We have recently demonstrated a reagentless, electrochemical method, termed E-DNA sensors that can detect anti-HIV antibodies in undiluted human serum at levels thousands of times lower than those seen in HIV-positive patient samples. The approach is rapid (sub-10 min), single-step, and quantitative, thus improving significantly on the convenience and/or clinical value of existing molecular diagnostics. It is supported on micron-scale electrodes, and thus can be multiplexed to the level of measuring dozens of diagnostic antibodies in a single finger-prick droplet. Given these attributes, our technology appears well suited for applications that would derive value from the ability to measure quantitative antibody levels or the ability to simultaneously monitor multiple diagnostic antibodies at the point of care or in the field. The focus of the proposed research program is to test this hypothesis by performing the initial, pre-clinical validation of this novel molecular detection platform. Specifically, we will fabricate E-DNA arrays supporting the detection of one to two dozen antibodies diagnostic of a panel of sexually transmitted infections, and perform side-by-side tests of them against a set of gold standard approaches when both are challenged using a large set of authenticated human samples.
There exists a critical need amongst physicians, public health agencies and the military to better monitor changes in the presence, prevalence, and spread of infectious diseases. In response we propose the development of a technology for the rapid, multiplexed detection of dozens of disease-specific antibodies in a single finger-prick blood sample. The proposed single-step, wash- and reagent-free devices will report in less than 10 minutes, are driven by inexpensive, field-portable electronics (closely analogous to the home glucose meter), and operate at a cost of a few dollars per assay. In short, the proposed, transformative technology will overcome the barriers that have historically relegated quantitative, multiplexed antibody detection to centralized facilities and move it to the point-of-care and into the field, greatly accelerating the speed with which actionable diagnostic information is delivered to front-line healthcare providers.
| Ricci, Francesco; Vallée-Bélisle, Alexis; Simon, Anna J et al. (2016) Using Nature's ""Tricks"" To Rationally Tune the Binding Properties of Biomolecular Receptors. Acc Chem Res 49:1884-92 |
| Kang, Di; Ricci, Francesco; White, Ryan J et al. (2016) Survey of Redox-Active Moieties for Application in Multiplexed Electrochemical Biosensors. Anal Chem 88:10452-10458 |
| Ranallo, Simona; Rossetti, Marianna; Plaxco, Kevin W et al. (2015) A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins. Angew Chem Int Ed Engl 54:13214-8 |
| Simon, Anna J; Vallée-Bélisle, Alexis; Ricci, Francesco et al. (2014) Using the population-shift mechanism to rationally introduce ""Hill-type"" cooperativity into a normally non-cooperative receptor. Angew Chem Int Ed Engl 53:9471-5 |
