Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Biosensors based on the extended gate field-effect transistor (EG FET) differ from the traditional FET- based biosensors in terms of creating a spatial separation between the EG sensing element and the FET transducer. Thus, EG can be employed as a cost-effective and disposable unit, while the FET transducer is retained as a reusable component. These features make EG particularly attractive for multiplexed biosensing since an EG electrode array can be easily integrated within a single chip, and individual electrodes can be separately modified for the recognition of diverse analyte types. Although the use of EG FET-based platforms has been successfully demonstrated in advanced biosensing applications,¹˒² they still suffer from practical disadvantages including limited multiplexing, complex nanofabrication of FET transducers, and reliance on bulky specialized high-performance measurement instruments for readout of low current levels (~nA range), all substantially reducing their suitability for many applications in point-of-care (POC) diagnostics and monitoring. We present a custom-designed multiplexed standalone EG FET-based potentiometric biosensing platform relying on a commercial FET transducer, portable modular electronics, and innovative assay format for potentiometric response enhancement based on the conjugation of analyte antibodies (Abs) to gold nanoparticles (AuNPs). To achieve simplified signal readout, we employ an in-house fabricated common reference electrode for all sensing points and operate the FET in constant charge mode. Potential shifts at the EG surface during sensing are indirectly detected as voltage changes between the reference electrode and the FET source terminal. We demonstrate the sensing of antibody-antibody interactions on the immunoglobulin G system and realize the 5-fold amplification of the potentiometric response compared to the traditional label-free assay by introducing AuNP-based labeling of the target analyte. Using the described configuration of the EG FET-based biosensing platform, we can simultaneously obtain astonishingly low limits of detection (down to the aM range) and reach sufficient sensitivity for reliable readout at voltage levels of ~1 V using conventional low-cost electronic modules driven by a microcontroller. Our biosensing approach shows great promise for ultrasensitive and reliable POC measurements in the clinical setting as it already vastly overcomes the limit of detection of gold-standard enzyme-linked immunosorbent assays by several orders of magnitude and allows for robust measurement statistics with the incorporated reproducible multiplexing.

1. Kim, K.; Kim, M.-J.; Kim, D. W.; Kim, S. Y.; Park, S.; Park, C. B. Clinically Accurate Diagnosis of Alzheimer’s Disease via Multiplexed Sensing of Core Biomarkers in Human Plasma. Nat. Commun. 11, 119 (2020).
2. Park, S.; Kim, H.; Woo, K.; Kim, J.-M.; Jo, H.-J.; Jeong, Y.; Lee, K. H. SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor. Nano Lett. 22, 50–57 (2022).