Linear ISFET arrays and optimisation methods for DNA detection

Abstract

In the early 1970s, at a time when Moore's law was getting up to speed, Piet Bergveld initially described and subsequently pioneered the use of silicon technology in an unconventional way. By combining the field effect present in insulated gate devices and the interfacial double layer formed at the membrane of a glass electrode, he showed that the operation of a MOSFET can be modulated by the ion activity in an aqueous solution. Such a device, aptly called an Ion-Sensitive Field-Effect Transistor, is able to provide chemical inputs to electronic circuits; a concept which has experienced vast developments and a wide range of application to-date. In this context, this thesis largely revolves around the utilization of ISFETs in a practical setting. This begins by exploring readout methods to facilitate linear pH-to-output transduction, achieved by operation in current-mode and biasing the device in the velocity saturation regime. Subsequently, the first ISFET array biased in velocity saturation is shown which leverages on current-mode to demonstrate ion imaging in a scalable, simple and area-efficient topology. This implementation, benefits from short-channel effects in a 0.35um CMOS process, to demonstrate a large linear range of operation that increases the robustness against offsets across the array. In addition, to further reduce mismatch across pixels, a programmable gate has been implemented in-pixel in a scalable way. The capacitor facilitating this operation is obtained as the parasitic capacitance across two interleaved metal structures located inside the pixel stack and can be used to fine tune mismatch. This approach has been adopted in a second array shown here for ion imaging which employs current-mode operation and demonstrates integrated compensation. Thirdly, a linear voltage-mode array has been designed which is loosely based on the widely-used source follower topology. Apart from being used to compare against the performance of the current-mode implementations, the combination of these designs has facilitated the derivation of algorithms and methods used to obtained standard metrics that can be used for the benchmarking of ISFET arrays. The second part of this thesis, focuses on techniques to improve the performance at both a sensor and array level. An investigation into the electrolyte-insulator interface revealed that the two major non-idealities, namely trapped charge and drift, are correlated therefore charge modulation techniques were shown to reduce drift. Additionally, a calibration algorithm is proposed, based on iterative gradient descent, that reduces mismatch due to trapped charge in one iteration step. Lastly, ISFET arrays are demonstrated for the detection of DNA amplification and the diagnosis of infectious diseases. The protocol and methods for improving the robustness of such as platform for monitoring DNA reactions are shown with significant potential towards Point-of-Care diagnostics.Open Acces