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Test: Smartphone-connected diagnostic tests

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Led by Prof Molly Stevens (Imperial College London), Prof Rachel McKendry (UCL), and Prof Deenan Pillay, and Dr Neil Keegan and Prof Anil Wipat (Newcastle University).

The aim of this research theme is to build smartphone-connected diagnostic tests to widen access to testing, support front-line health workers, and enable self-testing with linkage to online care. We are growing capabilities in ultra-sensitive nanomaterials (antibody and antigen detection), molecular sensing (DNA and RNA detection), and exploring handheld sequencing technologies.



    Research impact

    • Our point-of-care lateral flow tests are being developed using novel nanomaterials, including our HIV test that surpasses the sensitivity of the current industrial gold standard for detection of p24, an early biomarker for HIV.
    • Our portable mHealth tools and protocols have been adopted for quality assurance of HIV rapid tests by the Africa Health Research Institute, supporting healthcare workers and the local community by reducing the risk of false test results.

    Co-creating mHealth interventions for HIV with potential end-users (2019)

    Researchers from the m-Africa and i-sense projects have been working with communities in rural South Africa to understand how mobile health (mHealth) interventions can help address barriers to HIV testing and linkage to care. The formative work has just been published in the Journal of Medical Internet Research.

    Collaborative study shows promising results for colon cancer diagnostic (2019)

    A simple and sensitive test developed by i-sense engineers at Imperial College London, in collaboration with MIT, has produced a colour change in urine to signal growing tumours in mice.

    Bringing dengue diagnostics into the twenty-first century

    new review from i-sense members, published in AIDS, looks at the last 20 years of research around diagnostics that use p24, an important protein in the detection of early stage HIV.

    Building the future of mobile healthcare (2019)

    The combination of mobile devices with diagnostic tools offers new possibilities to test, track and treat infectious diseases as well as improve health systems, according to a new review published today in Nature.

    The review, led by i-sense researchers from Imperial College London in collaboration with University College London, Africa Health Research Institute (AHRI), University of KwaZulu-Natal and the London School of Hygiene and Tropical Medicine, discusses how mobile health (mHealth) solutions combined with connected diagnostics could increase access to testing and care for patients, and improve the ability of public health authorities to monitor outbreaks and intervene to stop them.

    p24 revisited: reassessing an old candidate for HIV diagnosis (2018)

    new review from i-sense members, published in AIDS, looks at the last 20 years of research around diagnostics that use p24, an important protein in the detection of early stage HIV.

    New connected test for HIV shows promising results (2018)

    New research from the McKendry group at UCL, published in Digital Medicine, reports a pilot clinical study using a shear horizontal surface acoustic wave (SH-SAW) biosensors based on low-cost components found in smartphones to diagnose HIV in 133 patients. The study builds on research published in Scientific Reports in 2017, which showed promising developments towards a smartphone-connected diagnostic tool that can detect HIV infection within seconds. The device comprises of a disposable biochip, a pocket-sized control box reader developed by OJ-Bio, and a mobile device to analyse display and transmit results.

    Harnessing video technology and paper microfluidics to measure protein binding affinities (2018)

    Measuring the binding affinity between the building block of life - proteins - lies at the heart of biochemistry, disease diagnostics, and drug discovery. However, despite widespread demand and potential applications, common methods rely on expensive laboratory-based equipment, such as surface plasmon resonance and interferometry. New research from Professor McKendry’s team at UCL suggests an approach that could be up to 500-fold cheaper to perform, using simply a digital camera, paper microfluidics, and computer vision algorithms to quantify protein binding constants and kinetic rates of reaction.

    HIV test for early stage infections surpasses gold standard (2017)

    i-sense researchers from Imperial College London and UCL have recently published landmark research on the development of a paper-based point-of-care test for HIV that surpasses the sensitivity of the current industrial gold standard for detection of p24, an early biomarker for HIV.

    Promising new technology for diagnosing immunity to Ebola (2017)

    New research from i-sense at Imperial College London and UCL provides a promising new approach to detecting immunity to Ebola virus infection. The new approach uses lateral flow technology, similar to that of a pregnancy test, coupled with smartphones to provide a promising alternative to lab-based testing.

