16 Feb 2015
Phase-contrast imaging looks useful for screening new drugs for their cardiac effects.
A research team at IMEC in Belgium has developed a lens-free microscope that shows cardiac cells starting to contract and “beat” spontaneously.
Veerle Reumers, a biomedical engineer at the research hub in Leuven, is working with optics specialists to come up with a completely new type of assay. It could have a dramatic impact on drug development, where cardiotoxicity – side-effects causing arrhythmias and even sudden death – is the main reason why new products are withdrawn from trials.
Reumers and her colleagues have taken specific types of cells, known as cardiomyocytes, from young rats. In tandem with pacemaker cells, these begin to contract spontaneously, generating a heartbeat when grouped together.
That cell contraction and conduction velocity – the speed of the electrical signal associated with the contraction - can now be watched directly on a microscope slide, across a field of view nearly 20 times larger than is possible with a conventional microscope but with comparable image quality.
“With a normal microscope we can see cells beating, but with this new system we can see speed and conductivity,” Reumers said. Those factors are critical for screening drugs that may cause arrhythmias.
The extra-large field of view with the lens-free approach also means that samples can be evaluated much faster, with a single “shot”, and without the need for manual adjustment of focus.
Phase contrast image
The prototype lens-free kit is based around a coherent source – in the case of IMEC’s Photonics West exhibition demonstration, a diode laser – and software reconstruction of the light diffracted from the sample in the form of a hologram. That means a phase-contrast image can be collected at the sensor, showing effects that are otherwise impossible to see.
In work presented at the BiOS conference running in parallel with Photonics West last week, the IMEC team showed how the lens-free microscope could image the effect of the drug verapamil. It is used to treat high blood pressure and angina, and works by blocking the uptake of calcium ions by muscles in the heart and in arteries.
After incubating the cardiac cells with increasing concentrations of the drug, the microscope images clearly showed a decrease in the frequency and strength of contractions, with no contractions at all at the highest verapamil concentrations.
As a result, the technique promises to complement the accepted assay method of electrophysiology, which measures cell contraction but has a number of shortcomings. “We need a way to predict how drugs affect the contraction of cells,” Reumer said.
The IMEC team is currently looking for partners interested in developing the approach, which looks ideal for scaling up to high throughputs, for more widespread use.