Imperial College London

ProfessorMartynBoutelle

Faculty of EngineeringDepartment of Bioengineering

Consul for the Faculty of Engineering and Business School
 
 
 
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Contact

 

+44 (0)20 7594 5138m.boutelle Website CV

 
 
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Location

 

B208Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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180 results found

Tyrrell J, Boutelle M, Campbell A, 2020, Measurement of electrophysiological signals in vitro using high-performance organic electrochemical transistors, Advanced Functional Materials, 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.

Journal article

Tageldeen MK, Gowers SAN, Leong CL, Boutelle MG, Drakakis EMet 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

Journal article

Masson J-F, Hashemi P, Boutelle MG, 2020, Analytical science in neurochemistry, ANALYST, Vol: 145, Pages: 3774-3775, ISSN: 0003-2654

Journal article

Moser N, Leong CL, Hu Y, Cicatiello C, Gowers SAN, Boutelle MG, Georgiou Pet 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.

Journal article

Bashford J, Masood U, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet 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.

Journal article

Gowers S, Samper I, Murray D-S, Smaith G, Jeyaprakash S, Rogers M, Karlsson M, Olsen M, Moller K, Boutelle Met 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.

Journal article

Hurst T, Pahl C, Tolias C, Jewell S, Boutelle M, Strong Aet 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

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw CEet 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.

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet 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]

Journal article

Hamaoui K, Gowers S, Sandhu B, Cook T, Boutelle M, Casanova-Rituerto D, Papalois Vet 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.

Journal article

Bashford JA, Wickham A, Iniesta R, Drakakis EM, Boutelle MG, Mills KR, Shaw CEet al., 2020, The rise and fall of fasciculations in amyotrophic lateral sclerosis., Brain Commun, Vol: 2

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a median survival of 3 years from symptom onset. Accessible and reliable biomarkers of motor neuron decline are urgently needed to quicken the pace of drug discovery. Fasciculations represent an early pathophysiological hallmark of amyotrophic lateral sclerosis and can be reliably detected by high-density surface electromyography. We set out to quantify fasciculation potentials prospectively over 14 months, seeking comparisons with established markers of disease progression. Twenty patients with amyotrophic lateral sclerosis and five patients with benign fasciculation syndrome underwent up to seven assessments each. At each assessment, we performed the amyotrophic lateral sclerosis-functional rating scale, sum power score, slow vital capacity, 30-min high-density surface electromyography recordings from biceps and gastrocnemius and the motor unit number index. We employed the Surface Potential Quantification Engine, which is an automated analytical tool to detect and characterize fasciculations. Linear mixed-effect models were employed to account for the pseudoreplication of serial measurements. The amyotrophic lateral sclerosis-functional rating scale declined by 0.65 points per month (P < 0.0001), 35% slower than average. A total of 526 recordings were analysed. Compared with benign fasciculation syndrome, biceps fasciculation frequency in amyotrophic lateral sclerosis was 10 times greater in strong muscles and 40 times greater in weak muscles. This was coupled with a decline in fasciculation frequency among weak muscles of -7.6/min per month (P = 0.003), demonstrating the rise and fall of fasciculation frequency in biceps muscles. Gastrocnemius behaved differently, whereby strong muscles in amyotrophic lateral sclerosis had fasciculation frequencies five times greater than patients with benign fasciculation syndrome while weak muscles were increased by only 1.5 times. Gastrocnemius d

Journal article

Leong CL, Coleman S, Nightingale AM, Sammer-ul H, Voegeli D, Boutelle MG, Niu Xet al., 2019, Lactate monitoring in droplet microfluidics: a cautionary tale in assay miniaturisation, ANALYTICAL METHODS, Vol: 11, Pages: 6119-6123, ISSN: 1759-9660

Journal article

Samper IC, Gowers SAN, Booth MA, Wang C, Watts T, Phairatana T, Vallant N, Sandhu B, Papalois V, Boutelle MGet 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

Journal article

Charalampidis S, Gowers S, Rogers M, Gopal J, Housby N, Learney R, Boutelle M, Papalois Vet 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

Conference paper

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet 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

Conference paper

Robbins EM, Jaquins-Gerstl A, Fine DF, Leong CL, Dixon CE, Wagner AK, Boutelle MG, Michael ACet 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.

