Minimally Invasive Microelectrode Biosensors Based on Platinized Carbon Fibers for in Vivo Brain Monitoring

Abstract

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.

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

“…Due to the rapid consumption of glucose by brain cells, a downhill gradient of glucose from blood towards the brain ISF is maintained. Basal, steady-state brain ISF glucose levels in normoglycemic subjects (plasma glucose concentration of 6 mM) is estimated to be 1.4 mM [16], which matches well with the measured value in the rat brain ISF [69]. According to this concentration gradient, GLUT1 favors the blood-to-brain transport of circulating glucose.…”

Fiber-Based Electrochemical Biosensors for Monitoring pH and Transient Neurometabolic Lactate

“…This improved sensitivity is comparable to similar lactate sensors reported in the literature. 13 , 14 , 34 The limit of detection (LOD) for our lactate sensor on a Pt black-coated electrode (calculated as the blank signal plus three times the blank signal) is 19 ± 7 μM ( n = 4). Both the sensitivity and LOD show that the sensor is capable of measuring lactate concentrations in physiologically relevant ranges.…”

“…Selectivity of similar sensors with the same barrier layer has been published elsewhere and shown negligible response to serotonin, dopamine, or ascorbic acid. 13 , 28 , 35 , 36 To confirm lactate is being measured without contribution from interferents, however, we fabricated control sensors. Control sensors (lacking the enzyme component required to detect lactate) show only a response to hydrogen peroxide and no response to lactate, Figure 5 F.…”

“…The observed increase in lactate concentration is in keeping with the current understanding of changes in the brain during SDs measured via rsMD 6 and electrochemical biosensors. 13 , 34 Further discussion on lactate use or relevance in the brain is beyond the scope of this work, as instead we highlight the value of real-time monitoring of lactate concentration changes.…”

Recent Advances in In Vivo Neurochemical Monitoring

“…Avoiding blood-brain barrier damage has been shown to greatly reduce inflammation in rats. Since the average distance between blood vessels is approximately 50 µm, sensors are frequently constructed to be smaller than that critical dimension [ 245 , 246 ]. Soft and flexible sensors are also often employed to reduce mechanical mismatches between the sensor and the tissue [ 247 , 248 , 249 ].…”