Reassessing the challenge of Debye length in field-effect biosensors

Biological field-effect transistor (bioFET) holds a great promise for future point-of-care and homecare medical diagnostics. Still, the unmediated detection of biological events in unprocessed physiological solutions is a great challenge due to high ionic concentrations with Debye length < 1 nm, rendering bioFET insensitive to electrostatic events beyond Debye distance away from the sensing area. This observation entirely removes the possibility of antibody-based recognition layers due to the massive dimension of antibodies, and triggered a vivid pursue for short receptors in order bring the interaction closer to the sensing area. On the other hand, recent reports do demonstrate that adsorbed antibodies are strongly tiled towards the surface, suggesting that binding events occur at a much greater proximity to the sensing area as previously suggested. Herein, the Meta-Nano-Channel (MNC) bioFET is demonstrated for specific, label-free, quantitative and real-time sensing of C-reactive protein (CRP), an important biomarker of inflammation and tissue damage, in unprocessed 0.5 μl blood and sweat samples with Debye lengths of 0.7 nm and 2.3 nm, respectively. The recognition layer is composed of anti-CRP antibodies. Limit-of-detection of 100 fg/ml and 10 fg/ml are recorded for blood and sweat samples, respectively. A dynamic range of 8 orders of magnitude and with excellent sensitivity and linearity are extracted for both blood and sweat. Hence, high-end sensing in physiological samples is possible with bioFETs provided these are specifically designed to address challenges associated with molecular sensing. These challenges and solutions are discussed in the study.