Using funding from a CRUK–EPSRC Multidisciplinary Project Award, a team of researchers from Imperial and the University of Leicester have pooled their expertise to develop a ‘lab on a chip’ for the early detection and therapeutic monitoring of breast cancer. Cancer specialist Charles Coombes, and Electrical Engineers Chris Toumazou and Melpomeni (Melina) Kalofonou, tell us how the project came about and discuss the potential of this disruptive technology.
Charles Coombes (CC): So this is the problem ... breast cancer comes back in 20-30% of cases, and if it’s not detected until you can see metastases on scans, it’s very likely to be fatal. We have been looking for many years now at ways of detecting recurrence far earlier. Back in 2011 and 2012, we published two papers showing that if you look in the blood—so called liquid biopsy—you can pick up signs of circulating tumour DNA (ctDNA) from early, hidden metastases, and furthermore, that the presence of ctDNA is a good predictor for which patient will relapse.
The ctDNA in the blood contains mutations that are typical of cancer, and there are expensive, complicated ways of looking at them. What we wanted was to develop a technology that was fast, cheap, and easy enough to use that it could be done in a GP surgery. A potential cancer diagnosis is terrifying, and I just felt if I had cancer I would want a blood test and I’d want the answer in half an hour. And that’s when I found Chris and Melina.
Chris Toumazou (CT): My background is in microchips, but about 15 years ago I established a group of scientists who, instead of putting logic gates on a microchip, could use DNA primers to get on/off signals, depending on whether the primer is bound to its complementary DNA strand. The technique was known as QPCR and enabled genome detection on a far smaller, cheaper scale; parenthetically, it went on to become the basis for a next-generation sequencing method called semiconductor sequencing. With QPCR right now, we can use saliva swabs or a few millilitres of blood to detect all sorts of things—HIV, pathogens, metabolic changes—and when Charles came to me, we knew that using our technology to look at ctDNA in blood samples was an obvious fit.
Melina Kalofonou (MK): The project is to develop a microchip-based liquid biopsy test that has the potential to detect tumour specific genetic markers, and can be repeated throughout the course of treatment to monitor progression of disease, as well as look for early recurrence. In three years we’ll be able to detect panels of breast cancer mutations using thousands of chemical sensors integrated on a small disposable microchip. And it’s important to say that we wouldn’t be able to apply our technology in developing a quick, sample-to-result test for breast cancer if the cancer community hadn’t conducted years of clinical and translational research, identifying and clinically validating circulating tumour DNA markers that now allow targeted monitoring and stratification of breast cancer patients.
CC: This is pretty disruptive technology. One of the potentials for use is in medical care in low and middle income countries (LMICs)—it could result in their taking a short cut to developing a national cancer service at far lower cost than we have. There’s little or no cancer screening in many LMICs, so people present with advanced inoperable cancer. If there were a simple and cheap blood or saliva test to detect cancer early, and you have the potential to resect tumours early enough for surgery alone to be curative.
CT: Billions of dollars have been spent in the microchip industry. We’re just translating that to a problem that it’s never been applied to before.
CC: As medics, we have no idea what these engineers are capable of! Every meeting that I have with Chris and Melina, I’m continually being educated. I have a different mindset to them, and it’s very difficult to cross into a different discipline—it’s like learning a new language, and it can take a long time.
MK: We are unique in that our research combines biology and electronics, all of which happens in multidisciplinary labs located on the same floor within our Centre for Bio-Inspired Technology. We see ourselves as problem solvers, but also as problem setters—sometimes we invent new technologies and then realise these can be used to solve new emerging challenges! For example, Chris and his group invented the technology for QPCR and semiconductor sequencing before next-generation sequencing was introduced as a detection method—it was real blue skies thinking. As engineers, we get the satisfaction of creating innovative technology, as well as finding practical applications.
CT: What the biologists are learning from the engineers is the What If? A biologist is very focussed on doing lots of experiments on one thing, whereas the whole of engineering is about systems, with the luxury of being able to think out of the box. The more open you can be to ideas, the better you are. It’s really tough for some of the biologists – this idea that you can just try this and that; that you don’t have to work on one problem. However, things are now changing: with biology taught on engineering degrees and engineering taught on biology degrees, we are entering an exciting new era of interdisciplinarity and translation.
Engineering is an interesting blend of creativity and sound business sense: translation into commercial value is something engineers are very comfortable with. We get excited when clinicians come to us with an idea for a gadget, but whether it’s commercially viable is a completely different story. We can work with the clinician for the sake of research but whether we can market what we have is different.
CC: Its great that CRUK have awarded us this multidisciplinary award, as this area of research is very hot at present, and the space is full of competitors. But this is a different enough approach that I believe we really have a chance to produce an instrument with huge potential for reducing the burden of cancer.