Project Lead(s): Alexis Vallée-Bélisle
An obstacle to better management of HIV in the developing world is the lack of mass testing, due to insufficient trained staff, clinics and hospitals.
An enormous step forward would be to provide health providers and even the general public with their own, inexpensive, easy-to-use HIV detection meter, which would drastically reduce the lag time before treatment, as well as prevent disease transmission.
The project team sought to develop an HIV meter – an inexpensive, easy-to-use, quantitative sensor – to detect and quantify antibodies that are diagnostic of HIV infection and progression.
To transduce the presence of the anti-HIV antibodies into an electrochemical current, the team designed a novel DNA-switch that is activated by antibody binding.
When activated, this switch separates an electro donor/acceptor element from an electrode, leading to a decrease in the electrochemical current.
The project team had already showed that this electrochemical switch detects antibodies directly in whole blood in less than five minutes.
In this project, the team sought to optimize the signalling mechanism of the switch and to adapt the meter for the detection of HIV antibodies by replacing test-epitopes by commonly used, standard HIV epitopes, such as the fragment 604–615 of the HIV protein gp41.
The intent was to then test the HIV meter on real human samples at the Howard Hospital in Zimbabwe and compare results with the results obtained from the HIV-strip immunoassays currently used at this hospital.
The project team was able to optimize the different components necessary to develop a working prototype of the HIV meter.
The attempt to adapt the DNA switch on a relatively inexpensive, portable potensiostat was unsuccessful because the switches did not provide sufficient electrochemical current (i.e., of at least 0.5 μA) to enable their detection.
As a result, the team concluded that an HIV meter prototype based on this first generation of switches would be too expensive (>$1,000) to achieve successful commercialization.
A second generation of antibody switches were then designed that could, in principle, provide an electrochemical signal that would be 100-fold higher.
This work led to the development of a new technology called ‘electrochemical Steric-Hindrance Hybridization Assays’ (eSHHA) for which a patent has been filed.
A further investment of around $500,000 $ to $1,000,000 is required to complete the optimisation and testing of the prototype
This new DNA-based technology generates sufficient electrochemical signals to support its adaptation on inexpensive potentiostats (e.g., in the range of 40 uAmp/cm2 of electrode).
It was also demonstrated that this DNA-based technology enables the rapid (five minute) detection of nanomolar concentration of antibodies directly in whole blood (which corresponds to a clinically relevant concentration).
Work is currently underway to adapt this second generation switch for the detection of HIV antibodies.
A patent has been submitted for the second generation switch.