    Relevant publications

    2020

    Kim, N., Thomas, M. R., Bergholt, M. S., Pence, I. J., Seong, H., Charchar, P., Todorova, N., Nagelkerke, A., Belessiotis-Richards, A., Payne, D. J., Gelmi, A., Yarovsky, I., and Stevens, M. M. 'Surface enhanced Raman scattering artificial nose for high dimensionality fingerprinting.' Nat Commun (2020); DOI: 10.1038/s41467-019-13615-2

    2019

    Takah, N. F., Brangel, P., Shrestha, P., and Peeling, R. 'Sensitivity and specificity of diagnostic tests for Lassa fever: a systematic review.' BMC Infect Dis. (2019); DOI: 10.1186/s12879-019-4242-6

    Bennett, I., Pyne, A., and McKendry, R. A. 'Rapid antimicrobial sensitivity testing by single cell nanoscale optical interference.' bioRxiv (2019); DOI: doi.org/10.1101/679399

    Loynachan, C. N., Soleimany, A. P., Dudani, J. S., Lin, Y., Najer, A., Bekdemir, A., Chen, Q., Bhatia, S. N., and Stevens, M. M. 'Renal clearable catalytic gold nanoclusters for in vivo disease monitoring.' Nature Nanotechnology (2019); DOI: doi.org/10.1038/s41565-019-0527-6

    Gray, E. R., Heaney, J., Ferns, R. R., Sequeira, P. C., Nastouli, E., and Garson, J. A. 'Minor groove binder modification of widely used TaqMan hydrolysis probe for detection of dengue virus reduces risk of false-negative real-time PCR results for serotype 4' Journal of Virological Methods (2019); DOI: 10.1016/j.jviromet.2019.03.006

    Wood, C., S., Thomas, M. R., Budd, J., Mashamba-Thompson, T., P., Herbst, K., Pillay, D., Peeling, R. W.,  Johnson, A., M., McKendry, R. A., and Stevens, M. M.   'Taking connected mobile-health diagnostics of infectious diseases to the field' Nature (2019); DOI: 10.1038/s41586-019-0956-2

    Miller, B., S., Gliddon, H., D., and McKendry, R. A. 'Towards a Future of Rapid, Low-Cost, Multiplexed Detection of Antimicrobial Resistance Markers for Tuberculosis and Other Pathogens' Clinical Chemistry (2019); DOI: 10.1373/clinchem.2018.296715

    Kim, E., Agarwal, S., Kim, N., Sydow Hage, F., Leonardo, V., Gelmi, A., Stevens, M. M. 'Bioinspired Fabrication of DNA–Inorganic Hybrid Composites Using Synthetic DNA' ACS Nano (2019); DOI: 10.1021/acsnano.8b06492

    2018

    Izci, D., Dale, C., Keegan, N., and Hedley, J. 'The Construction of a Graphene Hall Effect Magnetometer' IEEE Sensors Journal (2018): DOI: 10.1109/JSEN.2018.2872604

    Gelkop, S., Sobarzo, A., Brangel, P., Vincke, C., Romão, E., Fedida-Metula, S., Strom, N., Ataliba, I., Mwiine, F. N., Ochwo, S., Velazquez-Salinas, L., McKendry, R. A., Muyldermans, S., Lutwama, J. J., Rieder, E., Yavelsky, V., and Lobel L. 'The Development and Validation of a Novel Nanobody-Based Competitive ELISA for the Detection of Foot and Mouth Disease 3ABC Antibodies in Cattle' Frontiery in Vetinary Science (2018); DOI: 10.3389/fvets.2018.00250

    Samadhan B. Patil, S. B., Al-Jehani, R. M., Etayash, H., Turbe, V., Jiang, K., Bailey, J., Al-Akkad, W., Soudy, R., Kaur, K., McKendry, R. A., Thundat, T., and Ndieyira, J. W. 'Modified cantilever arrays improve sensitivity and reproducibility of nanomechanical sensing in living cells' Nature Communications Biology (2018); DOI: 10.1038/s42003-018-0179-3

    Schormans, M., Valente, V., and Demosthenous, A. 'A Low-Power, Wireless, Capacitive Sensing Frontend Based on a Self-Oscillating Inductive Link' IEEE Transactions on Circuits and Systems I: Regular Papers (2018); DOI: 10.1109/TCSI.2018.2835148

