Metastasis on a microchip

A lab-on-a-chip developed at

in The Netherlands will enable doctors to choose the right type and dosage of medication for cancer patients, and could help identify a mechanism to stop cancer spreading.

Dr Floor Wolbers, a scientist in the Lab-on-a-Chip group of the MESA+ Institute for Nanotechnology at Twente, developed the microfluidic chip as a diagnostic tool and a way to screen different drugs. It does this by allowing the doctor to examine cell death, a process called apoptosis.

In apoptosis of healthy tissue, dying cells break away from their colony, a process called anoikis. Cancer cells may release themselves but survive to migrate elsewhere to invade other tissues, a process known as metastasis.

'We wanted to look to see if the mechanism of apoptosis is changed, for example between normal cells or cancer cells, and how they respond in the presence of different drugs,' said Wolbers. 'So drug A can have a certain response, but B can have a totally different response. By using the patient's own cells, you can test which of these drugs will provide the best therapy.'

The chip consists of a small culture chamber with an inlet and an outlet over which flows a medium into which the drug under study can be introduced. The scientists can then determine whether the apoptotic behaviour of the cells has changed. 'If we can manipulate this mechanism, we have a new way to treat metastatic tumour formation,' said Wolbers.

One advantage of the chip is that it uses just a few of a patient's cells. The process can also be monitored in real-time at a single cell level, albeit in the presence of other cells to analyse how these cells act in a colony. Furthermore, statistics can be produced.

'This means you can also do dose-response analysis, where you start with a certain concentration and increase the concentration to check which dosage is best for this patient and what result will be achieved,' said Wolber.

So far the researchers have used laboratory-grown cancer and regular cell lines, but the next step is to use cells biopsied from a patient. As so few cells are used, they can be obtained with minimum inconvenience to the patient.

'My experiments were done with breast cancer cells, which you can obtain with a fine-needle biopsy with no need for an operation,' said Wolbers.

Currently, the process is monitored using a microscope, but electronics are under development that can be added to the chip for high-throughput screening.

'There are two ideas being developed,' said Wolbers. 'We want to have a micro flow cytometer to count the numbers of cells that have detached, but we also know that not every cell that detaches is a dead cell.

'We also want to grow cells on nanowires to see if a certain single cell will cope with the apostolic process with a proliferative response, for example, then see if there is a change with the addition of a chemical agent.'

Another future development will be the addition of multiple chambers to the chip. Cells from a single biopsy would be divided between the chambers and have tests for different drugs running on them at the same time.

The chip is now undergoing improvements to make it as effective as possible before tests on with human patients begin in the near future. After that, the team will look at marketing the device.

Twente's Lab-on-a-Chip group has already produced chips for medical applications, including one for single-cell exploration of stem cells where different DNA can be inserted into the cell to modify it.

Twente has also collaborated with MediMate, a company that specialises in point-of-care diagnostics, to produce a chip to measure lithium concentration. This will allow patients with bipolar disorder to monitor their own medication at home.