Title: Next Generation Mobile HIV Diagnostics with Wireless Connectivity
Funder: Department of Health (England)

Abstract: The aim of this proposal is to develop an affordable PoC handheld device to rapidly diagnose HIV-infected patients in GP surgeries and community-settings. SAWs have many advantages compared to competing technologies such as cantilevers, nanowires and optical biosensors. They have been in commercial use for more than 60 years. The telecommunications industry is the largest consumer, accounting for ~3 billion SAWs annually, primarily in mobile cell phones and base-stations where they act as bandpass filters. SAWS are competitively priced, inherently rugged, sensitive, intrinsically reliable and capable of being passively and wirelessly interrogated (no sensor power source required). The novelty of OJ-Bio's SAW chips is their microstructured coating that allows operation in liquids with high sensitivity.20-24 Different capture coatings can be tested immediately on a working prototype measurement unit, which is already in manufacture in OJ-Bio. This will be used to develop robust assays and then transferred to a simple hand-held format similar to a mobile phone, with inbuilt wireless connectivity. To diagnose HIV we will detect virological and immunological markers (viral antigens p24 and gp120; and patient antibodies - anti-p24 and anti-gp120). Lead capture antibodies/proteins have already been indentified as part of UCL's EPSRC Grand Challenge grant - including monoclonals and llama antibodies, with 1000 fold higher binding affinities compared to conventional antibodies teamed with broad efficacy against all major clades,8-9 high stability to temperature fluctuations - characteristics that will improve the performance and shelf-life of our device. To ensure that markers are detected with high sensitivity and specificity and to reduce the risk of false positives/negatives, we will develop a multiplexed system with in-situ control coatings and nanoparticle tags to increase device sensitivity. Finally the design of the chip and readout will be developed to give a simple yes/no or "seek medical advice" on a screen, which can be supplied in a variety of formats depending on application area e.g. linked to smart phones, hand-held device or completely disposable chips. To deliver our prototype device will require coordinated work in the following workpackages: WP0. Project Management (Athey, McKendry): Project aims, objectives and milestones will be met by careful management of individual WP tasks, resources and budgets. Deliverables : work plan, meeting minutes, quarterly & annual reports. WP1. Device Development (Yatsuda, Staff 1 & 2): Prototype chips and readers will be developed to measure multiple markers with high sensitivity. Current chip formats and readers will be supplied immediately to UCL, while OJ-Bio focuses upon multi-channel formats. Deliverables: prototype chips and readers. WP2. Surface Chemistry (McKendry, Weiss, Staff 3): Active, uniform, stable capture protein coatings will be developed to ensure high sensitivity and specificity, reducing the risk of false readings. To further improve SAW sensitivity we will test secondary antibody and nanoparticle sandwich assays. Deliverables : Optimised capture antibodies, surface chemistries and multiplexing, enhancement methods. WP3. Assay Development and Clinical Pilot Study (Emery, Pillay, Staff 4): Devices and capture coatings developed in WP1 & WP2 will be tested to establish detection limits and working ranges, benchmarking to gold-standard Alere lateral flow and ELISAs using NEQAS control panels, pedigree reagent, seroconvertor panels, and quality assurance panels available from NEQAS and NIBSC. Prototypes will undergo preliminary clinical testing of HIV-infected sera in accordance with ethical considerations. Deliverables : laboratory & clinical testing, benchmarking to gold-standards. WP4. Exploitation (Athey, McKendry, Pillay): Impact will be maximised by understanding stakeholder needs, market analysis, securing IP, publications, presentations at major conferences and trade shows. The IP landscape, down-stream regulatory and market access opportunities will be reviewed and potential partners identified for next stage commercial development. Deliverables : exploitation plan, stakeholder engagement, quarterly reports.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION