Electronic platform technology for in-vitro digital protein sensing

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

The primary outputs from the CDT will be cohorts of highly qualified, interdisciplinary postgraduates who are experts in a wide range of sensing activities. They will benefit from a world leading training experience that recognises sensor research as an academic discipline in its own right. The students will be taught in all aspects of Sensor Technologies, ranging from the physical and chemical principles of sensing, to sensor design, data capture and processing, all the way to applications and opportunities for commercialisation, with a strong focus in entrepreneurship, technology translation and responsible leadership. Students will learn in extensive team and cohort engaging activities, and have access to cutting-edge expertise and infrastructure. 90 academics from 15 different departments participate in the programme and more than 40 industrial partners are actively involved in delivering research and business leadership training, offering perspectives for impact and translation and opportunities for internships and secondments. End users associated with the CDT will benefit from the availability of outstanding, highly qualified and motivated PhD students, access to shared infrastructure, and a huge range of academic and industrial contacts.

Immediate beneficiaries of our CDT will be our core industrial consortium partners (MedImmune, Alphasense, Fluidic Analytics, ioLight, NokiaBell, Cambridge Display Technologies, Teraview, Zimmer and Peacock, Panaxium, Silicon Microgravity, etc., see various LoS) who incorporate our cross-leverage funding model into their corporate research strategies. Small companies and start-ups particularly benefit from the flexibility of the partnerships we can offer. We will engage through weekly industry seminars and monthly Sensor Cafés, where SME employees can interact directly with the CDT students and PIs, provide training in topical areas, and, in turn, gain themselves access to CDT infrastructure and training. Ideas can be rapidly tested through industrially focused miniprojects and promising leads developed into funded PhD programmes, for which leveraged funding is available through the CDT.

Government departments and large research initiatives are formally connected to the CDT, including the Department for the Environment, Food and Rural Affairs (DEFRA); the Cambridge Centre for Smart Infrastructure and Construction (CSIC); the Centre for Global Equality (CGE); the National Physics Laboratory (NPL); the British Antarctic Survey (BAS), who all push our CDT to generate impacts that are in the public interest and relevant for a healthy and sustainable future society. With their input, we will tackle projects on assisted living technologies for the ageing population, diagnostics of environmental toxins in the developing world, and sensor technologies that help replace the use of animals in research. Developing countries will benefit through our emphasis on open technologies / open innovation and our exploration of responsible, ethical, and transparent business models. In the UK, our CDT will engage directly with the public sector and national policy makers and regulators (DEFRA, and the National Health Service - NHS) and, with their input, students are trained on impact and technology translation, ethics, and regulatory frameworks.