192 results found
Robbins EM, Jaquins-Gerstl AS, Okonkwo DO, et al., 2023, Dexamethasone-Enhanced Continuous Online Microdialysis for Neuromonitoring of O2 after Brain Injury., ACS Chem Neurosci, Vol: 14, Pages: 2476-2486
Traumatic brain injury (TBI) is a major public health crisis in many regions of the world. Severe TBI may cause a primary brain lesion with a surrounding penumbra of tissue that is vulnerable to secondary injury. Secondary injury presents as progressive expansion of the lesion, possibly leading to severe disability, a persistent vegetive state, or death. Real time neuromonitoring to detect and monitor secondary injury is urgently needed. Dexamethasone-enhanced continuous online microdialysis (Dex-enhanced coMD) is an emerging paradigm for chronic neuromonitoring after brain injury. The present study employed Dex-enhanced coMD to monitor brain K+ and O2 during manually induced spreading depolarization in the cortex of anesthetized rats and after controlled cortical impact, a widely used rodent model of TBI, in behaving rats. Consistent with prior reports on glucose, O2 exhibited a variety of responses to spreading depolarization and a prolonged, essentially permanent decline in the days after controlled cortical impact. These findings confirm that Dex-enhanced coMD delivers valuable information regarding the impact of spreading depolarization and controlled cortical impact on O2 levels in the rat cortex.
Zeng J, Kuang L, Cicatiello C, et al., 2022, A LoC Ion Imaging Platform for Spatio-Temporal Characterisation of Ion-Selective Membranes, IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS, Vol: 16, Pages: 545-556, ISSN: 1932-4545
Ming DK, Jangam S, Gowers SAN, et al., 2022, Real-time continuous measurement of lactate through a minimally invasive microneedle patch: a phase I clinical study, BMJ Innovations, Vol: 8, Pages: 87-94, ISSN: 2055-8074
Introduction Determination of blood lactate levels supports decision-making in a range of medical conditions. Invasive blood-sampling and laboratory access are often required, and measurements provide a static profile at each instance. We conducted a phase I clinical study validating performance of a microneedle patch for minimally invasive, continuous lactate measurement in healthy volunteers.Methods Five healthy adult participants wore a solid microneedle biosensor patch on their forearms and undertook aerobic exercise for 30 min. The microneedle biosensor quantifies lactate concentrations in interstitial fluid within the dermis continuously and in real-time. Outputs were captured as sensor current and compared with lactate concentrations from venous blood and microdialysis.Results The biosensor was well-tolerated. Participants generated a median peak venous lactate of 9.25 mmol/L (IQR 6.73–10.71). Microdialysate concentrations of lactate closely correlated with blood. Microneedle biosensor current followed venous lactate concentrations and dynamics, with good agreement seen in all participants. There was an estimated lag-time of 5 min (IQR −4 to 11 min) between microneedle and blood lactate measurements.Conclusion This study provides first-in-human data on use of a minimally invasive microneedle patch for continuous lactate measurement, providing dynamic monitoring. This low-cost platform offers distinct advantages to frequent blood sampling in a wide range of clinical settings, especially where access to laboratory services is limited or blood sampling is infeasible. Implementation of this technology in healthcare settings could support personalised decision-making in a variety of hospital and community settings.
Gifford EK, Robbins EM, Jaquins-Gerstl A, et al., 2021, Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury, ACS CHEMICAL NEUROSCIENCE, Vol: 12, Pages: 3588-3597, ISSN: 1948-7193
Tyrrell JE, Petkos K, Drakakis EM, et al., 2021, Organic electrochemical transistor common‐source amplifier for electrophysiological measurements, Advanced Functional Materials, Vol: 31, Pages: 1-13, ISSN: 1616-301X
The portability of physiological monitoring has necessitated the biocompatibility of components used in circuitry local to biological environments. A key component in processing circuitry is the linear amplifier. Amplifier circuit topologies utilize transistors, and recent advances in bioelectronics have focused on organic electrochemical transistors (OECTs). OECTs have shown the capability to transduce physiological signals at high signal-to-noise ratios. In this study high-performance interdigitated electrode OECTs are implemented in a common source linear amplifier topology. Under the constraints of OECT operation, stable circuit component parameters are found, and OECT geometries are varied to determine the best amplifier performance. An equation is formulated which approximates transistor behavior in the linear, nonlinear, and saturation regimes. This equation is used to simulate the amplifier response of the circuits with the best performing OECT geometries. The amplifier figures of merit, including distortion characterizations, are then calculated using physical and simulation measurements. Based on the figures of merit, prerecorded electrophysiological signals from spreading depolarizations, electrocorticography, and electromyography fasciculations are inputted into an OECT linear amplifier. Using frequency filtering, the primary features of events in the bioelectric signals are resolved and amplified, demonstrating the capability of OECT amplifiers in bioelectronics.
