Integrated III-V Haemocytometer

Lead Research Organisation: Cardiff University
Department Name: School of Physics and Astronomy

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.

Planned Impact

Our initial route to impact is through our team members and advisory board (AB). We have carefully chosen the AB members to include representatives from companies forming a potential UK manufacturing chain (IQE, CST and Renishaw). We have studied the EPSRC landscape and (following review to avoid ruling out potential referees) will also include colleagues whose work might benefit from the complementarity with ours. From the medical field, cell cycle work and anti-cancer activities, we have already included Paul Smith (President of ISAC - see LOS) from Cardiff.

We believe we can make significant societal impact by producing a local, fast and cheap to implement solution for the assessment of human health from analysis of blood, one of the most widespread medical diagnostic procedures.
Our solution is in accord with the vision of the Photonics21 grouping[http://www.photonics21.org]: "Diagnostics will be complemented by versatile 'lab on a chip' biosensors that are non-invasive, light-based, and ultra-sensitive. These will allow monitoring many important patient parameters at the bedside, in the doctor's practice, at home, or even during our everyday lives in the form of wearable equipment."
This is "a paradigm shift moving from the current cost-intensive treatment after onset of the disease, to the detection and prevention of disease at the earliest possible stage" and is the only way to mitigate the "Projected global demographic changes that will have drastic consequences for the healthcare systems of the industrialized nations."

Photonics is a 300Bn Euro sector of the world economy and growing at 10% per year. Europe's share is 20%, rising to 45% in a number of key areas. The UK, which has a 12% share of the European volume, is a major manufacturer of photonic III-V materials through, for example, IQE, and has a growing device sector through companies such as CST.

We will license intellectual property and transfer knowledge to our AB members and to other industrial collaborators and, should it become appropriate, establish the value of an innovation through spin-out activity. Cardiff and Swansea Universities have devoted substantial resources in support of commercial exploitation and we already hold project relevant IP with more in the pipeline.

This is an excellent training opportunity for PDRAs in a UK relevant high technology and interdisciplinary field. We will hold tutorials for all team members by the staff in each specialist area to ensure cross fertilisation of physical and life sciences expertise. The PDRA training will also have direct economic impact via the provision of skilled workers to relevant companies.
Science Made Simple (SMS) [see letter of support] will provide a two-stage training program in outreach. Phase one covers generic aspects of communication, but also examines barriers to successful communication for our specific research. Phase two involves developing presentations on parts of the research, aimed at levels suiting audiences from school students to politicians. Following their presentations to members of the public, the researchers will discuss the overall experience with our wider research group so that all can learn and benefit for years to come as their careers develop.

We will disseminate our work via open scientific meetings including those with a mix of science and commercial activity and a significant life sciences component. We will publish in peer reviewed journals such as Nature Photonics and Nature Nanotechnology which are read by the researchers in ICT / Physics/ life sciences interface.
To ensure we stimulate interaction with additional end users we will hold a one day open workshop. This will focus on the industry / academic interface and aim to spread awareness of the opportunities our work stimulates to a wide a range of SMEs and larger business beyond our existing partners, making use of the relevant KTNs, the Welsh Optoelectronics Forum and other bodies

Publications

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Description We have developed understanding around the technologies and techniques essential for the production of a microscale device capable of blood sample analysis. The essential components of this device, including lasers and detectors integrated around a fluid filled channel, capable of counting, scattering and wavelength dependent absorption using cell line samples were developed. Important developments included a photonic integration platform with pump free microfluidics, InAsP quantum dot lasers, a 2-stage surface treatment for long-term stability of hydrophilic SU-8, mechanisms for enhanced wavelength turning, dual state lasing and the development of optical pumping.
Exploitation Route Further work could focus on further development of the system to promote a basic user interface, and manufacturability. Applications for other types of particle analysis.
Sectors Healthcare