Diagnostic Biochips - HES-SO · 2 Steering Committee of Diagnostic Biochips Programme hepia - sue Engineering tis laboratory Luc Stoppini [email protected] +41 22 546 24 96 hEi-VS

F a c u l t y o F E n g i n E E r i n g a n d a r c h i t E c t u r E

Diagnostic Biochips

T H E M A T I C R E S E A R C H P R O G R A M M EH E S - S O O N M I N I A T U R I S E D

D I A G N O S T I C A N D T O X I C O L O G I C A L T O O L S

2Steering Committee

of Diagnostic

Biochips Programme

hepia - tissue Engineering laboratoryLuc Stoppini [email protected]+41 22 546 24 96

hEi-VS – institute of life technologiesJean-Manuel Segura [email protected]

hEig-Vd – institute rEdSYann [email protected]

hEia-Fr – institute iPrintMarco [email protected]

hE-arc Engineering – Micro & nanosystems groupAlexandra [email protected]

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F A c u L T Y o F E n g i n E E r i n g A n d A r c H i T E c T u r E - d i A g n o S T i c B i o c h i p s

Editorial

programme, which develops analyses to identify the biochemical effects of specific molecules onhealth in a quick and convenient way. We are all well aware of the speed of technological change in the field of healthcare: anyone can acquire an infrared thermometer, a pregnancy test, and even a smartphone application for melanoma detection. We must

Applied research and development plays an integral part in the projects led by the HES-SO University of Applied Sciences Western Switzerland and is given particular emphasis at the faculty of Engineering and Architecture.

Supervised by our teaching staff, this research enables all partici-pants to develop the practical skills required by both society and industry. It also ensures we can keep offering cuttingedge courses to our students.

For the past four years, the Faculty of Engineering and Architecture has organised its applied research projects around six broad themes which, together, cover all the faculty's fields of research. These thematic programmes, ranging from energy, to agriculture optimisation to urban densification to connected objects, all seek to find practical solutions to the problems of our times.

We are keen to tell the general public and businesses about these programmes, and consequently we have published a seriesof brochures describing their strengths and the key skills that they develop. These publications also serve to showcase the practical outcomes of these programmes, achieved in close partnership with players from the involved industries. This brochure outlines the Diagnostic Biochips

olivier naef

dean of the Faculty of Engineering and Architecture

also ensure that healthcare profes-sionals have the tools they needto make their daily work easier. They too must benefit from advances in engineering, chemistry and biotechnology. This programme, which is carried out in close collaboration with direct healthcare professionals, showcases the skills that we nurture here at HES-SO.

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T H E r E S E A r c H p r o g r A M M


Diagnostic Biochips

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F A c u L T Y o F E n g i n E E r i n g A n d A r c H i T E c T u r E - d i A g n o S T i c B i o c h i p s F A c u L T Y o F E n g i n E E r i n g A n d A r c H i T E c T u r E - d i A g n o S T i c B i o c h i p s

health, we are working with the Swiss Centre for Applied Human Toxicology (SCAHT) and the Federal Office of Public Health. Together, we are developing a specialised platform, particularly in the area of neurotoxicology. Our ultimate goal is to help regulators validate products by providing more effective tools – keeping in mind that sooner or later, guidelines would ideally be standardised throughout the OECD. These technologies could lead to limit or even the complete elimination of animal experimentation.

Most of the projects in our programme were launched in 2014, and are now in their final phase. We look forward to completing our demonstrations shortly. They will be used to prove that our designs are effective prior to the prototype phase, which will let us market our tools to our various academic partners at public and private institutions.

The diagnostic Biochips programme has two priorities:preventive medicine and preventive toxicology. its aim is to provide tools to help doctors make diagnoses and to help regulators validate products before they are placed on the market.

three questions to cédric Bilat

cédric Bilat, a member of the teaching and research staff at the Haute Ecole Arc ingénierie, leads the i-Melanoma project. His aim is to facilitate the detection of melanomas and to reduce diagnostic costs, particularly via smartphones.

1 – how does your project differ from the smartphone diagnosis apps currently available on the market? A melanoma is a bit like an iceberg. Sometimes, it can appear risk-free on the surface, but still be dangerous underneath. So a simple smartphone camera is not enough. We have developed a multi-spectral dermatoscope, an innovative device that takes nine photos of the skin at different depths of the epidermis. it works by using specific wavelengths, each of which corresponds to a different skin depth, to light up the skin. A number of dermatologists from Western Switzerland have already tested it.

