Immunologically Modified Field Effect Transistor for Protein Detection in Biologic Fluids
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Date
2014-05
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The Ohio State University
Abstract
Field effect transistors (FETs) are solid-state electrical devices with semiconductor channels through which charge carriers migrate and generate current. The application of an electric field proximal to the conductive channel causes a change in current depending on the sign and magnitude of the field. FETs can be modified for protein sensing by deployment of antibodies as receptors on the channel surface to create an immunologically modified FET (immunoFET). Binding of analytes brings a layer of charge proximal to the channel surface, causing modulation of current that is easily detectable, allowing for quantitative detection of unlabeled analytes. The FET design may be scalable to allow for inexpensive, real-time, label-free, point-of-care diagnostic use. The distance between the analyte and the channel is crucial as sensitivity drops off due to counter-ion shielding, which historically was the reasoning behind assessing immunoFETs as infeasible. Bound proteins must therefore be held within a couple nanometers of the channel for successful detection. Following previous work showing successful detection of various analytes in PBS, we present the successful detection of Monokine induced by Interferon γ (MIG/CXCL9), a pro-inflammatory chemoattractant chemokine, in both murine serum and human urine from transplant patients using AlGaN/GaN heterojunction FETs (HFETs) modified with anti-CXCL9 IgG. ImmunoHFETs were modified with IgG antibodies specific to CXCL9 then exposed to human urine of renal transplant recipients. Baselines and changes in conductance were compared to determine levels of CXCL9 in clinical samples. We present the detection of CXCL9 in renal transplant urine at biologically relevant levels and correlated with rejection by renal biopsy. The presented work demonstrates the feasibility of immunoHFET sensor operation in physiologic buffers, and shows the potential to provide real-time quantification and monitoring of inflammatory mediators, allowing for low-cost and minimally invasive real-time interrogation of graft status.
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Keywords
immunoFET, protein detection, immunoassay, CXCL9, biosensing