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Ali K. Yetisen

Ali K. Yetisen

Nanotechnology

Nanoparticles

Diabetes

Drug Delivery

Diagnostics

Microfluidics

Nanophotonics


Office Phone: 01223767782

Research Interests

Developing non-invasive and accurate diagnostics that are easily manufactured, robust and reusable will provide monitoring of high-risk individuals in any clinical or point-of-care environment, particularly in the developing world. Our research involves the development of medical and environmental diagnostics in three main areas: (i) optical sensors, (ii) smartphone applications and (iii) microfluidics.


Building Optical Sensors for Disease Detection

Our research consists of the development and optimisation of optical colorimetric sensors for applications in point-of-care diagnostics. The sensing devices consist of metal or dielectric nanostructures periodically organised in a 10 μm thick functionalised hydrogel film. Such hydrogels may be selected from poly(2-hydroxyethyl methacrylate), polyacrylamide or gelatin, and they can be functionalised to be sensitive to a wide range of analytes such as pH, glucose, metal ions and antibodies. These hydrogels can be transformed into colorimetric devices by integrating periodically organised nanoparticles or highly crosslinked density regions within the matrix. We record diffraction gratings in these functionalised polymers by nanosecond pulsed laser writing. The gratings can be formed by photochemistry, laser ablation or photopolymerisation in Denisyuk reflection mode using a pulsed laser (6 ns, 532 nm, 350 mJ). The formed grating has a periodicity of half the wavelength of the laser light used since the grating is an image of the periodicity of the standing wave created during laser exposure. The image and periodicity can be controlled by changing the object and exposure conditions. When the fabricated sensor is illuminated with a white-light source, the grating produces visible-light diffraction and displays a monochromatic colour. This diffraction is governed by Bragg's law:

λpeak = 2 n d sin(θ)

where λpeak is the wavelength of the first order diffracted light at the maximum intensity in vacuo, n is the effective index of refraction of the recording medium, d is the spacing between the two consecutive recorded nanoparticle (or highly crosslinked regions) layers (constant parameter), and θ is the Bragg angle which is determined by the recording geometry.

   The mode of action of these sensors involves the modulation of Bragg diffraction gratings and localised refractive index changes. When a target analyte is introduced to the sensor in an aqueous solution, the target analyte binds to a receptor in the polymer matrix, and the binding process produces a change in Donnan osmotic pressure. This change in the osmotic pressure swells or shrinks the polymer matrix, which allows the diffraction grating to change periodicity and/or index of refraction, hence report on the concentration of the target analyte by fine changes in λpeak. Such sensors exhibit reversible wavelength shifts, and diffract the spectrum of narrow-band light over the wavelength range λpeak ≈ 300-1100 nm. λpeak measurements can be obtained by fully-quantitative readouts through spectrophotometry, and semi-quantitative results through visual readouts.

   The optical sensor represents a simple and label-free analytical platform for the quantification of clinical and environmental analytes, while showing potential scalability. We anticipate that our sensing platform will lead to many novel applications from printable devices to low-cost colorimetric biosensors.

Adapted from Advanced Optical Materials


Nanotechnology Takes on Diabetes

Diabetes is one of the most challenging health problems of the 21st century. Today, 382 million people live with diabetes. This epidemic on the rise all over the world and countries are struggling to keep pace in controlling this disease. The number of people with the disease is estimated to reach 592 million in less than 25 years. In 2035, one in ten people will have diabetes. The number of people with diabetes is rapidly increasing in the Middle East, Western Pacific, sub-Saharan Africa and South-East Asia where economic development has transformed lifestyles. These rapid transitions are bringing high rates of obesity and diabetes; developing countries are facing a healthcare challenge coupled with inadequate resources to protect their population. The new estimates show an increasing trend towards younger people developing diabetes.

Diabetes has been known to be ‘a disease of the wealthy’. But studies showed that this was not the case. 80% of people with diabetes live in low- and middle- income countries, and the socially disadvantaged in any country are the most vulnerable to the disease. The financial burden of diabetes is taking up 548 billion dollars in health spending, which is 11% of the global healthcare expenditure. Yet, it is estimated that 175 million people are undiagnosed today. This is because there are few symptoms during the early years of type 2 diabetes, or those symptoms may not be recognised as being related to diabetes. Type 2 diabetes can go unnoticed and undiagnosed for years. In such cases, those affected are unaware of the long-term damage being caused by this disease. Population-based diabetes studies consistently show that 40% diagnosed people live in low income countries. According to International Diabetes Federation, in sub-Saharan Africa, where resources lack and governments may not prioritise screening for diabetes, this proportion is as high as 90% in some countries.

