The human body is an extremely complex molecular machine, which can be studied in detail using so-called biomarkers. Unfortunately it is not possible to monitor these biomarkers live in patients, because they are present only in minuscule concentrations. Researchers from the Technical University Eindhoven have, however, developed a new technique that could be the breakthrough to the live monitoring of biomarkers and with extreme sensitivity.

Tiny concentrations

The substances that are essential for the body (such as proteins, hormones and medicines) are present in the blood in pico or nano molecular concentrations. These are concentrations that are comparable to one sugar crystal dissolved in an Olympic-size swimming pool – that is, extremely low, and very difficult to measure. In the Molecular Biosensing for Medical Diagnostics group at the TU Eindhoven, under the direction of professor Menno Prins, a sensor technique has been developed that can measure biomarker changes with extreme sensitivity as a function of time.

Brownian motion

The technique is based on the fact that minuscule particles in water are continuously in Brownian motion because of collisions with water molecules. The researchers tied the particles using a nanostrand to a small glass plate, so that they wiggled back and forth in place. They provided both the particles as well as the plate with adhesive molecules to which the to-be-measured biomarker has an affinity. The instant that a biomarker molecule attaches to both the wiggling particle as well as the plate the particle is suddenly stuck so that its movement is strongly reduced – until the biomarker lets go.

The mobility of the particles that are tied to the transparent glass can be easily measured with light. This new technique is therefore called BPM: Biomarker monitoring based on the sensing of Particle Mobility. Whenever an wiggling particle suddenly moves less and then moves more again, one biomarker molecule has been detected. The number of these events per minute gives away the concentration of the biomarker in the liquid with very high sensitivity.

Digital precision

The beauty of the BPM sensor technology is that it has digital precision and that both increases and decreases of the biomarker can be tracked over time. The technique has already proved itself for the monitoring of proteins and DNA. The technique has a broad range of applications, because for nearly all biomarkers suitable adhesion molecules are already available.

This flexibility, combined with the sensitivity and the expected miniaturisation of the technology, means that Prins and his research colleagues have great expectations that their technique has an excellent future. Prins has therefore already begun to establish a start-up that will develop practical sensors and applications. One of the possibilities is to couple a sensor to a catheter so that patients in the operating theatre or in intensive care can be accurately monitored. In addition to medical applications, Prins also has monitoring of biomolecules in industrial processes and water purification in mind.

The research has been published in Nature Communications.