    Lawry, B. M., Johnson, C. L., Flanagan, K., Spoors, J. A., McNeil, C. J., Wipat, A., and Keegan. N. 'Species-Specific Detection of C. difficile Using Targeted Antibody Design' Analytical Chemistry (2018); DOI: 10.1021/acs.analchem.8b03349

    Gray, E. R., Bain, R., Varsaneux, O., Peeling, R., Stevens, M. M., and McKendry, R. A. 'p24 revisited: a landscape review of antigen detection for early HIV diagnosis.' AIDS (2018); DOI: 10.1097/QAD.0000000000001982

    Gray, E. R., Turbe, V., Lawson, V. E., Page, R. H., Cook, Z. C., Ferns, R. B., Nasouli, E., Pillay, D., Yatsuda, H., Athey, D., and McKendry, R. A. 'Ultra-rapid, sensitive and specific digital diagnosis of HIV with a dual-channel SAW biosensor in a pilot clinical study' Digital Medicine (2018); DOI: 10.1038/s41746-018-0041-5

    Creamer, A., Wood, C. S., Howes, P. D., Casey, A., Cong, S., Marsh, A. V., Godin, R., Panidi, J., Anthopoulos, T. A., Burgess, C. H., Wu, T., Fei, Z., Hamilton, I., McLachlan, M. A., Stevens, M. M., and Heeney, M. 'Post-polymerisation functionalisation of conjugated polymer backbones and its application in multi-functional emissive nanoparticles' Nature Chemistry (2018); DOI: doi.org/10.1038/s41467-018-05381-4

    Miller, B. S., Parolo, C., Tube, V., Keane, C. E., Gray, E. R., McKendry, R. A. 'Quantifying Biomolecular Binding Constants Using Video Paper Analytical Devices' Chem. Eur. J. (2018); DOI: 10.1002/chem.201802394

    Brangel, P., Sobarzo, A., Parolo, C., Miller, B.S., Howes, P.D., Gelkop, S., Lutwama, J.J., Dye, J.M., McKendry, R.A., Lobel, L., Stevens, M.M. 'A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors' ACS Nano (2018); DOI: 10.1021/acsnano.7b07021

    2017

    Spicer, C. D., Jumeaux, C., Gupta, B., and Stevens, M. M. 'Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications' Chem. Soc. Rev., Advance Article (2018); DOI: 10.1039/C7CS00877E

    Loynachan, C.N., Thomas, M.R., Gray, E.R., Richards, D.A., Kim, J., Miller, B.S., Brookes, J.C., Agarwal, S., Chudasama, V., McKendry, R.A., Stevens, M.M. 'Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral Flow Immunoassays with Ultrabroad Dynamic Range' ACS Nano (2017); DOI: 10.1021/acsnano.7b06229

    Wang, S-T., Lin, Y., Spencer, R. K., Thomas, M. R., Nguyen, A. I., Amdursky, N., Pashuck, E. T., Skaalure, S. C., Song, C. Y., Parmar, P. A., Morgan, R. M., Ercius, P., Aloni, S., Zuckermann, R. N., Stevens, M. M. 'Sequence-Dependent Self-Assembly and Structural Diversity of Islet Amyloid Polypeptide-Derived β‑Sheet Fibrils' ACS Nano, 11, 8579−8589 (2017); DOI: 10.1021/acsnano.7b02325

    Turbé, V., Gray, E. R., Lawson, V. E., Nastouli, E., Brookes, J. C., Weiss, R. A., Pillay, D., Emery, V. C., Verrips, C. T., Yatsuda, H., Athey, D., McKendry, R. A. 'Towards an ultra-rapid smartphone- connected test for infectious diseases​' Scientific Reports 7, Article number: 11971 (2017); DOI:10.1038/s41598-017-11887-6

    Pilavaki, E., Demosthenous, A. 'Optimized Lateral Flow Immunoassay Reader for the Detection of Infectious Diseases in Developing Countries' Sensors 17(11), 2673 (2017); DOI:10.3390/s17112673

