New analytical technique to improve personalized medicine

In the future, even before the start of the treatment, physicians will be able to establish how patient's blood binds a given medicine and what doze should be applied in order to obtain the concentration in the body that would be optimal for the treatment. A new simple method of analysis of chemical reactions proceeding in solutions has been developed in the Institute of Physical Chemistry of the Polish Academy of Sciences.

Information on how strongly two dissolved substances react with each other is very important in many fields, in particular in chemistry, molecular biology, pharmacy and medicine. The new analytical technique, developed at the Institute of Physical Chemistry of the PAS (IPC PAS), allows the inexpensive and reliable determination of stability of complexes created as a result of reactions between chemical compounds in solutions. What is interesting, the measurement involves very simple physical phenomena and comes down to the examination of the flow of a solution of two compounds in a long and thin tube - a capillary.

Every angler knows that rivers flow fastest in the middle part of the stream, and near the banks the current is always slower. A liquid flowing through a capillary behaves in a similar way. If the flow is nonturbulent (laminar), the layers of the fluid that are closest to the centre of the capillary flow faster than the layers near the walls. "This is the fact that we use in our method, but the key are phenomena connected with diffusion," says PhD Anna Bielejewska from the IPC PAS. In reality, particles of a liquid may move (diffuse) from a layer flowing with a certain speed to another layer flowing with a different speed. If we insert a substance into a capillary filled with the solution of another substance, the diffusion rate will depend on how strongly the chemical compounds of both solutions react with each other. If particles move quickly between the layers, a detector will register a high and narrow peak. The slower the particles diffuse between layers, the wider the peak. "If we measure the width of the peaks before and after the introduction of a complexing agent into the capillary, we can determine the diffusion coefficients of a free substance and a complexed substance, and on this basis calculate a binding constant. It provides information whether given chemical substances bind with each other or not, and if yes, how permanent the bond is," explains PhD Bielejewska.

The device developed in the Institute of Physical Chemistry comprises a pump which guarantees the stable flow of the liquid at 0.05 millilitre per minute, an autosampler inserting a sample, a detector of visible and ultraviolet radiation and a 0.25 mm diameter capillary, 25 m long, wound around a small cylinder. The obtained results of measurement agreed perfectly with the data collected by classical chromatographic methods and figures cited in international scientific publications. In one of the numerous tests conducted, the capillary was filled with the solution of diluted blood plasma, which contains protein (albumin), after which warfarin, an organic chemical compound used as an anticoagulant, was injected. In this case the results of the experiment were also correct.

The new analytical technique, for which a patent application has already been submitted, may be applied not only in chemistry but also in medicine for the selection of dozes of medicines whose concentration in blood should be strictly determined. "At present a physician first prescribes a medicine to a patient, then takes a blood test and, if something is wrong, changes the doze, checks again and this procedure is repeated until it succeeds. Thanks to our method it will be possible to take several millilitres of blood once before the treatment and determine how strongly the blood binds a given medicine," says Bielejewska. A single analysis using this method lasts approximately half an hour. After this time appropriate software would provide the physician with a result in the form of a doze of medicine adapted to specific features of a given patient's organism.

"We have developed a new, efficient method for the analysis of chemical reaction equilibrium in solutions, for which cheap and simple measurement equipment is required. It is up to the industry whether the method becomes widespread," comments Prof. Robert Hołyst from the Institute of Physical Chemistry of the PAS.