We can screen for diabetes using glucose meters and urine dipsticks. These technologies might look low cost, but considering that 1 billion people live on less than $1.25 a day, they are not affordable. For example, glucometers, a lancing device, lancets and tests costs up to $115 for testing 100 people in the rural village. On the other hand, a urine dipstick test, which costs about $0.5, have low sensitivity and often provide erroneous results due to subjective reading. If we develop diagnostic tools that are low cost, reusable, user friendly, non-invasive and reliable, we can help deprived communities. We design and develop medical diagnostics that intend to satisfy these criteria.

The principle of operation of these sensors is based on swelling and shrinking of the holographic films, which in turn diffracts light at different wavelengths. These wavelengths are colours that can be read by naked eye. In this case, the smart material is made out of a polymer and boronic acid derivative that can reversibly bind to glucose so that we can see the colour change in the presence or absence of glucose. These sensors can be tuned to diffract light in the entire visible spectrum. It is also possible to pattern these devices to give written messages.

We can use a single sensor for about 100 times by washing with water and it costs 20¢. We recently completed clinical trials of this sensor by testing urine samples of diabetic patients. It has comparable performance with the commercial tests while also showing higher cost effectiveness. These sensors can be read by eye or quantitatively using spectrometers. However, alternative solutions such as generic smartphone applications we developed in our research group can also be used to read sensors semi-quantitatively. Such applications offer connectivity for global diagnostic data management. Such technologies can make a difference for monitoring disease where early diagnosis and the treatment are needed the most.


Delivering Telemedicine to the Developing World

The high mobile phone penetration and rapidly growing telecommunications infrastructure in the world represents an unprecedented opportunity for reading and transferring point-of-care diagnostic data. Global mobile-cellular subscriptions have grown 70% over the last 5 years, reaching 7 billion as of 2014. Hence, exploiting the existing mobile phone infrastructure to monitor health conditions and the environment will accelerate the efforts toward connected and readily available diagnostics, as well as low-cost healthcare for existing and emerging diseases.

Our research involves development and testing of smartphone apps that allow quantification of colorimetric tests at both Android and iOS operating systems. The app transforms the smartphone into a reader to quantify commercial colorimetric tests with high accuracy and reproducibility in measuring pH, protein, and glucose. Our further efforts in this area include research in the regulations of mobile medical applications. These studies evaluate the impact on academia, industry and other key stakeholders, such as patients and clinicians.

Smartphone app - Ali


Microfluidics

Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. Their efficient commercialisation has implications for biomedical sciences, veterinary medicine, environmental monitoring and industrial applications. In particular, market diffusion of microfluidic laboratory and point-of-care diagnostic devices can contribute to the improvement of global health. In their commercialisation, consultancy and patent protection are essential elements that complement academic publishing. The awareness of knowledge transfer strategies can help academics to create value for their research.

In this respect, our research efforts are directed to the analysis of microfluidics market, identification of issues, and evaluation of commercialisation strategies. We also study patent law in the US, EU, Japan and internationally. Awareness of the patent law and rights allows obtaining optimised, valid and valuable patents, while accelerating implementation to market route. Striking a balance between academic publishing, consultancy to industry and patent protection can increase commercial potential, enhance economic growth and create social impact.

Key Publications

1. Yetisen, A.K., Naydenova, I., Vasconcellos, F.C, Blyth, J., Lowe,C.R. Holographic Sensors: Three-Dimensional Analyte-Sensitive Nanostructures and their Applications. Chemical Reviews. DOI: 10.1021/cr500116a (2014) link

2. Yetisen, A.K, Montelongo, Y., Vasconcellos, F.C., Martinez-Hurtado, J.L., Neupane, S., Butt, H., Qasim, M.M., Blyth, J., Burling, K., Carmody, J.B., Evans, M., Wilkinson, T.D., Kubota, L.T., Monteiro, M.J., Lowe, C.R. Reusable, Robust, and Accurate Laser-Generated Photonic Nanosensor. Nano Letters, 14 (6), 3587-3593 (2014) link

* Sensors: Photonic sugar detector. Nature Photonics, 8 (8), 585 (2014) link

3. Yetisen, A.K., Butt, H., Vasconcellos F.C., Montelongo, Y., Davidson, C.A.B., Blyth, J., Chan, L., Carmody, J.B., Vignolini, S., Steiner, U., Baumberg, J.J., Wilkinson, T.D., Lowe, C.R., Light-Directed Writing of Chemically Tunable Narrow-Band Holographic Sensors. Advanced Optical Materials, 2 (3), 250-254 (2014) link

4. Yetisen, A.K., Qasim, M., Nosheen, S., Wilkinson, T.D., Lowe, C.R. Pulsed laser writing of holographic nanosensors. Journal of Materials Chemistry C, 2 (18), 3569-3576 (2014) link

5. Yetisen, A.K., Martinez-Hurtado, J.L., Garcia-Melendrez, A., Vasconcellos, F.C, Lowe, C.R. A smartphone algorithm with inter-phone repeatability for the analysis of colorimetric tests. Sensors and Actuators B: Chemical, 196, 156-160 (2014) link

* Selected for Lab on a Chip Top 10% and Hot Article

7. Yetisen, A.K., Martinez-Hurtado, J.L., Vasconcellos, F.C., Simsekler, M.C.E., Akram, M.S., C.R., Lowe. The regulation of mobile medical applications. Lab Chip, 14 (5), 833-840 (2014) link

13. Yetisen, A.K., Akram, M.S., Lowe, C.R. Paper-based microfluidic point-of-care diagnostic devices. Lab Chip, 13 (12), 2210-2251 (2013) link

* This manuscript is thought as course material in the undergraduate curriculum in diagnostic design class, Innovations in International Health, Massachusetts Institute of Technology (MIT), Selected for Lab on a Chip Top 10%

14. Martinez-Hurtado, J.L., Akram, M.S., Yetisen, A.K., Iridescence in meat caused by surface gratings. Foods, 2(4), 499-506 (2013) link

15. Yetisen, A.K., Jiang, L., Cooper, J.R., Qin, Y., Palanivelu, R., and Zohar, Y. A microsystem-based assay for studying pollen tube guidance in plant reproduction. J. Micromech. Microeng. 21, 054018 (2011) link

16. Farandos, N.M.,* Yetisen, A.K.,* Monteiro, M.J., and Lowe, C.R. Contact Lens Sensors in Ocular Diagnostics. Advanced Healthcare Materials (in press) (2014) *equal contribution

17. Yetisen, A.K., Blyth, J., Montelongo, Y., Butt, H. Qasim, M.M., Wilkinson, T.D., and Lowe, C.R. Nanocrystal Bragg Grating Sensor for Colorimetric Detection of Metal Ions (under review) (2014)

18. Kong, X.T., Khan, A.A., Kidambi, P.R., Deng, S., Yetisen, A.K., Dlubak, B., Hiralal, P., Montelongo, Y., Bowen, J., Xavier, S., Jiang, K., Amaratunga, G.A.J., Hofmann, S., Wilkinson, T.D., Dai, Q., Butt, H. Graphene based Ultra-Thin Flat Lenses (under review) (2014)

19. Akram, M.S., Daly, R., Vasconcellos, F.C., Yetisen, A.K., Hutchings, I., Hall, E.A.H. Applications of Paper-Based Diagnostics. Lab-on-a-Chip Devices and Micro-Total Analysis Systems. Eds. Castillo-Leon, J., Svendsen, W. E. Springer. ISBN 978-3-319-08686-6 (2014) link

Patents

20. Del Rossi, J., Dunlop, P., Michael, S., Sanchez, S., Schoonmaker, S.P., Yetisen, A.K. Cell Staining with Air Quenched Steam Heating, WO2011139976 (2011) link