    Pyne, A., Pfeil, M-P., Bennett, I., Ravi, J., Iavicoli, P., Lamarre, B., Roethke, A., Ray, S., Jiang, H., Bella, A., Reisinger, B., Yin. D., Little, B., Muñoz-García. J. C., Cerasoli, E., Judge, P. J., Faruqui, N., Calzolai, L., Henrion, A., Martyna, G. J., Grovenor, C. R. M., Crain, J., Hoogenboom, B. W., Watts, A., Ryadnov, M. G. 'Engineering monolayer poration for rapid exfoliation of microbial membranes' Chem. Sci., 8, 1105-1115 (2017); DOI: 10.1039/C6SC02925F

    Ruiz-Sanchez, A. J., Parolo, C., Miller, B. S., Gray, E. R., Schlegel, K., McKendry, R. A. 'Tuneable plasmonic gold dendrimer nanochains for sensitive disease detection' Journals of Material Chemistry B (2017); DOI: 10.1039/C7TB01394A

    Soh, J.H., Lin, Y., M. R. Thomas, M.R., Todorova, N., Kallepitis, C., Yarovsky, I., Ying, J.Y., Stevens, M.M. 'Distinct Bimodal Roles of Aromatic Molecules in Controlling Gold Nanorod Growth for Biosensing' Advanced Functional Materials (2017) 1700523; DOI: 10.1002/adfm.201700523

    Kim, E., Howes, P.D., Crowder, S.W., Stevens, M.M. 'Multi-Amplified Sensing of MicroRNA by a Small DNA Fragment-Driven Enzymatic Cascade Reaction' ACS Sensors (2017); DOI: 10.1021/acssensors.6b00601

    Lin, Y., Pashuck, E.T., Thomas, M.R., Amdursky, N., Wang, S.-T., Chow, L.W., Stevens, M.M. 'Plasmonic Chirality Imprinting on Nucleobase-Displaying Supramolecular Nanohelices by Metal–Nucleobase Recognition' Angew. Chem. Int. Ed. (2017), 56, 2361; DOI: 10.1002/anie.201610976

    Wang, S.-T, Lin, Y., Hsu, C.-C., Amdursky, N., Spicer, C.D., Stevens, M.M. 'Probing amylin fibrillation at an early stage via a tetracysteine-recognising fluorophore' Talanta (2017); DOI: 10.1016/j.talanta.2017.05.015 

    Gray, E.R., Brookes, J.C., Caillat, C., Turbe, V., Webb, B.L., Granger, L.A., Miller, B.S., McCoy, L.E., El Khattabi, M., Verrips, C.T., Weiss, R.A., Duffy, D.M., Weissenhorn, W., McKendry, R.A. 'Unravelling the molecular basis of high affinity nanobodies against HIV p24: in vitro functional, structural and in silico insights.' ACS Infectious Diseases (2017); DOI: 10.1021/acsinfecdis.6b00189

    Richards, D, A.,  Maruani, A.,  Chudasama, V. 'Antibody fragments as nanoparticle targeting ligands: a step in the right direction' Chem. Sci., 8, 63-77 (2017); DOI: 10.1039/C6SC02403C

    Lee, M. T. W., Maruani, A., Richards, D.A., Baker, J. R., Caddick, S., Chudasama. V. 'Enabling the controlled assembly of antibody conjugates with a loading of two modules without antibody engineering' Chem. Sci., 8, 2056-2060 (2017); DOI: 10.1039/C6SC03655D

    2016

    Valente, V., Demosthenous, A. 'Wideband Fully-Programmable Dual-Mode CMOS Analogue Front-End for Electrical Impedance Spectroscopy' Sensors16(8), 1159 (2016); DOI:10.3390/s16081159

    Jauset-Rubio, M., Svobodová, M., Mairal, T., McNeil, C., Keegan, N., Saeed, A., Abbas, M. N., El-Shahawi, M. S., Bashammakh, A. S., Alyoubi, A. O., O'Sullivan, C. K. ‘Ultrasensitive, rapid and inexpensive detection of DNA using paper based lateral flow assay.’ Scientific Reports, 6, 37732, (2016); DOI: 10.1038/srep3773

    Jauset-Rubio, M., Svobodová, M., Mairal, T., McNeil, C., Keegan, N., El-Shahawi, M. S., Bashammakh, A. S., Alyoubi, A. O., O’Sullivan, C. K. 'Aptamer Lateral Flow Assays for Ultrasensitive Detection of β-Conglutin Combining Recombinase Polymerase Amplification and Tailed Primers.' Analytical Chemistry (2016); DOI: 10.1021/acs.analchem.6b03256

    Maruani, A., Richards, D.A. & Chudasama, V. 'Dual modification of biomolecules' Org. Biomol. Chem (2016); DOI: 10.1039/C6OB01010E.

