Understanding silicon nanowire field-effect transistors for biochemical sensing

There is an ever increasing need for inexpensive chemical and biochemical sensors for medical diagnostics, drug screening as well as environmental monitoring. State-of-the-art methods require either expensive or time-consuming labeling and are not suitable for large-scale integration. Advances in biotechnology, microfluidics and micro- and nanotechnology have led to various approaches of micro-analytical systems. In particular systems based on silicon field-effect transistors (Si FETs) have a great potential for biochemical sensing due to their potentially cheap fabrication in a CMOS-compatible process and simple electronic readout. Thereby, the gate oxide material of the FET is in direct contact with the analyte solution, leading to the ion-sensitive field-effect transistor (ISFET). The detection principle of ISFETs is based on the change of the transistor current caused by charges adsorbed at the sensor surface. It has been suggested recently that by downscaling the devices to the nanoscale, increased sensitivities can be expected. In particular, ISFETs based on silicon nanowires (Si NWs) are therefore intensively studied.
Despite the achievements obtained in the last years, commercial products based on ISFETs are using the device as a pH sensor only. The reason for this development lies in the incomplete understanding of the complex interface between the electrolyte and the solid-state sensor as well as the difficulties related to the design of surfaces which selectively bind a targeted analyte.
In this PhD project, we address these points by studying arrays of ISFETs based on silicon nanowires (Si NWs) fabricated by a top-down lithography approach and investigate their potential as an integrable sensing platform. First we characterize the devices and analyze their pH response. We find a response to pH at the fundamental (Nernst) limit, due to the special properties of the gate oxide materials used for the devices. We further demonstrate that the sensor signal is not affected by the width of the NWs, i.e. enhanced sensing is not observed for nanoscale devices. However, we reveal that the low-frequency noise of the devices decreases for increasing NW width, an aspect which has to be considered when ultimate integration is targeted. For the specific detection of ionic species, the sensor surface needs to be modified with functional groups, which selectively bind the target analyte. Unfortunately, the high pH sensitivity of oxide surfaces greatly complicates the detection of any target analyte other than pH. To circumvent this problem, we propose the use of an additional coating with a material with minimal sensitivity to pH. We find that gold is a promising candidate easily applied for this purpose. The gold layer allows immobilizing ligands via the well-established thiol-based chemistry thereby providing a platform suitable for surface functionalization. Using the additional gold layer, we demonstrate the successful detection of different ions such as sodium, calcium and fluoride ions with a differential setup having both functionalized and control NWs on the same sample. Furthermore, we find that the residual pH response of the gold layer still influences the detection of the targeted species by affecting the effective binding constant via the surface potential. To take this effect into account, an extended site binding model is proposed. Finally, we show that SiNWs have the potential to even monitor binding kinetics of ligand-protein systems and we obtain concentration dependent signals for a clinically relevant protein.