For over 30 years, field effect transistors (FETs) have been used as sensors. In the past, Ion-Sensitive-FETs (ISFET) were based on bulk Metal-Oxide-Semiconductor (MOS) FET designs and the device was gated by biasing the electrolyte through the reference electrode. Recently, functionalized silicon nanowires and silicon-on-insulator (SOI) devices have been introduced for their greater sensitivity in detecting proteins, DNA and even single viruses. This work focuses on a variety of issues that impact the properties of SOI FET nanoribbon sensors.  The ability to
stabilize and control the attachment of cells on the sensor surface is critical. Therefore, the reliability and reproducibility of self-assembled-monolayers such as aminosilanes will be presented. Biological solutions consist of protein or DNA in an electrolytic solution containing salt ions. Some of these ions, such as Na, have long been known to cause instabilities in MOS devices. The effect of mobile ions on SOI-based sensors will be presented. The SOI-based sensor structure results in the electrolyte voltage being capacitively coupled to the back gate voltage. The impact of this coupling on sensor response will be described. Physically realistic SPICE models were developed and illustrate the response of both pH and biosensors with a multi-gate model. The model demonstrates good agreement to experimental data including the impact of Debye screening and site binding charge.