Integrated III-V Haemocytometer

通过分析血液样本来评估人类健康是最广泛的医疗诊断程序之一；在英国各地的数百家诊所和手术中，每天都有数千名患者提供样本。然而，这仍然是一个缓慢的过程，因为必须将样本送到卫生信托机构数量有限的专科中央服务机构，从获取样本到提供评估需要几天的时间。无论是分析的直接成本，还是由于获得结果的时间延迟而导致患者健康恶化所造成的下游成本，都是昂贵的。我们提出了一种毛细管驱动的微型一次性芯片仪器，用于非技术用户，提供已建立和理解的诊断参数。基本装置将由围绕流体通道集成的激光器和探测器组成，以方便计数、散射和波长相关的吸收测量。这将区分红细胞和白细胞，区分主要的白细胞类型——单核细胞、淋巴细胞、中性粒细胞和粒细胞，并提供这些亚群的细胞计数。第二阶段建立在相同的技术平台上，通过使被测细胞成为激光的主动部分，从而最大限度地提高光/细胞的相互作用，从而提高灵敏度和增加功能。在第三阶段，我们将用附着在金属颗粒上的荧光染料标记细胞（由Keyes集团提供），并增加特定细胞的吸收，最多可达6个数量级，并且还可以进行荧光寿命测量（使用我们已获得专利的方法），从而分析细胞功能以及细胞区分。我们在项目中拥有血液分析专业知识，可以最大限度地发挥第一阶段的优势，专注于细胞周期和抗癌研究的同事将相互作用，最大限度地发挥该设备的优势，远远超出当前的血液检测能力。我们将开发的微尺度系统具有许多优点：微尺度减少了所需的血液量，改变了血液诊断的使用方式。对血液学状态的即时和准连续监测是可行的，可用于手术或分娩等急性情况。随着进一步的发展，这也为日常生活中的持续监测提供了一条现实的途径。半导体微加工为低成本系统的大规模生产提供了途径。将血液检测的成本从技术人员转移到检测试剂盒，并引入分布式成本模式（按试剂盒付费），而不是单一的主要资本投资。允许一次性芯片格式，并提供均匀性和可重复性，有助于消除对专业操作员在护理点使用的需求，例如发展中国家。我们将利用我们开发的量子点半导体系统的特性来实现这一切，该系统为集成和相关波长的激光传感提供了特别的优势（主要是对光学损耗微小变化的灵敏度）。除了能够广泛部署、低成本和增强临床功能的设备所带来的重大医疗效益外，我们还看到了英国的重大商业效益，因为英国有一个确定的制造供应链。该项目汇集了广泛的互补经验，包括半导体器件设计，制造和表征，微流体，系统分析和数据处理，血液分析和细胞术，生物光子学和临床验证。

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.