Electronic platform technology for in-vitro digital protein sensing

Lead Research Organisation: University of Cambridge
Department Name: Engineering

Abstract

Biosensors provide highly important benefits for society in vital fields such as health care, security, and life sciences. Real-time, in-vitro sensing is highly important for system biology studies, drug discovery, genetic screening and detection, disease biomarkers and personalized and precision medicine. For this purpose, different optical-based methods are currently used as sensing devices. However, the cost and complexity of the optical systems and the need for bulky optical components are significant limitations of most of the optical-based sensing devices. To avoid the use of optical-based methods, electrical detection of chemical and biological species has been introduced a long time ago and in the past decade nanomaterials such as graphene showed promising materials for different bio-applications. The current state-of-art graphene-based sensors such as Graphene Field Effect Transistor (GFET) is DC read-out of graphene conductivity changes upon protein binding. The DC operation of the GFET suffers from low sensitivity at high ionic strength solutions such as physiological salt environment (eg. blood) due to different reasons including Debye screening effects. AC operation of the GFET in a relatively high frequency will be studied in this project to overcome the drawbacks of the DC operation and to improve the sensitivity of the sensor.

All electronic biosensors to date are analogue in the read-out. The ultimate goal of the project is to introduce truly digital electronic biosensor arrays based on GFET that work based on signal/no signal readout. The vision is to introduce multiplexed digital electronic single-molecule counting, which is faster, more scalable, cheaper and via multi-mode sensors more information-dense. Therefore, the system could be used in the quantitative measurement of binding kinetics and affinities between two biomolecules such as DNA, RNA, proteins and ligands which is a central experiment in molecular biology. Furthermore, it could be used for diagnosing purposes providing a rapid, portable and easy-to-use platform that reduce diagnosis time and mitigate treatment delay. This point of care device could significantly help to reach the personalized diagnostics which could make a big revolution in the healthcare domain.

This ambitious goal cannot be reached using the current GFET biosensor, the low sensitivity of the current system makes it impossible to detect a single molecule in the analyte. Therefore, to reach the digital electronic biosensor arrays, several objectives should be reached using the following methods:
- Improve SNR of analogue 2DLM based field effect devices by characterizing all its aspects. This characterization will be done by developing a simple testing platform, consisting of the GFET sensor, a readout circuitry and microfluidic system to deliver the analyte onto the top of the sensor. Furthermore, the sensitivity of the sensor will be improved by investigating different bio-interface functionalization. Several studies showed that incorporating a porous and biomolecule permeable polymer layer on the FET sensor has improved the sensitivity of the sensor beyond the Debye length at high ionic strength solutions.
- Develop a well characterised AC-GFET biosensor by exploring operating the GFET in ambipolar mode around its neutrality point and AC, hetero-dyne, and lock-in approaches to improve signal-to-noise ratios. The objective of this step is to have a well-defined and highly sensitive GFET biosensor which is working in physiological salt environments such as blood serum.
- Develop an electronic digital biosensor array that works based on signal/no signal sensor readout embedded into micro/nanofluidics to enable preparative and analytical operations on very small analyte volumes at high through-put.

Research areas:
- Sensors and instrumentation
- Graphene and carbon nanotechnology
- Chemical biology and biological chemistry

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 01/10/2019 31/03/2028
2262314 Studentship EP/S023046/1 01/10/2019 30/09/2023 Abdul Wadood Tadbier