Journal article

Gowers S, Rogers M, Booth M, Leong C, Samper I, Phairatana T, Jewell S, Pahl C, Strong A, Boutelle Met 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.

Journal article

Shuttleworth CW, Andrew RD, Akbari Y, Ayata C, Balu R, Brennan KC, Boutelle M, Carlson AP, Dreier JP, Fabricius M, Farkas E, Foreman B, Helbok R, Henninger N, Jewell SL, Jones SC, Kirov SA, Lindquist BE, Maciel CB, Okonkwo D, Reinhart KM, Robertson RM, Rosenthal ES, Watanabe T, Hartings JAet al., 2020, 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.

Journal article

Helbok R, Hartings JA, Schiefecker A, Balança B, Jewel S, Foreman B, Ercole A, Balu R, Ayata C, Ngwenya L, Rosenthal E, Boutelle MG, Farkas E, Dreier JP, Fabricius M, Shuttleworth CW, Carlson Aet al., 2019, What should a clinician do when spreading depolarizations are observed in a patient?, Neurocritical Care, Vol: 32, Pages: 306-310, ISSN: 1541-6933

The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, "What should a clinician do when spreading depolarizations are observed in a patient?" Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. 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 formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors.

Journal article

Kontojannis V, Hostettler I, Brogan RJ, Raza M, Harper-Payne A, Kareem H, Boutelle M, Wilson Met al., 2019, Detection of intracranial hematomas in the emergency department using near infrared spectroscopy., Brain Inj, Vol: 33, Pages: 875-883

Hypothesis: Traumatic brain injury (TBI) is one of the most important causes of morbidity and mortality in our society. The development of near infrared technology for the detection of intracranial hematomas may assist earlier diagnosis of TBI. This in turn may enable earlier targeted treatments minimizing the harm and subsequent social and economic effects of TBI. Methods: A handheld, noninvasive Near Infrared Spectroscopy device, Infrascanner 2000, (Infrascan Inc., Philadelphia, PA, USA) was used in a major trauma center to screen for traumatic intracranial hematomas. The Infrascanner was used successfully in 205 patients on their arrival in the emergency department prior to CT head. Results: In the whole cohort, sensitivity was 75%, specificity was 50.43%, with negative predictive value 72.84%, and positive predictive value 53.23%. In 45 patients, where the volume of blood was >3.5mL, the sensitivity was 89.36%, specificity 48.73% with negative predictive value 93.9% and positive predictive value 34.15%. Conclusions: The Infrascanner has a relatively high specificity and negative predictive value; therefore, it could in association with the Neurological examination, help in the triage of the trauma patient with potential brain injury. Further investigation is necessary to determine the use of Infrascanner 2000 as a diagnostic method in TBI.

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2019, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis, Clinical Neurophysiology, Vol: 130, Pages: 1083-1090, ISSN: 1388-2457

OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. METHODS: Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. RESULTS: By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/- 0.2 SEM), specificity of 91.6% (+/- 0.1 SEM) and classification accuracy of 87.9% (+/- 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). CONCLUSION: We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

Journal article

Nightingale AM, Leong CL, Burnish RA, Hassan S-U, Zhang Y, Clough GF, Boutelle MG, Voegeli D, Niu Xet al., 2019, Monitoring biomolecule concentrations in tissue using a wearable droplet microfluidic-based sensor, Nature Communications, Vol: 10, ISSN: 2041-1723

Knowing how biomarker levels vary within biological fluids over time can produce valuable insight into tissue physiology and pathology, and could inform personalised clinical treatment. We describe here a wearable sensor for monitoring biomolecule levels that combines continuous fluid sampling with in situ analysis using wet-chemical assays (with the specific assay interchangeable depending on the target biomolecule). The microfluidic device employs a droplet flow regime to maximise the temporal response of the device, using a screw-driven push-pull peristaltic micropump to robustly produce nanolitre-sized droplets. The fully integrated sensor is contained within a small (palm-sized) footprint, is fully autonomous, and features high measurement frequency (a measurement every few seconds) meaning deviations from steady-state levels are quickly detected. We demonstrate how the sensor can track perturbed glucose and lactate levels in dermal tissue with results in close agreement with standard off-line analysis and consistent with changes in peripheral blood levels.