2 – how do you go about achieving optimum reliability? We use a ‘machine learning’ approach. We teach a computer how to make a diagnosis. A dermatologist will, for example, provide us with a photograph of a melanoma, with certain characteristics – such as colour, shape or texture – which indicate that risk is present. We then feed this data into the machine, which analyses each image pixel. Thereafter, it will know that these characteristics indicate a potential danger. However, no diagnosis can ever be 100% reliable. our device provides information, much like a thermometer does. Then, it is up to users to decide whether they should ask for consultation or not.

3 – What are the limits to a smartphone device? nowadays, our system only operates with an internet connection. The smartphone sends the data to our system in the cloud to be analysed. This is a problem for developing countries where not everybody has access to internet. We are aware of this, and that is why we are looking at how to include everything in a single device which would not be simply a smartphone, but would be a mobile, cheap, all-in-one machine.

The two main goals of the Diagnostic Biochips programme are to get closer to patients and to analyse the effects of chemical molecules on biological tissue.We want to develop integrated, compact, even implantable technology that can deliver diagnoses faster by creating point-of-care testing and improve patients' lives. These biochemical and biological tests can, for example, be administered in mini laboratories using a single drop of blood.

These practices could reduce healthcare costs significantlyif they became widespread. To reach that scale, we have drawn on the expertise available at HES-SO and have worked in close collaboration with the medical world, in particular CHUV hospital and the HUG.

To reach our second goal to identify and evaluate the effects of the chemical molecules present in our environment and food on our

luc Stoppini HES-So diagnostic Biochips programme coordinator currently teaches Bioengineering at hepia

HE-Arc ingénierie

HEig-Vd

hepia

HEiA-Fr

HEi-VS

14.4 billionin dollars, the global market of Biochips from now to 2018.(Source: 2013, dixit cK.)

Schools involved

Diagnostic Biochips

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CellBarrSensLaunch date: January 2014

goal: To develop a device allowing the continuous monitoring of in vitro biological barriers.

HES-So Schools: hepia, HEI-VS, HEIA-FR and HE-Arc Ingénierie

description: CellBarrSens has developed tools measuring electrical impedance specially to assess the porousness of biological barriers, like the blood-brain barrier or the intestinal epithelium. Testing in vitro cultures of these two barriers paves the way for high-volume screening, the develop-ment of new medications, and better evaluations of the toxicity of new chemical products.

MOVABLELaunch date: February 2014

goal: Create a system to detect CD4+ and malaria.

HES-So Schools: HEIG-VD and HEI-VS

description: This project seeks to detect CD4 + cells (linked to a level of infection) and calculate the level of parasitaemia in the case of malaria with an optimized, low-cost blood analysis system. Technicians currently complete the diagnosis with a high risk of error, but the Movable system will be completely automated.

MiniBioDetLaunch date: October 2014

goal: Develop the technological bricks for the miniaturization of a biomarker detector.

HES-So Schools: hepia, HEI-VS, HEIA-FR and HE-Arc Ingénierie

description: MiniBioDet hopes to develop the tools to detect portable and unlabeled biomarkers using an electrical method. Based on a spectroscopic measure of electrical impedance, the technology relies on a new type of biosensor manufactured by ink printing and surface activation. The project is also developing the tools to detect and measure the presence of biosensors.

CapSenseLaunch date: October 2015

goal: Create a platform for energy and data transfer using capacitive coupling.

HES-So Schools: HEIA-FR and HE-Arc Ingénierie

description: Due to poor scaling properties of magnetics, at micrometer-level, capacitive coupling will result in a more efficient method for transferring power and data. Project goal is to build an RFID tag, capacitive coupled, with a dimen-sion in the order of a cubic centimeter, intended for implantable systems.


SupraDiagLaunch date: February 2014

goal: To develop a new type of molecular biosensor.

HES-So Schools: HEI-VS and HEIA-FR

description: The SupraDiag project’s new supramolecular biosensors can be used to quantify a biomarker in a biological fluid with modulated optical signal. They will be central to a new generation of point-of-care diagnostic testing. The concept will be used in the dosing of methotrexate, a cancer drug.

MuchsensLaunch date: July 2014

goal: To develop intelligent membranes and flexible sensors.

HES-So Schools: HE-Arc Ingénierie, HEIA-FR and hepia

description: Sample preparation plays a key role in fluid diagnostics. The Muchsens project develops membranes (i.e. PDMS, parylene, graphene) enabled with smart technology like flow measurement. The membranes are flexible and can be integrated into mobile diagnostic devices.