Weddell T, Bashford J, Wickham A, et al., 2021, First-recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 599, Pages: 4117-4130, ISSN: 0022-3751
Jewell S, Hobson S, Brewer G, et al., 2021, Development and evaluation of a method for automated detection of spreading depolarizations in the injured human brain, Neurocritical Care, Vol: 35, Pages: 160-175, ISSN: 1541-6933
BACKGROUND: Spreading depolarizations (SDs) occur in some 60% of patients receiving intensive care following severe traumatic brain injury and often occur at a higher incidence following serious subarachnoid hemorrhage and malignant hemisphere stroke (MHS); they are independently associated with worse clinical outcome. Detection of SDs to guide clinical management, as is now being advocated, currently requires continuous and skilled monitoring of the electrocorticogram (ECoG), frequently extending over many days. METHODS: We developed and evaluated in two clinical intensive care units (ICU) a software routine capable of detecting SDs both in real time at the bedside and retrospectively and also capable of displaying patterns of their occurrence with time. We tested this prototype software in 91 data files, each of approximately 24 h, from 18 patients, and the results were compared with those of manual assessment ("ground truth") by an experienced assessor blind to the software outputs. RESULTS: The software successfully detected SDs in real time at the bedside, including in patients with clusters of SDs. Counts of SDs by software (dependent variable) were compared with ground truth by the investigator (independent) using linear regression. The slope of the regression was 0.7855 (95% confidence interval 0.7149-0.8561); a slope value of 1.0 lies outside the 95% confidence interval of the slope, representing significant undersensitivity of 79%. R2 was 0.8415. CONCLUSIONS: Despite significant undersensitivity, there was no additional loss of sensitivity at high SD counts, thus ensuring that dense clusters of depolarizations of particular pathogenic potential can be detected by software and depicted to clinicians in real time and also be archived.
Bashford JA, Wickham A, Iniesta R, et al., 2021, Accurate interpretation of fasciculation frequency in amyotrophic lateral sclerosis hinges on both muscle type and stage of disease, BRAIN COMMUNICATIONS, Vol: 2
Booth MA, Gowers SAN, Hersey M, et al., 2021, Fiber-based electrochemical biosensors for monitoring pH and transient neurometabolic lactate., Analytical Chemistry, Vol: 93, Pages: 6646-6655, ISSN: 0003-2700
Developing tools that are able to monitor transient neurochemical dynamics is important to decipher brain chemistry and function. Multifunctional polymer-based fibers have been recently applied to monitor and modulate neural activity. Here, we explore the potential of polymer fibers comprising six graphite-doped electrodes and two microfluidic channels within a flexible polycarbonate body as a platform for sensing pH and neurometabolic lactate. Electrodes were made into potentiometric sensors (responsive to pH) or amperometric sensors (lactate biosensors). The growth of an iridium oxide layer made the fiber electrodes responsive to pH in a physiologically relevant range. Lactate biosensors were fabricated via platinum black growth on the fiber electrode, followed by an enzyme layer, making them responsive to lactate concentration. Lactate fiber biosensors detected transient neurometabolic lactate changes in an in vivo mouse model. Lactate concentration changes were associated with spreading depolarizations, known to be detrimental to the injured brain. Induced waves were identified by a signature lactate concentration change profile and measured as having a speed of ∼2.7 mm/min (n = 4 waves). Our work highlights the potential applications of fiber-based biosensors for direct monitoring of brain metabolites in the context of injury.
