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IOP PhOtOnIc DevIces 10 appealing projects
Preface That a relatively small country like The Netherlands ranks amongst the leading countries in the world when it comes to photonics is something I feel we can take pride in. These successes are the outcome of a sound economic policy that recognised the potential of investing in new innovative technologies like photonics; one of the key enabling technologies. Enabling technologies are the type of progressive technologies that not only explore uncharted terrains but also give birth to new innovative businesses. The IOP Photonic Devices has contributed to the success of Dutch photonics by first and foremost being a collaborative platform that centralised strategic alliances. A place where academic expertise is bolstered with industrial potential, supported by a willing government.
From the outset the IOP Photonic Devices has concentrated on two distinct themes. On the one hand it has focussed on the application of photonic devices in health and medicine. Projects that provide us with the reassurance that diagnostics and treatment will not only be less invasive in the future but also more effective. On the other hand, the IOP Photonic Devices has sought to stimulate research into photonics itself by developing its’ generic properties. Focussing on the design, process development and cost-effectiveness of the technology itself, has resulted in a thriving academic and economic environment that is able to turn intricate knowledge into state-of-the-art photonic devices with a broad application potential.
This document before you is testimony to the impressive results achieved by projects that the IOP Photonic Devices has supported. It is crucial that we now cement these accomplishments by embedding them in a flourishing economy. I feel that with the right support from the government and the country’s most dominant innovative organisations, but also through to new platforms like PhotonicsNL and Memphis we can guarantee that photonics will make a decisive contribution to tackling global societal challenges by meeting them with distinctly Dutch solutions.
Dr. Bart h.verbeekChairman Advisory Committee IOP Photonic Devices
nurturing enabling technologies for a bright tomorrow
www.rvo.nl/iopphotonicdevices www.photonicsnl.org
www.smartmix-memphis.nl
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Photonics in the netherlandsIn the world of photonics everything is illuminated. If the 20th century was catapulted forward by the electron, then the 21th century may well be thrust forward by the photon. In photonics everything revolves around photonic components that can generate, detect and manipulate light.
socially relevant and sustainable business solutionsPhotonics is a base technology that is used for a wide-range of applications. Without knowing it we encounter photonics on a daily basis. The internet, smartphones and Led lighting being just a few practical examples. Today, photonics is found in nearly every forward thinking industry, from consumer electronics, to telecommunications and medical applications. Photonics has become so crucial that the European Commission has identified it as one of six key enabling technologies. In 2006, The Netherlands already earmarked its’ importance by setting up the IOP Photonic Devices. This platform formed the basis for the ongoing collaboration between the industry and research centers to turn photonic possibilities into socially relevant devices and sustainable business applications.
In the world of photonics everything revolves around components that
can generate, detect and manipulate light.
The Netherlands supports photonics in a number of
ways including: the IOP Photonic Devices and the Topsector High-Tech
Systems and Materials.
This enables Dutch technology and research to be at the
pinnacle of global developments in the many fields that photonics plays an increasingly important role in such as:
Healthcare, ICT, Telecommunications, Safety, Water, Agriculture.
This support is translated into research in photonics and the education
of students about its potential, as well as allowing for the development and
engineering of photonic devices and applications.
components
support
Position
Progress
Photonics
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Photonics stem from Optics and exploits the properties of light for practical applications. The invention of the laser and fiber-optics has propelled the usage of light sources in an increasing number of scientific and technological fields. In the Netherlands we see that the development of photonic solutions helps to become leading in for example sensors, precision farming, hightech IC-manufacturing and medical diagnostics and therapy.
The market for photonic devices is growing both in size and economic value. This is why RVO.nl, part of the ministry for Economic Affairs, has actively supported the collaboration between research centres and companies in the form of the IOP Photonic Devices and continues to do so through the High Tech Systems and Material Topsector. This ongoing support does not only allow for the valorisation of knowledge but also bolsters the country’s’ leading position in the field of photonics. Mastering these types of enabling technologies will allow the Netherlands to successfully transform into a prosperous knowledge-based society, the creation of jobs and let’s not forget, a brighter tomorrow.
Photonics manufacturing supply chainKey in becoming a leader in the field of Photonics is organising the manufacturing supply chain. The IOP Photonic Devices has done so by building-up the supply chain and organising the development of ‘generic’ photonic technologies providing miniaturised Photonic IC’s. The results that are presented in this brochure have only been possible by the good collaboration between industry and universities in the Netherlands.
supporting Innovation for real life applicationsMost of the results here have applications in the medical field. Despite the many opportunities for photonics solutions in the societal challenges in all other fields, the IOP Photonic Devices has focused to stimulate the development of generic photonic technology as well as photonics in the medical application. Photonic solutions are especially eye-catching for diagnostic and therapeutic purposes in the medical field. An ageing population means that new ways of administering care and treating illnesses are vital in order to sustain an affordable and state-of-the art healthcare system. The Netherlands has a substantial pool of sophisticated expertise in the medical photonics field and a relatively large number of companies are able to convert both existing and yet-to-be developed knowledge into a full range of innovative products.Photonics will be at the heart of creating not only a more affordable system but also a far less invasive one. The increased miniaturisation of photonic devices and development of generic photonic technology allows them to be at the core of a future range of instruments available to physicians, general practitioners and healthcare workers.
www.photonicsnl.org
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1 • Cost effective ambulant monitoring with hIP
10 • sizeable improvements by making things smaller
4 • Improving FLIM by a bright joining of forces
8 • something new under the sun
5 • no sight without light
6 • the nanophone proves better inter-vascular imaging is within reach
7 • Larger than the sum of its parts
9 • towards a more objective judicial system
2 • hympacting history
3 • Making an IMPAct on surgical oncology
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Cost effective ambulant monitoring with hIP In July of 2014, The New York Times published an article outlining the synchronised global slowdown in medical costs. This slow down in the rate of health cost growth was attributed to a few causes, one of which is a new strategy that reduces the need for expensive hospital stays by performing treatments and diagnostics in out care facilities and by administering ambulant care. Another reason for this decline in healthcare cost per capita and the main reason behind increased ambulant and out patient care are the improved drugs and instruments that are coming onto the market. Hemodynamic monitoring is one of these technologies that can help in creating a more comfortable and affordable state-of-the-art healthcare system.
HIP
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state-of-the-art comfort and careA cost-effective healthcare system is important for keeping care affordable but on the other hand, especially with a shift in the populations demographic, it is also vital that we make care more comfortable for the patient and less invasive. Striving for a more comfortable way of monitoring thecondition of the patient becomes even more desirable under ambulatory settings. On the other hand cardio-vascular diseases are more prevalent from a certain age onwards and demand constant and reliable monitoring techniques to ensure the well-being of the patient in question. Tissue perfusion, heart rate, blood pressure and blood saturation measurements can for example be indicators of potential cardio-vascular problems. Closely monitoring these types of values, especially when these illnesses have already manifested themselves earlier, is therefore essential and may even prevent heart attacks in a number of cases. While blood pressure and pulse can be easily monitored at home nowadays, this is not yet the case for other crucial characteristics like tissue perfusion and oxygen saturation.
‘the results of the hIP project
have shown great promise.’
About this project
Project: HIPIPD083359
Contact information:Paul UrbachT 015 278 94 06E [email protected]
Participants:• TU Delft• TU Eindhoven• Philips Electronics
Nederland Eindhoven• Hemolab Eindhoven
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with respect to motion induces artifacts. New information also becomes available as a result of more sophisticated monitoring. For example, research carried out in this project in signal processing by the group of Prof. Dr. Jan Bergmans of TU Eindhoven has also shown that monitoring of return of spontaneous circulation (ROSC) can considerably help in saving lives in cases where cardiopulmonary resuscitation has to be done. This also helps in early rehabilitation of the patient.
Into the futureWe are also cautiously optimistic that we cannot only improve the current cardiovascular measurements but that we, based on the result of our research can also add more functionalities to the current devices. The current saturation measurements indicate what percentage of red blood cells are carrying oxygen. Pulse meters determine the patients pulse and the amplitude gives an indication of the saturation of the tissue. Combining the oxygen saturation measurements with the bio-speckle interferometry will potentially provide a more conclusive perfusion index along with other haemodynamic parameters. “For now we have concentrated on the procedure but our laboratory set-up proves that our assumptions are correct”, says Prof. Urbach of the Delft University of Technology, “we still require additional testing and to that effect the HIP programme has devised a dedicated testing platform that mimics the effects of the human vascular system. Tissue phantoms, or artificial arteries, developed by LifeTec B.V., through which we pump fluids like milk, which has similar optical properties to blood, allows us to test both the software and hardware component of this research project”.
Whilst there might not be a ready-made prototype just yet, the preliminary results look promising and a proof of concept has been delivered.
hemodynamic measurementsHemodynamic measurement devices which monitor cardiovascular properties currently, are still big, delicate and sensitive to interference which prevents accurate measurements. A deciding factor in improving on this process is the ability to filter out, either by signal processing or by hardware, motion artefacts, i.e. disturbances of the signal caused by patient movements. Bio-speckle interferometry can help to solve that problem effectively. Coherent light illuminates the skin, ideally a rough thin part of the skin like the finger. The reflected light has a speckled pattern. The reflection is picked up by an image sensor which can provide the cardiovascular parameters.Integrating sensor systems onto a single chip that is placed into a small hand held device will lead to more complex blood value diagnostics to be obtained from the comfort of the patients’ home. These devices have also been shown to be more robust than current techniques
‘We are looking forward to invite commercial partners to the table slightly closer to the conclusion of our studies into this innovative and promising technology to explore its commercial potential.’
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hympacting historyLearning that you have cancer is a dramatic experience. Unfortunately, thousands of people are diagnosed with this life crippling disease on a daily basis. Something that cannot be overstated enough is the role that early detection and correct diagnosis play in improving the survival rates of patients. The partners in the HYMPACT project are putting innovation into practice to improve the situation of potentially millions of women worldwide.
Hympact
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X-rays use ionising radiation which may have carcinogenic potential itself. This is due to the high energies that are being transferred during the x-mammography that may cause changes to the DNA structure. Further, the contrast between cancer and breast tissue is low especially in younger breasts. The more contrast the affected area shows with its surrounding healthy tissue, the more effective this diagnostic technique becomes. Echoscopy is very effective
Breast cancer researchBreast cancer is the most prevalent form of cancer amongst women in The Netherlands, with one in nine women being affected at some point during their lives.“Doctors and technicians that examine patients with the current equipment are doing an amazing job at saving patients’ lives each and every day.”, says Dr. ir. Srirang Manohar of the Biomedical Photonic Imaging Group of the University of Twente, “Unfortunately both x-ray mammography and echoscopy each have their limitations. X-ray mammography has been around since the 1960’s when less was known about the drawbacks, echoscopy has been around for even longer, that is why we are now exploring the possibilities for more comfortable ways of conducting this procedure in a less harmful way and with even more accurate outcomes”.
‘We are working hard on realising
the acceptance of photoacoustic
mammography into clinical practice.’
About this project
Project: HYMPACTIPD083374
Contact information:Srirang ManoharT 053 489 31 64E [email protected]
Participants:• Universiteit Twente• Erasmus Medisch
Centrum Rotterdam• Luminostix Rotterdam• Oldelft Delft• Medisch Spectrum
Twente Enschede
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This project demonstrates that new technologies hold the key to a better and more effective healthcare system. “We have successfully proven that our findings and set-up work”, says Manohar, “but more work needs to be done. Each cancer has its’ own unique properties, studying the effects that each cancer has on our equipment will make our device more effective, one cancer at a time.”. Many of us are trying to cement our place in history, doing this by attempting to better the perspective of millions of women worldwide is not only noble but also allows us to be a little bit more optimistic about the future to come.
in finding benign abnormalities such as cysts. It is less accurate in imaging solid tumours in the breast, because they do not show that much contrast, as a cyst, making it harder to detect cancer.
PhotoacousticsHuman cancers grow relatively quickly which makes them gluttonous. Their need for nutrients and oxygen makes them hijack surrounding blood vessels so they can feed off of their supply equally. It is exactly this ungraceful parasitic behaviour that gives these cancers away and allows photoacoustic devices to successfully locate them. Cancer cells are surrounded by high concentrations of haemoglobin. When a laser pulse of the right wavelength is absorbed by a haemoglobin molecule it generates heat. If the pulse illuminates a piece of tissue that contains a lot of haemoglobin, the heating leads to a temperature rise. This is then followed by thermal expansion creating a mechanical wave or ultrasound that travels through tissue easily. This can easily be detected by sensitive echoscopy detectors. It is this principle that the HYMPACT group exploits with their device and which circumvent the downsides of the classical mammography procedure by combining the advantages of photonics and acoustics. Another highly advantageous benefit is that the breast no longer needs to be compressed during the procedure. Therefore, photoacoustic imaging makes this traditionally very painful process not only highly accurate and less invasive but also much more comfortable for the patient.
‘We are also working on gaining
crucial clinical evidence gathered
in well-designed expanded patient
studies.’
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Making an IMPAct on surgical oncologyA large percentage of all patients that undergo surgical oncology have to return to the hospital to receive additional treatment. The outcome of the IMPACT project offers surgeons superhuman vision and improved chances of removing all cancer in one single operation.
Impact
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the tumours as soon as they are hit by light at a specific wavelength. This makes the contours of the cancer cells clearly visible to the surgeon who picks up the fluorescent signal through a camera above the patient for open surgery or that is mounted on his laparoscope for minimal invasive surgery. This makes it far more straightforward to cut the cancerous tumour away without harming the surrounding healthy tissue. The surgeon knows that all the cancer has
Many of us will have little trouble pointing out Amsterdam or London on a map with a great deal of accuracy. It becomes harder however when you’re asked to swiftly point out Lille or Strasbourg on a piece of paper containing only the outline of the country that these cities are in. This is a problem that also arises in oncology. Today, oncologists have an arsenal of sophisticated imaging techniques at their disposal to accurately locate tumours. Surgically removing these tumours based on these scans is however a painstaking and difficult process since surgeons still rely on their experience, vision and tactile sense.
the story of the eyeSubstantial progress can be made on current procedures. Selectively “staining” tumour cells with a fluorescent dye coupled to (a) cancer specific marker(s) will illuminate
‘since surgical removal of tumours
is still the most important cancer
treatment, this new technology can
count on a large market.’
About this project
Project: IMPACTIPD100020
Contact information:Clemens LowikT 071 526 30 75E [email protected]
Participants:• LUMC, Leiden• AMC Amsterdam• Universiteit van
Amsterdam• Percuros Enschede• O2 View Marken• Quest Medical Imaging
Middenmeer
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sentinel Lymph node For a long time it has been standard practice to remove all lymph nodes when a person is diagnosed with breast cancer. This is done to determine whether the cancer has spread beyond the breast and to decide on the appropriate treatment. However, this procedure often results in long-term discomfort to the patient, as removing all lymph nodes may cause lymphedema, a condition that causes a painful swelling in the arm. “This may soon be a procedure of the past”, explains Löwik, “our technology allows us to identify the sentinel lymph node, (the first lymph node the tumour drains to and therefore metastasises to), with certainty by using our camera and a technique similar to the one we use for staining cancers simply by using an agent with different properties. We now only have to remove the sentinel lymph node for diagnostics and when it proves clean then that automatically means that all other lymph nodes are free of cancer and that there is no longer a need to remove any subsequent lymph nodes with substantial benefits to the patient.”
A quick peek into the future“We are still looking for areas in which we can further improve on what we have developed already”, says Löwik despite the already prolific results of the IMPACT project, “we now have added a third channel to our device containing a laser which would allow us to kill the tumours using photodynamic therapy (PDT) using new photosensitizers or tumour targeting nanoparticles containing a photosensitizer. PDT using this new photosensitizer is already being successfully applied on many patients in Russia with truly impressive results. Still, we take great pride in our achievements so far, the success of the project has been down to bundling the wealth of expertise that we have in The Netherlands and the opportunities that we have had by being part of the IOP Photonic Devices.”
been removed once no more illuminated particles light up on the camera. “We knew that the current cameras did not suffice”, explains Prof. Dr. Clemens Löwik of LUMC, one of the partners and Prinicipal Investigator in this project, “that’s why we built a fully mobile hand-held camera that shows the surgeon in colour where the tumours are located in the body during surgery. By allowing the camera to work in the near infra-red, we ensure that it picks up more than can be perceived by the human eye and enables us to penetrate deeper into the tissue. Finally, our camera that is already successfully used in hospitals, allows for spectral unmixing which reduces the effects of native tissue auto fluorescence. Although this is something that is fairly standard in fluorescent microscopy, it is relatively new to cameras used in-vivo”.
‘the camera developed in this project can make the tumour visible by exposing the nanoparticles with a laser, making it possible for the surgeon to remove the tumour tissue.’
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Improving FLIM by a bright joining of forcesEvery good relationship is built on trust and mutual understanding. The MEM-FLIM project that seeks to take FLIM (Fluorescence Lifetime Imaging Microscopy) technology beyond its current state demonstrates that old acquaintances can make for excellent partners.
MEM-FLIM
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structureThe structure of the IOP programme requires a combination of research and commercial organisations to work collaboratively. Shared commitment, combined effort and realising each others’ potential add to the effectiveness of these types of consortia. This methodology, based on valorisation, ensures that dedicated research is converted into tangible marketable results. That this approach is a successful one can be deduced from the attention it has received over the years, with most recently the United States following suit by making $100,000,000 available for collaborative developments in the field of photonics alone.
shared expertiseLambert Instruments already had a proven track record in Fluorescence Lifetime Imaging Microscopy (FLIM) when they brought together a consortium of partners to improve on the existing FLIM technology. “We already knew each partner intimately before we started this collaborative project. The Dutch National Cancer Institute, for example, already had one of our existing FLIM devices, we had already collaborated with the TU Delft from the late 90’s
‘A functional proof-of-concept
demonstrates the potential that
is there, despite certain areas
still demanding attention.’
About this project
Project: MEM-FLIMIPD083412
Contact information:Ted YoungT 015 278 53 90E [email protected]
Participants:• TU Delft • Lambert Instruments Roden• Teledyne DALSA Eindhoven• NKI Amsterdam
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“The sample thus creates a sort of light echo”, explains de Jong, “the short time in which the light re-emits tells biologists a great deal about the interactions within that cell, as interactions have an effect on the lifetime of the back transmitted light. This information is measurable. Conventional microscopes measure the fluorescence, the colour and the intensity, however in this project we looked specifically at the delay. This makes the system not only simpler and more robust but also, as the delay can be objectively measured, results directly in quantifiable data.
In touching distance of the finish lineThe current range of FLIM microscopes makes use of complex intensified CCD cameras that require high frequency amplifiers and high voltage circuitry. The image intensifier tube of today’s device is highly sensitive to overexposure, making it fragile. On top of that the properties of the image intensifier and the way it is connected to the camera add noise and reduce the image resolution. Not to mention the price level, with current systems starting upwards of $100,000, excluding the microscope itself. This is why this project looked at developing a viable alternative by replacing the intensified CCD component with a custom-designed solid state CCD chip that is combined with its driver electronics on a printed circuit board. This not only improves the sensitivity and resolution found in the current system, but will further improve the FLIM technology as a whole and as a consequence with a more competitive price. “The proof of concept has been delivered as a direct result of our participation in the IOP PD”, concludes de Jong, “we are now in touching distance of the finish line and whilst we are still developing the camera, we expect a market introduction in the foreseeable future. In addition, we are looking forward to several forthcoming publications in high-ranking scientific journals”.
onwards and the company Teledyne DALSA, located in Eindhoven, is the only organisation in the world that could actually produce the sensors in which we were interested. In turn, we could bring our software and commercial expertise to the table. This combination of familiarity and expertise is what has helped to drive this project forward”, says Sander de Jong of Lambert Instruments.
A fluorescence lifetime imaging microscope enables researchers to follow the interactions between proteins that are taking place in a cell. This process is predominantly applied in fundamental research into living cells by cell biologists. The obtained information is especially valuable to furthering research into cancer.
Objective and Quantifiable FLIM makes use of the fact that some molecules are fluorescent: when molecules absorb light, in a short time they emit part of that light back but at a longer wavelength.
‘Lambert Instruments together with teledyne DALsA and potential other partners will develop a commercial version of the MeM-FLIM system, whilst the academic partners are fully intent on further developing the system so that even more can be gained from the technology.’
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no sight without lightLight is electromagnetic radiation. Light represents only a small portion of the electromagnetic spectrum. Light is the electromagnetic radiation we humans can perceive with our eyes. Optical Coherence Tomography makes use of the properties of light and the wave like characteristics of photons themselves.
OCT
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Tomography gives ophthalmologists the ability to take an in-depth look at the retina, the vital tissue responsible for sensing light and sending information to the brain. That the technology is full of promise, also for other diagnostic fields, is demonstrated in this project.
