©Stéphane Marinesco / Inserm, Photograph of an implantable chemical sensor (bottom right) made with platinized carbon fiber and coated with a recognition enzyme, placed next to a human hair (top).

A team of Inserm and CNRS researchers has succeeded in developing new-generation chemical sensors to monitor the brain’s metabolism, particularly during stroke, trauma or epileptic seizure. Measuring less than 15 µm in diameter, these minimally-invasive tools monitor what is happening in the brain in order to obtain data that are much more reliable and representative of the neurochemical exchanges. This research has been published in ACS Central Science.

Analyzing the interstitial fluid of the brain can reveal important chemical information about the state of the latter. In the clinic or in laboratory animals, the ability to detect, over time, the levels of metabolites characteristic of brain energy (such as glucose) can help detect the onset of brain lesions, enabling doctors to act before it is too late. In addition, the activation of neuronal networks leading to a release of neurotransmitters can be detected in interstitial fluid. However, up until now the size of the probes and the local injury caused by their implantation were parameters which disrupted the quality of the measurements obtained. In particular, the rupture of small cerebral blood vessels during implantation represents a major trigger for inflammation. Within the first hour after implantation, local chemical brain tissue composition can be affected.

The first innovation presented by the scientists in this research consisted of developing miniature sensors.

Invisible to the naked eye, they measure less than 15 microns in diameter (compared with 50 to 250 microns, currently), making them narrower than a strand of hair. The major advantage of being able to miniaturize the sensors to this extent is that implanting them no longer causes lesions in the nervous tissues. “Their size is smaller than the average distance between two brain capillaries, meaning that they are not damaged by the device” explains Stéphane Marinesco, Inserm researcher in charge of the study.

The second innovation was to coat the carbon fibers with platinum followed by a very thin layer of enzyme.

Up until then, electrochemical analysis using carbon fiber microelectrodes was limited to a highly-restrictive number of so-called “oxidable” molecules. Coating them with platinum makes it possible to attach enzymes and detect a potentially unlimited number of molecules. For Marinesco, “while platinum deposition is a commonly used technique in the field of microelectronics, it is usually performed with flat silicon substrates. Our results show that, despite their unusual cylindrical geometry, carbon fibers could be successfully covered with a platinum layer. The sensitivity achieved is similar or better than that of the thicker solid platinum wires which are commercially available.”

When these sensors were implanted in the brains of rats during laboratory testing, no injuries to the brain tissue or blood vessels were detected.

In addition, these microelectrodes supplied more precise and reliable evaluations of glucose, lactate and oxygen concentrations compared with conventional sensors (in which one sensor per parameter is necessary by implanting a multi-microelectrode “comb”). Numerous tests were performed on these new microelectrodes, in particular on their stability over time because they were also tested after 6 months of storage (room temperature in darkness).

Marinesco clarifies that: “This minimally invasive device represents a major advance in our ability to analyze the brain interstitial fluid, paving the way for the measurement of new physiological parameters and multiple applications. This novel tool could be used to test the effect of certain medicinal products on the brain. Finally, in the longer term, monitoring the human brain could provide invaluable information to doctors in order to better understand how a patient with brain lesions recovers after a head injury or stroke. This device could also help them to take the best therapeutic decisions depending on the patient’s condition”.