20 results found
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.
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
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.
Samper I, Gowers S, Rogers M, et 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.
Gowers SAN, Freeman DME, Rawson TM, et al., 2019, Development of a minimally invasive microneedle-based sensor for continuous monitoring of β-lactam antibiotic concentrations in vivo, ACS sensors, Vol: 4, Pages: 1072-1080, ISSN: 2379-3694
Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual. New sensing approaches that track antimicrobial concentration for each patient in real time could allow individualized drug dosing. This work presents a potentiometric microneedle-based biosensor to detect levels of β-lactam antibiotics in vivo in a healthy human volunteer. The biosensor is coated with a pH-sensitive iridium oxide layer, which detects changes in local pH as a result of β-lactam hydrolysis by β-lactamase immobilized on the electrode surface. Development and optimization of the biosensor coatings are presented, giving a limit of detection of 6.8 μM in 10 mM PBS solution. Biosensors were found to be stable for up to 2 weeks at -20 °C and to withstand sterilization. Sensitivity was retained after application for 6 h in vivo. Proof-of-concept results are presented showing that penicillin concentrations measured using the microneedle-based biosensor track those measured using both discrete blood and microdialysis sampling in vivo. These preliminary results show the potential of this microneedle-based biosensor to provide a minimally invasive means to measure real-time β-lactam concentrations in vivo, representing an important first step toward a closed-loop therapeutic drug monitoring system.
Rawson TM, Gowers S, Rogers M, et al., 2018, Towards a minimally invasive device for continuous monitoring of beta-lactam antibiotics, Publisher: ELSEVIER SCI LTD, Pages: 109-109, ISSN: 1201-9712
Pagkalos I, Rogers M, Boutelle MG, et al., 2018, A high-performance application specific integrated circuit for electrical and neurochemical traumatic brain injury monitoring, ChemPhysChem: a European journal of chemical physics and physical chemistry, Vol: 19, Pages: 1215-1225, ISSN: 1439-4235
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 0.35μm 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.
Booth MA, Gowers SAN, Leong CL, et al., 2017, Chemical Monitoring in Clinical Settings: Recent Developments toward Real-Time Chemical Monitoring of Patients., Analytical Chemistry, Vol: 90, Pages: 2-18, ISSN: 0003-2700
Rogers ML, Leong CL, Gowers SAN, et al., 2017, Simultaneous monitoring of potassium, glucose and lactate during spreading depolarisation in the injured human brain - proof of principle of a novel real-time neurochemical analysis system, continuous online microdialysis (coMD), Journal of Cerebral Blood Flow and Metabolism, Vol: 37, Pages: 1883-1895, ISSN: 1559-7016
Spreading Depolarisations (SDs) occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an SD requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential. In the injured brain this is difficult because local blood flow is often low and unreactive. In this study we use a new variant of microdialysis, continuous on-line microdialysis (coMD), to observe the effects of SDs on brain metabolism. The neurochemical changes are dynamic and take place on the timescale of the passage of an SD past the microdialysis probe. Dialysate potassium levels provide an ionic correlate of cellular depolarisation and show a clear transient increase. Dialysate glucose levels reflect a balance between local tissue glucose supply and utilization. These show a clear transient decrease of variable magnitude and duration. Dialysate lactate levels indicate non-oxidative metabolism of glucose and show a transient increase. Preliminary data suggest that the transient changes recover more slowly after the passage of a sequence of multiple SD’s giving rise to a decrease in basal dialysate glucose and an increase in basal dialysate potassium and lactate levels.
Boutelle M, Samper I, Leong A, et al., 2017, Faster neurochemical measurements using continuous on-line microdialysis: Towards microdialysis 2.0, 253rd National Meeting of the American-Chemical-Society (ACS) on Advanced Materials, Technologies, Systems, and Processes, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Sharma S, Huang Z, Rogers M, et al., 2016, Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring, Analytical and Bioanalytical Chemistry, Vol: 408, Pages: 8427-8435, ISSN: 1618-2650
We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T90) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3–6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these.
Papadimitriou K, Wang C, Rogers M, et al., 2016, High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring, Frontiers in Human Neuroscience, Vol: 10, ISSN: 1662-5161
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 TBI’s 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 brain’s 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 realisation 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.
Hamaoui K, Gowers S, Damji S, et al., 2016, Rapid sampling microdialysis as a novel tool for parenchyma assessment during static cold storage and hypothermic machine perfusion in a translational ex vivo porcine kidney model, Journal of Surgical Research, Vol: 200, Pages: 332-345, ISSN: 1095-8673
BackgroundViability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period.MethodsTwenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s.ResultsOn commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 μM) and HMP (124 μM, P > 0.05) but lower after 10 h of SCS (SCS: 68 μM versus HMP: 230 μM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys.ConclusionsThis preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.
Boutelle MG, Rogers ML, Leong CL, et al., 2013, The dynamics of glucose and lactate metabolism in the injured brain during spreading depolarisation, 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry, Publisher: WILEY-BLACKWELL, Pages: 48-48, ISSN: 0022-3042
Rogers ML, Feuerstein D, Leong CL, et al., 2013, Continuous Online Microdialysis Using Microfluidic Sensors: Dynamic Neurometabolic Changes during Spreading Depolarization, ACS CHEMICAL NEUROSCIENCE, Vol: 4, Pages: 799-807, ISSN: 1948-7193
Rogers ML, Brennan PA, Leong CL, et al., 2013, Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery, ANALYTICAL AND BIOANALYTICAL CHEMISTRY, Vol: 405, Pages: 3881-3888, ISSN: 1618-2642
Rogers ML, Boutelle MG, 2013, Real-Time Clinical Monitoring of Biomolecules, ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 6, Vol: 6, Pages: 427-453, ISSN: 1936-1327
Patel BA, Rogers M, Wieder T, et al., 2011, ATP microelectrode biosensor for stable long-term in vitro monitoring from gastrointestinal tissue, BIOSENSORS & BIOELECTRONICS, Vol: 26, Pages: 2890-2896, ISSN: 0956-5663
Rogers M, Leong C, Niu X, et al., 2011, Optimisation of a microfluidic analysis chamber for the placement of microelectrodes, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 13, Pages: 5298-5303, ISSN: 1463-9076
Hannan S, Ready D, Jasni AS, et al., 2010, Transfer of antibiotic resistance by transformation with eDNA within oral biofilms, FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, Vol: 59, Pages: 345-349, ISSN: 0928-8244
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