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MUBIOSLaunch date: April 2014

goal: To develop a new point-of-care diagnosis system.

HES-So Schools: HEIG-VD and hepia

description: The MUBIOS project aims to develop a recycled glass chip with embedded electronics. This device is intended for cell culture monitoring in response to a therapeutic treatment for example, and the diagnostic analysis of organic fluids (glycaemic dose, cholesterol, detection of infectious agents, etc.), quickly and cheaply.

DrugSensLaunch date: March 2016

goal: To create a system for hospital-based chemotherapy.

HES-So Schools: HEI-VS, HE-Arc Ingénierie and HEIA-FR

description: The DrugSens project aims to fix the side effects of serious drug treatments by continuously monitoring of the concentration of the therapeutic substances in the blood to adjust dosages accordingly. The new device located on the patient carries out blood tests in minute quantities on a regular basis and analyses them on the spot.

BiowatchLaunch date: July 2016

goal: To design a watch test with bio-impedance measurement.

HES-So School: HEI-VS

description: Biowatch seeks to integrate a bioimpedance sensor into a watch, and create a personalised medical device that is comfortable to wear and can be connected to the outside world. This combination is attractive for the user as it combines practical usefulness with elegance.


AptaprintLaunch date: July 2015

goal: To develop methods for preparing and printing testing components.

HES-So Schools: HEI-VS, hepia, HEIG-VD and HEIA-FR

description: The Aptaprint project wants to identify and use aptamers and/or antibodies as tools to capture biomarkers in the blood to develop better diagnostic tests. The project also examines the printing techniques which allow these reagents to be placed on measurement electrodes.

DiaFevLaunch date: May 2016

goal: To develop a rapid, new multifold test for fever diagnosis. HES-So Schools: HEI-VS, HEIG-VD and HE-Arc Ingénerie

description: The DiaFev project’s new diagnostic fever test can provide sensitive detection of bacterial infections that require antibiotics by analyzing three biomarkers. The test requires just one drop of blood placed on a bitewing film which can be read by a mobile optical scanner.

smartH2OgelLaunch date: April 2014

goal: To create intelligent hydrogels for tissue engineering and biomedi-cal applications.

HES-So Schools: HEIA-FR, hepia and HEI-VS

description: SmartH2Ogel focuses on developing biopolymer- and/or synthetic polymer-based hydrogels and functional modifiers such as peptides. These ‘smart’ hydrogels determine the ionic, hydrophilic and biological mediums with a goal of stimulating cell growth. They are intended for cell culture and the distribution of medicines.

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RF3sens(Radio Frequency Flexible Flow Sensing)

Launch date: July 2016

goal: To construct an ultra-flexible, Wi-Fi-enabled flow sensor.

HES-So Schools: HE-Arc ingénierie and hepia

description: RF3sens wants to measure the cerebrospinal fluid in patients with hydrocephulus using a demonstration Wi-Fienabled flow sensor. It is a follow-up to the Muchsens project in response to the request of the firm Codman (J&J) for more research on the energy efficiency and measuring range of the device.

MeaZureLaunch date: December 2015

goal: To develop a device to continuously monitor nervous tissue and biological barriers.

HES-So Schools: hepia, HEI-VS, HEIA-FR, HE-Arc Ingénierie and HEIG-VD

description: The blood-brain barrier lets substances required for the well-being of the brain through. The MeaZure project is developing a model to study the movement of molecules or of drugs through this barrier and their potential toxic effects on the brain tissue, by monitoring both the electrophysiological activity of the nervous system and the sturdiness of the BBB.

d i A g n o S T i c S B i o c H i p S p r o J E c T S : d E M o n S T r A T o r S

I-MelanomaGPULaunch date: October 2014

goal: To provide a screening tool for melanoma for the general public, mobile and cheap.

HES-So Schools: HE-Arc Ingénierie, HEI-VS and HEIG-VD

description: The development of dermatoscope to enable visualisation of the epidermis at different depths is one of the major innovations of this project. The dermatoscope is connected to via a smartphone, where powerful GPU calculators analyse the images they receive. This device is intended for preventive medicine at the patient point of care.

H3POCLaunch date: July 2016

goal: To develop a mobile, high-performance medical diagnosis platform.

HES-So Schools: HE-Arc Ingénierie, HEIG-VD and HEI-VS

description: This project seeks to help early diagnosis of malaria and melanomas in countries of the Third World, to be used by the general public on a wide scale. A mobile, afford-able and high-performance platform is central to the i-MelanomaGPU and MOVABLE projects. It can be used both in medical clinics and ‘mobile screening’.

