Title: Integrated III-V Haemocytometer
Funder: Engineering and Physical Sciences Research Council

Abstract: The assessment of human health from analysis of blood samples is one of the most widespread medical diagnostic procedures; with thousands of patients providing samples every day in hundreds of clinics and surgeries across the UK. However, it remains a slow process because samples have to be sent to a limited number of specialist central services in health trusts, with a turn-around of days between sample acquisition and assessment delivery. It is expensive, both in terms of direct cost of the analysis and downstream costs due to deterioration of patient health as a result of the time delay in accessing results. We propose a capillary driven, microscale disposable chip instrument for non-technical users that provides the established and understood diagnostic parameters. The basic device will consist of lasers and detectors integrated around a fluid channel to facilitate counting, scattering and wavelength dependent absorption measurements. This will differentiate red blood cells from white blood cells, discriminate between the main white blood cell types - monocyte, lymphocyte, neutrophil and granulocyte - and provide cell counts of these sub groups. Stage 2 builds on the same technology platform to enhance sensitivity and add functionality by making the cell under test an active part of the laser thus maximising light / cell interaction. In stage 3 we will label cells with fluorescent dye attached to metal particles (provided by Keyes group) and increase the absorption of particular cells, by up to 6 orders of magnitude, and also access fluorescent lifetime measurements (using an approach we have patented) allowing the analysis of cell function as well as cell discrimination. We have blood analysis expertise within the project to maximise the benefits of stage 1 and co-workers focussed on cell cycle and anti-cancer research will interact and maximise the benefits of the device that goes well beyond current blood test capability. The microscale system we will develop offers a number of advantages: Micro scaling reduces the volume of blood required changing the way blood-based diagnostics are used. Immediate and quasi-continuous monitoring of the haematological state is feasible and can be used in acute situations such as surgery or child birth. This also offers, with further development, a realistic route to continuous monitoring during everyday life. Semiconductor micro fabrication provides the route to mass manufacture of low cost systems Shifts the cost of blood testing from technician to test kit and introduces a distributed cost model (pay per kit) rather than a single, major capital investment. Allows disposable chip format and provides uniformity and repeatability, contributing to the removal of the need for specialist operator - use at point of care, e.g. developing world. We will achieve all this by exploiting the properties of a quantum dot semiconductor system that we have developed and which provides particular advantages for integration and for laser based sensing at relevant wavelengths (a major one being the sensitivity to small changes in optical loss). In addition to the significant medical benefits resulting from the ability to widely deploy, low cost and enhanced clinical functionality devices we also see a significant commercial benefit to the UK, with an identified UK manufacturing supply chain. The project brings together a wide range of complementary experience, including semiconductor device design, fabrication and characterisation, microfluidics, systems analysis and data handling, blood analysis and cytometry and biophotonics and clinical validation.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE