Label-free Electronic Detection of the Antigen-Specific T-Cell Immune Response Export

@article{citeulike:3509424, abstract = {Abstract: Detection of antigen-specific T-cells is critical for diagnostic assessment and design of therapeutic strategies for many disease states. Effective monitoring of these cells requires technologies that assess their numbers as well as functional response. Current detection of antigen-specific T-cells involves flow cytometry and functional assays and requires fluorescently labeled, soluble forms of peptide-loaded major histocompatability complexes (MHC). We demonstrate that nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology can be employed to allow direct, label-free electronic detection of antigen-specific T-cell responses within seconds after stimulation. Our approach relies on detection of extracellular acidification arising from a small number of T-cells (as few as \~{}200), whose activation is induced by triggering the T-cell antigen receptor. We show that T-cell triggering by a nonspecific anti-CD3 stimulus can be detected within 10 s after exposure to the stimulus. In contrast, antigen-specific T-cell responses are slower with response times greater than 40 s after exposure to peptide/MHC agonists. The speed and sensitivity of this technique has the potential to elucidate new understandings of the kinetics of activation-induced T-cell responses. This combined with its ease of integration into conventional electronics potentially enable rapid clinical testing and high-throughput epitope and drug screening.}, address = {Departments of Biomedical Engineering, Electrical Engineering, Applied Physics, and Chemical Engineering, Yale University, 55 Prospect Street, New Haven, Connecticut 06511}, author = {Stern, Eric and Steenblock, Erin R. and Reed, Mark A. and Fahmy, Tarek M.}, citeulike-article-id = {3509424}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/nl801693k}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/nl801693k}, day = {8}, doi = {10.1021/nl801693k}, journal = {Nano Lett.}, keywords = {nanotech}, month = {October}, number = {10}, pages = {3310--3314}, posted-at = {2008-11-13 18:13:47}, priority = {2}, title = {Label-free Electronic Detection of the Antigen-Specific T-Cell Immune Response}, url = {http://dx.doi.org/10.1021/nl801693k}, volume = {8}, year = {2008} }

TY - JOUR ID - citeulike:3509424 L3 - citeulike-article-id:3509424 N2 - Abstract: Detection of antigen-specific T-cells is critical for diagnostic assessment and design of therapeutic strategies for many disease states. Effective monitoring of these cells requires technologies that assess their numbers as well as functional response. Current detection of antigen-specific T-cells involves flow cytometry and functional assays and requires fluorescently labeled, soluble forms of peptide-loaded major histocompatability complexes (MHC). We demonstrate that nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology can be employed to allow direct, label-free electronic detection of antigen-specific T-cell responses within seconds after stimulation. Our approach relies on detection of extracellular acidification arising from a small number of T-cells (as few as ~200), whose activation is induced by triggering the T-cell antigen receptor. We show that T-cell triggering by a nonspecific anti-CD3 stimulus can be detected within 10 s after exposure to the stimulus. In contrast, antigen-specific T-cell responses are slower with response times greater than 40 s after exposure to peptide/MHC agonists. The speed and sensitivity of this technique has the potential to elucidate new understandings of the kinetics of activation-induced T-cell responses. This combined with its ease of integration into conventional electronics potentially enable rapid clinical testing and high-throughput epitope and drug screening. IS - 10 JF - Nano Lett. AD - Departments of Biomedical Engineering, Electrical Engineering, Applied Physics, and Chemical Engineering, Yale University, 55 Prospect Street, New Haven, Connecticut 06511 EP - 3314 TI - Label-free Electronic Detection of the Antigen-Specific T-Cell Immune Response VL - 8 SP - 3310 KW - nanotech AU - Stern, Eric AU - Steenblock, Erin AU - Reed, Mark AU - Fahmy, Tarek PY - 2008/10/08/ UR - http://dx.doi.org/10.1021/nl801693k ER -