* This device was commercialised by Diagnostics Division of Hoffmann-La Roche

* BenchMark ULTRA: Automated IHC/ISH slide staining system link

Books

21. Yetisen, A.K., Holographic Point-of-Care Diagnostic Devices, Springer (in press) (2015)

Press Coverage

Holographic Sensing

Wired Magazine: Low-cost 'smart' holograms can monitor diabetes, Gizmag: Smart holograms can test for and monitor diseases, Chemistry World: Cheap and colourful holographic sensors, Extremetech: A new hydrogel uses holograms to warn you about your health, Science 2.0: Holographic Diagnostics, Med device: Holographic DiagnosticsFuturistech:  Color changing holograms developed for portable medical tests from infections to diabetes, Co.exist: Colorful Nanotechnology Holograms Make Cheap Medical Testing In The Field, Impresive Magazine: Smart Holograms Monitor Health Conditions, University of Cambridge Research: Holographic Diagnostics, Business Weekly: 10p medtech sensor could lead to smartphone test, The Economic Times:Smart holograms that detect and monitor diseases developed, News Medical: 'Smart' holograms could be used to monitor diabetes, cardiac function, infections, Electronics Weekly: Cambridge uses holograms on your smartphone to monitor diabetes, Genetic Engineering & Biotechnology news, Cambridge Enterprise: Holographic Diagnostics, ScienceDaily: Holographic Diagnostics in Medicine, PhysOrg: Holographic diagnostics, World Health: Holograms for Health, Liberty: Color-changing holograms may be used to monitor glucose levels, UPI: Colorful, smart holograms could be used to monitor health conditions, my science: Holographic Diagnostics, Medilink UK: Smart Holograms can Test for and Monitor Diseases, body1: Diseases Diagnosed by 'Smart' Holograms, eurekalert: Holographic diagnostics, Cambridge Network: Researchers develop holographic diagnostics, Product Design and Development: Responsive Holograms Change Color, Laboratory Equipment: Holograms Can Monitor Disease, tcetoday: Holographic sensors change colour, Technology.org: Holographic diagnostics, e! Science News: Holographic Diagnostics, Hispanic Business: Holographic diagnostics, Medical Design Technology: Holographic Diagnostics, Azonano: Responsive Holograms, My Biologica: Holographic diagnostics in medicine, Health Medicine Network: Holographic diagnostics, iMedicalApps: Researchers starting clinical trials of low cost holographic test that monitors diabetes, The Watchers: Researchers develop holograms that change colour, diabetes1: Diabetes Diagnosis by 'Smart' Holograms, CEB: Responsive holograms act as sensors for medical diagnostic applications

Diabetes Screening

Chemical & Engineering News: Low-cost, Reusable Glucose Sensor, Varsity: Nanotechnology tackles developing world diabetes, Controlled Environments Magazine, Phys.org, Cambridge University News: Nanotechnology takes on diabetes, Cambridge Network, HealthTech Event: Low-cost, Reusable Glucose Sensor, Cambridge Africa, Laboratory Equipment: Nanotech Screens for Diabetes, Bioscience technology, Headlines & Global News: U.K. Researchers Use Nanotechnology to Combat Diabetes, Nano Werk, Mumbai Mirror, Wn.com, Diabetes News, Bio Portfolio, Nano Magazine, Bangalore Mirror, Nanocomputer: 20 Pence Reusable Sensor To Detect Diabetes, Public Health at Cambridge, Device Space, myScience, Hispanic Business, Today's Medical Developments, Med Device Design Newsroom, Bioethics, Diabetes Forum: Researchers develop low-cost nanotechnology sensor for diabetes screening, TG Techno, Investor Intel, Biospace, Brunch News, Today's Medical Developments

Mobile Medical Applications

The Daily Beast: New Camera-Centric Smartphone App Puts Healthcare in Your Pocket, Yahoo news: Diagnostics On the Go, The Times of India: Cambridge University scientists develop diagnostic app, University of Cambridge Research News: Pocket diagnosis, Smartphone app to change the status quo in point-of-care diagnostics, Business Standard: Now, app that turns smartphone into portable medical diagnostic device, Phys.org: Pocket Diagnosis, my Science: Pocket Diagnosis, Colorimetrix test reader, USANews: Pocket Diagnosis, Medical Daily: ‘Mobile Healthcare’ Can Help Stop Spread Of Pandemics: New Phone App, ‘Colorimetrix,’ To Monitor Diabetes And Kidney Disease, Science Daily: Pocket diagnosis: App turns any smartphone into a portable medical diagnostic device, R&D Magazine: New app delivers pocket diagnosis, Public Health at Cambridge: Smartphone diagnostics, Qmed: Colorimetrix App Turns Smartphones into Lab Test Readers, Cambridge Network: New app enables pocket diagnosis, Wireless Design Magazine: Pocket Diagnosis, Hindustan Times, ANI News, Z News, ECN Magazine: Pocket Diagnosis, Fast Company: This App Turns Your Smartphone Into A Medical Diagnostic Device, Green Technology World: QMED -Colorimetrix App Turns Smartphones into Lab Test Readers, Fierce Mobile Healthcare: Smartphone app aims for faster, more accurate, body fluid testing, Tree Hugger: New app turns smartphone into portable medical diagnosis device, Lab Manager: Pocket Diagnosis, Ghana Health Nest: This new app turns any smartphone into a portable diagnostic device, Hispanic Business: Now, app that turns smartphone into portable medical diagnostic device, Science and Enterprise: Smartphone App for Point-of-Care Diagnostics in Development, Innovation Toronto: App turns a smartphone into a portable medical diagnostic device, Hispanic Business: Colorimetrix App Turns Smartphones into Lab Test Readers, Fierce Diagnostics: Mobile app could offer inexpensive Dx in developing world, Medical News Today: New app turns any smartphone into a portable medical diagnostic device, Press News: Pocket Diagnosis, Bio-Medicine: Pocket Diagnosis, The Outbreak: Colorimetrix: New App provides Pocket diagnosis, Eurekalert!: Pocket Diagnosis, Science Codex: Pocket diagnosis, Global Biodefence: Cambridge Researchers Develop Pocket Diagnosis App, TMC News: University of Cambridge - Pocket diagnosis, The Siasat Daily: Now, app that turns smartphone into portable medical diagnostic device, Smashits, Kurzweil: Fabrication of pH-Sensitive Holograms, Thisisreallyinteresting: Pocket Diagnosis, NDTV: Colorimetrix smartphone app to help diagnose diseases, The Health Site: Now a smartphone app which can diagnose diseases!, Business Standard: New smartphone app to diagnose diseases, TechMagnifier: Colorimetrix app for Smartphone reads Colorimetric Test Strips Accurately, Art of Healthy Living: Colorimetrix - the smartphone app for disease diagnosis, CSR Journal: New app turns smartphone into portable medical diagnosis device, Post: New smartphone app to diagnose diseases including HIV, Deccan Herald: New smartphone app to diagnose diseases, Electronics Bulletin: Pocket Diagnosis, medGadget: New App from University of Cambridge Accurately Reads Colorimetric Test Strips, Tech and Gadget News: Android Beta App ‘Colorimetrix’ May be the First Medical Tricorder, Wireless Design Magazine: New App Provides Pocket Medical Diagnosis, Lab Manager: Pocket Diagnosis, Clinical Innovation and Technology: New app aims to simplify colorimetric tests, The New Zealand Herald: Stickly Colour, Internet Medicine: A DIY medical diagnosis app, SnapMD: Test for Kidney Disease On Your Smart-Phone, Idea Connection: Smartphone App Reads Colorimetric Test Strips

