve a more stable blood flow to vital organs (brain, heart, among others) during emergency situations (like when there is a great bleeding through a wound or when the body temperature decreases significantly). Despite the relevance of obtaining instant and truthful information about the real-time condition of the patient, specially, when his/her life is in danger, emergency medical experts who day by day deal with vital signs measurement procedures have expressed the difficulties that current used pulse oximeter presents. The experts said that this device displaces easily, and it takes valuable minutes to provide a reliable data about oxygen saturation of the patient. A wrong measurement of oxygen saturation, and so, of oxygen supplement, increases up to 30% the chance of death due neural damage. That is why it is of great medical relevance to find a way to quickly and accurately measure the oxygen saturation of patients with vasoconstriction in emergency environments. In order to answer that need, we designed and tested a novel device, Oxycure, which allows the medical staff to measure oxygen saturation in non-peripheral areas (as the ear canal). This implies that the measurement can be done quickly and accurately because it is possible to set the device in parts near to vital organs as the brain. These organs have a more continuous flow that can be used as an appropriate reference for evaluating the oxygen saturation. In Colombia, the expected market is focused to the IPS that provide the service of both ground and air ambulances. Additionally, Oxycure can be used in hospital environments such as operating rooms and intensive care rooms, where patients are in a state of vasoconstriction. According to the WHO, it is required to have 1 ambulance by each 25.000 habitant. Taking that into account, and the annual population growth of 8%, It is excepted to sell 2000 Oxycure devices during the first year. In addition, it must be included in the current business contact with the companies SISMÉDICA and Ambulancias Aéreas de Colombia to start with potential customers Potential customers that are expected to extend the effectiveness of Oxycure through word-to-word method. Other kind of commercialization pathway will be with a Web site and national distribution, with a Comdata contract and attending medical device conferences. To develop the devices, we will acquire the raw material and outsourcing for the assembly. An app was constructed to be able to receive the data that is being sent by the Arduino, the max30100 sensor and an HC05 Arduino module. This app was created using App inventor which is an application that was created by MIT. This application permitted us to create an app on the fly so that any Bluetooth capable device can read the data recollected by the sensor. It´s important to

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mention that we used de HC05 Arduino module to send this information wirelessly to said Bluetooth capable device.

Figure 26: App interface

First the interface was developed then the functionality was added little by little. The Bluetooth symbol is an interface tool that once clicked upon searches for the device and then it syncs up with the Arduino module to start receiving the data in real time. As we can see in figure 20 the number is displayed along with the percentile symbol in order to demonstrate to the user that he is receiving the saturation value. Finally, the one pager of the product can be found in the appendix 5 and the web site can be visit in the link https://danielbaron104.wixsite.com/oxycure . 9.11. Team The necessary team to be able to have a high probability of success in the company is conformed at this moment by a group of engineers highly varied in their abilities and tasks. These are roughly five biomedical engineers, of which two are also mechanical engineers and one is an electronic engineer. Among the activities carried out by this group is the refinement of the current device, the purchase of materials and manufacturing processes for the assembly of devices, the investigation of new technologies and possible competition, the assembly of devices, among others.

Likewise, the vacancies that this team will need to be complete are a graphic designer to produce manuals and ensure an appropriate communication from the company to the users, an administrator to supervise the financial area and an app designer to elaborate the interface for the oximeter. This person will also be in charge of the webpage. 10 Impacts and Considerations Oxycure is a medical device that aims to measure fast and accurately oxygen saturation in patients under vasoconstriction. It is ideal to be used in emergency environment and in unfavorable temperature, physiological and light conditions. Because of that, the impact of Oxycure as an engineering solution in societal context will be to contribute in the reduction of deaths due to complications in ambulances, and so on, to reduce the reported data of deaths in Colombia during ambulances intervention. By another side, it is important to denote that it will be an effect on societal and at the same time economic context because Oxycure aims to reduce the wrong or inaccurate supply of oxygen to patients. It is relevant to determine the actual oxygen saturation of

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patients because a lower supply does not treat correctly the hypoxia of the patient, but a higher supply increases in 30% the probability of death for the patient [19]. The economic impact is related to a less expend for the State or private companies providing health services, in more difficult treatments to illnesses or complications generated due to incorrect supply of oxygen to patients because the difficulty of obtaining an accurate value in the real state of the vital sign of oxygen saturation. Oxycure can be implemented in other contexts different to transportation, as surgical environment, or to people with special conditions. Its technology based on reflectance avoids the need of setting the oximeter in fingers or other body extremities with small size. This implies an impact in inclusion of people in condition of mental or physical disability, which is also a societal impact. The specialist will be allowed to measure faster and easier the fifth vital signs (oxygen saturation), even in special condition patients and children. It is important to remark that the specialist in emergency area expressed that complication as a daily challenge in their job performance. It will favor in the first instance the ambulance medical personnel in Colombia, who intervene in the 800 daily accidents in Bogotá. This means saving more lives (reducing the number of deaths in traffic accidents) and costs for the health system and health providers, in subsequent treatments to more complex complications caused by difficulties in measuring oxygen saturation. Oxycure offers a solution for an oxygen saturation measuring problem that transport specialists’ physicians and emergency attendance staffs all around the world have frequently. The ethical considerations of Oxycure can be evaluated according to the impact of the device in stakeholders, as the patients, medical staff, and etc. Stakeholders must be well informed about the functions and scope of the results offered by Oxycure. There must be a previous solid evaluation of the well performance of the medical device. Tests in real context will be done inside all professional and academic requirements. The respective research protocols and informed consent will be made. In addition, the medical device will have to fulfill INVIMA requirements to introduce Oxycure in the market. 11 Discussion and Conclusion According to the research conducted throughout the report, and the final solution presented, it can be said that this is the right solution to the solution to problems encountered on the erroneous measurement of oxygen saturation in the peripheral area. This can be justified by various prototype tests that were performed, which could evaluate the convenience, speed, ease of location and understanding. Based on these variables and the results obtained, the selection of the prototype was adequate. By the operation, it cannot be said that it is suitable for the problem since no tests could be performed to verify. Based on the design made, it can be said that the shape and size are suitable for the necessary standards for medical work, and if necessary, for the patient. A model of a physical ear was made to locate the device made, it is observed that it is of a shape and size suitable for medical transport standards. Now, the limitations found in the final work are related to the electronic part of it. This is because the circuit proposed to solve the problem has a large size related to the size of the ear cavity, which is where it should be located at the beginning. Due to this, a full functional test could not be performed; To solve this problem, the Oxycure team proposes the realization of a more compact

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circuit where the separation of the pulse oximetry module from the worked module, mentioned above, is carried out. This separation was not made at the time because it could only be done at the industrial level, and the contacts were not available and enough time to do it correctly. Finally, for future work it is proposed to make the circuit more compactly so that it can be in the auditory channel, where it should finally be located from the beginning. Additionally, it is desired to implement a temperature sensor in the place where it is in contact with the auditory canal, this thanks to the fact that there would be more measurement variables that make the result of the device closer to the real one; Also, the Bluetooth module will be implemented to avoid excess cables around the patient, which can make the work difficult for the medical team of the ground or air ambulance. Now, for the part of the business model, a more in-depth investigation of the market will be carried out to be clearer to our customers and users, as well as the necessary capital to start production. In conclusion, having an accurate measurement of the oxygen saturation in blood has a vital importance for a patient. If the measurement is lower the treatment will not improve the patient's health, and if it is higher it increases the chance of neural damage up to 30%. The measurement of oximetry can be affected because of vasoconstriction, which is a common condition on medical transport. The traditional technologies to measure oximetry are not accurate on these conditions, thus, it is necessary to design a new oximeter. The ear canal has a constant blood flow, then it would be appropriate to measure oximetry in that area. Arduino has a module that works with light reflection to measure oximetry, and this modulo can be adapted to the ear canal to develop the new oximeter. Also, the new oximeter might be stable, and its design should not let the outside light leak to its sensor. 12 Acknowledgements Oxycure wants to offer its sincere thanks to all the people who contributed in a certain way to make possible the realization of this great project, among them, Dr. Yadine Alvárez for allowing us to carry out an interview about the main inconveniences that appeared in the transport of Patients, Dr. Fabio Reyes for providing us with valuable information about problems presented on the air transport of patients, the Doctor and Manager of SÍSMEDICA Rafael Suárez for providing valuable information about the problems presented in the patient transport environment, also for suggesting the development of a measurement device of oxygen saturation, Dr. Alejandra Suarez for helping us to validate the proposal made by Oxycure, the teacher Mario Valderrama for being the tutor of this project, the teacher Juan Carlos Briceño for providing us contacts to be able to perform the observation stage, in addition to the suggestion of ideas for the solution of Oxygen saturation problem, the teacher Johann Osma for his suggestions on the circuit design of the project, the teacher Erika Muñoz for helping us with the design of the device as well as her help in the elaboration of the specifications of the device and finally, the graduated assistant Fernando García for helping us in the implementation of the different sensors. Without all the collaboration on the part of these people, it would not have been possible to achieve the objectives of the course and the development of the project had not been successful. To all of them, thank you very much for your collaboration.