Olsen MH, Olesen ND, Karlsson M, et al., 2021, Randomized blinded trial of automated REBOA during CPR in a porcine model of cardiac arrest, RESUSCITATION, Vol: 160, Pages: 39-48, ISSN: 0300-9572
Tyrrell J, Boutelle M, Campbell A, 2021, Measurement of electrophysiological signals in vitro using high-performance organic electrochemical transistors, Advanced Functional Materials, Vol: 31, Pages: 1-12, ISSN: 1616-301X
Biological environments use ions in charge transport for information transmission. The properties of mixed electronic and ionic conductivity in organic materials make them ideal candidates to transduce physiological information into electronically processable signals. A device proven to be highly successful in measuring such information is the organic electrochemical transistor (OECT). Previous electrophysiological measurements performed using OECTs show superior signal‐to‐noise ratios than electrodes at low frequencies. Subsequent development has significantly improved critical performance parameters such as transconductance and response time. Here, interdigitated‐electrode OECTs are fabricated on flexible substrates, with one such state‐of‐the‐art device achieving a peak transconductance of 139 mS with a 138 µs response time. The devices are implemented into an array with interconnects suitable for micro‐electrocorticographic application and eight architecture variations are compared. The two best‐performing arrays are subject to the full electrophysiological spectrum using prerecorded signals. With frequency filtering, kHz‐scale frequencies with 10 µV‐scale voltages are resolved. This is supported by a novel quantification of the noise, which compares the gate voltage input and drain current output. These results demonstrate that high‐performance OECTs can resolve the full electrophysiological spectrum and suggest that superior signal‐to‐noise ratios could be achieved in high frequency measurements of multiunit activity.
Wannop K, Bashford J, Wickham A, et al., 2020, Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis, Muscle and Nerve, Vol: 63, Pages: 392-396, ISSN: 0148-639X
IntroductionPrognostic uncertainty in amyotrophic lateral sclerosis (ALS) confounds clinical management planning, patient counseling, and trial stratification. Fasciculations are an early clinical hallmark of disease and can be quantified noninvasively. Using an innovative analytical method, we correlated novel fasciculation parameters with a predictive survival model.MethodsUsing high-density surface electromyography, we collected biceps recordings from ALS patients on their first research visit. By accessing an online survival prediction tool, we provided eight clinical and genetic parameters to estimate individual patient survival. Fasciculation analysis was performed using an automated algorithm (Surface Potential Quantification Engine), with a Cox proportional hazards model to calculate hazard ratios.ResultsThe median predicted survival for 31 patients was 41 (interquartile range, 31.5-57) months. Univariate hazard ratios were 1.09 (95% confidence interval [CI], 1.03-1.16) for the rate of change of fasciculation frequency (RoCoFF) and 1.10 (95% CI, 1.01-1.19) for the amplitude dispersion rate. Only the RoCoFF remained significant (P = .04) in a multivariate model.DiscussionNoninvasive measurement of fasciculations at a single time-point could enhance prognostic models in ALS, where higher RoCoFF values indicate shorter survival.
Tageldeen MK, Gowers SAN, Leong CL, et al., 2020, Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application, Journal of NeuroEngineering and Rehabilitation, Vol: 17, ISSN: 1743-0003
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 cl
Masson J-F, Hashemi P, Boutelle MG, 2020, Analytical science in neurochemistry, ANALYST, Vol: 145, Pages: 3774-3775, ISSN: 0003-2654
Moser N, Leong CL, Hu Y, et al., 2020, CMOS potentiometric FET array platform using sensor learning for multi-ion imaging., Analytical Chemistry, Vol: 92, Pages: 5276-5285, ISSN: 0003-2700
This work describes an array of 1024 Ion-Sensitive Field-Effect Transistors (ISFETs) using sensor learning techniques to perform multi-ion imaging for concurrent detection of potassium, sodium, calcium and hydrogen. Analyte specific ionophore membranes are deposited on the surface of the ISFET array chip, yielding pixels with quasi-Nernstian sensitivity to K+, Na+ or Ca2+. Uncoated pixels display pH sensitivity from the standard Si3N4 passivation layer. The platform is then trained by inducing a change in single ion concentration and measuring the responses of all pixels. Sensor learning relies on k-means clustering and DBSCAN to yield membrane mapping and sensitivity of each pixel to target electrolytes. We demonstrate multi-ion imaging with an average error of 3.7 % (K+), 4.6 % (Na+), and 1.8 % (pH) for each ion respectively, while Ca2+ incurs a larger error 24.2 % and hence is included to demonstrate versatility. We validate the platform with a brain dialysate fluid sample and demonstrate reading by comparing with a gold-standard spectrometry technique.
