Specific, label-free and real-time sensing of glial fibrillary acidic protein (GFAP) in 0.5 μL drop of whole blood with a field-effect biosensor

Accurate and timely diagnosis of brain disorders is a major unmet clinical need. Glial fibrillary acidic protein (GFAP) is a promising biomarker for detecting brain pathology. The study demonstrates specific and label-free detection of GFAP in 0.5 μL drops of whole blood with the Meta-Nano-Channel (MNC) field-effect (FET) biosensor. Importantly, the detection is performed directly in unprocessed as-is whole blood and no pre-measurement washing steps are performed. The suggested method may therefore be suitable for point-of-care, bedside or homecare settings. The MNC biosensor is specifically designed to address the challenge of solution potential in FET-based biosensors, and the challenge of localized gating induced by molecular interactions. The surface bound recognition layer is composed of anti-GFAP antibodies. The study reports limit-of-detection of 10 fg/mL, a dynamic range of 11 orders of magnitude, and with excellent linearity and sensitivity. The MNC biosensor is fabricated using a standard complementary metal-oxide-semiconductor (CMOS) process, leveraging the inherent semiconductor-grade stability, robustness, and established infrastructure required for scalable, low-cost mass production. Furthermore, CMOS-driven miniaturization enables unparalleled multiplexing capabilities within ultra-small sample volumes, seamlessly integrated with on-chip circuitry for enhanced signal processing. The study is supported by three-dimensional numerical device calculations, surface characterization of biofunctionalizations, and control measurements to validate specificity and to quantify the extent of non-specific signals.