Diagnostic Biochips T H E M ATI C R E S E A R C H PRO GR A M M E H E S -S O ON MINI AT U RIS E D DIAGNOSTIC AND TOXICOLOGIC AL TOOLS
F a c u l t y o f E n g i n ee r i n g a n d A r c h i t e c t u r e
hepia - Tissue Engineering Laboratory Luc Stoppini luc.stoppini@hes-so.ch +41 22 546 24 96
HEI-VS – Institute of life technologies Jean-Manuel Segura jmanuel.segura@hevs.ch
HEIG-VD – Institute REDS 2
Steering Committee of Diagnostic Biochips Programme
Yann Thoma yann.thoma@heig-vd.ch
HEIA-FR – Institute iPrint Marco Mazza marco.mazza@hefr.ch
HE-Arc Engineering – Micro & Nanosystems group Alexandra Homsy alexandra.homsy@he-arc.ch
Editorial 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 participants to develop the practical skills required by both society and industry. It also ensures we can keep offering cuttingedge courses to our students.
programme, which develops analyses to identify the biochemical effects of specific molecules on health 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
also ensure that healthcare professionals have the tools they need to 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. Olivier Naef Dean of the Faculty of Engineering and Architecture
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 series of 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
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T H E r esea r c h p r o g r amm
Diagnostic Biochips
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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.
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.
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. Luc Stoppini HES-SO Diagnostic Biochips Programme Coordinator Currently teaches Bioengineering at hepia
These practices could reduce healthcare costs significantly if 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.
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.
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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.
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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.
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To reach our second goal to identify and evaluate the effects of the chemical molecules present in our environment and food on our
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.
Schools involved
HE-Arc Ingénierie HEIG-VD
hepia
14.4
billion
HEIA-FR
HEI-VS
In dollars, the global market of Biochips from now to 2018. (Source: 2013, Dixit CK.)
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9 B i o c h i p s d i a g n o st i c s PRO J E T S : te c h n o l o g i c al B r i c ks
CapSense
MOVABLE
SupraDiag
October 2015
February 2014
February 2014
Goal: Create a platform for
Goal: Create a system to detect CD4+
Goal: To develop a new type
energy and data transfer using capacitive coupling.
and malaria.
of molecular biosensor.
HES-SO Schools:
HES-SO Schools:
HEIG-VD and HEI-VS
HEI-VS and HEIA-FR
Description: This project seeks
Description: The SupraDiag
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 dimension in the order of a cubic centimeter, intended for implantable systems.
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.
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.
CellBarrSens
MiniBioDet
Muchsens
January 2014
October 2014
July 2014
Goal: To develop a device allowing
Goal: Develop the technological
the continuous monitoring of in vitro biological barriers.
bricks for the miniaturization of a biomarker detector.
Goal: To develop intelligent membranes and flexible sensors.
HES-SO Schools:
HES-SO Schools:
hepia, HEI-VS, HEIA-FR and HE-Arc Ingénierie
hepia, HEI-VS, HEIA-FR and HE-Arc Ingénierie
Description: CellBarrSens has
Description: MiniBioDet hopes
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 development of new medications, and better evaluations of the toxicity of new chemical products.
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.
Launch date:
Launch date:
HES-SO Schools: HEIA-FR and HE-Arc Ingénierie
Description: Due to poor
Launch date:
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Launch date:
Launch date:
Launch date:
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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7 d i a g n o st i c s B i o c h i p s p r o jets : d em o n st r at o r s
smartH2Ogel
MUBIOS
Aptaprint
April 2014
April 2014
July 2015
Goal: To create intelligent hydrogels for tissue engineering and biomedical applications.
Goal: To develop a new point-of-care
Goal: To develop methods for
diagnosis system.
preparing and printing testing components.
HES-SO Schools:
HEIG-VD and hepia
HES-SO Schools:
Description: The MUBIOS project
HEI-VS, hepia, HEIG-VD and HEIA-FR
Launch date:
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.
Launch date:
HES-SO Schools:
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.
Launch date:
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.
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DiaFev
Biowatch
DrugSens
May 2016
July 2016
March 2016
Goal: To develop a rapid, new
Goal: To design a watch test with
Goal: To create a system for
multifold test for fever diagnosis.
bio-impedance measurement.
hospital-based chemotherapy.
HES-SO School:
HES-SO Schools:
HEI-VS
HEI-VS, HE-Arc Ingénierie and HEIA-FR
Description: Biowatch seeks to
Description: The DrugSens project
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.
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.
Launch date:
Launch date:
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.
Launch date:
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d i a g n o st i c s B i o c h i p s PRO J E c T S : d em o n st r at o r s
I-MelanomaGPU
H3POC
October 2014
July 2016
Goal: To provide a screening tool
Goal: To develop a mobile,
for melanoma for the general public, mobile and cheap.
high-performance medical diagnosis platform.
HES-SO Schools:
HES-SO Schools:
HE-Arc Ingénierie, HEI-VS and HEIG-VD
HE-Arc Ingénierie, HEIG-VD and HEI-VS
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.
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, affordable and high-performance platform is central to the i-MelanomaGPU and MOVABLE projects. It can be used both in medical clinics and ‘mobile screening’.
MeaZure
RF3sens
Launch date:
Launch date:
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(Radio Frequency Flexible Flow Sensing)
Launch date:
December 2015
Launch date:
Goal: To develop a device to
July 2016
continuously monitor nervous tissue and biological barriers.
Goal: To construct an ultra-flexible, Wi-Fi-enabled flow sensor.
HES-SO Schools:
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.
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.
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fla g sh i p p r o je c t
SupraDiag
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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.
HES-so What does the SupraDiag project do that's new? JMS We have created supramolecular 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 materials, 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. 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 HES-so
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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 developing field, especially in Switzerland. These technologies can lead to a faster diagnosis, which is critical in situations of life or death like heart attacks.
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Point-of-care testing also cuts down on diagnosis costs, which is particularly relevant for developing 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 biosensors 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 beginning 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 HESSO Valais-Wallis. It will be a beautiful continuity of the interdisciplinary of our project.
The C-reactive protein is one of the biomarkers analyzed by SupraDiag technology. It indicates whether an infection is bacterial or not depending on its amount in the blood.
Schools involved
HE-Arc Ingénierie HEIG-VD
HEIA-FR
HEI-VS
“The speed of a diagnosis can be the difference between life or death”
27.5
millions In dollars, the estimated global market for point-of-care diagnosis in 2018. (Source: PR Newswire)
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Diagnostic Biochips Research Programme on Miniaturised Diagnostic and Toxicological Tools A publication of HES-SO University of Applied Sciences and Arts Western Switzerland
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Diagnostic Biochips