We have recently demonstrated a reagentless, electrochemical method - termed E-DNA sensors - that achieves the detection of anti-HIV antibodies directly in undiluted, unprocessed human blood serum at concentrations orders of magnitude lower than those seen in HIV-positive patient samples. The approach is rapid (sub-10 min), single-step, and quantitative, thus improving on the convenience and/or clinical value of existing point-of-care molecular diagnostics. Further speaking to its potential value, the approach is supported on micron-scale electrodes and can thus be multiplexed to the level of measuring dozens of diagnostic antibodies in a single finger-prick sample. Given these attributes, our technology appears well suited for applications that would derive value from the ability to measure quantitatively the levels of multiple antibodies outside of central laboratories The focus of the proposed research program is to test this hypothesis by performing the initial, pre-clinical validation of the E-DNA antibody detection platform. Specifically, we will fabricate E DNA arrays for the measurement of one to two dozen antibodies diagnostic of a panel of three sexually transmitted infections, and perform side-by-side comparison of these against current gold standard laboratory approaches when both are challenged using authentic human samples.
There exists a critical need among physicians, public health agencies and the military to better monitor changes in the presence, prevalence, and spread of infectious diseases. In response we propose here the development and initial, pre-clinical validation of a technology for the rapid, multiplexed measurement of dozens of disease-specific antibodies in a single finger-prick blood sample. This quantitative, single-step, wash- and reagent-free device will report in less than 10 minutes, is driven by inexpensive, field-portable electronics (closely analogous to the home glucose meter), and operates at a cost of a few dollars per assay. In short, the proposed, 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 delivery of actionable diagnostic information to front-line healthcare providers.
|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; VallÃ©e-BÃ©lisle, 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|