    Hermans, R.L., Dueck, B., Ndieyira, J.W., McKendry, R.A. & Aeppli, G. 'Optical diffraction for measurements of nano-mechanical bending' Sci. Reports 6: 26690 (2016); DOI: 10.1038/srep26690.

    Brookes, J.C., Bufacchi, R., Kondoh, J., Duffy, D.M., McKendry, R.A. 'Determining biosensing modes in SH-SAW device using 3D finite element analysis' Sensors & Actuators: B. Chemical 234, 412-419 (2016); DOI: 10.1016/j.snb.2016.03.103.

    Gliddon, H.D., Howes, P.D., Kaforou, M., Levin, M., Stevens, M.M. 'A nucleic acid strand displacement system for the multiplexed detection of tuberculosis-specific mRNA using quantum dots' Nanoscale (2016); DOI: 10.1039/C6NR00484A.

    Almeida, C.S., Herrmann, I.K., Howes, P.D. & Stevens, M.M. 'Tailoring Cellular Uptake of Conjugated Polymer Nanoparticles Using Modular Amphiphilic Peptide Capping Ligands' Chemistry of Materials 27, 6879-6889 (2016); DOI: 10.1021/acs.chemmater.5b03337.

    Kostkova P., Brewer H., De Lusignan S., Fottrell E., Goldacre B., Hart G., Koczan P., Knight P., Marsolier C., McKendry R.A., Ross E., Sasse A., Sullivan R., Chaytor S., Stevenson O., Velho R. & Tooke J. 'Who Owns the Data? Open Data for Healthcare' Front. Public Health 4, 2296-2565 (2016); DOI: 10.3389/fpubh.2016.00007.

    Madsen, C., McLaughlin, J.A., Mısırlı, G., Matthew Pocock, M., Flanagan, K., Hallinan, J., Wipat, A. 'The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs' ACS Synth. Biol., 5 (6), pp 487–497 (2016); DOI: 10.1021/acssynbio.5b00210

    Chudasama, V., Maruani, A., Caddick, S. 'Recent advances in the construction of antibody–drug conjugates' Nature Chemistry volume 8, pages114–119 (2016); DOI: 10.1038/nchem.2415

    2015

    Soh, J.H., Lin, y, Rana, S, Ying, J.Y. & Stevens, M.M. 'Colorimetric detection of small molecules in complex matrixes via target-mediated growth of aptamer-functionalized gold nanoparticles' Analytical Chemistry 87, 7644-7652 (2015); DOI: 10.1021/acs.analchem.5b00875.

    Patil, S.B., Manuel V., Webb, B., Mazza, G., Pinzani, M., Soh, Y., McKendry, R.A. & Ndieyira, J.W. 'Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays' Nature Nanotechnology 10, 899-907 (2015); DOI: 10.1038/nnano.2015.174.

    Hayward, A.C. et al. 'Natural T Cell–mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study' AJRCMB 191, 1422-1431 (2015); DOI: 10.1164/rccm.201411-1988OC.

    2014

    Kappeler, N. 'Cantilevers for biological monitoring: opportunities for classical and quantum physics' Contemporary Physics, (2014); DOI: 10.1080/00107514.2014.966615

    Flanagan K., Harwood C., Lawry B. & Wipat A. 'A distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci', J Integr Bioinform., 11, 242, (2014); DOI: 10.2390/biecoll-jib-2014-242

    Howes, P.D., Chandrawati, R. & Stevens, M.M. 'Colloidal nanoparticles as advanced biological sensors' Science, 346, 1247390–1247390 (2014); DOI: 10.1126/science.1247390

    Howes, P.D., Rana, S. & Stevens, M.M. 'Plasmonic Nanomaterials for Biodiagnostics' Chem. Soc. Rev., 43, 3835–3853 (2014); DOI: 10.1039/C3CS60346F

    Ndieyira, J. W., Kappeler, N., Logan, S., Cooper M.A., Abell, C., McKendry R.A. & Aeppli, G. 'Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum' Nature Nanotechnology 9, 225–232 (2014); DOI: 10.1038/nnano.2014.33.