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13 References [1] Alexander, C. M., Teller, L. E., & Gross, J. B. (1989). Principles of Pulse Oximetry. Anesthesia & Analgesia, 68(3). doi:10.1213/00000539-198903000-00035 [2] Tremper, K. K., & Barker, S. J. (1986). Pulse Oximetry and Oxygen Transport. Pulse Oximetry,19-27. doi:10.1007/978-1-4471-1423-9_2 [3]DAN H100B MANUAL, 2., EDANUSA,EU, San Diego, USA, 2010, pp. 66-68. [4] Pulse Oximeter PM-60, 2., Shenzhen Mindray Bio-Medical Electronics Co, MINDRAY, Hamburg, Germany, 2010, pp. 77-78. [5] CARE, G. P. CLINICAL USE OF PULSE OXIMETRY. [6] GmbH, C. F. (n.d.). Retrieved February 08, 2018, from https://www.cismst.org/en/loesungen/im-ohr-sensor/ [7] J. Gonzalez, “Radiografía del servicio de ambulancias en Bogotá,” El Espectador, 05-May-2016. [8] Aerocivil, “BASE DE DATOS MES AMBULANCIA AÑO 2011 HASTA AÑO 2015.” [9] Redacción Bogotá. (Mayo, 2016) En promedio, líne a de emergencias de Bogotá atiende al día 137 llamadas falsas. El Espectador [En línea] Recuperado de :https://www.elespectador.com/noticias/bogota/promedio-linea-de-emergencia-de-bogota-atiende-al-dia-1-articulo-633155 [10] Biodesign: The Process of Innovating Medical Technologies. (2009).S.l.: Cambridge University Press. [10] “Where Are the Major Arteries in Your Ears? If You Puncture a Major Artery When You Pierce Your Ear, Will You Die? | Socratic.” Socratic.org, socratic.org/questions/where-are-the-major-arteries-in-your-ears-if-you-puncture-a-major-artery-when-yo. [11] Focus on biocompatibility at Medical Plastics 95. (1995, September 1). Biomedical Materials. [12] “Current Thinking on Testing Protective Earthing.” EBME Biomedical and Clinical Engineering Website., 21 Sept. 2013, www.ebme.co.uk/articles/electrical-safety/333-classes-and-types-of-medical-electrical-equipment. [13] How to Conduct a Failure Modes and Effects Analysis. (n.d.). Retrieved March 19, 2018, from https://www.fictiv.com/hwg/design/how-to-conduct-a-failure-modes-and-effects-analysis [14] “HC-05 Bluetooth Module User’s Manual V1.0 - GM electronic.” [Online]. Available: https://www.gme.cz/data/attachments/dsh.772-148.1.pdf [Accessed: 19-Mar-2018]. [15] Maxim Integrated, “MAX30100 Pulse Oximeter and Heart-Rate ... - Maxim Integrated.” [Online]. Available: https://datasheets.maximintegrated.com/en/ds/MAX30100.pdf [Accessed: 19-Mar-2018]. [16] Arduino, “ARDUINO NANO,” Arduino Nano. [Online]. Available: https://store.arduino.cc/usa/arduino-nano. [Accessed: 20-Mar-2018]. [17] Artero, O. T. (2013). Arduino: curso práctico de formación. México D.F.: Alfaomega. [18] U.S. Food & Drug Administration. (2017). Code of federal regulations. [Online] Available: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=870.2710 [19] Fuller, B., Page, D., Wessman, B., Ablordeppey, E., Mohr, N., Trzeciak, S., & Roberts, B. (2018). 20: EMERGENCY DEPARTMENT HYPEROXIA AND INCREASED MORTALITY IN MECHANICALLY VENTILATED PATIENTS. Critical Care Medicine, 46(1), 10. [20] EL ESPECTADOR, "Radiografía del servicio de ambulancias en Bogotá | ELESPECTADOR.COM", ELESPECTADOR.COM, 2016. [Online]. Available: https://www.elespectador.com/noticias/bogota/radiografia-del-servicio-de-ambulancias-bogota-articulo-630822. [Accessed: 18- May- 2018].

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[21] C. Tiempo, "2017 quebró década en aumento de muertes por accidentes de tránsito", El Tiempo, 2018. [Online]. Available: http://www.eltiempo.com/justicia/servicios/cifras-de-accidentes-de-transito-en-colombia-2017-161390. [Accessed: 18- May- 2018]. [22] Ralston, A. C., Webb, R. K., & Runciman, W. B. (1991). Potential errors in pulse oximetry III: effects of interference, dyes, dyshaemoglobins and other pigments. Anesthesia, 46(4), 291-295. [21] MINISTERIO DE SALUD Y PROTECCIÓN SOCIAL Instituto Nacional de Vigilancia de Medicamentos y Alimentos - INVIMA, "ABC DE DISPOSITIVOS MÉDICOS", Invima.gov.co, 2013. [Online]. Available: https://www.invima.gov.co/images/pdf/tecnovigilancia/ABC%20Dispositivos%20Medicos%20INVIMA.pdf. [Accessed: 30- Nov- 2018]. [22] Swedlow, D. B., Mannheimer, P. D., & Warring, J. A. (1993). U.S. Patent No. 5,267,563. Washington, DC: U.S. Patent and Trademark Office. [23] Sánchez, et al. “TECHNOVIGILANCE AND RISK MANAGEMENT AS TOOLS TO IMPROVE PATIENT SAFETY IN COLOMBIAN HEALTH CARE INSTITUTIONS.” Revista EIA, Escuela De Ingenieria De Antioquia, www.scielo.org.co/scielo.php?script=sci_arttext&pid=S1909-97622017000100008. [24] “Plan-Do-Check-Act (PDCA) Cycle.” What Is a Quality Management System? | ASQ, ASQ, asq.org/learn-about-quality/project-planning-tools/overview/pdca-cycle.html. [25] J, Vivas, “Colombia, solo cuenta con 1.7 camas hospitalarias por cada mil habitantes”, El Tiempo, 2018https://www.eltiempo.com/colombia/otras-ciudades/colombia-solo-cuenta-con-1-7-camas-hospitalarias-por-cada-mil-habitantes-249374

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14 Appendices

Appendix No. 1: Photographs taken in the problem sites.

In these photos, we can see how the actual device for the measurement of oxygen saturation is used in adult and newborn patients, this is in an air ambulance.

These photos are placed in a ground ambulance. In this we can see different problems in the car.

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The video of the travel can be seen in: https://youtu.be/WADXeA_Kvss.

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Appendix No. 2: Interview conducted to know the field.

