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Point-of-care-ready nanoscale ISFET arrays for sub-picomolar detection of cytokines in cell cultures
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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.
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Most cited references50
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is a postdoctoral researcher and a lecturer at the Institute of Materials in Electrical Engineering 1 (IWE1) in the Faculty of Electrical Engineering and Information Technology, RWTH Aachen University. At the IWE1, he leads a research group focusing on micro- and nano-electronic sensors for biosensing and environmental sensing applications.
did his doctoral studies at the Max Planck Institute for Polymer Research in Mainz, Germany, and received his Dr. rer. nat. degree (2001) from the University of Mainz, Germany. After 1 year as Postdoctoral Researcher at the Frontier Research Program, RIKEN, Japan, he joined‚ in 2002‚ the Institute of Bio- and Nanosystems at the Forschungszentrum Jülich GmbH, Germany, as a group leader. From 2008 to 2017, he was Professor of Biomedical Instrumentation at the University of Applied Sciences Kaiserslautern, Germany. In 2018, he moved to the RWTH Aachen University on a Chair Professorship for Micro- and Nanosystems and he is Director of the Institute of Materials in Electrical Engineering 1. He is working at the interface between biosensing, biotechnology, cell biology, nanotechnology, electronics, and micro- and nanosystem technology.
did his doctoral studies at the Department of Nanoscale Science, Max Planck Institute for Solid State Research (MPI-FKF), Stuttgart. He is currently research group leader of the Nanomaterials and BioNanoInterfaces Group at the Institute for Materials in Electrical Engineering 1, RWTH Aachen University. The main interests of his research group are new materials integration, evolution of bio-nano interfaces for advanced sensor design and the role of such integrated materials and interfaces in emerging post-CMOS technologies.
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