Optically controlled fluid flow: enabling smart paper-based medical diagnostic devices

Access to affordable, reliable, user-friendly and rapid medical diagnostic tests has been identified by the World Health Organization (WHO) as a global imperative. In both the developed and developing world, point-of-care (POC) devices are the diagnostic tool of choice, where an answer is provided in a matter of minutes to questions that currently address the relatively straightforward conditions relating to pregnancy or diabetes. Affordable, but user-friendly testing must also be directed to other major complaints and conditions such as HIV, Hepatitis, Malaria, TB and a range of allergies. Moving beyond a simple binary yes/no result, as for a pregnancy test, to tests that provide a quantitative or semi-quantitative result is a global imperative and together with the added demands for greatly enhanced sensitivity and limit of detection are the holy-grail for the diagnostic industry. A multi-testing environment in a paper-based format, where fluid flow can be routed, delayed, gated and mixed will implement these provisions and optimize the outcome of the testing procedure. This is the aim of our novel optically-assisted gated fluid flow technology, which will usher in a much-needed transformative breakthrough that hugely expands the application-domain of fluidics-based diagnostic devices namely lateral flow devices (LFDs) and paper-based analytical devices.

While paper-based fluidic devices that rely on their current passive self-wicking process can address some basic functionalities , enabling triggerable on-demand fluid flow using responsive photopolymers will provide a hugely significant step-change in their diagnostic capability through inclusion of the following features : (a) incubation of fluidic sample with a desired biochemical reagent within a channel to maximize the sensitivity and limit of detection; (b) timed on/off gating to allow dispensing of pre-determined sample volume for semi-quantitative detection; (c) triggering-on the sample flow at a desired time for controlled and user-friendly testing and (d) dynamic flow control within multiple flow channels to enable multistep reactions. Our proposal is to develop a paper platform where liquid flow can be controllably switched on and off via non-contact illumination of responsive photopolymers using low power optical addressing. Such a capability will massively transform the current passive lateral flow devices (LFDs) into true lab-on-chip type multi-functional test-beds bringing immediate and quantifiable impact within the medical diagnostic and healthcare sectors.

Rapid diagnostic capability is an ever-present requirement to combat the global burden of healthcare for a population that now exceeds 7.5 billion. In the UK this is a particular problem as the National Health Service (NHS) is under a constant constraint of treating more people with fewer resources, and the small increase in projected government funding goes nowhere near solving the healthcare 'crisis' which is looming. One obvious answer therefore is to look at the possibilities of enabling early, rapid, high-sensitivity, or quantitative diagnosis using cheap, easily accessible and user-friendly technologies so that the public can make a personal and valuable contribution to the problem by diagnosing at home, in a clinic or doctor's surgery in locations that do not require the resources of personnel or space as in a hospital environment. While this applies within the UK environment, it is even more relevant to the situation within developing countries where the lack of resources is far more of an issue, and hence the technology we are developing will play a crucial role on the world stage. Rapid, accurate and easy-to-implement testing is crucial for global 21st century healthcare provision.

In terms of Economic Impact, we can frame the benefits of the proposed project into two parallel strands.

Firstly there are the economic consequences of an increasing incidence and effect of diseases such as TB on the world population. Death from TB occurs most often to the economically active segment of the population, with 75% of the deaths being for people between the ages of 15 and 54, and this greatly increases the economic burden in developing countries, as it represents a loss of that fraction of the population who may contribute most to the economy of the country. In financial terms, the global economic burden of TB according to the most recent WHO estimates amounts to approximately $25 billion from decline in productivity and from deaths annually in India alone, and the World Bank estimates that TB is responsible for a production decrease of 4-7% of some countries' GDP. Although we have used TB as an example for this proposal, it applies equally well to a range of other debilitating and ultimately fatal diseases where the same trend holds true.

Secondly, in terms of economic benefit to the UK (in this case), once such tests with novel functionalities have been developed, bearing in mind the current global value of such lateral flow devices, which currently amounts to more than $5 billion, it is easy to see that such new diagnostic devices could and should represent considerable revenue generation. It makes sound economic sense to undertake such research and then, via suitable follow-on funding, e.g. from Innovate UK, to produce and sell such products.

In terms of Societal Impact, it is easy to understand the problems that a lack of early and sensitive diagnostic capability has on the wellbeing of every country worldwide. TB is a tremendous social burden, with developing countries being affected most, as 95% of new TB cases and 98% of deaths from TB are in developing countries. Additionally, TB kills more women annually than all causes of maternal mortality combined, and this is an obvious example of gender inequality. There is also an immense social stigma that accompanies TB which has crippling implications on the patients and their families. Those patients suffering from TB also require physical isolation, which only further exacerbates their feeling of social isolation.

We believe that the development of such 'smart' diagnostics is a very powerful agent for change, which will facilitate prompt, accurate antibiotic prescriptions, potentially transforming treatments of millions of patients and minimising the threat of TB and other diseases. The economic and societal benefits are clear and easy to quantify and hence we believe this proposal goes a long way to satisfy the global needs we have identified.