Entrevista No. 1 Dr. Rafael Suárez

Empresa SISMÉDICA Transporte Aeromédico y terrestre

1. ¿Cuáles son las complicaciones que pueden presentar los equipos usados en las intervenciones médicas durante el transporte?

El medio aeronáutico, de por sí, es un medio hostil, y es hostil porque está sometido a unos llamados factores de estrés de vuelo. Pero los equipos biomédicos, más allá de un medio puntual, que ahorita les digo, están diseñados para que no se vean afectados por esos factores de estrés de vuelo, los cuales son: Temperatura, humedad, hipoxia, vibración, entre otros. Entonces no tendrían por qué afectarse, salvo que requieran utilizar baterías que minimicen el riesgo de incendio y explosión a bordo y que la emisión de ondas electromagnéticas, no tengan la capacidad de activar una atmósfera comprimida que pueda estallar dentro de la aeronave. Así que ustedes pueden tener un monitor que se usa en la unidad de cuidados intensivos X, y allí, por ser una instalación fija, lo único que deben hacer es mantenerlo enchufado, no se preocupan por el tema de la batería. Pero si lo que van a hacer es transporte, debe tener una batería de carga, de soporte, y esa batería debería ser aquella que tenga un mínimo riesgo de explosión, por lo demás, no cambia nada, porque es el mismo monitor, porque ninguno de los factores de estrés de vuelo, están incidiendo sobre los equipos. Ahora bien, uno se sube a un avión, y el avión tiene un componente que se llama la aviónica, y la aviónica es lo que el ingeniero, que lo ha diseñado, dispone que le va a permitir a la aeronave cumplir sus funciones: encender el motor, rodar, levantar la nariz, ascender, mantener crucero, bajar la nariz, descender y aterrizar. Cualquier cosa que se use al interior de la aeronave, sobre todo si debe ser conectada en alguna parte, debe garantizarse que no dañe la aviónica de la máquina. Esa es una de las razones por las que le dicen a uno, que apague el celular, mientras están haciendo la programación del computador de vuelo, porque las ondas electromagnéticas podrían llegar a modificar los indicadores, pero lo que se afecta es el avión, no el equipo, y ustedes son ingenieros biomédicos, no ingenieros aeronáuticos. 2. En el procedimiento, desde subir el paciente al vehículo aeronáutico, hasta bajarlo de este,

¿qué tipo de complicaciones o percances se podrían presentar? Yo soy especialista en medicina de aviación y alguna vez traíamos un paciente de Arauca y aterrizamos en Rio Negro, en Medellín. Y la tripulación de la ambulancia terrestre sacó su ventilador para hacer la transición con el ventilador nuestro, del vuelo, y lo dejó caer y no hubo nada qué hacer. Nos tocó montarnos con el paciente, con nuestro ventilador, perder 2 horas de estancia en el aeropuerto, e ir hasta el hospital. Ahora, a manera de información, las operaciones aéreas tienen estas fases: prevuelo, taxeo, carrera de despegue, ascenso, crucero, descenso, aterrizaje y establecido. En todo esto, se deben tener en cuenta las condiciones súbitas en vuelo y la más importante es la turbulencia. Entonces qué es lo que pasa con todo esto. En el prevuelo, si estamos hablando de transporte aéreo de pacientes, que los equipos tengan mantenimiento, que los equipos estén calibrados, que los equipos funcionen, que las alarmas funcionen. En el taxeo, el taxeo es que ya uno está abordo, ya cerraron la cabina, ya el paciente está abordo, ya está acomodado en su camilla, y la aeronave, se está acomodando hacia la posición de despegue, esperando que la torre de control de superficie, autorice el despegue. O sea que ahí uno está como en el “Apriete aquí”,

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“Cuidado que no se caiga esto”, cosas preliminares. En la carrera de despegue, no hay nada qué hacer. Lo que usted no ajustó, se fue desajustado. Porque va de V1 a V3 y en V3 puede alcanzar los 180 km/h no más, eso va a toda velocidad. En el ascenso, una vez que se supera el nivel límite de los 10.000 pies sobre el nivel medio del mar, ya uno se suelta, viene, evalúa al paciente y continúa. Y en el crucero, es el momento ideal, ahí es donde uno se “vacanea”, todo va bien. O esperaría que, si se va a presentar alguna complicación, sea ahí, porque ahí la aeronave va horizontal, hasta los pilotos ponen piloto automático. Lo que es el descenso, entonces usted empieza a experimentar una serie de cambios, que tienen que ver con esta información: supongamos que este es el nivel del mar. Esto es Barranquilla, esto es Bogotá y esta es la capa atmosférica. Si esta es la capa atmosférica, aquí abajo hay un aire que pesa, y ese es el aire que define la presión atmosférica. El individuo que está aquí parado, está sometido a esa capa de aire. Entonces en la medida que esquemáticamente, esto pesa más, aquí las moléculas están más “pegaditas”, por eso es que uno a nivel del mar nada, corre, ingiere licor, trasnocha y no pasa nada. Pero cuando uno se viene aquí, la columna de aire es más pequeña, así que aquí las moléculas están más dispersas, y por eso es cuando uno sube de aquí a acá, se siente mal. Porque aquí con una inhalación, ya mete 21% de Oxígeno, y si bien es cierto, aquí también hay 21% de oxígeno, para que uno alcance a coger las moléculas que están dispersas, debe inhalar con mayor fuerza, irlas buscando. Y eso significa, que, si bien es cierto que la presión de oxígeno es lo mismo, allá que aquí, la presión a la que está sometido ese oxígeno, acá es menor. Lo mismo pasa con el avión entonces, usted tiene el avión en el aeropuerto Ernesto Cortissoz de Barranquilla y allí, el avión el contenido de aire en su interior, incluyendo el que va en las turbinas, los ocupantes, incluyendo el paciente, están sometidos a 760mmHg que es la presión atmosférica, que es más o menos, 22,24psi, que es la manera como se muestra en el avión. Cuando el avión asciende, en el mejor de los casos, sale de Barraquilla y llega a Santa Marta, y ahí no pasa nada, va a 10.000 pies, y lo único que tiene que hacer el piloto es prender el compresor de las turbinas, para que la presión al interior de la aeronave, se presurice, el avión se infla y el avión sube y vuelve y baja. Pero si usted está en Barranquilla y viene a Bogotá, usted pretendería mantener esa presión atmosférica a bordo del vuelo. Entonces cuando cierran las puertas de la aeronave, el avión empieza a ascender, y en la medida en la que asciende, reduce presión barométrica, entonces el piloto prende los compresores, el avión se empieza a presurizar y a pesar de que el avión ascienda, trata de mantener una presión semejante, que puede llegar a ser hasta ¾ de atmósfera, o sea, unos 620mmHg, porque está por allá arriba. Por eso cuando uno está abordo, puede respirar sin necesidad de oxígeno, en cabina presurizada, pero no existe en el mundo un avión que tenga la capacidad de mantener la presión atmosférica del nivel del mar. Por eso es que cuando uno viaja, le pregunta, cómo estuvo el vuelo, y uno responde que un poquito cansado y no es porque la maleta pese ni nada, sino es porque a lo largo del vuelo, sin que uno se dé cuenta, se empieza a respirar más rápido, para compensar la falta de presión. El avión digamos que sale de Barranquilla a Bogotá. El avión asciende a 31.000 pies sobre el nivel medio del mar, pero Bogotá está a 8.500 pies, entonces el avión sube, mantiene su presión de cabina a esto, pero cuando va a aterrizar, tiene que nivelarse a esto. Si acá estaba a 0 pies sobre el nivel medio del mar, aquí va a venir a 8.500 pies sobre el nivel medio del mar, entonces a lo largo del vuelo, el piloto, si estaba acá a 8.000, el piloto acá mantuvo la cabina a 5.000. Cuando aterriza, pues lo tiene que nivelar a 8.000, es decir, lo tiene que meter en hipoxia, y esa es la hipoxia que usted tiene que cuadrar aquí, en el descenso. Cuando uno va en el descenso, se acerca al piloto y le pregunta, cuál es la presión en el destino, y él le pregunta al controlador cuál es la presión en el destino. El piloto corrige el altímetro, y le dice a uno es esta, entonces yo ya tengo que estar preparado, porque seguramente yo traigo al paciente con un ventilador, pasándole una fracción inspiratoria de oxígeno de 90%, y si voy a tener que el paciente capte más oxígeno, al 95%, pero los equipos están hechos para eso.

