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.
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 average 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.
Mobile Medical Applications
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.
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.
1. 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
2. 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 (in press) (2014)
* This manuscript is thought as course material in the undergraduate curriculum in diagnostic design class, Innovations in International Health, Massachusetts Institute of Technology (MIT),
16. Farandos, N.M. andContact Lens Sensors in Ocular Diagnostics. Advanced Healthcare Materials (in press) (2014)
17. 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)
18. 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 (2014) link
* This device was commercialised by Diagnostics Division of Hoffmann-La Roche
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 Diagnostics, Futuristech: 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 testNews Medical: , 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
Mobile Medical Applications
Yahoo news: Diagnostics On the Go, The Daily Beast: New Camera-Centric Smartphone App Puts Healthcare in Your Pocket, 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, , : Stickly ColourInternet Medicine: A DIY medical diagnosis app, SnapMD: Test for Kidney Disease On Your Smart-Phone, Idea Connection: Smartphone App Reads Colorimetric Test Strips
Chemical & Engineering News: Low-cost, Reusable Glucose Sensor, Varsity: Nanotechnology tackles developing world diabetes, , MagazinePhys.org, , 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
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
Printable holograms offer security and data storage solutions link
Department of Chemical Engineering and Biotechnology
Biotechnology CET I - Lent Term 2014
Entrepreneurship - ETECH Projects - Lent Term 2014
Fellow,, Department of Medicine
Affiliate Member, Royal Society of Chemistry
Alumnus, Roche Continents
Member, Tau Beta Pi and Phi Kappa Phi
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