Research DirectorProfessor Christofer Toumazou FRS

We are living in an era that has experienced significant technological revolutions as well as advances in medicine and health management, improving our quality of life, giving us the opportunity to be the protagonists of a trend in personalised medicine. Significant advances in the field of genetic technology have been made, with the development of semiconductor based platforms for point-of-need diagnostics, on-the-spot genetic testing and next-generation DNA sequencing to provide lab-free, fast, robust, easy-to-use and cost-effective solutions for healthcare. This realisation has been enabled with the use of CMOS technology, which brings with it the capability of integration of millions of sensors per microchip, enabled by the relentless scaling according to Moore’s law.

CMOS based detection systems are expected to revolutionise medical practice, with multiple areas benefiting from these, from genetic analysis of infectious agents and bacterial genome sequencing to early screening of cancer markers and monitoring of chronic disease progression. In addition to genetic changes, epigenetic events play a significant role in multiple stages of disease development. Epigenetic profiles of genes can be used to distinguish diseased from normal cells, and are a powerful tool for risk markers used in early detection strategies.

Our research at the Centre for Bio-Inspired Technology involves the development of ‘lab-on-chip’ platforms for detection of genetic and epigenetic biomarkers, by integrating CMOS based ISFET sensors with application-specific biochemical assays. Emphasis is given in the areas of genotyping, genetic/epigenetic detection and monitoring of cancer as well as epigenetic monitoring of chronic kidney disease.

Genetic testing has been conventionally based on complex chemical, lab-based methods to detect DNA sequences. With the use of standard CMOS microchip technology, this can be simplified to a lab-free, sample-to-result answer, a YES or NO output as a result of a ‘match’ or ‘mismatch’ of DNA base pairs, translated into an ON or OFF state of a chemically sensitive transistor. Research in the Centre led to the development of the Genalysis® technology platform, a low cost microchip based platform built into a USB-sized device, capable of delivering fast and accurate on-the-spot tests for detection of any target nucleic acid sequence in either DNA or RNA as well as nucleotide insertions. Disposable ‘lab-on-chip’ cartridges housing biochemical reagents, advanced microfluidics and low-power silicon biosensors are key to this novel technology, with each cartridge to be customised to a variety of applications and markets. Built on the reliability, scalability and processing power of silicon microchip technology, this platform technology is mass-producible and highly portable. The commercialisation of this technology is being undertaken by DNA Electronics Ltd., a spinout company from the Centre.

Research in genetic technology continues in the Centre with a specific focus on:

Epigenetic testing and monitoring of biomarkers involved in the initiation and progression of tumour development could provide valuable information in the clinical monitoring of cancer and the assessment of treatment efficacy. The role of DNA methylation in several stages of tumour development has shown great potential in detection, diagnosis, prognosis and monitoring of disease, through disruptions in gene expression leading to aberrant gene inactivation. We have developed a semiconductor based platform with integrated chemical sensors, able to detect DNA methylation based biomarkers in real-time, avoiding the use of fluorescent dyes or labels. This will be used in cancer risk identification and early diagnosis by measuring simultaneously multiple epigenetic targets on a single microchip.

Epigenetics also plays an important role during the progression of chronic kidney disease (CKD), a condition resulting from chronic kidney damage and prolonged renal dysfunction, often leading to renal replacement therapy. We are applying the same technology to chronic kidney disease monitoring using DNA methylation based biomarkers. The implementation of an efficient detection system aids developments in related epigenetic therapy for typically irreversible kidney damage, preventing the need for dialysis and renal transplantation.

Semiconductor based DNA sequencing has revolutionised the cost of sequencing of the human genome making it more affordable and therefore accessible for healthcare applications where rapid diagnostics is strongly needed for the right treatment to be provided at the right time. This is possible due to pH based DNA detection using Ion-sensitive Field Effect Transistors (patented by our group), which are implemented in CMOS and therefore scale according to Moore’s law. This research focuses on creating CMOS based systems with local intelligence, which can efficiently sequence the human genome for a variety of diseases including sepsis, cancer and diabetes.