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

Abstract

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.

Monitoring Neurochemistry in Traumatic Brain Injury Patients Using Microdialysis Integrated with Biosensors: A Review

“…Figure 3 highlights the diversity of the biosensor technologies and their respective setups in tandem with microdialysis. For instance, Figure 3 A–D all have measured cerebral metabolites in dialysates of TBI patients, while Figure 3 E has quantified blood in the dialysates of subcutaneous interstitial fluid [ 45 , 47 , 49 , 50 , 65 ]. The development of biosensors in monitoring cerebral metabolism is challenging, and this is evident as no biosensor has been approved for clinical use.…”

“…A few studies have shown both glucose and lactate measurements in TBI using electrochemical sensors integrated with microdialysis. Tageldeen and colleagues have achieved both glucose and lactate measurements using wearable electrochemical sensors [ 47 ]. They were able to demonstrate dynamic metabolic changes ranging from 0 to 1 mM with 0.25 mM steps.…”

“… Biosensors coupled to microdialysis for quantification of clinical analytes. ( A ) Proof-of-concept design for a wireless, portable bio-instrument to monitor neurochemicals in brain injured patients [ 47 ]. Previous work from the same group developed a biosensor setup ( B ): ( I ) is the combined needle with a PDMS microfluidic chip placed within a LabSmith automated platform for glucose detection, ( II ) tip of needle electrode, and ( III ) potassium ion selective electrode [ 45 ].…”

“…( E ) is another optical based biosensor set up for glucose monitoring in the dialysates of subcutaneous interstitial fluid [ 66 ]. Images ( A – D ) originally appeared in [ 45 , 47 , 49 , 50 ], respectively, published Open Access CC BY, copyright The Authors. The diagram in ( E ) is published with permission of the Publisher and Corresponding Author*; it originally appeared in H. M. Heise*, V. R. Kondepati, U. Damm, M. Licht, F. Feichtner, J.K. Mader, and M. Ellmerer.…”

Recent Advances in In Vivo Neurochemical Monitoring

“…Wireless data logging systems that meet the standard for hospital use are becoming smaller and cheaper. A recent battery-powered potentiostat and wireless data transmission system with integrated biosensors and a microfluidic system for use with microdialysis manufactured by the Boutelle group costs less than £500 to build [260]. The Tiny FSCV potentiostat and wireless transmission system costs less than $75 [261] and is made with commercially available parts.…”