Miniaturisation, integrated photonics and cost-effective productionMiniaturisation, integrated photonics and cost-effective production possibilities are a common thread throughout projects supported by the IOP PD and this is no different in this project and not without reason. The current equipment makes use of bulky, energy-intensive and expensive optical components. These properties limit the wider adoption of the technology in other clinical fields that demand smaller more manouverable tools.
In a simplified definition, OCT is an optical ultrasound that provides physicians with detailed information about the composition and potential problems of the tissue they are examining. Since its development in the 1990s, OCT has become the standard diagnostic tool for western ophthalmologists. By creating a cross-sectional image of the tissue at a resolution of several microns, Optical Coherence
‘this progamme has brought the scientific and commercial world closer together and has generated a better understanding of another’s requirements.’
About this project
Project: OCTIPD100019
Contact information:Ton van LeeuwenT 020 566 55 62E [email protected]
Participants:• AMC Amsterdam• Universiteit Twente• Lionix Enschede• VTEC Eindhoven• Oclaro Technology (UK)
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diagnostics like biopsies. A good example, is integrating the OCT technology into in-vivo usable catheters for taking optical biopsies of the intestines or arteries. Traditionally, these are not only invasive procedures but also painful ones. A physician, for example, will for diagnostic purposes be tempted to remove several samples from the intestines when a patient is suffering from persistent gastric problems. Optically examining the intestines first by sending a miniaturized OCT device through them will reduce the need for unnecessary multiple biopsies as the problematic areas will already have been identified. Another procedure that stands to benefit is cardiac catheterization. OCT does not require the same contrast agents that are traditionally used and sometimes cause painful or allergic reactions in patients. OCT merely uses a salt solution to temporarily move the blood whilst the condition of the artery is being mapped.
Other medical fields like urology, plastic surgery, dermatology and oncology also stand to benefit from improving on the current OCT devices, as well as commercially interesting fields beyond medicine such as engineering and forensics. “Biomedical optics is the oldest tool available to doctors”, jokes van Leeuwen, referencing that doctors first and foremost should trust their eyes when examining a patient. “The better we understand the OCT signals, the better we understand tissue”, van Leeuwen continues, “add to that quantitative information obtained from that tissue and being able to cross-reference that information with physiological parameters and you have a highly sophisticated imaging modality that is a fine addition to the imaging techniques that currently exist in hospitals. Improving the device itself will add functionality and its enhance commercial potential. This combination, in turn, will open doors to new exciting applications for the technology and its marketability.”
“A smaller, cheaper and more manageable OCT device will decisively improve the clinical potential of the technology beyond ophthalmology and whilst we are not quite there yet, a substantial amount of progress has been made”, explains Prof. Dr. van Leeuwen of the biomedical engineering & physics department of Academic Medical Center of the University of Amsterdam.
Biopsies and new applicationsMiniaturizing the technology, by making use of advances in other fields like telecommunications, makes it perfectly suitable to guide and reduce more invasive forms of
‘new Dutch companies that commercialise swept light sources for Oct have been established already and in turn will contribute to an improved more affordable healthcare system.’
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the nanophone proves better inter-vascular imaging is within reachHospitals increasingly work with advanced techniques for diagnostic and therapeutic purposes. Instrumentation, or in other words, using measuring instruments for monitoring and controlling these processes is therefore increasingly important. Inter-vascular ultrasound imaging benefits from an all optical array receiver, the Nanophone, that makes use of photonics to measure acoustic wave fields. The all-optical sensor of acoustic waves is a generic acoustic detector which can also be used in other applications such as non-destructive testing of materials.
Orivus Nanophone
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no electronic interferenceAcoustic light sensors consisting of a ring resonator on a silicon membrane make up the basis for the device. A change in acoustical amplitude will cause the siliconmembrane to deform and thus causes a shift in the opticalresonance frequency of the ring resonator. This shift of optical resonance frequency is monitored using an optical interrogator system.The sensors can be mass-produced by making use of a process called optical lithography. “Using integrated optics allows us take the size down substantially”, says Prof. Paul Urbach of TU Delft. “Two PhDs have been working on this project: one was concentrating on the optics of the device, the other is working on the acooustical performance. The design on chip of the ring resonator makes our device small and hence suitable for new applications, but also allow us to mass-produce the chips making them affordable”. This combination of optics to acoustical detection has another added advantage. A great deal of work in hospitals takes place in environments that are filled with highly-sensitive machinery. Electronics interfere with one another which creates noise and
‘the project has already delivered
a fully operational prototype.’
About this project
Project: ORIVUSIPD100026
Contact information:Paul UrbachT 015 278 94 06E [email protected]
Participants:• TU Delft• HQSonics Waalre• Technobis Alkmaar
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Dutch partners will have a positive effect on the diagnosis of this life threatening formation of plaque. Currently, the most common form of detecting Atherosclerosis relies on sending a cylinder shaped probe through the blood vessels to the heart in order to localise this vulnerable plaque. This procedure has various drawbacks, not least that it is highly susceptive to the patient’s breathing and the flow of blood through the veins causing the catheter to move constantly, resulting in blurred images. The Nanophone makes use of many sensors simultaneously which drastically improves the resolution of the images as the acoustic waves are measured from multiple positions simultaneously.
