Chips with a beat

Delta, 28 April 2010

The remarkable combination of silicon chips with beating heart muscle cells promises interesting applications, ranging from drug toxicity tests to self-powered implants, says professor Ronald Dekker.

‘Athlete drops dead at athletics meet’. Headlines like this are illustrative of what may well be the rare side-effects of apparently harmless pharmaceuticals, which can often be purchased prescription-free at drug stores. An infamous example is the first generation of histamine inhibitors, which are used to alleviate hay fever. As recently as last month, the Dutch physician’s magazine, Geneesmiddelenbulletin, cited the hay fever drug fexofenidine as having a disturbing influence on heart rhythm. The drug can make the heart beat dangerously slow. Nonetheless, this drug can still be purchased off the shelf as ‘STP-free’ or ‘Telfast’ in the Netherlands, although not in the United States.
Occurrences of lethal side-effects may be rare, but a drug that shows serious side-effects at some stage and then subsequently retreats off the market certainly isn’t. Dr. Stefan Braam, of the Leiden University Medical Centre (LUMC), says that over the last 30 years some 28 percent of the drugs taken off the market had caused serious side-effects for the heart, including rhythm disturbances. “The pharmaceutical industry has set up special safety pharmacology labs where each new drug is extensively tested for cardiac by-effects”, Braam says.
These labs may soon profit from a new device, in which their products can be tested on actual living human heart cells. This device is currently under development at Pluriomics, a techno-starter, which has won the 2009 Netherlands Genomic Initiative Venture Challenge. Pluriomics is a joint initiative of the LUMC, a pharmaceutical industry partner, and professor Ronald Dekker, of the Dimes lab at the faculty of Electrical Engineering, Mathematics and Computer Science (microelectronics & computer engineering).
Professor Dekker is mainly involved with the design of this device. The first prototype consists of a small array of contacts on the glass bottom of a tiny dish in which heart muscle cells are kept alive and kicking in a nutritious solution. Outside the dish, a selection of the contacts may be read out to record the electrical activity of the heart muscle cells. Add some drug with known a side-effect and one can actually see the repolarisation of the heart muscle cells slow down, which in a real heart manifests itself as disturbances of the heart rhythm. “The principles works”, says Dekker, who is quick to point out that selecting and growing the right heart cells is crucial for the device’s success.
Braam, who completed his PhD under the supervision of stem cell expert professor Christine Mummery in Leiden, is responsible for the cell cultures. He explains that skin cells can be reprogrammed into stem cells by adding three genes crucial in early foetal development. Stem cells can be persuaded under the right conditions to grow out into contracting lumps of heart muscle cells, which must then be eased apart in order to line them up on the test chip.
Being able to make stem cells from adult specialised cells is an important step. By taking tissue from someone who is known to have suffered the cardiac side-effects, the researchers are confident that the cultured tissue will be sensitive to the side-effects.
Dekker and Braam estimate that they will need another three to four months before they can present their prototype drug tester. Meanwhile the design is being improved to best accommodate the heart cells. “The cells get stressed when they are mounted on rigid glass”, Braam explains. So now the researchers are experimenting with a softer and more flexible substrate, which can be stretched periodically (by air pressure) to mimic the beating heart tissue.
For Dekker, the fun has only just begun. He likes to fantasise about the possible combination of micro electrical or mechanical devices and living cells. One of his favourites is a dynamo driven by one’s own heart muscle cells. Such a bio-battery could be used to power implants, like drug pumps or pacemakers. And it would never need to be replaced. A lifetime guarantee.

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