We report a novel single neural probe for real-time simultaneous monitoring of multiple neurochemicals and direct-current electrocorticography (DC-ECoG). A major advance of this probe is the inclusion of two iridium oxide reference electrodes to improve sensor accuracy. The ECoG reference electrode is identical to the ECoG recording electrodes to significantly improve DC stability, while the reference for electrochemical sensors has 10-fold lower polarization rate to minimize the small current-induced drift in the reference electrode potential. In vitro, the single probe selectively measured oxygen (r(2)=0.985 ± 0.01, concentration range=0-60 mmHg, limit of detection=0.4 ± 0.07 mmHg) and glucose (r(2)=0.989 ± 0.009, concentration range=0-4mM, limit of detection=31 ± 8 µM) in a linear fashion. The performance of the single probe was assessed in an in vivo needle prick model to mimic sequelae of traumatic brain injury. It successfully monitored the theoretically expected transient brain oxygen, glucose, and DC potential changes during the passage of spreading depolarization (SD) waves. We envision that the developed probe can be used to decipher the cause-effect relationships between multiple variables of brain pathophysiology with the high temporal and spatial resolutions that it provides.

We present a microfabricated neural catheter for real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables that are critical to the diagnosis and treatment of evolving brain injury. The first generation neural catheter was realized by polyimide-based micromachining and a spiral rolling packaging method. The mechanical design and electrical operation of the microsensors were optimized and tailored for multimodal monitoring in rat brain such that the potential thermal, chemical and electrical crosstalk among the microsensors as well as errors from micro-environmental fluctuations are minimized. In vitro cytotoxicity analyses suggest that the developed neural catheters are minimally toxic to rat cortical neuronal cultures. In addition, in vivo histopathology results showed neither acute nor chronic inflammation for 7 days post implantation. The performance of the neural catheter was assessed in an in vivo needle prick model as a translational replica of a "mini" traumatic brain injury. It successfully monitored the expected transient brain oxygen, temperature, regional cerebral blood flow, and DC potential changes during the passage of spreading depolarization waves. We envisage that the developed multimodal neural catheter can be used to decipher the causes and consequences of secondary brain injury processes with high spatial and temporal resolution while reducing the potential for iatrogenic injury inherent to current use of multiple invasive probes.

This paper presents an infinite impulse response (IIR) temporal filtering technique for real-time stimulus artifact rejection (SAR) based on template subtraction. A system architecture for the IIR SAR algorithm is developed, and the operation of the algorithm with fixed-point computation is analyzed to obtain the number of bits for the internal nodes of the system, considering dynamic range and fraction length requirements for optimum performance. Further, memory initialization with the first recorded stimulus artifact is proposed and shown to significantly decrease the IIR system response time, especially when artifacts are highly reproducible in consecutive stimulation cycles. The proposed system architecture is hardware-implemented on a field-programmable gate array (FPGA) and tested using two sets of prerecorded neural data from a rat and an Aplysia californica (a marine sea slug) obtained from two different laboratories. The measured results from the FPGA verify that the system can indeed remove the stimulus artifacts from the contaminated neural data in real time and recover the neural action potentials that occur on the tail end of the artifact (as close as within 0.5 ms after the artifact spike). The root-mean-square (rms) value of the pre-processed stimulus artifact is reduced on average by a factor of 17 (Aplysia californica) and 5.3 (rat) post-processing.

Cerebral blood flow (CBF) plays a critical role in the exchange of nutrients and metabolites at the capillary level and is tightly regulated to meet the metabolic demands of the brain. After major brain injuries, CBF normally decreases and supporting the injured brain with adequate CBF is a mainstay of therapy after traumatic brain injury. Quantitative and localized measurement of CBF is therefore critically important for evaluation of treatment efficacy and also for understanding of cerebral pathophysiology. We present here an improved thermal flow microsensor and its operation which provides higher accuracy compared to existing devices. The flow microsensor consists of three components, two stacked-up thin film resistive elements serving as composite heater/temperature sensor and one remote resistive element for environmental temperature compensation. It operates in constant-temperature mode (~2 °C above the medium temperature) providing 20 ms temporal resolution. Compared to previous thermal flow microsensor based on self-heating and self-sensing design, the sensor presented provides at least two-fold improvement in accuracy in the range from 0 to 200 ml/100 g/min. This is mainly achieved by using the stacked-up structure, where the heating and sensing are separated to improve the temperature measurement accuracy by minimization of errors introduced by self-heating.

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