The fever chip

Studentship strategic priority area:Healthcare device innovation
Keyword:Diagnosis, infection, silicon chip, immunoassay fever

Fever is an extremely common symptom of most infectious diseases as well as a range of non-communicable diseases too. In countries such as Uganda where malaria is widespread and the most frequent cause of fever, there is an unfortunate trend to assume anyone presenting with fever as having malaria without making a formal diagnosis. This practise is dangerous for several reasons. Firstly, there is a risk that a patient with fever diagnosed and treated for malaria is actually infected with another infectious agent. Not only will that patient be at risk due to a failure to take appropriate action against their specific infection, they will also act as a reservoir to transmit those diseases. Given the potentially explosive danger associated with some infections that first present as fever, e.g. Ebola virus, having easy and routine test for the virus could also enhance the speed at which such diseases are discovered, allowing the fastest possible implementation of public health programmes to stop their spread. Treatment of the patient with anti-malarials also introduces a risk of selection of anti-malarial resistance, since that person may actually become infected with malaria retrospectively when drug levels in their blood have diminished to concentrations not lethal to the malaria parasite (Plasmodium falciparum, or other Plasmodium species) and yet offering some selective advantage to parasites that carry mutations rendering them less sensitive to drug. Although good tests exist for malaria, these are often not employed due to cost and specialisation required in their use. For other infectious diseases, diagnostic approaches are often not well advanced. Even where they are, their use in resource-poor settings, like Uganda, is constrained.
We propose to develop a simple, cheap "Fever chip" capable of making differential diagnosis of malaria and an (expandable) range of other infectious diseases. The device will be integrated with smart phone reader technology enabling rapid interpretation of results at reference centres thus opening use to many health workers with different qualifications.
We have already developed prototypic devices that could successfully identify HIV and Hepatatis C infection.
Our platform is remarkably simple. Antigens that are specific for individual pathogens, and known to promote seroconversion in infected patients, are fixed to clearly demarcated domains on a CMOS chip surface. Serum, containing antibodies from patients, is then applied to the surface and if antibodies indicative of infection are present they bind to their cognate antigen. Once bound, secondary antibodies, with enzyme's linked to them, can bind to the primary antibody. The enzyme then converts a colorimetric substrate to a product that absorbs light emitted from narrow bandwidth LEDs. Photodiode sensors at the CMOS chip surface detect the change in photon penetrance and transmit this an electronic signal to our reading app built into a smart phone.
Below we outline a number of antigens that are either already in clinical use for serological diagnosis of malaria and a number of other diseases, or else are being investigated for potential future use. The list we give below is not comprehensive and the technology can be readily adapted to the inclusion of any new antigen that may be of use in identifying an infectious disease. We plan to initiate our work within a Ugandan context where we have close collaborators, but also emphasise that the basic platform can be adapted to include agents endemic in other localities.