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A microfluidic chip to monitor the effect of different drugs on the process of dying in cancer cells
Measuring what will be the effect of a specific drug on a patient’s own cancer cells before starting therapy: this is possible with the special microfluidic chip developed by dr. Floor Wolbers of the University of Twente. With this chip it is possible in short terms to determine which medication is the most effective to treat cancer. Floor Wolbers, who has performed this work at the BIOS, the Lab-on-a-Chip group of the MESA+ Institute for Nanotechnology, had her PhD defense the 8th of June.
This special chip offers new opportunities for the diagnosis and treatment of cancer. Only a few cells of a patient are needed, collected via a special procedure, not needing operative biopsy. At a single-cell level you can follow what the effect of a specific drug. In this way it is possible to, in an ex vivo situation, decide which medication is the most effective, before the actual therapy starts. There is no need to first culture a million cells the conventional way, which causes cellular modifications. The chip is made of disposable materials, which meet the strict requirements of the hospital, and above all the costs are low.
Breast cancer cells
Wolbers analysed the process of programmed cell death, apoptosis, of healthy cells and cancer cells, in the presence of the right stimulating drugs. The main difference between healthy cells and cancer cells is a phenomenon referred to as ‘anoikis’: when healthy cells detach form their surface, they are dying. Cancer cells can detach from their surface, stay viable and move to other places in the body (metastases), thus not dying. As a fact, in cancer cells the process of apoptosis and anoikis is disturbed.
The difference between healthy cells and cancer cells is clearly demonstrated in the experiments performed on chip: healthy endothelial cells, in the presence of a drug called TNF-α, first become apoptotic, and then detach from their surface. However, for breast cancer cells present in the chip, this drug causes these cells to become apoptotic, though they do not detach, thus no anoikis. Moreover, these cancer cells move to other places in the chip, thereby staying alive. This was also clearly shown when the widely used drug in adjuvant hormone therapy ‘tamoxifen’ was used. According to Wolbers this is a clear indication that healthy cells and cancer cells respond differently to the same therapy.
Monitoring on chip offers the doctor the possibility to quickly compare different cell types (or cells of different patients) with different cytostatics.
Schematic of the microfluidic chip with a chamber for cell culture and channels to add the drug of interest (courtesy S. Le Gac)
This new technique and method is already applicable for the clinic. At the moment, the effect of different drugs is monitored optically with a microscope. For ‘high-throughput’ analysis of more cells and drugs simultaneously, the chip will be expanded with electronic detection. In this set-up, more culture chambers will be present on one chip.
Experimental set-up of the microfluidic chip onto the microscope stage
During her PhD, Floor Wolbers has collaborated with the department of Clinical Chemistry (prof. dr. I. Vermes) and the department of Gynaecology (dr. H.R. Franke) of the local hospital Medisch Spectrum Twente.
Floor Wolbers got her doctoral degree cum laude the 8th of June on her thesis entitled ‘Apoptosis chip for drug screening’ at the Faculty of Electrical Engineering, Mathematics and Computer Science of the University of Twente. Her work was performed at the BIOS, the Lab-on-a-Chip Group of prof. dr. ir. Albert van den Berg.
