One-dimensional electrical nanosensors, such as semiconductor nanowires, are particularly important due to their suitability for large-scale, high-density integration and interfacing to conventional electronic systems, hence are attractive for low cost portable sensing systems. Silicon nanowire field-effect biosensors have been reported extensively for the highly sensitive, label-free, and real time detection of biomolecular binding of DNA and proteins. The high detection sensitivity of silicon nanowire biosensors has been attributed to their large surface-to-volume ratio and the three-dimensional multigate structure; both contribute to the improved sensitivity compared to conventional planar devices. However, device and technology development have been limited to a small number of research laboratories typically relying on expensive nanolithography or specialized equipment and processes. We recently reported a new scalable silicon nanowire fabrication technology based on a combination of conventional microfabrication steps that does not require expensive nanolithography to form sub-30 nm feature sizes. The main advantage of our technology is that moderately dense sensor arrays, with precisely controlled dimensions and atomically smooth surfaces, are simultaneously fabricated with thick microscale electrical contact regions from a continuous layer of single crystal silicon using a novel size reduction method. Silicon nanowire sensor arrays with lateral dimensions down to 5 nm and lengths up to 100 microns can be fabricated with high wafer-level yields. Our simple fabrication technology can be manufactured in any conventional microfabrication cleanroom.

The unique property of our silicon nanowires is that all of the sensing surfaces have near-atomically smooth (111) surface orientation that are ideally suited for alkylation, which is the direct covalent attachment of organic molecules to the silicon surface using the carbon-silicon (C-Si) bond. The selective functionalization of C-Si monolayers on our all-(111) surface silicon nanowires offers several advantages for biosensing compared to conventional silicon nanowire geometries and silicon dioxide passivation layers, which includes: receptor molecule conjugation exclusively on the nanowire surface thus eliminating receptors in the non-sensor regions, improved detection sensitivity, Si-(111) surfaces support the highest-quality C-Si monolayers and can have low interface trap densities for H-Si and C-Si interfaces. We have recently reported improved nanowire sensor performance due to reduced electronic interfacial states and the elimination of fixed-oxide charges, which are problematic for nanoscale silicon devices with oxidized surfaces.

More recently we have developed a small sample volume microfluidic analytical microsystem with integrated nanowire biosensors that are being used to detect the hybridization of certain nucleic acid sequences using an all-electrical readout. We have developed a differential measurement configuration that provides the capability to cancel environmental sources of noise and interference yielding measurements that better represent hybridization events compared to single sensor configurations.

Although significant progress has been made in demonstrating the detection of molecular binding to modified silicon nanowire surfaces, few quantitative descriptions of the physical and chemical mechanisms during the binding and detection process have been reported. In principle, silicon nanowire sensors perform the same measurement as conventional planar ion-sensitive field-effect sensors, first reported over forty years ago, since both device configurations measure surface potential changes in the form of device conductance changes; however, silicon nanowires have a multigate device structure that can provide increased sensitivity. We have recently reported a comprehensive analytical model of the silicon nanowire sensor, which is based on a two-dimensional physical electronics model of the device conductance as a function of the dielectric surface potential, and the combination of the Gouy-Chapman-Stern and Site-Binding models to describe the electrical double-layer at the dielectric surface and the surface reactivity of the potential determining ions in solution with the dielectric surface groups, respectively. Measured pH responses from titrations of different dielectric oxide layers resulted in extremely large sensitivities near the theoretical Nernstian limit. We are currently developing a combined electrical, electrochemical and hydrodynamic flow model to quantitatively describe biomolecular hybridization to nanowire arrays in both static and dynamic sample flow conditions.