DNA detection using just a USB microchip
Bioengineering the future of personalised medicine
In this article, we are presenting an overview of the research taking place at the Centre for Bio-inspired Technology (CBIT), whose director is the British-born Cypriot Engineer Prof Chris Toumazou from the Department of Electrical and Electronic Engineering at Imperial College London. He also holds the Winston Wong Chair in Biomedical Circuits at the same academic institution and he has founded two companies. One of them is called DNA Electronics, which was founded in 2013 as spin-out of Imperial College London. In 2014, he won the European Inventor Award by the European Patent Office for ‘Rapid DNA test on a USB stick’.
CBIT was formed from Bionics Research Group in December 2009 and it is housed within the Institute of Biomedical Engineering hosting a team of approximately 50 researchers.
As Cypriot Scientists and Engineers (CySE) we wanted to learn more about the research conducted at the centre, so we contacted Nicholas Miscourides, a PhD Candidate working at the centre while also supervised by Dr Pantelis Georgiou, regarding the work on DNA detection using a standard computer microchip. The original research was published in Nature Methods (http://dx.doi.org/10.1038/nmeth.2520) with work carried out by researchers at DNA Electronics and Imperial College London.
Explaining the essence of this research work to the general public
As Nicholas explains, DNAs are formed out of four bases (A, C, G and T) that spell out sequences that define our individual characteristics, ranging from hair colour to how probable it is to develop an inherited disease (predisposition). Scientists believe that the ability to identify and classify the precise order of bases within a DNA molecule, called DNA sequencing, has a profound impact on our understanding of the life sciences and medicine. DNA sequencing has been particularly important for fields including cancer, human genetics and infectious diseases.
Traditionally, DNA sequencing requires expensive and bulky equipment as well as resource-rich laboratories. The methods described in this study eliminates the need for all of this by showing how rapid DNA detection can be carried-out on a semiconductor-based system, designed with the same process flow used to manufacture all standard computer microchips. As a result, DNA obtained from saliva samples can now be sequenced on a fingernail-sized microchip in as short as 30 minutes, showing that fusing DNA chemistry and commercial microchip technology is possible.
Furthermore, Nicholas expects that the ability to rapidly detect DNA from an individual using a disposable platform paves the way for truly personalised medicine, where individuals are treated based on their unique genetic traits. These platforms can revolutionise healthcare by facilitating personalised drug therapy, detecting specific genetic mutations and used as point-of-care diagnostic devices.
The impact of the work in its own research field
In the field of bioelectronics, this study presents an integrated circuit (IC or microchip) capable of detecting and amplifying in real-time the pH variations observed when DNA polymerisation takes place. The microchip relies on integrated Ion-Sensitive Field-Effect Transistors (ISFETs) to detect the variations in pH and forms a full system-on-chip platform. Both PCR and LAMP amplification techniques have been successfully demonstrated on the chip as well as discriminating single nucleotide polymorphism (SNP) variations of the cytochrome P450 family from human saliva. According to Nicholas, this work eliminates the need for bulky, external apparatuses for SNP discrimination thus enabling the creation of portable and low-cost platforms for DNA analysis.
The importance in research fields other than bioelectronics
Finally, he explained to us that this work presents a pH-sensing semiconductor microchip capable of real-time detection and amplification of small amounts of nucleic acid. Using this technology, low-cost and disposable genetic sequencing platforms can be designed to provide rapid detection of specific sequences and single-nucleotide polymorphisms (SNPs). The microchip can be used to carry-out the two most popular DNA amplification techniques, namely PCR and LAMP, in a fraction of time than what is currently needed and can be a useful tool to molecular biologists and geneticists. Additionally, he anticipates that rapid DNA detection will be an irreplaceable tool towards the grand vision of personalised medicine in healthcare.
The team behind the publication
Prof Chris Toumazou is a Regius Professor of Engineering, Chair in Biomedical Circuit Design, Director of the Centre for Bio-Inspired Technology and Founder and Chief Scientist for the Institute of Biomedical Engineering at Imperial College. He is also Founder, Chairman or CEO of two successful Medical Device Companies (Toumaz Technology and DNA Electronics) and Chief Scientific Advisor to GENEU. He is distinguished for his innovative silicon technology and integrated circuit design for electronic device in the field of devices for medical diagnosis and therapy. Professor Toumazou is pre-eminent amongst the global community of contemporary medical engineers. In 1994, Toumazou was appointed the youngest Professor ever to be appointed at Imperial College, at the age of 33. In 2013 he became London’s First Regius Professor of Engineering conferred to Imperial College during the Queen’s Diamond Jubilee.
He is the recipient of the 2005 Institute of Electrical and Electronic Engineers (IEEE) CAS Education Award for pioneering contributions to biomedical circuits and systems. In 2006 he founded IEEE BioCAS. He received the UK Royal Academy of Engineering Silver Medal in 2007 for pioneering contributions to British industry and the UK Institute of Engineering Technology (IET) Premium best paper award and the IEEE CAS outstanding young author award. He was elected in 2006 to Academia Europea. In 2008 he was appointed to the Fellowship of the Royal Academy of Engineering and the Fellowship of the Royal Society, which is the highest honour in UK science. He was appointed a Fellow of Academy of Medical Sciences in 2013 and is now one of the few who is a Fellow of three premium societies.
Dr Pantelis Georgiou is a Senior Lecturer within the Department of Electrical & Electronic Engineering and is also the head of the Bio-inspired Metabolic Technology Laboratory in the Centre for Bio-Inspired Technology and part of the Medical Engineering Solutions in Osteoarthritis Centre of Excellence. His research includes bio-inspired circuits and systems, CMOS based lab-on-chip technologies and application of micro-electronic technology to create novel medical devices. He conducted pioneering work on the silicon beta cell and is now leading the project forward to the development of the first bio-inspired artificial pancreas for Type I diabetes.
He is a member of the IEEE and IET. He has been elected a member of the BioCAS and Sensory Systems Technical Committee of the IEEE Circuits and Systems Society and is the CAS representative on the IEEE sensors council.
DNA Electronics Ltd is a pioneer in next generation sequencing (NGS), dedicated to applying their proven molecular diagnostic technology to bring real, life-saving benefits to patients.
The following co-authors from the company were involved: Christofer Toumazou, Leila M Shepherd, Samuel C Reed, Ginny I Chen, Alpesh Patel, David M Garner, Chan-Ju A Wang, Chung-Pei Ou, Krishna Amin-Desai, Panteleimon Athanasiou, Hua Bai, Ines M Q Brizido, Benjamin Caldwell, Daniel Coomber-Alford, Karen S Jordan, John C Joyce, Maurizio La Mura, Daniel Morley, Sreekala Sathyavruthan, Sara Temelso, Risha E Thomas & Linglan Zhang.
More information regarding the work at the CBIT can be found at: http://www.imperial.ac.uk/bio-inspired-technology
We are grateful to PhD Candidate Nicholas Miscourides for providing us with the relevant information needed to write this article. We would like to wish him all the best in the future. Credits should also be given to “Centre for Bio-inspired Technology, EEE, Imperial College London” for material presented in this article.
