Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application.

BACKGROUND: Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU. METHODS: We propose a complete system consisting of a wearable wireless bioinstrument and a cloud-based application for real-time TBI monitoring. The bioinstrument can simultaneously record up to ten channels including both ECoG biopotential and neurochemicals (e.g. potassium, glucose and lactate), and supports various electrochemical methods including potentiometry, amperometry and cyclic voltammetry. All channels support variable gain programming to automatically tune the input dynamic range and address biosensors' falling sensitivity. The instrument is flexible and can be folded to occupy a small space behind the ear. A Bluetooth Low-Energy (BLE) receiver is used to wirelessly connect the instrument to a cloud application where the recorded data is stored, processed and visualised in real-time. Bench testing has been used to validate device performance. RESULTS: The instrument successfully monitored spreading depolarisations (SDs) - reproduced using a signal generator - with an SNR of 29.07 dB and NF of 0.26 dB. The potentiostat generates a wide voltage range from -1.65V to +1.65V with a resolution of 0.8mV and the sensitivity of the amperometric AFE was verified by recording 5 pA currents. Different potassium, glucose and lactate concentrations prepared in lab were accurately measured and their respective working curves were constructed. Finally,the instrument achieved a maximum sampling rate of 1.25 ksps/channel with a throughput of 105 kbps. All measurements were successfully received at the cloud. CONCLUSION: The proposed instrument uniquely positions itself by presenting an aggressive optimisation of size and cost while maintaining high measurement accuracy. The system can effectively extend neuroelectrochemical monitoring to all TBI patients including those who are mobile and those who are outside the ICU. Finally, data recorded in the cloud application could be used to help diagnosis and guide rehabilitation.

Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness.

We present approaches to facilitate the use of microfluidics outside of the laboratory, in our case within a clinical setting and monitoring from human subjects, where the complexity of microfluidic devices requires high skill and expertise and would otherwise limit translation. Microfluidic devices show great potential for converting complex laboratory protocols into on-chip processes. We demonstrate a flexible microfluidic platform can be coupled to microfluidic biosensors and used in conjunction with clinical microdialysis. The versatility is demonstrated through a series of examples of increasing complexity including analytical processes relevant to a clinical environment such as automatic calibration, standard addition, and more general processes including system optimisation, reagent addition and homogenous enzyme reactions. The precision and control offered by this set-up enables the use of microfluidics by non-experts in clinical settings, increasing uptake and usage in real-world scenarios. We demonstrate how this type of system is helpful in guiding physicians in real-time clinical decision-making.

High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring.

Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30-40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation.