A group of biotechnologists and engineers from the University of Freiburg demonstrated, for the first time, that it is possible to determine the concentration of antibiotics in the body of mammals using breath samples.
The researchers used a biosensor — a multiplex chip that permits concurrent measurement of various specimens and test substances — that would allow personalized dosing of medicines against infectious diseases on-site and helps lessen the development of resistant strains of bacteria. The breath measurements also equaled the antibiotic concentrations present in the blood.
The sensor was created by scientists led by Dr. Can Dincer and H. Ceren Ates, FIT Freiburg Center for Interactive Materials and Bioinspired Technologies, and Professor Dr. Wilfried Weber, Professor of Synthetic Biology and a member of the team of speakers at the Cluster of Excellence CIBSS — Centre for Integrative Biological Signalling Studies.
The sensor is based on synthetic proteins that react to antibiotics, resulting in a current change. The observations have been published in the Advanced Materials journal.
Previously, researchers could only detect traces of antibiotics in the breath
The scientists tried the biosensor on plasma, blood, saliva, urine and breath samples of pigs administered antibiotics. They revealed that the result obtained with biosensors in the pigs’ plasma were precise to the standard medical laboratory process. Earlier, it was not possible to measure antibiotic levels in exhaled breath samples.
Until now researchers could only detect traces of antibiotics in the breath. With our synthetic proteins on a microfluidic chip, we can determine the smallest concentrations in the breath condensate and they correlate with the blood values.
Dr. Can Dincer, FIT Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg
Sensor will help to keep antibiotic levels stable in severely ill
It is necessary that physicians maintain antibiotics levels within a personalized therapeutic range for patients undergoing severe infections — patients at the risk of threats like sepsis and organ failure or even death. Insufficient antibiotic administration enables bacteria to mutate and become resistant — the medicines no longer work.
Rapid monitoring of antibiotic levels would be a huge advantage in hospital. It might be possible to fit the method into a conventional face mask.
H. Ceren Ates, FIT Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg
Dincer is creating wearable paper sensors for the constant measurement of biomarkers from exhaled breath in another project at the University of Freiburg. Clinical trials are to be carried out to validate the antibiotic biosensor by analyzing the system with human samples.
Bacterial proteins as sensor
The microfluidic biosensor carries proteins that can identify beta-lactam antibiotics like penicillin, attached to a polymer film. The antibiotic of interest in the sample and an enzyme-coupled beta-lactam compete to attach to these bacterial proteins. This competition creates a current change — similar to a battery: the more antibiotics present in the sample, the lower the development of enzyme product, which in turn leads to a lower measurable current.
The mechanism is based on a natural receptor protein that resistant bacteria utilize to detect the antibiotics that threaten them.
You could say we are beating the bacteria at their own game.
Dr. Wilfried Weber, Professor, Synthetic Biology, Centre for Integrative Biological Signalling Studies, University of Freiburg
Ates, H. C., et al. (2021) Biosensor-Enabled Multiplexed On-Site Therapeutic Drug Monitoring of Antibiotics. Advanced Materials. doi.org/10.1002/adma.202104555.