title: Antigen-Dissociation from Antibody-Modified Nanotransistor Sensor Arrays as a Direct Biomarker Detection Method in Unprocessed Biosamples.
abstract: The detection of biomolecules is critical for a wide spectrum of applications in life sciences and medical diagnosis. Nonetheless, biosamples are highly complex solutions, which contain an enormous variety of biomolecules, cells, and chemical species. Consequently, the intrinsic chemical complexity of biosamples results in a significant analytical background noise and poses an immense challenge to any analytical measurement, especially when applied without prior efficient separation and purification steps. Here, we demonstrate the application of antigen-dissociation regime, from antibody-modified Si-nanowire sensors, as a simple and effective direct sensing mechanism of biomarkers of interest in complex biosamples, such as serum and untreated blood, which does not require ex situ time-consuming biosample manipulation steps, such as centrifugation, filtering, preconcentration, and desalting, thus overcoming the detrimental Debye screening limitation of nanowire-based biosensors. We found that two key parameters control the capability to perform quantitative biomarkers analysis in biosamples: (i) the affinity strength (koffrate) of the antibody-antigen recognition pair, which dictates the time length of the high-affinity slow dissociation subregime, and (ii) the "flow rate" applied during the solution exchange dissociation step, which controls the time width of the low-affinity fast-dissociation subregime. Undoubtedly, this is the simplest and most convenient approach for the SiNW FET-based detection of antigens in complex untreated biosamples. The lack of ex situ biosample manipulation time-consuming processes enhances the portability of the sensing platform and reduces to minimum the required volume of tested sample, as it allows the direct detection of untreated biosamples (5-10 μL blood or serum), while readily reducing the detection cycle duration to less than 5 min, factors of great importance in near-future point-of-care medical applications. We believe this is the first ever reported demonstration on the real-time, direct label-free sensing of biomarkers from untreated blood samples, using SiNW-based FET devices, while not compromising the ultrasensitive sensing capabilities inherent to these devices.
authors: School of Chemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Tel Aviv 69978, Israel.
authors: Vadim
authors: V
authors: Krivitsky
authors: School of Chemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Tel Aviv 69978, Israel.
authors: Marina
authors: M
authors: Zverzhinetsky
authors: School of Chemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Tel Aviv 69978, Israel.|Department of Materials Science and Engineering, The Iby and Aladar Fleischman Faculty of Engineering, Tel-Aviv University , Tel Aviv 69978, Israel.
authors: Fernando
authors: F
authors: Patolsky
mesh_terms: D055910:Antibodies, Immobilized / Q000737:chemistry*; D015415:Biomarkers; D015374:Biosensing Techniques; D006801:Humans; D053770:Nanowires; D014173:Transistors, Electronic; D020107:Troponin T / Q000032:analysis
chemical_list: D055910:Antibodies, Immobilized; D015415:Biomarkers; D020107:Troponin T
keywords: Nanowire; antibody; biomolecules; biosensors; field effect transistors; ionic screening; preconcentration; separation