Semiconductor Electronic Label-Free Assay (SELFA) with Novel Nanowire Field-Effect Transistor Biosensors
Biomolecular assays are biochemical tests used for quantitative measurement of target biomolecular analytes from specimens. This is usually achieved with labelling techniques where target biomolecules were conjugated with labels for signal readout. Label-free assay provides an alternative route to detect target biomolecules without secondary label conjugation. The technique enables high-throughput and real-time measurements of analyte samples which is of primary significance in many biological applications (e.g. drug screening, point-of-care diagnosis).
One promising candidate for real-time label-free biomolecular detection is using field-effect transistor (FET) biosensors. A FET without a gate electrode is designed to detect immunological antigen-antibody binding reactions. Charged target biomolecules are bound with specificity onto biological receptors anchored on the oxide dielectric surface. The induced electric field mediated by oxide dielectric is directly translated into current change without any labeling. Nanowire FET (nwFET) biosensors have been demonstrated to have exceptional biomolecule sensitivity with lower limit of detection (LLOD) down to sub-picomolar range. However, the inherently low output-signal levels are impractical for their use outside of the research lab. In addition, variability issues originated from device fabrication, system integration and during sensing experiment prohibit reliable quantitation of target biomolecules in the scenarios of interest. As a result, label-free biomolecular assays have not been meaningfully adopted and impacted the biomedical and pharmaceutical industry even after decades of intense research.
To boost output signal level of FET sensors, we previously proposed a novel T-shape nwFET (T-nwFET) structure by itself as an integrated sensor-amplifier to amplify output signals at close proximity. However, the concept of T-nwFET as a biosensor has not been implemented in biomolecular detections. In this work, we first understood and improved the sensitivity of T-nwFET biosensors using a signal-to-noise ratio metric, and validated the performance in practical settings. We also investigated theoretical and practical approaches to improve selectivity, which is crucial for accurate quantitation of biomolecules. We proposed a novel per-sensor based calibration scheme to mitigate device-to-device and test-to-test variability. We then developed the T-nwFET into a holistic biomolecular assay platform, SELFA, and its performance was evaluated by implementations in predictive toxicology and clinical studies.