Bashford J, Masood U, Wickham A, et al., 2020, Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis, Muscle and Nerve, Vol: 61, Pages: 745-750, ISSN: 0148-639X
IntroductionFasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing.MethodsFasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high‐density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time‐points during a single day.ResultsDaytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20).DiscussionThere was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients’ accounts.
Gowers S, Samper I, Murray D-S, et al., 2020, Real-time neurochemical measurement of dynamic metabolic events during cardiac arrest and resuscitation in a porcine model, The Analyst, Vol: 145, Pages: 1894-1902, ISSN: 0003-2654
This work describes a fully-integrated portable microfluidic analysis system for real-time monitoring of dynamic changes in glucose and lactate occurring in the brain as a result of cardiac arrest and resuscitation. Brain metabolites are sampled using FDA-approved microdialysis probes and coupled to a high temporal resolution 3D printed microfluidic chip housing glucose and lactate biosensors. The microfluidic biosensors are integrated with a wireless 2 channel potentiostat forming a compact analysis system that is ideal for use in a crowded operating theatre. Data are transmitted to a custom-written app running on a tablet for real-time visualisation of metabolic trends. In a proof of-concept porcine model of cardiac arrest, the integrated analysis system proved reliable in a challenging environment resembling a clinical setting; noise levels were found to be comparable with those seen in the lab and were not affected by major clinical interventions such as defibrillation of the heart. Using this system, we were able, for the first time, to measure changes in brain glucose and lactate levels caused by cardiac arrest and resuscitation; the system was sensitive to clinical interventions such as infusion of adrenaline. Trends suggest that cardiopulmonary resuscitation alone does not meet the high energy demands of the brain as metabolite levels only return to their values preceding cardiac arrest upon return of spontaneous circulation.
Hurst T, Pahl C, Tolias C, et al., 2020, Response to Stevens et al. (DOI: 10.1089/neu.2018.6175) Glucose Dynamics of Cortical Spreading Depolarization in Acute Brain Injury: A Systematic Review, JOURNAL OF NEUROTRAUMA, Vol: 37, Pages: 1266-1267, ISSN: 0897-7151
Bashford J, Wickham A, Iniesta R, et al., 2020, Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis, Clinical Neurophysiology, Vol: 131, Pages: 265-273, ISSN: 1388-2457
ObjectivesFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline.MethodsSix ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection.ResultsAssessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2–13.1 minutes), processing times (10.7–49.5 seconds) and fasciculation frequencies (27.4–71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6–79.4 IQR).ConclusionWe hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings.SignificanceLongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.
Tamborska A, Bashford J, Wickham A, et al., 2020, Non-invasive measurement of fasciculation frequency demonstrates diagnostic accuracy in amyotrophic lateral sclerosis, BRAIN COMMUNICATIONS, Vol: 2
Bashford JA, Wickham A, Iniesta R, et al., 2020, The rise and fall of fasciculations in amyotrophic lateral sclerosis, BRAIN COMMUNICATIONS, Vol: 2
Bashford J, Wickham A, Iniesta R, et al., 2020, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis (vol 130, pg 1083, 2019), Clinical Neurophysiology, Vol: 131, Pages: 350-350, ISSN: 1388-2457
[Correction to https://doi.org/10.1016/j.clinph.2019.03.032]
Hamaoui K, Gowers S, Sandhu B, et al., 2020, Cold ischaemia time: is too long really too bad? studies using a porcine kidney ex-vivo reperfusion model, International Journal of Surgery Open, Vol: 23, Pages: 39-47, ISSN: 2405-8572
IntroductionPost-ischaemic hypothermic machine perfusion (HMP) may be beneficial in recovery of marginal kidney grafts. The full capacity of conventional HMP (with passive oxygenation) to recondition an organ has not been realised. We investigated whether HMP can ameliorate ischemic damage caused by extremely prolonged static cold storage (SCS).MethodsPorcine kidneys underwent 4-h (SCS4,n = 4) or 52-h (SCS52,n = 4) SCS, followed by 10 h of HMP and were then subjected to 2 h of isolated normothermic reperfusion (NRP).ResultsThere was a post-SCS graft weight loss in SCS52 vs SCS4 kidneys. SCS52 kidneys showed viable perfusion dynamics during HMP, with significantly shorter times to reach viable parameters vs SCS4 kidneys (p < 0.027). During NRP SCS52 kidneys demonstrated similar trends in perfusion dynamics, renal function, oxygen consumptions, lactate production, and tubular injury to SCS4 kidneys.ConclusionGraft weight loss after SCS, reducing resistance to perfusion, may facilitate better HMP dynamics and graft reconditioning. Clinicians utilising HMP should be aware of this phenomenon when using HMP in kidneys exposed to extreme periods of SCS. HMP after an extended period of SCS can resuscitate kidneys to a level equitable of viability as those after a short period of SCS. Utilising passive oxygenation however may be limiting such recovery and interventions utilising active oxygenation may provide benefit in such organs.