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3. ¿Cuáles son los efectos que la aceleración y desaceleración podrían tener sobre pacientes con deficiencias cardiacas, debido a que la sangre podría desplazarse hacia un lado u otro, generando un esfuerzo mayor?

En el plano cartesiano se plantean las aceleraciones en diferentes planos. Definitivamente las que generan, a menos que se presente un problema en el avión, que puede llegar a ser fatal. Antes que eso, los tipos de avión que hay son de ala fija y ala rotatoria, ala fija es lo que comúnmente llamamos avión, y ala rotatoria es lo que comúnmente llamamos helicóptero, haciendo la aclaración de que ambos son aviones. En este orden de ideas, el ala rotatoria tiene la capacidad de ascender y descender verticalmente, pero a menos que la aceleración sea muy brusca, esta aceleración, digamos que no tan considerable. Mientras que ala fija, tiene una aceleración en el despegue y una aceleración en el aterrizaje, por consiguiente, esta aceleración sí es bastante considerable. De manera que cuando uno sube un paciente a una aeronave, esta es la nariz del avión, esta es la cola del avión. Entonces cuando va a hacer el despegue, este es el sentido de la aceleración, y cuando va a hacer el aterrizaje, este es el sentido de la desaceleración. Definitivamente es más intensa la aceleración que la desaceleración, porque en la aceleración, la máxima potencia del motor, sumado el torque tiene que lograr una velocidad suficiente para que el aire impulse el avión, lo sustente, y lo saque; Mientras que la desaceleración con los frenos aerodinámicos, o sea los flaps, más los frenos del piloto, el avión se detiene. Lo que sucede con esto es que si usted pone el paciente con la cabeza hacia la cola es decir en contra de la nariz de la aeronave en la aceleración, es decir en el despegue que es donde se da la aceleración más intensa, los fluidos incluyendo líquidos y gaseosos se vienen al cráneo, así que, si tiene un trauma craneoencefálico, el edema cerebral es total. Mientras que, si usted pone al paciente en el sentido contrario, es decir, la cabeza hacía la nariz del avión, en la dirección del vuelo cuando la aeronave arranca el despegue, el desplazamiento es favorable. Solo nos queda la desaceleración del aterrizaje y para eso la camilla debe tener arnés de hombros, para mitigar esa fuerza negativa. Aquí cobra vital importancia el concepto de las fuerzas G a bordo. Entonces no directamente relacionado con los equipos biomédicos, pero sí, con el kit de la camilla, donde va el paciente y los equipos biomédicos, y es que ese kit tiene que estar diseñado para que, en sus puntos de apoyo, coloquialmente, en las soldaduras, exista la capacidad de aguantar fuerzas G que son a las que se va a someter la aeronave, cuando se debe maniobrar. Entonces eso tiene que ver mucho con la posición del paciente aborde. 4. ¿Consideraría innecesaria un tipo de camilla que se mantenga balanceada a pesar de la

turbulencia? Lo que pasa es que esos virajes que da la aeronave, no inciden dramáticamente en el paciente, a no ser que el avión se vaya en picada. En cambio, hacer que el paciente fluctúe en realidad complica más la situación porque entonces el paciente está navegando, entonces usted no lo tiene fijo para intervenir. Una de las principales marcas de camillas para maniobras aéreas es Spectrum y hay otra muy buena, no tan sofisticada que se llama LifePort, así que, si la investigación de ustedes tiene que ver con equipos biomédicos, el medio aeronáutico no ofrece condiciones críticas. Por el contrario, uno de los temas críticos para las empresas de transporte médico es el tema de estandarización de calibración de equipos biomédicos. Determinar cuándo es verdaderamente necesaria dicha calibración, por los costos que esto implica para la empresa. Son $400.000 por la calibración de cada equipo y son al menos 6 por cada ambulancia. Ahora si ustedes quieren campo

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de trabajo, nosotros tenemos 142 ambulancias rodando por todo el país, así que escojan a dónde quieren ir, y nos ayudan con el resultado para que nosotros podamos tener un fundamento técnico, con todos los componentes académicos, para poder definir, de acuerdo a la evidencia cuál es la verdadera frecuencia de calibración de los equipos. Hay dos criterios que usted necesita en la evaluación de un paciente crítico y son la oxigenación y la capnografía. En la capnografía, usted necesita tener una adecuada hemodinamía porque el CO2 se evalúa en el aire exhalado y para que el CO2 llegue al alveolo capilar, necesita que la bomba haya movido la sangre, y que la sangre sea suficiente para llevar el CO2 en forma de bicarbonato. Entonces si el paciente tiene bajo gasto, está en shock hipovolémico, está en paro cardiaco, pues no hay movimiento de la sangre, así que no llega el CO2 al alveolo, y si no llega al alveolo, no hay exhalación, entonces cualquiera diría, hay una hipocamnia, hay baja presión de CO2 en sangre, y eso es un falso negativo. Y en cuanto a la oxigenación, a menos de que se trate de gases arteriales, mediante una punción arterial, usted lo que hace es que coloca un oxímetro de pulso, pero el oxímetro de pulso está sujeto a que haya suficiente volumen de sangre, que pase a través de la extremidad del dedo, para que, mediante una onda fotométrica, se pueda censar la cantidad de hemoglobina que está cogida de oxígeno, y ¿si el paciente está con frío, hay una vasoconstricción periférica? No hay oxigenación. Entonces: - “¿Cuánto satura?” – “No, no, es no censa, el monitor no censa, no censa”. Y usted está perdiendo tiempo. Esto es muy importante, y esto lo tiene a uno a baja oxigenación ¡todos los días! Esos dos escenarios que les estoy mostrando, son espectaculares para presentar un trabajo de grado en un congreso mundial. Cuando un paciente pierde sangre en un trauma, el riñón se da cuenta que no hay sangre, entonces le pide al corazón que le mande más sangre, entonces el corazón cree que, pulsando más, lo va a compensar, pero pulsa tan rápido que no tiene tiempo de llenarse, así que no sirve, entonces se le mando una indicación al pulmón pidiéndole oxígeno, y el pulmón empieza a respirar más rápido, pero respira tanto que no tiene tiempo de llenarse, entonces tampoco sirve. Entonces qué hace el riñón, le quita sangre a la piel a ver si con eso compensa. Por eso el paciente con una hemorragia está taquicárdico, está polimnéico y está pálido, frío. Pero al final eso termina siendo insuficiente, entonces lo único que queda es que mientras el paciente llega a un hospital a que le pongan sangre o a que le corrijan la hemorragia, hay que tratar de sacar la sangre de donde haya para traerla al corazón y que el corazón la bombee. Y la única forma es aumentar la presión negativa en el espacio pleural, para que haga un efecto de vacío y succione la sangre en el entorno venoso, y el corazón reciba la sangre. Este dispositivo (ResQGuard) lo logra, porque cuando inhala, el paciente, el dispositivo se pega, y al pegarse, hace una maniobra de mansalva invertida, profundiza más la presión negativa, y chupa la sangre que se devuelve al corazón. Eso lo vamos a hacer en nuestras ambulancias este año. La prueba piloto del dispositivo en Colombia. Esto es otra cosa que ustedes pueden analizar (Combat Gauze). En el mundo cuando se presenta una hemorragia, la investigación ha buscado frenarla, y ha desarrollado, diferentes cosas, una de ellas es el ácido tranexámico. Es un antifibrinólico que lo que busca es frenar el fibrinógeno para que no se destruya el coágulo, que esa es una condición fisiológica del cuerpo. El otro es el factor IIA recombinante que es aumentar los factores de coagulación en la cascada extrínseca de la coagulación. Y hay otros, y uno de ellos es un agente inerte inorgánico que se llama caolín que activa la cascada de la coagulación. Entonces coger una gaza de poliéster, la impregnan en caolín, cuando uno está en el combate, el individuo lo hieren, empieza a sangrar y uno le llena la herida con la gaza. Cuando el caolín entra en contacto con la fuente de la hemorragia, activa la cascada de coagulación y forma el coágulo. Explorar alternativas para reducir el riesgo de hemorragia. Esta es la tercera