 

Nanosensors

New sensing platform enables novel point-of-care diagnostics link

Paper-based Microfluidics

Paper-based microfluidic point-of-care diagnostic devices link

Patent Protection and Licensing in Microfluidics

GenomeWeb: Q&A: University of Cambridge Researchers on a Roadmap for Patenting Microfluidic Devices link

The Regulations of Mobile Medical Applications

The GP of the future: mobile medical applications link

Printable Devices

Printable holograms offer security and data storage solutions link

Activities

Undergraduate Teaching:

Department of Chemical Engineering and Biotechnology

       Biotechnology CET I - Lent Term 2014

Center for Entrepreneurial Learning, Judge Business School

       Entrepreneurship - ETECH Projects - Lent Term 2014

Fellow, Cambridge Infectious Diseases, Department of Medicine

Affiliate Member, Royal Society of Chemistry

Alumnus, Roche Continents

Member, Tau Beta Pi and Phi Kappa Phi

Collaborators

Yunuen Montelongo, Department of Engineering, University of Cambridge

Michael Monteiro, Australian Institute for Bioengineering & Nanotechnology, The University of Queensland, Australia

Izabela Naydenova, Dublin Institute of Technology, Ireland

Jeff Blyth, Department of Chemical Engineering and Biotechnology, University of Cambridge

Malik Qasim, Department of Engineering, University of Cambridge

Haider Butt, School of Mechanical Engineering, University of Birmingham

Tim Wilkinson, Department of Engineering, University of Cambridge

Lisa Volpatti, Department of Chemistry, University of Cambridge

J. Bryan Carmody, The Children's Hospital of the King's Daughters, Norfolk, VA, USA

Mark Evans, Institute of Metabolic Science, Addenbrooke's Hospital

Sankalpa Neupane, Institute of Metabolic Science, Addenbrooke's Hospital

Keith Burling, The Core Biochemical Assay Laboratory, NHS, Addenbrooke's Hospital

Ateeq Suria, XLab, Stanford University

Karl Gerhardt, Bioengineering, Rice University

Juan L. Martinez-Hurtado, Technical University of Munich, Germany

Lukas Chvatal, Institute of Scientific Instruments of the ASCR, Czech Republic

Pavel Zemanek, Institute of Scientific Instruments of the ASCR, Czech Republic

Silvia Vignolini, Department of Chemistry, University of Cambridge

Jeremy Baumberg, Cavendish Laboratory, University of Cambridge

Caterina Ducati, Department of Materials Science and Metallurgy, University of Cambridge

Ullrich Steiner, Cavendish Laboratory, University of Cambridge