Laboratory in microdrops: Credit card-size microflow system handles thousands of experiments

A group of scientists from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS), headed by D.Sc. Piotr Garstecki, constructed a microflow system allowing the streams of drops containing various solutions to merge. The new system makes it possible to produce and precisely control concentrations of reaction micromixtures, and it operates several times faster and with smaller volumes of liquids than the microtitre plate method currently popular at laboratories. "The device developed by us will allow even tens of thousands of biochemical experiments to be conducted daily," says Garstecki. The microlab may significantly affect the manner in which experiments are carried out with respect to chemical synthesis and medical diagnostics and biotechnologies.

The microflow system constructed in the IPC PAS is a miniature chemical reactor with the size of a credit card. Reactions proceed inside tiny drops moving along specially designed, small channels. Volumes of the drops are controlled with the use of a computer and are usually equal to approx. one microlitre. The system can work at a speed that allows mixing three drops per second. Additionally, instead of microvalves which it is difficult to construct scientists used inexpensive typical big valves which they placed outside the device. "Miniaturisation of everything is simply not economical. Taking the valves outside the micro-system, the chip itself can be made simple, cheap and disposable. The most important thing is that the chemical reactions themselves proceed in a microscale under precisely controlled conditions," explains Krzysztof Churski, a PhD student.

The invention of researchers from the Institute of Physical Chemistry of the PAS has already got a potential to significantly influence the development of numerous areas of chemistry and medicine, in particular screening. Currently, screening is carried out with the use of microtitre plates -- plates with several hundreds of wells filled in by a robotic handler. In this type of research cost of a single reaction reaches approx. three dollars, but the value of reagents is approx. 20 cents; the remaining part is the cost of maintenance of apparatus and its infrastructure. Since in a typical project to search for a new drug the number of tested compounds ranges from several hundreds to as many as several millions, the costs can reach millions of dollars. "Our microflow system not only reduce all costs but also significantly shortens the time necessary to conduct research," emphasises Garstecki.

The microflow system from the IPC PAS may be particularly useful in looking for new medicines, especially composed of several antibiotics. Pairs of antibiotics usually have stronger (synergistic pairs) or weaker (antagonistic pairs) effect than each of their components individually. However, it is particularly interesting that certain antagonistic pairs show high effectiveness in fighting microorganisms, which cannot be easily predicted. The existing laboratory methods allow for description of such pairs but demand conducting a huge number of labour intensive experiments. The apparatus constructed at the IPC PAS can quickly identify the interesting pairs of antibiotics that could prevent one of the basic problems of modern medicine -- the creation of drug-resistant strains.

Tests conducted in the Institute of Physical Chemistry of the PAS allowed scientists to demonstrate the operation of the microflow system in the conditions simulating the run of automated screening. Each microdrop merged with two microdrops of antibiotics, chloramphenicol and tetracycline, and the volumes of the former two were changed dynamically, which regulated the proportions between the drugs. The drops mixed in the microflow system were left for three hours in order to incubate bacteria. Then the intensity of light emitted by metabolism markers was analysed, which allowed vitality of colonies in individual drops to be easily determined. The entire process was automated and showed that the mixture of the antibiotics examined is the least effective where the proportion of the components is equal.

Microflow techniques are seen as the future of chemical engineering. They go back to the 1990s when the works on the first systems of channels began. At that time, liquids with chemical reagents were let through the channels with diameters of a tenth or hundredth of millimetre. Where small volumes are used, the flow is laminar and it is subject to effects related to viscosity, which makes it easier to control the run of the reaction (macroscale flows are often dominated by inertia and turbulence). Systems producing drops are simple and inexpensive, substances in microchannels mix very well and their flow is usually caused by the difference in pressure, i.e. a physical phenomenon that does not influence the chemical composition of a liquid (contrary to, for instance, flows that are caused by an electric field). In future the volume of drops can be reduced to nanolitres or even pictolitres. Many scientists agree that microflow systems will change the nature of modern chemistry as dramatically as integrated circuits changed electronics in the 1970s.