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generación (Combat Gauze), porque la primera generación era con la aplicación de una piedra volcánica, pero esta tenía la capacidad de una reacción exotérmica y llegaba a producir hasta 600°C de temperatura en contacto con la humedad. Cauterizar era un efecto secundario, porque lo que uno buscaba era que la piedra volcánica absorbía el contenido líquido de la sangre dejando a los factores de coagulación solos, para que pudieran trabajar, y generaba el coágulo estable. Esa fue la primera generación, pero presupuesto evolucionó por las quemaduras. En cambio, el caolín no tiene ese efecto secundario. El principio se llama QuickClot de la casa fabricante Z-Médica. Yo quiero presentar una investigación que tiene que ver con el trauma craneoencefálico y tiene que ver con el hecho de que cuando un individuo tiene trauma craneoencefálico, se modifican los procesos fisiológicos vasculares. Si el individuo tiene un trauma, el trauma inflama, la inflamación colapsa los vasos sanguíneos, y en el peor de los casos, los vasos sanguíneos se desgarran y sangran. Eso incrementa el edema y la mala perfusión del tejido cerebral. Y una de las cosas que uno debe hacer es favorecer que llegue suficiente sangre, y que llegue oxigenada, y a veces tratar de mantener una suficiente presión para que llegue, hace que llegue más sangre y aumente el edema, y al meterle más oxígeno, hace que se cierren los vasos sanguíneos y hay menos oxígeno en el cerebro. Yo quisiera hacer una investigación sobre la manera exacta de medir, cuánto es el oxígeno que requiere ese paciente, para poderlo transportar a un hospital sin que yo le esté haciendo más daño. Yo aquí, le puedes decir a Wilson (Padre de Alejandra Riveros), las puertas están abiertas. Todo hay que hacerlo de una manera muy seria, muy protocolaria. Si la universidad de los Andes quiere, a través de ustedes considerar que nosotros podemos ser un buen escenario de investigación, bienvenidos. Y lo único que, si es que los invito a que, si la investigación sale de una buena manera, adelante, me acompañen a alguno de esos escenarios de congresos mundiales. Que ustedes vayan y presenten el caso. Que eso es una mejora para el mundo y para nosotros. Me interesa muchísimo esa parte de investigación. Así que, si requieren algo en el camino, me llaman.

Información de contacto:

Dr. Rafael Suarez Gerente Operativo de SISMÉDICA

Dirección: Cll. 127a 7-19 Oficina 301C Cel.: 3102637857

Entrevista No. 2

Dr. Fabio Hernando Reyes Martínez Ambulancias aéres de Colombia

Transporte Aeromédico

1. ¿Quién es usted y a que se dedica? Mi nombre es Fabio Hernando Reyes Martínez, soy director médico de ambulancias aéreas de Colombia. Empresa dedicada al traslado de pacientes críticos en el territorio nacional y a nivel internacional. 2. ¿Qué es ambulancias aéreas? Ambulancias aéreas es una empresa privada de traslados aéreo-medicos de pacientes críticos. Poseemos 4 aviones, 3 beechcraft c90 y un cessna ubicado en el llano. Los helicópteros que pueden llegar a ser usados en traslados son sub arrendados de otros proveedores.

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3. ¿Qué diferencia hay entre traslado aéreo-médico y traslado terrestre? La diferencia es muy grande porque las aeronaves viajan a alturas donde cambia la presión atmosférica y se disminuye la presión parcial del oxígeno lo cual conlleva a alteraciones fisiológicas considerables. También hay más ruido y vibraciones que dificultan la realización del tratamiento adecuado. En esencia los pacientes además de poseer su patología están expuestos a riesgos adicionales. 4. ¿En qué momentos durante el vuelo se presentan dificultades? Tanto para la tripulación médica y los pacientes las etapas más complicadas del transporte aéreo-medico es el ascenso y descenso. 5. ¿Por qué diría usted que en estos momentos se dificultan las situaciones? En ese momento aumenta la aceleración y también influye el cambio de presión, tanto en el momento de acenso como descenso. Estos momentos afectan de sobre manera a neonatos, adultos de tercera edad, embarazadas y pacientes con problemas cardiacos y o respiratorios. 6. ¿Cómo funciona el sistema de presurizado y como resguarda a la tripulación?

La presurización de un avión se realiza con un aparato controlado por los pilotos en la cabina, la altura de cabina se pone al nivel de Bogotá (5000 ft – 8000 ft) sin embargo los vuelos alcanzan una altura de 22000 pies y los cambios atmosféricos se sienten, sobretodo la expansión de los gases lo cual causa dolor en el oído y a nivel intestinal. Otro factor importante es que si se aterriza al nivel del mar en Cartagena o Barranquilla el aparato no alcanza a regular el cambio de presión adecuadamente y esto afecta de manera negativa a neonatos, ancianos o a personas que estén en debilidad hemodinámica. 7. ¿El sistema de presurizado puede presentar fallas durante el vuelo?

Se pueden presentar fallas lentas, que haya un agujero en la puerta o en una ventana y se altere la presión del avión, pero también puede ocurrir que súbitamente se abra una puerta o una ventana y esto causa una despresurización repentina, afectando a los tripulantes del avión. 8. ¿Los aparatos empleados en el transporte aéreo-medico son especializados para esta tarea o

son los mismos que se emplean en las unidades de cuidados intensivos? Algunos aparatos si son especializados, de acuerdo a la experiencia internacional y la experiencia nuestra son aparatos que están avalados por la fuerza aérea de estados unidos. Por ejemplo, el ventilador y las bombas de transporte tienen que ser resistentes al cambio de presiones. Sin embargo, las incubadoras de neonatos son las mismas que se emplean en ámbito terrestre.

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ENTREVISTA – TRABAJO DE CAMPO Entrevistada: Dra. Yadine

1. ¿Qué tipo de interferencias existen para la correcta medición de oximetría en un paciente que

es trasladado en una ambulancia? Mala medición del oxímetro debido al movimiento, contaminación con la luz, incomodidad del paciente y el retiro por su voluntad. 2. ¿Qué otros mecanismos existen para la medición de saturación de oxígeno en un paciente? Existen diferentes partes del cuerpo en las cuales puede ser medida la saturación de oxígeno, sin embargo, la más utilizada es en las extremidades superiores o inferiores debido a su fácil acceso y su usabilidad. La saturación de oxigeno puede ser medida en diferentes canales, entre ellos los canales auditivos, dentro del conducto. Este debería ser desechable, aunque es importante tener en cuenta el costo de desechamiento y la adaptación del dispositivo a las diferentes formas del oído. Podrían plantear un dispositivo con una parte desechable y la otra de uso constante, esto reduciría los costos considerablemente. 3. ¿Cuánto es el costo de un oxímetro de pulso? ¿Estos se reutilizan o son desechables? Los oxímetro de pulso cuestan entre 45 mil y 120 mil COP, estos son reutilizados, se limpian con un desinfectante y únicamente son cambiados cuando el dispositivo se daña, cuando haya que cambiarle las pilas o en otros casos específicos. 4. ¿Cuál es la vida útil de estos dispositivos? En ambulancia, el nuestro es relativo debido a que la ambulancia lo pide a Secretaria, pero la medicalizada siempre usa es el monitor, los que más utilizan los sensores son los de ambulancia básica, por lo tal el sensor de dedo se utiliza muy poco, siempre permanece guardado en la caja. En cuanto a la vida útil no sabría decirte debido a que no se nos ha dañado el primero. 5. ¿En todas las ambulancias es necesaria la existencia de un oxímetro de pulso o algún

