Smartdetect

Finding rare cancer cells in blood

Wednesday 24 Feb 16

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Rodolphe Marie
Groupleader, Associate Professor
DTU Health Tech
+4545 25 57 53

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Anders Kristensen
Head of Sections, Professor
DTU Health Tech
+4545 25 63 31
In future, it might be possible to diagnose many types of cancer by taking a simple blood test. Researchers at DTU Nanotech have shown that a microfluidic separation method can be used for separating cancer cells from blood cells. Once separated, the cancer cells can be analysed to identify the specific type of cancer.

A blood sample might be the way to diagnose cancer. It is simple to get and a millilitre of blood can contain malignant cells originating from tumours almost anywhere in the body. However, these cells are rare compared to white and red blood cells, in fact as rare as a single one among a million white blood cells. This is as close as it gets to finding a needle in a haystack.

Circulating tumour cells

Various ways to detect tumours in a patient already exist but recently the so-called circulating tumour cells have become the focus of attention. Shed by tumours and released to the blood stream, they carry information about the type of cancer from which they originate. Cancer diagnosis is then possible using a simple blood sample, if the few malignant cells can be retrieved from the millions of blood cells.

Most of the blood constituents are very different in size from cancer cells and these can easily be removed by routine laboratory procedures such as centrifugation.

Associate Professor Rodolphe Marie says: “The critical step is to distinguish between cancer cells and white blood cells - in fact, most circulating cancer cells are similar in size to white blood cells and therefore hard to distinguish”.

One established way is to capture the largest cells using a filter and then identify the cancer cells by labelling them with for example fluorescence tags. However, there is no clear size difference and some cancer cells may pass through the filter and never be found.

Microfluidic solution

Microfluidics is increasingly competing with porous filters. Recently, researchers from DTU Nanotech and collaborators from the Weatherall Institute at Oxford University, UK, have succeeded in purifying cancer cells from white blood cells using a microfluidic size separation technique. The technique is called pinched flow fractionation (PFF).

In a PFF device, cells are aligned against a wall upon the continuous action of a fluid flow. Once they are aligned they leave this part of the device by following a path that corresponds to their size. Downstream, all the cells that are ’too small’ are removed and the bigger ones are collected. PFF is thus basically a size separation technique and although cancer cells have a size similar to white blood cells, good purification is achieved. (See figure 1).

Illustration 
Figure 1. Cancer cells (red) and white blood cells (blue) before and after purification by pinched flow fractionation.

How can this be? Rodolphe Marie says that “we believe that during the purification, the cells are under a large mechanical stress from the fluid inside the microfluidic separation device and that under such a stress the cancer cells are mechanically different from the white blood cells”. In other words, the mechanical stress in the device enhances the separation of the two types of cells that is otherwise purely based on size differences.

Compared to the traditional porous filter, microfluidics has the advantage that the cells of interest do not end up attached to a solid support. Instead, the rare cells are collected in a solution and are alive and ready for further culture or analysis. Typically, DNA sequencing is one such analysis that can reveal what type of cell one has captured and from which type of cancer it originates. 

The technology is part of a lab-on-a-chip technology developed in the EU-funded CELL-O-MATIC project.

The work is described in the article by M. Pødenphant et al. in Lab-on-a-Chip, DOI: 10.1039/C5LC01014D.

Read more about the Optofluidics research group.