Journal article

Samper I, Gowers S, Rogers M, Murray D-S, Jewell S, Pahl C, Strong A, Boutelle Met al., 2019, 3D printed microfluidic device for online detection of dynamic metabolite concentration changes with high temporal resolution in human brain microdialysate, Lab on a Chip, Vol: 19, Pages: 2038-2048, ISSN: 1473-0189

This paper presents the design, optimisation and fabrication of a mechanically robust 3D printed microfluidic device for the high time resolution online analysis of biomarkers in a microdialysate stream at microlitre per minute flow rates. The device consists of a microfluidic channel with secure low volume connections that easily integrates electrochemical biosensors for biomarkers such as glutamate, glucose and lactate. The optimisation process of the microfluidic channel fabrication, including for different types of 3D printer, is explained and the resulting improvement in sensor response time is quantified. The time resolution of the device is characterised by recording short lactate concentration pulses. The device is employed to record simultaneous glutamate, glucose and lactate concentration changes simulating the physiological response to spreading depolarisation events in cerebrospinal fluid dialysate. As a proof-of-concept study, the device is then used in the intensive care unit for online monitoring of a brain injury patient, demonstrating its capabilities for clinical monitoring.

Journal article

Khan M, Boutelle M, 2019, The military applications of physiological sensors, TRAUMA-ENGLAND, Vol: 21, Pages: 3-5, ISSN: 1460-4086

Journal article

Cicatiello C, Moser N, Boutelle M, Georgiou Pet al., 2019, Live Demonstration : A Portable Multi-Ion Platform with Integrated Microfluidics, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025

Conference paper

Gowers S, Hamaoui K, Vallant N, Hanna G, Darzi A, Casanova D, Papalois V, Boutelle Met al., 2018, An improved rapid sampling microdialysis system for human and porcine organ monitoring in a hospital setting, Analytical Methods, Vol: 10, Pages: 5273-5281, ISSN: 1759-9660

Online organ monitoring could provide clinicians with critical information regarding organ health prior to transplantation and could aid clinical decision-making. This paper presents the methodology of online microdialysis for real-time monitoring of human organs ex vivo. We describe how rapid sampling microdialysis can be incorporated with organ perfusion machines to create a robust organ monitoring system and demonstrate its use in monitoring human and porcine kidneys as well as human and porcine pancreases. In this paper we also show the potential usefulness of this methodology for evaluating novel interventions in a research setting. The analysis system can be configured either to analyse two analytes in one organ, allowing for ratiometric analysis, or alternatively to monitor one analyte in two organs simultaneously, allowing direct comparison. It was found to be reliable over long monitoring periods in real clinical use. The results clearly show that the analysis system is sensitive to differences between organs and therefore has huge potential as an ex vivo organ monitoring tool.

Journal article

Cunnea P, Gorgy T, Petkos K, Gowers S, Lu H, Morera C, Wu W, Lawton P, Nixon K, Leong C, Sorbi F, Domenici L, Paterson A, Curry E, Gabra H, Boutelle M, Drakakis E, Fotopoulou Cet al., 2018, Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients., Scientific Reports, Vol: 8, ISSN: 2045-2322

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis. Consistently different biopotential values were detected in cancerous tissue versus non-cancerous tissue across all cases (p < 0.001). High tumour biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour load, and negatively correlated with stroma. Within our EOC cohort and specifically the high-grade serous subtype, low biopotential levels associated with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively). Changes in biopotential levels significantly correlated with common apoptosis related pathways. Lactate and glucose levels measured in paired tissues showed significantly higher lactate/glucose ratio in tissues with low biopotential (p < 0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite monitoring as a biomarker modality profiling EOC to predict surgical and clinical outcomes.