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SupraDiag

HES-So What does the Supradiag project do that's new?JMS We have created supramolecu-lar biosensors. They are intelligent molecules that change shape when they enter in contact with a substance, like a drug. With the transformation, they also dim their light intensity. We can measure this dimming and calculate the quantity of the substance in the organism. This can prevent drug overdoses, for example. There are other biosensors than ours, but they require a mix of several ma-terials, can only recognize a small number of substances, and are

single-use. Our biosensors adapt to almost all biomarkers and can be used several time, allowing for continuous monitoring.

HES-So When would it be useful to have continuous monitoring?JMS When it is vital to avoid overdoses, for example. During chemotherapy treatments, for example, our intelligent molecule targets methotrexate, a very powerful anti-cancer drug with serious side effects. Today, we can only control the dosage of the drug a few times each day. Analyses take time because they must take place

Since 2014, Supradiag has developed a new type of supramolecular biosensor. given a single drop of blood, these “intelligent” molecules can quickly measure the amount of a certain substance in the body. Question-and-answer with Jean-Manuel Segura, the project manager and a researcher at the HES-So Valais-Wallis – Haute École d'ingénierie – HEi.

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27.5 millionsin dollars, the estimated global market for point-of-care diagnosis in 2018.(Source: PR Newswire)


in the laboratory. Our technology allows analyses every ten minutes. They are done at the patient's bedside, or point-of-care, avoiding trips to the lab.

A single drop of blood is enough to measure the quantity of the drug in the organism. A little box connected to the needle could analyze it directly, then send the results to the doctor over WiFi.

HES-So Point-of-care testing has become increasingly important...JMS Indeed, it's a rapidly develo-ping field, especially in Switzerland. These technologies can lead to a faster diagnosis, which is critical in situations of life or death like heart attacks.

Point-of-care testing also cuts down on diagnosis costs, which is particularly relevant for deve-loping countries. Democratizing access to quality health care is one of the goals of our projects. For us, point-of-care testing leads mostly to a faster analysis, but in these countries, technologies like ours can make diagnoses that were previously impossible to make much more accessible.

HES-So What are some possible applications for your project?JMS Our technology can facilitate a fever or pneumonia diagnosis so doctors know whether or not to prescribe antibiotics. Our biosen-sors can reveal if an infection is of viral or bacterial origin. We can also measure the amount of anesthetics in the body, or even the amount of stress, by analyzing biomarkers in saliva!

The device itself can be used with a smartphone, for example. The camera can be a detector, if we add an optical extension. It's really interesting because a lot of people have smartphones. On the other hand, the camera quality causes some ethical problems. If it muddles the diagnosis, who is responsible? The obsolescence of the devices is also a challenge, because you would need updates for each new model.

HES-So are you already thinking of commercializing the technology?JMS We are just at the very begin-ning of the process. We first needed to show that the idea worked. On paper, it's always the case, but it's very risky. The chemistry is very complex and our initial attempts all failed. These days, we have obtained the expected results and are applying for a patent. Our technology has led to two other projects, DrugSens and DiaFiev. The first is about measuring drugs in the blood. We are reaching out to several Swiss-French companies, because we would very much like for our technology to benefit the local economy. The second focuses on diagnosing fever. We hope to eventually create a start-up to commercialize the product as well. We will do so in collaboration with third-year students from the HES-SO Valais-Wallis. It will be a beautiful continuity of the interdisciplinary of our project.

“The speed of a diagnosis can be the difference between life or death”

Schools involved

The c-reactive protein is one of the biomarkers ana-lyzed by Supradiag technology. it indicates whether an infection is bacterial or not depending on its amount in the blood.

HE-Arc ingénierie

HEiA-Fr

HEi-VS

HEig-Vd

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Impressum

diagnostic Biochips research Programme on Miniaturised diagnostic and toxicological toolsA publication of HES-So universityof Applied Sciences and ArtsWestern Switzerland

EditionHES-So rectoratroute de Moutier 142800 delémontSwitzerland

copyrightcover – Thierry parelp. 3 – Bertrand reyp. 4 – Thierry parelp. 9 – nicolas duc

ProductionLargenetworkpress agencyrue Abraham-gevray 61201 genevaSwitzerland

Diagnostic Biochips

Documents

Diagnostic Biochips - HES-SO · 2 Steering Committee of Diagnostic Biochips Programme hepia - sue Engineering tis laboratory Luc Stoppini [email protected] +41 22 546 24 96 hEi-VS