More than a clinical tool“We have proved the effectiveness of the Nanophone in theory and experiments already”, Urbach continues, “This however does not mean that we are satisfied yet. We would like to be able to measure higher frequencies as this would improve the Nanophone’s clinical potential. We continue to push our research forward. Apart from the medical applications, the generic device can also be applied to other acoustical applications such as non-destructive testing. The next step, as part of the Memphis program, will see us not only integrate the sensors onto the chip, but also the acoustic source. This means we will have successfully integrated all the base components onto a single chip with obvious benefits to the clinical potential, but also for the commercial opportunities of the Nanophone”.
‘A follow-up version should now be developed with a dedicated application in mind and the possibilities to do so are out there.’
interference. But the light based photonics acoustical sensor does not have this problem which makes the technology usable in rooms containing sensitive MRI equipment, for example. One PhD has completed his research and received cum Laude.
AtherosclerosisCoronary diseases are still one of the most common diseases from which people die in The Netherlands. Atherosclerosis is in many cases the underlying problem. This disease is characterised by the formation of fatty streaks in the larger arteries and if undetected, will in many cases lead to the patient suffering a heart attack. The Nanophone being developed by the consortium of
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Larger than the sum of its partsEvery IOP Photonic Devices’ supported project is worth as much as the sum of its parts. This equally means that not every point of departure dictates the eventual outcome of a project. That much can be gained from going through the sometimes challenging motions of developing an idea together, is embodied by the Raman Pen Project.
Raman Pen
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Raman spectroscopy is a non-destructive optical technology that is increasingly common in a wide number of industries and has an even wider range of applications. Raman spectroscopy is based on the scattering of monochromatic light by molecules. Emitting laser light onto molecules will cause the atoms in that molecule to vibrate and rotate l.”
exploring new terrains for Raman spectroscopyThe Raman pen project, focussed on developing a pocket size device. It makes use of Raman spectroscopy for the early stage detection of eczema in children, so that preventive steps can be taken. Launched in 2007, the Raman Pen Project was a direct outcome of the first ever meeting of the IOP PD. The project took a close look at the various possibilities for miniaturising the Raman technology. “Our bench top model is currently distributed worldwide and can be found in the clean rooms of organisations like Johnson & Johnson and Loreal”, says Gerwin Puppels, Chief Technology Officer at RiverD, “taking a closer look at the possibilities for miniaturising the Raman technology was therefore the logical next step.”
‘this project has shown us that
developing simple devices based on
Raman spectroscopy is a real possibility
and that there is real potential for doing so.’
About this project
Project: Raman PenIPD067767
Contact information:Gerwin PuppelsT 010 704 48 41E [email protected]
Participants:• Erasmus Medisch
Centrum Rotterdam• River D Rotterdam• TU Delft• Universiteit Twente• Lionix Enschede• NRC (Canada)
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Knowledge beyond the projectThe consortium of research, development and commercial partners involved in this project responded to the call of the IOP PD. Despite the consortium’s best efforts, integrating all necessary components, whilst also making use of inexpensive mass producible parts, that would result in a commercially viable Raman pen, proved harder than envisioned. Exploiting the generic qualities of a technology leans heavily on miniaturisation and cost-effectiveness but equally demands stability and functionality. And whilst this project might not have directly resulted in a fully functional prototype much has been gained in terms of knowledge and ways of circumventing pitfalls for the future. “We might have been too optimistic and overly ambitious in our efforts”, explains Puppels, “however, we remain very optimistic about the potential for Raman Spectroscopy and we are taking on board the lessons learned from this project. This will allow us to make an even more valuable contribution to the current and future projets we are involved in, like the Raskin Project, another Raman spectroscopy based IOP PD supported project”.
Future potentialThe use of Raman spectroscopy is growing in popularity in a great number of fields. The technology is applied in horticulture, in-line production processes, chemistry and medical diagnostics amongst many others. Having had the resources available for researching ways to develop this technology beyond its’ current state, has therefore been valuable. With the rate that the developments are coming along, so will the opportunities for commercially exploiting the expertise gained from this project, as the research and lessons learned allow all the partners to continue to be one step ahead of the pack.
The composition of the molecule will dictate how much energy is transferred from the photon to the molecule and thus allows for measuring the differential between the entering and exiting photons. Raman spectra are unique for each molecule and by accurately reading them enables for making distinct observations about the molecules concerned. This might seem complex and scientific but imagine the following: Raman spectroscopy is widely used in the diamond industry, an industry that for obvious reasons has little trouble investing in this currently still bulky and expensive technology as the difference between an actual diamond and a synthetic man-made version can be millions of euros. The Raman spectrum in each of these two cases would be decisively different and therefore accurately distinguishing the fake from the actual diamond would therefore be with this technique much easier.
‘the netherlands has an excellent reputation in Raman-spectroscopic analysis of tissue and cells and a wealth of academic and commercial knowledge in the field of photonics.’
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something new under the sunThe Netherlands is expecting some 6,000 cases of melanoma in 2015 but early detection of this lethal skin cancer dramatically improves the survival rates of patients. The Raskin project, supported by the IOP PD, is in the process of developing an affordable diagnostic collection probe that makes use of Raman spectroscopy to diagnose melanoma at an early stage.
Raskin
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Beauty ideals are subject to the fashions of their day. In the 17th century it would be considered a sign of wealth and decadence to have a complexion as pale as possible. Today we pride ourselves in our tans, we consider them signs of a healthy, affluent and beautiful life. Where the nobility of the 17th century were trying to communicate that there was no need for them to leave their parlours to work in the glaring sun, we today seem to want people to see that we can spare the time and resources to take breaks from our hectic office bound lives. That these lifestyle changes are not without their dangers is apparent from the ongoing global increase in skin cancer cases diagnosed every year.
early stage clinical diagnosis of Melanoma Melanoma is the most deadly form of skin cancer and like other forms of skin cancer is primarily caused by elongated unprotected exposure to ultraviolet light (UV). Whilst substantially less common than other forms of skin cancer, melanoma is by far the most lethal with approximately 55,000 deaths on a reported 235,000 cases globally in
‘the RAsKIn technology makes
earlier diagnosis of Melanoma possible
and therefore may significantly
help to lower skin cancer’s death toll.’
About this project
Project: RASKINIPD12004
Contact information:Marijn SandtkeT 088 866 64 73E [email protected]
Participants:• TNO Industrie en Techniek
Delft• Erasmus Universiteit
Rotterdam• TU Delft• Philips Electronics
Nederland Eindhoven• Avantes Apeldoorn• LUMC Leiden• River D Rotterdam
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variation in energy levels between the entering and exiting photons we are able to effectively determine the molecular composition of the pigmented lesion. Benign cancers and healthy tissue each have a very different and distinct signature which enables us, by referencing the obtained data against our clinical data set, to determine whether a lesion is indeed melanoma or not.”
Infra-redMelanoma diagnostics present their own unique challenges which the Raskin project had to overcome. Melanomas are dark, or nearly black in colour, which means they absorb nearly all the light and cause a great deal of background fluorescence. Background fluorescence is an occurrence where the molecules give off such a strong background signal that it becomes very hard to obtain with Raman spectroscopy the molecular fingerprint. It is a bit like looking for green confetti on a green background” simplifies Sandtke, “this means that we have to ensure that we develop a device that allows us to measure beyond the fluorescence in the infra-red to obtain the information we are interested in.”
“There are still obstacles to overcome and components to develop”, explains Sandtke, “with each partner bringing in their specific expertise we are convinced that together we will be able to build a dedicated mobile device that will do exactly what we expect of it, but we also plan to make it substantially cheaper than current devices which cost up to €250,000. Our so-called collection probe will obviously be able to focus the laser light on the correct position and collect data from the lesion, but it will also be ergonomic, light and cost a fraction of the current equipment. Above all, this means that the new technology will be available to a broader range of dermatologists, oncologists and even general practitioners, making quick and accurate diagnosis possible.
2012 alone. The upside is that if melanoma is detected at an early stage and the patient receives treatment the survival rates are very good. The downside however, is that clinical diagnosis of early stage melanoma is very difficult without the appropriate tools and the tools available are very expensive. In most cases dermatologists still rely on their experience and eye-sight, resulting in some 30% of Melanoma cases being undetected.
Raman spectroscopy“Photonic techniques and devices can play a relevant role in early diagnosis”, explains Dr. ir. Sandtke of TNO, one of the project partners, “Raman spectroscopy allows us to objectively examine lesions without the need for surgically removing sample tissue. By pinpointing a laser we can determine the molecular composition of the exact area that we are interested in. The laser in this case causes vibrations and rotations in the molecules, by measuring the
‘having this technology offers excellent opportunities for Dutch organisations to develop profitable state-of-the-art medical instruments that positively impact society.’
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towards a more objective judicial systemAccurately and objectively determining foul play in domestic violence, child abuse or even murder cases is of vital importance to any modern self-respecting judicial system. Traditional spectral cameras for blood splatter or bruise analysis are cumbersome, that is why the smaller, portable and cheaper Spectr@phone, a hand-held spectral imaging device, is destined to have an impact on future forensics.
Spectr@phone
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of light to measure the chemical composition of tissue or blood. Illuminating the absorption area, or in other words, the bruise on the body, allows for measuring the returning light’s intensity and colours. This, using tuneable filters, will subsequently allow you to effectively and accurately date-stamp a bruise by cross-referencing the obtained information like the bilirubin and haemaglobin concentrations against a sophisticated data-bank of
Whilst this project has only been supported by the IOP since 2013, it already has some impressive achievements to show for itself. One of the applications of the device truly captures the imagination; the accurate back dating of bruises in child abuse cases. Child abuse, especially in the early stages of the child’s development due to the lack of a full vocabulary, is notoriously hard to detect. The ability to differentiate between an accident prone child and the devastating long-term effects of child abuse is therefore a real concern. Today, detecting child abuse still largely depends on attentive doctors, teachers and parents, unfortunately often these observations are far from unbiased or objective.
spectral imagingThe Spectr@phone tackles this issue by using spectral imaging. This technique makes use of the properties
‘the spectr@phone project has resulted in a unique spectral
filter that holds valuable potential
for a wide range of applications.’
