The ability to monitor the chemical composition of brain interstitial fluid remains an important challenge in the field of bioanalytical chemistry. In particular, microelectrode biosensors are a promising resource for the detection of neurochemicals in interstitial fluid in both animals and humans. These biosensors can provide second-by-second temporal resolution and enzymatic recognition of virtually any redox or nonredox molecule. However, despite miniaturization of these sensors to 50–250 μm in diameter to avoid vascular and cellular injury, inflammation and foreign-body reactions still occur following their implantation. Here, we fabricated microelectrodes with platinized carbon fibers to create biosensors that have an external diameter that is less than 15 μm. Platinization was achieved with physical vapor deposition, and increased sensitivity to hydrogen peroxide and improved enzymatic detection were observed for these carbon fiber microelectrodes. When these devices were implanted in the brains of rats, no injuries to the parenchyma or brain blood vessels were detected. In addition, these microelectrodes provided different estimates of basal glucose, lactate, and oxygen concentrations compared to conventional biosensors. Induction of spreading depolarization in the cerebral cortex further demonstrated the greater sensitivity of our microelectrodes to dynamic neurochemical changes. Thus, these minimally invasive devices represent a major advance in our ability to analyze brain interstitial fluid.

Chemical analyses of brain interstitial fluid can reveal important information about local brain metabolism and neurochemistry, and can enhance our understanding of how neuronal networks respond to physiological or pathological stimuli. Among brain monitoring methods currently available, microelectrode biosensors provide real‐time analyses with high temporal resolution and minimal perturbation to living tissue by using oxidase enzymes for biological recognition. Two types of microelectrodes are used: cylindrically shaped wire electrodes provide the smallest implantable devices to date, and microfabricated multi‐electrode needles can monitor several molecules simultaneously. They have already contributed significantly to our understanding of brain energy metabolism with glucose and lactate detection, and to neurotransmitter systems with glutamate, D‐serine, acetylcholine, and purine detection. They have the potential to undergo further technological developments in future studies.

This work reports on the development, and preliminary results of a multiphysics probe for deep brain monitoring of neurotransmitters and metabolites in the glioblastoma environment. We made the proof of the concept of our probe with common mice glioblastoma cells GL261 modified with Green Fluorescent Protein. A silicon probe with a platinum electrode at the tip was functionalized with an enzyme in order to detect, for example, Glucose, D-serine, Lactate or Glutamate. In addition, an optical fiber was inserted in a groove in the middle of the probe for light excitation and detection of glioblastoma cells by fluorescence.