Leong CL, Coleman S, Nightingale AM, et al., 2019, Lactate monitoring in droplet microfluidics: a cautionary tale in assay miniaturisation, ANALYTICAL METHODS, Vol: 11, Pages: 6119-6123, ISSN: 1759-9660
Samper IC, Gowers SAN, Booth MA, et al., 2019, Portable Microfluidic Biosensing System for Real-Time Analysis of Microdialysate in Transplant Kidneys, ANALYTICAL CHEMISTRY, Vol: 91, Pages: 14631-14638, ISSN: 0003-2700
Charalampidis S, Gowers S, Rogers M, et al., 2019, CONTINUOUS ONLINE MICRODIALYSIS AS A NOVEL TOOL FOR CONTINUOUS CREATININE MEASUREMENT AND PARENCHYMA ASSESSMENT DURING NORMOTHERMIC MACHINE PERFUSION IN A TRANSLATIONAL EX VIVO PORCINE KIDNEY MODEL, Publisher: WILEY, Pages: 425-425, ISSN: 0934-0874
Bashford J, Wickham A, Iniesta R, et al., 2019, THE SURFACE POTENTIAL QUANTIFICATION ENGINE INTEGRATES ACTIVE VOLUNTARY IDENTIFICATION TO ENHANCE FASCICULATION ANALYSIS IN AMYOTROPHIC LATERAL SCLEROSIS, Annual Meeting of the American-Association-of-Neuromuscular-and-Electrodiagnostic-Medicine (AANEM), Publisher: WILEY, Pages: S3-S3, ISSN: 0148-639X
Robbins EM, Jaquins-Gerstl A, Fine DF, et al., 2019, Extended (10-Day) Real-Time Monitoring by Dexamethasone-Enhanced Microdialysis in the Injured Rat Cortex., ACS Chem Neurosci, Vol: 10, Pages: 3521-3531
Intracerebral microdialysis has proven useful for chemical monitoring in patients following traumatic brain injury. Recent studies in animals, however, have documented that insertion of microdialysis probes into brain tissues initiates a foreign-body response. Within a few days after probe insertion, the foreign body response impedes the use of microdialysis to monitor the K+ and glucose transients associated with spreading depolarization, a potential mechanism for secondary brain injury. Herein, we show that perfusing microdialysis probes with dexamethasone, a potent anti-inflammatory glucocorticoid, suppresses the foreign body response and facilitates the monitoring of spontaneous spreading depolarizations for at least 10 days following controlled cortical injury in the rat. In addition to spreading depolarizations, results of this study suggest that a progressive, apparently permanent, decline in pericontusional interstitial glucose may be an additional sequela of brain injury. This study establishes extended dexamethasone-enhanced microdialysis in the injured rodent cortex as a new paradigm for investigating trauma-induced metabolic crisis.
Gowers S, Rogers M, Booth M, et al., 2019, Clinical translation of microfluidic sensor devices: Focus on calibration and analytical robustness, Lab on a Chip, Vol: 19, Pages: 2537-2548, ISSN: 1473-0189
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.
Shuttleworth CW, Andrew RD, Akbari Y, et al., 2019, Which Spreading Depolarizations Are Deleterious To Brain Tissue?, Neurocrit Care
Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.
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