About this project
Project: Spectr@phoneIPD12017
Contact information:Maurice AaldersT 020 691 72 33E [email protected]
Participants:• AMC, Amsterdam• TU Delft• Saxion Hogeschool
Enschede• Avantes Apeldoorn• Forensic Technical
Solutions Amsterdam• Anteryon International
Eindhoven
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turning a negative into a positiveVTT a Finnish organisation was part of the original consortium. Their tuneable Fabry Pérot filter plus a mosaic filter and a camera made up the core of the device. “VTT developed a method to combine several transmission bands with an image sensor with pixels that are sensitive to different colours”, explains Dr. Maurice Aalders of AMC, “When they realised the potential of their invention and the world came calling they pulled out of the project”. The fact that failings can sometimes make things stronger was embodied by how the consortium responded. Anteryon who were originally involved in the project to build a lens module using WaferOptics®, realised the predicament and took it upon themselves, despite technical challenges, to build a filter that could do exactly what the Finnish model could. This, despite an obvious delay, has not only allowed for the project’s continuity but also ensured that this advanced expertise is now available in The Netherlands. The potential of the Spectr@phone and filter are already substantial despite the project still being in its’ early stages. A test set-up is showing positive signs. Apart from forensics, this hand-held device also shows promising potential for other applications such as crop inspection or melanoma diagnostics. The Spectr@phone project demonstrates that enabling widespread use of sophisticated technology does not only result in a marketable product but also helps to tackle pressing real-life issues like child abuse.
samples using an algorithm. “The data-bank and the algorithm are unique”, says AMC’s Maurice Aalders, “We are receiving requests for our expertise from all over the world”.
the spectr@phoneExisting spectral imaging cameras have a number of drawbacks. The cameras in use are voluminous and static which renders them unsuitable for crime scene research. The restricted mobility of the camera’s arm means that sample images have to be corrected to compensate for the person’s movement. Finally, the current acousto-optical or liquid crystal tuneable spectral filters are expensive. The Spectr@phone circumvents these obstacles by using smart phone camera technology, allowing for an accurate, affordable, miniaturised device.
‘the low-cost modestly sized filter will open exciting new avenues for spectral imaging in a great number of fields.’
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sizeable improvements by making things smaller Accuracy and precision are base requirements for fundamental research as well as for many advanced high-tech production processes. The frequency comb, a light source that emits laser pulses with high precision, makes extremely accurate time measurements possible that form the basis for increasingly accurate measurement of distance. Today, frequency combs are used for precision measurements in space travel, complex precision engineering processes.
Frequency Comb
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frequency comb that would be interesting for a wider range of applications.
Many of the projects supported by the IOP Photonic Devices have dealt with similar miniaturisation processes but none illustrate the requisites for doing so as clearly as the Frequency Comb project. Over the last years highly stable lasers, so-called mode-locked lasers, have undergone
chipping the current limitations awayFrequency comb devices can be found in many research centers around the world. Having this equipment available has led to many new discoveries that required more sensitive measuring equipment. Successful valorisation is partly hindered by the current equipment itself. The equipments’ power requirements,size and price levels perhaps do not pose so much of a problem for the well-equiped and well-funded western laboratories or high-tech production companies. However when it comes to making this technology available to new users and suitable for new applications, these are obstacles that need to be resolved. Miniaturisation through optical integration is therefore an essential step. This is why the consortium looked at the possibilities for making use of integrated optical circuits. In other words, chips, that would result in a usable
‘this project has demonstrated
that the distance in frequency
between the lines in the comb can
be controlled accurately.’
About this project
Project: Frequency Comb deviceIPD083346
Contact information:Erwin BenteT 040 247 51 06E [email protected]
Participants:• TU Eindhoven• VU Amsterdam• XIO Photonics Enschede• Universiteit Twente• Toptica Photonics (D)• Philips Electronics
Nederland Eindhoven
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between satellites in space. Using the existing frequency combs in a space environment would be out of the question with the current available technology, as the lasers would be too fragile to survive the launch; and weight and size would effectively rule out such endeavours. A light-weight chip on which the lasers could be fitted would circumvent all the problems that prohibit the use of a frequency comb in space. Just like with other applications developed for space, the development of this frequency comb for this purpose presents also great promise for other practical applications on earth.
Business and Research driven resultsPerhaps the most interesting application for the chip-based frequency comb, from a commercial perspective, is to be found in complex engineering processes that take place in a vacuum. ASML’s lithography division for example is continuously working on shrinking the widths of their printed circuit boards, thereby enabling their customers to cut the size or add extra functionality to their integrated circuits. ASML has in its machines measuring issues where the frequency comb maybe could be used. With innovative organisations like ASML or Philips, in The Netherlands, pushing the envelope in terms of developing their technology, so does the demand for novel solutions.
spectacular development. With these lasers it’s possible to time the interval between the pulses so accurately that it is more reliable at measuring time than an atomic clock. The name of the device derives its name from the accuracy of these intervals as the frequency peaks are spread in such a way that it represents a comb. The basic principle of the precision measurement with the laser is straightforward, the sample or object upon which a laser pulse is emitted will bounce back a reflection that can be measured in time. The duration of the reflection in turn determines the distance to the object.
space travel The developments in frequency comb devices allow for a quantifiable way of measuring distance in a vacuum. Especially as the absence of matter ensures that the speed of light remains at a constant, making the technology well-equipped for space use. The are used here for example for effectively and accurately measurement of the distance
‘We are now working, together with Dutch companies, on stabilising the whole comb for the applications that we are interested in.’
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© Netherlands Enterprise Agency | February 2015Publication number: RVO-019-1501/BR-DUZA
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