Biochips separate cancer cells from blood cells

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Published: 12 Aug 2014
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Prof Lim Chwee Teck - National University of Singapore, Singapore

Prof Lim Chwee Teck discusses his work trying to make biochips which are able to diagnose cancer via a liquid biopsy (blood test). By combining mechanics and biology, it is hoped that the chip could separate cancer cells from blood cells. The procedure would be less invasive than a tumour biopsy and could indicate a person's risk of relapse, alerting to the need for further tests and treatment.

 

We are interested in developing microfluidic biochips that are capable of detecting and diagnosing cancer. So the way it works is this microfluidic biochip actually comprises a unique arrangement of microfluidic channels where if we route blood through this chip we are able to actually separate the cancer cells from the blood cells of cancer patients.

How do you differentiate cancer cells form normal cells?

Basically when a person contracts cancer, if the cancer becomes malignant the cancer cells are capable of spreading from a primary tumour to another part of the body. When these cancer cells spread they are able to spread through the bloodstream. So what we are trying to do is to be able to take blood from the patients and then route it through this microfluidic chip to separate the cancer cells from the blood of the cancer patient. The way it works is this, if there are cancer cells in blood typically the cancer cells are much larger or stiffer than the blood cells so we specially make an arrangement on the microfluidic chip such that when the blood is moving through these microfluidic channels the larger and stiffer cancer cells are able to separate from the smaller and more deformable blood cells. That’s how we are able to separate the cancer cells from the blood cells.

Is this technique on the market?

Currently we actually have already commercialised this technology through a university spin-off company called Clearbridge Biomedics. Actually we are undergoing tests in various cancer centres and hospitals in the US, UK and Japan as well as Korea and soon in China.

What will be the future developments in the field?

If we are able to detect cancer cells from the blood of patients this is what we call a liquid biopsy and is actually a much less painful and less invasive way of collecting cancer cells from patients instead of doing it through tumour biopsies which is, of course, much more painful, more invasive, you cannot do it frequently. So it has many uses, for example one potential application is in terms of early cancer detection. If we are able to detect CTCs even before the tumour is detectable then that’s one way we can better detect cancer from patients at a very early stage. The next is from just counting the number of CTCs and research has shown that the number of CTCs do correlate with cancer stage. So if you, for example, collect a small number, less than ten, say, per ml of blood compared to, say, hundreds per ml of blood, we are able to determine whether patients are at the early or late stage of cancer.

I think that the third is in terms of providing a way of monitoring cancer treatment. So again, if a patient before going to chemotherapy has a hundred CTCs in 1ml of blood and as the patient undergoes chemotherapy treatment and we collect cancer cells from the blood every two weeks or every month and the number starts to drop from a hundred to fifty to twenty to ten then we know the patients are responding well. So that’s one way for us to also monitor cancer treatment.

The fourth, which is actually of great interest to clinicians, is in terms of being able to capture these cancer cells and then to do a genetic sequencing to look at any specific mutation in these cells. So if we do find any druggable mutations then we can actually be able to administer the right drug to the right patient and also at the right time. So this will actually contribute to what we call personalised treatment of patients.

The last one is actually in terms of post cancer monitoring. So again when the person has gone into remission and the first five years are very important, perhaps a few months, every six months or a year, we can do a blood test, we see if there any cancer cells in the blood. If there are then that may be an indication of a relapse and we can actually advise the patients to go for further tests to see if that’s the case.

Are you developing other technologies in your lab?

We are now developing other types of microfluidic chip to be able to perform single cell analysis. There is a way when we go into that, it’s because when we collect cancer cells from patients we found that they are extremely heterogeneous. So some cells are more epithelial type, some are more mesenchymal. Some cells are undergoing what we call EMT or epithelial mesenchyme transition and there are some that maybe actually cancer stem cells. So what we are trying to do now is to develop some other technologies for us to be able to collect those cells and then to perform analysis of each of these cells to see what cells these are. The reason why we are going to do that is because if you look at metastasis not all the cells can successfully metastasise to another part of the body. In fact, research has shown that it could be less than 1% or even much less than that. So it means that some cells, some cancer cells, matter more than others. So what we hope to do through this technology is to be able to better diagnose all these cancer cells and see which are the important ones that we need to target.

What does the future hold?

My hope is that someday these technologies that we develop in our lab will be used in every hospital and clinic around the world because I truly believe in liquid biopsies, that means detecting, collecting and analysing these cancer cells from blood. Of course clinicians are still much more familiar with tumour biopsies. We can do both liquid biopsies in conjunction with tumour biopsies to better diagnose the patients and also to perform what we call real time feedback of the cancer patients’ data through using this technology.