dispositivo para medir saturación de oxígeno en los pacientes? Por supuesto, por normatividad debe existir un oxímetro de monitor y el oxímetro de pulso. Cuando tu miras las historias clínicas de los pacientes, todas tienen los signos vitales, y la saturación de oxigeno hace parte de los signos vitales del paciente, entonces debes tomarla. ¿Tu como sabes si el paciente está dormido y está saturando adecuadamente? O ¿él bebe está saturando adecuadamente? Es por eso que la saturación de oxigeno se convirtió en un signo vital, antes no aparecía registrado como un signo vital, solo se realizaba la medición en ambulancias medicalizadas, ahora las ambulancias básicas también deben saber este signo vital. Un doctor no puede saber si el paciente está dormido por hipoxia, dormido por hipoglicemia y por eso tenemos oxímetro, glucómetro, entonces es un kit completo que todas las ambulancias lo deben tener, inclusive las ambulancias básicas. 6. ¿Cómo se diferencia en sensor de monitor y el sensor de pulso?

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Lo que pasa es que el de pulso usted lo usa en casos de emergencia, debido a que usted no va a bajar de la ambulancia el monitor, no va a bajar los soportes, para eso está el sensor de pulso, el cual se encuentra en un maletín de primera respuesta, es portátil. En cambia, el sensor que va acoplado al monitor se queda dentro de la ambulancia para su único uso dentro de la ambulancia. Existen unos sensores especiales para bebes, los que son llamados pediátricos. Estos sensores vienen en un material suave, como de caucho, son de meter el dedito, igual tienen su sensor, su infrarrojo. Existen otros pediátricos que son de manilla, para los bebes más pequeños, porque la pinza lastima la piel del bebe debido a que no cabe todo el pie, en la parte que queda al borde de la pinza por mucho tiempo y si usted no está pendiente todo el tiempo o lo que sea, le va a marcar y a lastimar la piel, y si es un prematuro pues lo va a lastimar mucho más. Es por eso que la mayoría de las ambulancias tienen estos sensores de manilla, más que todo por la seguridad del paciente. 7. ¿Alguna vez has tenido problemas con la medición de la saturación de oxigeno con algún

paciente? Si claro, hay pacientes que vienen muy hipoperfundidos y están fríos, entonces es muy difícil censarlos, hay que calentarles la mano, o búsquele en la oreja, porque la pinza se puede poner en la oreja, pero se cae. Pero ¿en un paciente bebe como se le pone la pinza en el oído? Entonces algunas veces hay inconvenientes en ese sentido, o la ambulancia va muy rápido y el sensor no mide nada o el paciente está muy agitado, se quita el sensor, o el bebe está llorando y patalea, entonces e sensor no mide adecuadamente, entonces no se puede saber con certeza el estado del paciente. Entonces el paramédico debe tener el sensor para evitar que se caiga, o acomodarlo para poder tener una certeza de cuando está saturando. 8. Nuestra propuesta para un oxímetro es en forma de audífono, que vaya acoplado al conducto

auditivo y tenga soporte en el oído, ¿Qué te parecería la idea? Me parecería bueno, porque es que imagínate, el oxímetro de dedo fácilmente se cae o el paciente se lo quita, hay pacientes que ya son abuelitos y no les gusta tener el sensor en el dedo, por lo que hay que darles indicaciones, ¡No se quite el sensor¡, ¡Póngase el sensor¡, ¡No bote el sensor al piso¡ Si se pone en un paciente crítico, ventilado, hipoventilado, hipoperfundido, con los mil goteos, que obviamente está haciendo vasoconstricción periférica por necesidad, un sensor ahí me parece genial. 9. ¿En el oído se genera vasoconstricción periférica? Esta parte del cuerpo no realiza vasoconstricción periférica porque es cartílago, es la última que hace vasoconstricción periférica, por eso un sensor en dicha parte me parece genial, como el que tú dices que se abrase al oído y cense. 10. También estamos analizando la posibilidad de implementarlo en la cavidad nasal ¿Qué te

parece la idea? Lo que pasa es que en la nariz hay mucha secreción de fluidos, el contacto con los vellos y tendría que ser todo el tiempo desechable. En comparación con el implementado en el oído, que lo podrías limpiar siempre que lo necesitaras usar de nuevo. 11. ¿Qué problemas tienes con la parte alámbrica del sensor?

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Cuando conectas el monitor la interferencia se hace en la parte del electro, en el visoscopio como tal, pero en la oximetría no hay complicación como tal. La parte de monitoria del paciente es bien difícil, la toma de tensión es difícil debido al movimiento, no se puede saber si es real o no el valor mostrado de tensión. 12. ¿En qué valor numérico de saturación de oxigeno es preocupante? Por debajo de 90 empieza a haber alerta, si llevas un paciente ventilado que se bajó la saturación de oxigeno por debajo de 90, hay que mirar si el paciente se descompenso, está en paro cardiaco, se acabó la bala de oxigeno o el sensor no tiene la columna ni la curva adecuada. La curva presentada es una imagen real de la oximetría, si la curva no fuese constante, si no tuviese una adecuada altura ni una forma adecuada, no sería algo real, no se puede confiar en esta saturación. Este dispositivo tiene unas alertas, este dispositivo lo permite hasta 89 y hasta 99. Por encima de 98 empieza a pitar también, está significa que el paciente está hiperoxigenado, el oxígeno es un medicamento, si abusas con la administración esto tiene unos síntomas, puede tener unas reacciones adversas. 13. ¿Cómo te das cuenta si está fallando el medidor o es una medida real? Por la curva y la columna, la curva es constante, rítmica regular, al igual que la columna. ¿Si ves la columna del 90? Y la curva con el mismo color que el 90. La cresta y el valle de la gráfica indica inspiración y espiración, es rítmica, es regular. Esta medida utiliza el pulso detectado por el oxímetro, es más creíble el valor del 100 que el de 71, ves, porque tengo un marcapasos, y suele suceder, que no sea concordante el latido cardiaco, con la oximetría de dedo. Muchas veces la medida cardiaca no es confiable solo por oximetría, porque puede esta hipoperfundido, estar en paro. 14. ¿Qué más problemas son frecuentes cuando están trasladando un paciente? El espacio reducido, todas las ambulancias al igual que los aviones ambulancias tienen un espacio reducido. Otra cosa es el movimiento, el conductor tiene que frenar y acelerar, aquí en Bogotá el tráfico es terrible, algunas veces se puede pedir la calzada de Transmilenio, algunas veces no porque no contestan, entonces esto dificulta el traslado. Sin el permiso no se puede ingresar a la calzada de Transmilenio, así de fácil, y si no hay ingreso pues usted se come todo el trancón, con su paciente crítico. Hay pacientes que obviamente no lo ameritan, como este paciente (paciente que estaba siendo trasladado) que obvio tiene un marcapasos, pero está estable, esta sin dolor, su marcapasos funcional. 15. ¿Es posible cambiar los ‘Leads’ observados por el ECG? ¿tienen la capacidad de ver los 12

‘Leads’? No es posible ver los 12, únicamente se pueden observar las derivaciones 1, 2 y 3. Los monitores no nos permiten conocer bien afondo, es una visión superficial del latido, puedes ver las 3 caras y simplemente. Si ya quieres algo más profundo, tienes que ir a realizar un electro, que es el único que sería de las 12 caras o derivas. Pero la monitoria no te va a dar las 12 derivas, no he visto el primer monitor que lo haga. He visto desfibriladores que pueden tomar la monitoria completa, incluyendo saturación, pero nunca vas a tener un electro integrado. 16. ¿Por qué no cargan las pilas?

