Silicon Nanostructures for Biosensing: From Field-Effect Transistors to Photonic Resonators, and the Long Road to the Clinic
Silicon has a unique combination of properties that makes it one of the best material choices for biosensor platforms: it is inexpensive, its native oxide is atomically smooth, its fabrication processes are CMOS-compatible and have been refined for more than three decades, and it can support many transduction mechanisms in biosensor design. Over the past thirty years, researchers and engineers have used silicon nanostructures to produce ion-sensitive transistors, ultrasensitive nanowire field-effect biosensors, refractive-index-based porous silicon films, microring photonic resonators, suspended cantilevers, luminescent quantum dots, and solid-state nanopores. These device families have demonstrated successful sensing capabilities at the single-molecule, single-virus, or sub-femtomolar level under laboratory conditions; however, they have rarely been widely deployed in clinical assays. This gap is mainly caused by several well-characterized bottlenecks: for nanowire BioFETs, device variability and Debye screening; for porous silicon, fouling, pore wetting, and surface stability; for silicon photonics, thermal drift, spectral readout, and packaging; and across all platforms, calibration, reproducibility, and validation in real biofluids. In this review, we trace the development of silicon biosensors from their early stages to their current state, search and organize the literature focusing on the three most mature platforms and a set of emerging directions, summarize and compare the performance and bottlenecks of different platforms, and argue that progress over the next decade will come primarily from integrated readout, interface engineering, and systematic benchmarking rather than from the discovery of new silicon nanostructures.