Journal article

Peyton G, Farzaneh B, Soleimani H, Boutelle MG, Drakakis EMet al., 2018, Quadrature synthetic aperture beamforming front-end for miniaturized ultrasound imaging, IEEE Transactions on Biomedical Circuits and Systems, Vol: 12, Pages: 871-883, ISSN: 1932-4545

A quadrature synthetic aperture front-end receiver for B-mode ultrasound imaging is presented. The receiver targets small-scale imaging applications such as capsule endoscopy and low-cost portable devices. System complexity, area, power consumption, and cost are minimized using synthetic aperture beamforming (SAB), whereby signals are processed in a sequential manner using only a single channel. SAB is combined with quadrature (I/Q) sampling, which further reduces the bandwidth and computational load. I/Q demodulation is carried out using a full custom analog front-end (AFE), which comprises a low-noise, variable gain preamplifier, followed by a passive mixer, programmable gain amplifier (PGA) and active lowpass filter. A novel preamplifier design is proposed, with quasi-exponential time-gain control and low noise (5.42 nV√Hz input-referred noise). Overall, the AFE consumes 7.8 mW (static power) and occupies 1.5 mm × 1.5 mm in AMS 0.35 μm CMOS. Real-time SAB is carried out using a Spartan-6 FPGA, which dynamically apodises and focuses the data by interpolating and applying complex phase rotations to the I/Q samples. For a frame rate of 7 Hz, the power consumption is 3.4 mW/channel across an aperture of 64 elements. B-mode images were obtained using a database of ultrasound signals (2.5 MHz center frequency) derived from a commercial ultrasound machine. The normalized root mean squared error between the quadrature SAB image and the RF reference image was 13%. Image quality/frame rate may be tuned by varying the degree of spatial compounding.

Journal article

Peyton G, Boutelle MG, Drakakis EM, 2018, Comparison of synthetic aperture architectures for miniaturised ultrasound imaging front-ends, BioMedical Engineering OnLine, Vol: 17, ISSN: 1475-925X

BackgroundPoint of care ultrasonography has been the focus of extensive research over the past few decades. Miniaturised, wireless systems have been envisaged for new application areas, such as capsule endoscopy, implantable ultrasound and wearable ultrasound. The hardware constraints of such small-scale systems are severe, and tradeoffs between power consumption, size, data bandwidth and cost must be carefully balanced.MethodsIn this work, two receiver architectures are proposed and compared to address these challenges. Both architectures uniquely combine low-rate sampling with synthetic aperture beamforming to reduce the data bandwidth and system complexity. The first architecture involves the use of quadrature sampling to minimise the signal bandwidth and computational load. Synthetic aperture beamforming (SAB) is carried out using a single-channel, pipelined protocol suitable for implementation on an FPGA/ASIC. The second architecture employs compressive sensing within the finite rate of innovation framework to further reduce the bandwidth. Low-rate signals are transmitted to a computational back-end (computer), which sequentially reconstructs each signal and carries out beamforming.ResultsBoth architectures were tested using a custom hardware front-end and synthetic aperture database to yield B-mode images. The normalised root-mean-squared-error between the quadrature SAB image and the RF reference image was 13%while the compressive SAB error was 22% for the same degree of spatial compounding. The sampling rate is reduced by a factor of 2 (quadrature SAB) and 4.7 (compressive SAB), compared to the RF sampling rate. The quadrature method is implemented on FPGA, with a total power consumption of 4.1mW, which is comparable to state-of-the-art hardware topologies, but with significantly reduced circuit area.ConclusionsThrough a novel combination of SAB and low-rate sampling techniques, the proposed architectures achieve a significant reduction in data transmission

Journal article

Pagkalos I, Rogers M, Boutelle MG, Drakakis EMet al., 2018, A high performance application specific integrated circuit for electrical and neurochemical traumatic brain injury monitoring, ChemPhysChem, Vol: 19, Pages: 1215-1225, ISSN: 1439-7641

This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neuralphysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5mm2 ASIC fabricated in the commercially available AMS 0.35um CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics-based electrochemical biosensors. The potentiostats use switched-capacitor charge integration to record currents with 100fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a "behind the ear" wireless microplatform modality, which could enable the monitoring of currently non-monitored mobile TBI patients for the onset of secondary brain injury.

Journal article

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