Research focuses on the development of semiconductor based fully integrated Lab-on-Chip platforms for detection of genetic markers in applications ranging from rapid diagnostics to on-the-spot genetic testing

Research DirectorProfessor Christofer Toumazou FRS

Infection, Cancer, Kidney disease and infertility, are examples of medical conditions where prevention, control, early detection and continuous monitoring have become the primary goals for the creation of a more evidence-based disease management model of healthcare. The fast growing information gained from molecular and clinical research on the identification and mapping of major genetic and epigenetic targets has provided insight on their role in susceptibility of disease and has led to a deeper understanding of their diagnostic, predictive and prognostic significance. Additionally, advances in diagnostic testing, genotyping, sequencing and the development of new technologies for Point-of-Care testing, are creating a paradigm-shift in modern medicine practices, ranging from the translation of technology innovations for emerging clinical applications towards the realization of a more affordable and stratified clinical model. Current methods for detection of genetic markers are mainly optical-based, are dependent on the use of fluorescent labels and of complex sample processing steps for isolation and discrimination of DNA sequences, therefore are difficult to scale. They are also mainly based on central laboratory facilities, with tests performed by skilled personnel and are of high cost. Given the needs for simplicity, low cost, speed, scalability and intelligence, genetic testing can now be simplified to lab-free, fast sample-to-result tests with the use of semiconductor technology, which allows for the integration of sensors, intelligent circuitry, signal processing and microfluidics, all in a single fullyintegrated scalable platform.

Our group has demonstrated that semiconductor technology can enable label-free, non-optical, real-time simultaneous amplification and detection of genetic targets using chemically sensitive transistors, also known as ISFETs (Ion-Sensitive Field-Effect Transistors), silicon chip-based chemical sensors traditionally utilised for measuring changes in ionic concentrations in solutions. Our group’s expertise of over a decade in design and fabrication of robust chemical sensor arrays combined with microelectronics in CMOS integrating analog/digital circuitry, has resulted in numerous Lab-on-Chip platforms developed. Specifically in the area of diagnostics and disease prevention, where the emergence of smart sensory systems is evident, the capability for these integrated platforms to perform intelligent sensing and actuation would improve significantly the speed for decision making at the point of need, delivering fast and on-the-spot results for detection of any target nucleic acid sequences in either DNA or RNA as well as nucleotide insertions.

This technology has been successfully commercialized through one of our spinout companies, DNA Electronics, to create next generation technology for on-chip sequencing and sample analysis. Applications in the Centre are ranging from fast genetic analysis of infectious targets (bacteria/ viruses) for rapid and controlled deployment of antibiotics and prevention of antimicrobial resistance – Infection Technology, to early screening of cancer markers and monitoring of progression targeting the personalisation of cancer treatment – Cancer Technology. Furthering the application of genetic technology in medicine, our research also focuses on the role of epigenetic markers and specifically the role of DNA methylation in prediction and monitoring of disease. DNA methylation is a widely applied epigenetic biomarker, a chemical tag that can modify the genetic function and regulatory mechanisms of gene expression. It has been extensively applied in the field of cancer with previous work at the Centre to have led in the development of an ISFET based pH-mediated Lab-on-Chip platform for detection of DNA methylation ratio in well-studied cancer markers.

The same technology is also applied in chronic kidney disease (CKD) management, a condition resulting from chronic kidney damage and prolonged renal dysfunction, often leading to renal replacement therapy. Focusing on methods for microRNA quantification and DNA methylation detection, we are developing a detection system that could aid developments in related epigenetic therapy for typically irreversible kidney damage, preventing the need for dialysis and renal transplantation.

The ISFET based technology is also being applied in a new field in the group, that of reproductive medicine and specifically of infertility, aiming for the development of a novel diagnostic sample-to-result test for detection of human male infertility acting as a prognostic tool for any Assisted Reproductive Technology (ART) laboratory, based on the analysis of DNA methylation marks in human sperm samples through the use of isothermal nucleic acid chemistries.

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Centre for Bio-Inspired Technology
Imperial College London
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E-mail: bioinspired@imperial.ac.uk