Point-of-care-ready nanoscale ISFET arrays for sub-picomolar detection of cytokines in cell cultures
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Point-of-care-ready nanoscale ISFET arrays for sub-picomolar detection of cytokines in cell cultures Dipti Rani 1 & Yogesh Singh 2 & Madhuri Salker 3 & Xuan Thang Vu 1,4 & Sven Ingebrandt 1,4 & Vivek Pachauri 1,4 Received: 24 April 2020 / Revised: 21 June 2020 / Accepted: 14 July 2020 # The Author(s) 2020
Abstract Rapid and frequent screening of cytokines as immunomodulation agents is necessary for precise interventions in severe pathophysiological conditions. In addition to high-sensitivity detection of such analytes in complex biological fluids such as blood, saliva, and cell culture medium samples, it is also crucial to work out miniaturized bioanalytical platforms with potential for high-density integration enabling screening of multiple analytes. In this work, we show a compact, point-of-care-ready bioanalytical platform for screening of cytokines such as interleukin-4 (IL-4) and interleukin-2 (IL-2) based on one-dimensional ion-sensitive field-effect transistors arrays (nanoISFETs) of silicon fabricated at wafer-scale via nanoimprint lithography. The nanoISFETs biofunctionalized with receptor proteins alpha IL-4 and alpha IL-2 were deployed for screening cytokine secretion in mouse T helper cell differentiation culture media, respectively. Our nanoISFETs showed robust sensor signals for specific molecular binding and can be readily deployed for real-time screening of cytokines. Quantitative analyses of the nanoISFET-based bioanalytical platform was carried out for IL-4 concentrations ranging from 25 fg/mL (1.92 fM) to 2.5 μg/mL (192 nM), showing a limit of detection down to 3–5 fM, which was found to be in agreement with ELISA results in determining IL-4 concentrations directly in complex cell culture media. Keywords Ion-sensitive field-effect transistors . Silicon nanowires . Immunosensor . Cytokines . Label-free
Introduction Cytokines are secreted by immune cells such as lymphocytes (T cells) and epithelial cells, as low molecular weight proteins which are responsible for management of various host defense Published in the topical collection ABC Highlights: authored by Rising Stars and Top Experts Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02820-4) contains supplementary material, which is available to authorized users. * Vivek Pachauri [email protected] 1
Department of Computer Sciences and Microsystem Technology, University of Applied Sciences Kaiserslautern, Amerikastrasse 1, 66482 Zweibruecken, Germany
2
Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University Tuebingen, Calwerstraße 7, 72076 Tübingen, Germany
3
Women’s Hospital, Eberhard-Karls University Tuebingen, Calwerstraße 7/6, 72076 Tübingen, Germany
4
Institute of Materials in Electrical Engineering 1 (IWE1), RWTH Aachen University, Sommerfeldstrasse 24, 52074 Aachen, Germany
mechanisms. In response to an infection, specialized T cells change their function and provide biomolecular triggers to the immune system by initiatin
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