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Porque no las necesitamos, ningún de nuestros dispositivos tienen esas pilas. Si las normas lo pidieran tendríamos esas pilas. 17. ¿El oximetro de pulso se desconecta con facilidad durante el transporte de pacientes? Si por ejemplo ahorita se acaba de desconectar y a la hora de conectarlo hay que esperar a que la curva vuelva a normalizarse. 18. ¿Qué tipo de alimentación eléctrica está recibiendo el oximetro? En este caso el oximetro está conectado al monitor de signos vitales, si el monitor esta prendido el oximetro estará detectando constantemente. Existen oximetros portátiles que exponen de manera individual la señal, sin embargo estos requieres de una batería aparte.

19. ¿Cómo es la alimentación eléctrica dentro de la ambulancia? La ambulancia está equipada con una batería adiciona que alimenta los equipos, alimentándolos así con 120 V. 20. ¿Cuánto cuestan estos monitores de señales vitales? En este momento no sabría decirte pero cuando lo compramos costo casi 9 millones de pesos. Hay unos más pequeños, otros más grandes. Este es de larga duración por que se requiere que aguanten mucho. Pues el trabajo aquí es pesado. La batería le dura casi 5 horas. Este en particular ya tiene 5 años. 21. ¿La aceleración y des-aceleración cuanto afecta a los pacientes? Se supone que no debería pero acá no se puede parar. O sigues o siegues. Hay pacientes que tienen una aneurisma y toca ir muy despacio, muy despacio. Un mal movimiento y se puede morir el paciente. Con los neonatos en incubadora también hay que ser muy prudente. Entonces todo depende de la complejidad de paciente. 22. ¿Existe una codificación por colores de las señales vitales? Generalmente el verde está ligado a la frecuencia cardiaca y el azul a la saturación de oxígeno, pero hay equipos en el mercado que no cumplen esta convención. Pero cada señal está acompañado con sus siglas representativas entonces independientemente del color de la señal, es fácil identificarlas por sus siglas. Por otro lado los colores deben ser llamativos ya que es un monitor que da alarmas. Sin alarmas no sería monitor. Hay gente que prefiere apagar el sonido, porque no le gusta el ruido. Pero para el personal médico escuchar el sonido es importante para identificar que algo está fallando. Ya que el estado del paciente se puede intuir de acuerdo a los cambios del sonido. Todos los equipos de sonido traen equipos diferentes, acá por ejemplo me está diciendo que está bajando de 90 a 89. Si se mantiene más de 30 segundos él va a pitar y me va a avisar. Las alarmas también pueden ser visuales, digamos si la saturación disminuye por debajo de 85 habrá una alarma visual que me indica que la saturación esta baja.

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Hubiera sido chévere que el paciente estuviera ventilado, para que pudieran censar que es sentir el movimiento de la ambulancia con paciente crítico. 23. El diseño propuesto es un oxímetro acoplado al canal auditivo como lo habíamos hablado

anteriormente. Descartando diversos lugares del cuerpo que podrían limitar el efecto de las vibraciones y ruido lumínico, a su vez que mejorar la lectura en estados de baja perfusión. ¿Qué opina del presente diseño?

Pues en verdad me parece que es una idea muy buena ya que es una problemática grande, sobre todo en el transporte de pacientes, sobre todo transporte por que el paciente está en constante movimiento y el riesgo que el dispositivo se desacople continuamente es persistente. A menor tamaño de paciente y a mayor edad es más complejo. Por ejemplo los pacientes especiales, los niños con síndrome de down, ellos se quitan todo, no les gusta dejarse nada. Si uno les dice ven te pongo música y le ponemos el dispositivo, le va aparecer súper cool, como dice mi hijo, así no tengo que preocuparme que se lo vaya a quitar. Además que la comodidad y la estabilidad garantizan que ello no pase. 24. ¿Qué diferencia existe entre las ambulancias terrestres y las aéreas en cuanto a insumos? Según la norma, muy poco. Ambas deben contar con los mismos insumos solo que las ambulancias aéreas deben tener chalecos salva vidas y los dispositivos deben estar alabados para el funcionamiento en los cambios de presión atmosférica. Deben contar con monitor de señales vitales, desfibriladores, ojímetros… etc. Igual que nosotros. Conclusiones del recorrido: En resumen, se puede concretar que un oximetro capaz de reducir los problemas asociados a la contaminación lumínica, movimiento excesivo y lecturas en estado de baja perfusión es de gran requerimiento en el ámbito colombiano. Se concordó que el diseño de forma de auricular para el oximetro ofrece varias ventajas sobre los actualmente utilizados ya que permite una mayor comodidad y estabilidad. Esto disminuye la problemática presente (vibraciones, desacoplamiento, ruido lumínico) lo cual limitaría el tiempo y error asociado a las lecturas inadecuadas de estos dispositivos. Importante resaltar que lecturas inadecuadas por razones aparentemente triviales, movimiento y ruido lumínico, pueden retardar el tratamiento de un paciente en estado de emergencia. A su vez se determinó que la perfusión en el canal auditivo se mantiene constante así el paciente este sufriendo de vasoconstricción en zonas periféricas, lo cual le otorga un plus a nuestro dispositivo propuesto ya que sería capaz de medir adecuadamente la saturación de oxígeno en la sangre sin importar el estado del paciente. Dado que en emergencias se encuentra de forma constante pacientes en estado crítico la posibilidad de leer adecuadamente la saturación de oxigeno es importante para el doctor y las decisiones que pueda tomar en base a la información presente.

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Appendix No. 3: Physiological explication.

Sustento cuantitativo de la necesidad del dispositivo de oximetría propuesto A partir de la retroalimentación realizada por el doctor Roberto Rueda, en la cual solicitaba mayor sustento del proyecto planteado, se llevó dicha inquietud al profesor asesor Juan Carlos Briceño, quien nos indicó que la manera de soportar cuantitativamente el proyecto era a través de la búsqueda de bibliografía especializada, en la cual se expusieran cifras que corroboran la necesidad del proyecto en cuestión, así como la observación de pacientes en la salas de urgencias. Frente al último ítem, Juan Carlos Briceño facilitó el contacto del Director del Hospital Simón Bolívar para llevar a cabo la observación en la sala de urgencias de dicho hospital. Se adjunta el correo con la respuesta obtenida del doctor. Por otro lado, respecto a la viabilidad cuantitativa del proyecto, se encontró que en un estudio realizado a una muestra de 532 pacientes transportados en ambulancias, el 11% del total se encontraba en estado de desaturación de oxígeno, siendo éste definido como un RA SpO2 inferior al 91% [1]. De ese porcentaje, el 7,3% se encontraba con SpO2 inicial entre 81 y 90%, el 1,1% con SpO2 inicial entre 71 y 80%, el 0.4% con SpO2 inicial entre 61 a 70% y el 2,1% con SpO2 inicial inferior al 60% [1]. Así mismo, dicho estudio evidencia la necesidad de implementar un dispositivo para la medición de oxígeno que presente alta precisión, especialmente en el transporte de ambulancias, bien sea de helicóptero de ala fija o móvil, puesto que, a partir de las mediciones obtenidas por medio de un pulsoxímetro, el 25% de los pacientes atendidos con unidades de soporte de vida básicos (BLS) fueron tratados de manera inapropiada en cuanto al suplemento de oxígeno que requerían, y el 4% de los pacientes atendidos por medio de unidades de soporte de vida avanzados (ALS), fueron inapropiadamente tratados en cuanto al restablecimiento o mantenimiento de óptima saturación de oxígeno. A partir de las cifras anteriores, el no tratamiento apropiado de regulación de la saturación de oxígeno, que se puede dar, como previamente se evidenció, por una medición no acertada, de los dispositivos actualmente usados, implica consecuencias de extrema gravedad, en el caso de exponer a los pacientes en condiciones de estado crítico, a hipoxia, puesto que dicha condición implica un muy alto riesgo de daño de órganos [2]. Así mismo, una exposición excesiva a compensación del oxígeno en pacientes mal diagnosticado respecto a su verdadero nivel de saturación de oxígeno (hiperoxemia), resulta riesgoso debido a las consecuencias fisiológicas de deterioro del estado del paciente, especialmente en pacientes que sufren de enfermedad de obstrucción pulmonar crónica (COPD) [2]. Por otro lado, a partir de una auditoria hecha al uso de oxígeno en ambulancias que atienden casos de emergencia, así como en el departamento de emergencias de un hospital, en Reino Unido, se determinó que el 17% de los pacientes analizados (1022 en total), se encontraban en condición de saturación inferior al 94%, y del 7% presentaba nivel de SpO2 inferior al 90%. De ese 7% el 33% de los pacientes, presentaba la condición de COPD, la cual fue en un 42% mal diagnosticada (no identificados) en el ambiente prehospitalario, por medio del uso de pulsoxímetros convencionales. Así mismo, dicho estudio corrobora el uso común de medición y tratamiento de oxígeno en ambulancias, equivalente a 2,2 millones de episodios anualmente, en el Reino Unido, de los cuales, en concordancia con la cifra dada por el mismo estudio, 528.000 de los pacientes atendidos al año,

