Nanobiosensors based on silicon nanowire field effect transistors offer advantages of low cost, label-free detection, and potential for massive parallelization. As a result, these sensors have often been suggested as an attractive option for applications in point-of-care (POC) medical diagnostics. Unfortunately, a number of performance issues, such as gate leakage and current instability due to fluid contact, have prevented widespread adoption of the technology for routine use. High-k dielectrics, such as hafnium oxide (HfO2), have the known ability to address these challenges by passivating the exposed surfaces against destabilizing concerns of ion transport. With these fundamental stability issues addressed, a promising target for POC diagnostics and SiNWFETs has been small oligonucleotides, more specifically, microRNA (miRNA). MicroRNAs are small RNA oligonucleotides which bind to mRNAs, causing translational repression of proteins, gene silencing, and expressions are typically altered in several forms of cancer. In this paper, we describe a process for fabricating stable HfO2 dielectric-based silicon nanowires for biosensing applications. Here we demonstrate sensing of single-stranded DNA analogues to their microRNA cousins using miR-10b and miR-21 as templates, both known to be upregulated in breast cancer. We characterize the effect of surface functionalization on device performance using the miR-10b DNA analogue as the target sequence and different molecular weight poly-l-lysine as the functionalization layer. By optimizing the surface functionalization and fabrication protocol, we were able to achieve <100 fM detection levels of the miR-10b DNA analogue, with a theoretical limit of detection of 1 fM. Moreover, the noncomplementary DNA target strand, based on miR-21, showed very little response, indicating a highly sensitive and highly selective biosensing platform.

Analysis of cell-to-cell variation can further the understanding of intracellular processes and the role of individual cell function within a larger cell population. The ability to precisely lyse single cells can be used to release cellular components to resolve cellular heterogeneity that might be obscured when whole populations are examined. We report a method to position and lyse individual cells on silicon nanowire and nanoribbon biological field effect transistors. In this study, HT-29 cancer cells were positioned on top of transistors by manipulating magnetic beads using external magnetic fields. Ultra-rapid cell lysis was subsequently performed by applying 600–900 mVpp at 10 MHz for as little as 2 ms across the transistor channel and the bulk substrate. We show that the fringing electric field at the device surface disrupts the cell membrane, leading to lysis from irreversible electroporation. This methodology allows rapid and simple single cell lysis and analysis with potential applications in medical diagnostics, proteome analysis and developmental biology studies.

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and spacemultiplex reactions on a single integrated circuit. Our method positions droplets on an array of individual silicon microwave heaters on chip to precisely control the temperature of droplets-in-air, allowing us to perform biochemical reactions, including DNA melting and detection of single base mismatches. We also demonstrate that ssDNA probe molecules can be placed on heaters in solution, dried, and then rehydrated by ssDNA target molecules in droplets for hybridization and detection. This platform enables many applications in droplets including hybridization of low copy number DNA molecules, lysing of single cells, interrogation of ligand-receptor interactions, and rapid temperature cycling for amplification of DNA molecules.nanowire | on-chip heating | evaporation