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se encuentran en estado de hipoxia, correlacionada con hipovolemia, y que por consiguiente, requiere de un dispositivo capaz de medir de manera más precisa, el nivel de saturación de oxígeno real del paciente, para así evitar las letales consecuencias, mencionadas previamente, que la hipoxemia genera en pacientes en estado crítico [2]. En cuanto a otro factor que corrobora la necesidad de un dispositivo de oximetría apropiado para las condiciones que se presentan en las ambulancias, es la dificultad de la medición de la presión sanguínea debido a, entre otros factores, al movimiento de las ambulancias, así como al ruido de tipo sonoro y lumínico que es característico de dicho entorno [3]. Para determinar la influencia de dichos factores en la obtención de una apropiada medición de los niveles de saturación de oxígeno, se encontró un estudio el cual comparó la toma de mediciones en un entorno quieto y comparado con un entorno en movimiento como el de las ambulancias. Se encontró que la lectura de uno a otro entorno difería en un cerca 40% [3], para el caso de la medición de un parámetro cercano al de interés en el proyecto en cuestión de oximetría, como lo es la medición de la presión sanguínea. Se encontró, así mismo, que a pesar de que se usaran instrumentos que cumplían a cabalidad con los requerimientos internacionales, se encontraba una diferencia de cerca del 23% entre ambos entornos [3]. A partir de lo anterior, se corrobora la influencia de factores característicos del ambiente de ambulancias en la toma de mediciones requeridas en pacientes transportados en estas [2]. Referencias [1] Cydulka, R. K., Shade, B., Emerman, C. L., Gersham, H., & Kubincanek, J. (1992). Prehospital pulse oximetry: useful or misused? Annals of emergency medicine, 21(6), 675-679. [2] Hale, K. E., Gavin, C., & O’Driscoll, B. R. (2008). Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emergency Medicine Journal, 25(11), 773-776. [3] Prasad, N. H., Brown, L. H., Ausband, S. C., Cooper-Spruill, O., Carroll, R. G., & Whitley, T. W. (1994). Prehospital blood pressures: inaccuracies caused by ambulance noise? The American journal of emergency medicine, 12(6), 617-620. Appendix No. 4: Testing step videos. Test 1: https://www.youtube.com/watch?v=KfukLSzbPPU Prototype 1: Setting test: https://www.youtube.com/watch?v=PPqcsRez1G8 Stability: https://www.youtube.com/watch?v=fH-lOveRWvI Prototype 2: Setting test: https://www.youtube.com/watch?v=Bop5ZvG-jqQ Stability: https://www.youtube.com/watch?v=YNCtevmZhMs Users perception: https://youtu.be/6TgKFe5Efv8 https://youtu.be/fOtkWSvG

Appendix No. 5: One-Pager.

Contact: Manuela VargasEmail: m.vargas12@unian-des.edu.coPhone: (318) 711 - 8166

Management:- Daniel Barón - César Pinzón- Sebastián Reyes- Alejandra Riveros- Manuela Vargas

Industry:Medical Device

Company Founded:2018

Strategy Partnerships:SISMEDICA

Current Users/Custo-mers:None (Prototype stage)

Market Feedback:Comodato contract with SISMÉDICA and Ambu-lancias Aéreas de Colom-bia. 10 Oxycure proto-types will be given to them to receive feed-back about its perfor-mance in the field.

Demo Status:First prototype design currently in development and proofs

Current Investors:None (Prototype stage)

Amount Financing Sought:100.000.000 COP

Mission:Our mission is to identify and provide the solution for needs in air transport and land transport of patients in a state of vasoconstriction and low perfusion, to allow ade-quate detection of blood oxygen saturation levels and emergency contexts.

Products & Technology:Oxycure offers a device that measure the oxygen satura-tion in blood based on the reflectance phenomenon. Also, the device is focused on the measurement of this vital sign in conditions of vasoconstriction. For that reason, it will be placed inside the ear cavity. This medical equipment is reu-sable after proper sterilization, as it will be in contact with body fluid like ear wax. Finally, Oxycure seeks the reduc-tion of white noise, discomfort of the patient, costs, weight and size of the device and instability.

For achieving this, Oxycure implements a GY-MAX30100 Module, an Arduino Nano, a Liquid Crystal Display LCD and a HC-05 Bluetooth module. In the external components, the packing of the pieces will be done with the mold injec-tion technique. The device will present a headset, a support for the ear and a box where the information is pro-cessed and sent. This box can be located in the arm or at a certain distance from the patient's ear canal due to its func-tion.

Oxycure

Use of Funds:Complete product and manufacturing design

Revenue:None

IP Status:None

Regulatory Status:None

Market Opportunity:In Colombia, the expected market is focused to the IPS that provide the service of both ground and air ambulances. Addi-tionally, Oxycure can be used in hospital environments such as operating rooms and intensive care rooms, where patients are in a state of vasoconstriction. According to the WHO, it is required to have 1 ambulance by each 25.000 habitant. Taking that into account, and the annual population growth of 8%, it is excepted to sell 2000 Oxycure devices during the first year. In addition, it must be included in the current business contact with the companies SISMÉDICA and Ambulancias Aéreas de Colombia to start with potential customers Potential custo-mers that are expected to extend the effectiveness of Oxycu-re through word-to-word method. Other kind of commerciali-zation pathway will be with a Web site and national distribu-tion, with a Comdata contract and attending medical device conferences. To develop the devices, we will acquire the raw material and outsourcing for the assembly.

Business Model:The target customers include public and private ambulances companies (first target market). Surgery centers and intensive care rooms are also included. The strategy for selling will be a Comdata contract with the two companies (SISMÉDICA and Ambulancias Areas de Colombia) for a previous word-to-word publicity. Online sales are also expected to perform as the main communication channel with potential customers. The first year will give a net profit margin of 14,75% assuming to sell 2000 devices during this year and with an annual growth of 0,8%.

Competition:The products currently on the market that represent competi-tion to Oxycure are the commercial pulse oxymeters which cost between 40.000 to 150.000 COP. Another method to quantify oxygen saturation in blood is the arterial blood gases measurement which is an invasive but accurate method. However, this cannot be performed in emergency contexts because of the time and required procedure. The pediatric device LIIP also allows to measure oxygen saturation with accuracy but it is not used in adult patients and its price is around 230 euros.

Oxycure