96 results found
Cass AEG, O’Hare D, Sharma S, 2020, Recent Developments in Continuous Monitoring Diagnostics with Microneedle Arrays, Pages: 337-339, ISSN: 1680-0737
© 2020, Springer Nature Singapore Pte Ltd. Compared with therapeutics, diagnostic devices account for a relatively small proportion of healthcare expenditure (less than 10%) and yet timely diagnosis as well as continuous monitoring of molecular markers can have a major impact on disease outcomes. In particular point of care (or near patient) tests can empower individuals to become active participants in the management of their conditions, giving them and their medical support greater insight into both their conditions and their response to treatment. In an extension of the point of care paradigm, continuous monitors of biomarkers and/or therapeutics allow high frequency data to be gathered and patterns of variation to be analyzed in ways that are not possible with infrequent and sporadic testing. The advent of novel materials, fabrication methods and data analysis have opened the way to new devices, assay formats and molecular targets. In this paper we will discuss some aspects of our work in this area with a particular focus on microneedles for continuous, minimally invasive sensing and the use of nucleic acid aptamers in both electrochemical and lateral flow assays.
Rawson TM, Gowers SAN, Freeman DME, et al., 2019, Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers, The Lancet Digital Health, Vol: 1, Pages: e335-e343, ISSN: 2589-7500
BackgroundEnhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers.MethodsThis first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK). The study was approved by London-Harrow Regional Ethics Committee. Volunteers were identified through emails sent to a healthy volunteer database from the Imperial College Clinical Research Facility. Volunteers, who had to be older than 18 years, were excluded if they had evidence of active infection, allergies to penicillin, were at high risk of skin infection, or presented with anaemia during screening. Participants wore a solid microneedle β-lactam biosensor for up to 6 h while being dosed at steady state with oral phenoxymethylpenicillin (five 500 mg doses every 6 h). On arrival at the study centre, two microneedle sensors were applied to the participant's forearm. Blood samples (via cannula, at −30, 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) and extracellular fluid (ECF; via microdialysis, every 15 min) pharmacokinetic (PK) samples were taken during one dosing interval. Phenoxymethylpenicillin concentration data obtained from the microneedles were calibrated using locally estimated scatter plot smoothing and compared with free-blood and microdialysis (gold standard) data. Phenoxymethylpenicillin PK for each method was evaluated using non-compartmental analysis. Area under the concentration–time curve (AUC), maximum concentration, and time to maximum concentration were compared. Bias and limits of agreement were investigated with Bland–Altman plots. Microneedle biosensor limits of detection were estimated. The study was registered with ClinicalTria
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.
Wilson RE, Stoianov I, OHare D, 2019, Continuous chlorine detection in drinking water and a review of new detection methods, Johnson Matthey Technology Review, Vol: 63, Pages: 103-118, ISSN: 2056-5135
Chlorination is necessary to prevent epidemics of waterborne disease however excess chlorination is wasteful, produces harmful disinfection byproducts, exacerbates corrosion and causes deterioration in aesthetic qualities, leading to consumer complaints. Residual chlorine must be continuously monitored to prevent both under- and over-chlorination and factors including pH, temperature and fouling must be considered as these also affect the disinfectant strength of residual chlorine. Standard methods used by water utility companies to determine residual chlorine concentration in drinking water distribution systems are appraised and found to be unsuitable for continuous monitoring. A selection of newly developed methods for residual chlorine analysis are evaluated against performance criteria, to direct research towards the development of chlorine sensors that are suitable for use in water systems. It is found that fouling tolerance in particular is generally not well understood for these selected sensor technologies and that long-term trials in real systems is recommended.
Gillespie P, Ladame S, O'Hare D, 2019, Molecular methods in electrochemical microRNA detection, ANALYST, Vol: 144, Pages: 114-129, ISSN: 0003-2654
Rawson T, Ming D, Gowers S, et al., 2019, Public acceptability of computer-controlled antibiotic management: an exploration of automated dosing and opportunities for implementation, Journal of Infection, Vol: 78, Pages: 75-86, ISSN: 0163-4453
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
Kim J-Y, O'Hare D, 2018, Monolithic nano-porous polymer in microfluidic channels for lab-chip liquid chromatography, Nano Convergence, Vol: 5, ISSN: 2196-5404
In this paper, a nano-porous polymer has been integrated into the microfluidics device as on-chip monolithic liquid chromatography column for separation of chemical and biological samples. Monolithic nano-porous polymer (MNP) was formed and firmly grafted on the surface of the microfluidic channel. Neurotransmitters, 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptamine (serotonin, 5-HT), were successfully separated with the developed on-chip MNP column.
Zafeiropoulos G, O'Hare D, Drakakis E, PANACEA 2.0: A Wireless, High-Performance Multi-instrument for (Bio)Signals Recording, BioMedEng18
Rawson T, o'hare D, Herrero P, et al., 2018, Delivering precision antimicrobial therapy through closed-loop control systems, Journal of Antimicrobial Chemotherapy, Vol: 73, Pages: 835-843, ISSN: 0305-7453
Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.
Bell CG, Seelanan P, O'Hare D, 2017, Microelectrode generator-collector systems for electrolytic titration: theoretical and practical considerations, ANALYST, Vol: 142, Pages: 4048-4057, ISSN: 0003-2654
Rawson TM, Sharma S, Georgiou P, et al., 2017, Towards a minimally invasive device for beta-lactam monitoring in humans, ELECTROCHEMISTRY COMMUNICATIONS, Vol: 82, Pages: 1-5, ISSN: 1388-2481
Antimicrobial resistance is a leading patient safety issue. There is a need to develop novel mechanisms for monitoring and subsequently improving the precision of how we use antibiotics. A surface modified microneedle array was developed for monitoring beta-lactam antibiotic levels in human interstitial fluid. The sensor was fabricated by anodically electrodepositing iridium oxide (AEIROF) onto a platinum surface on the microneedle followed by fixation of beta-lactamase enzyme within a hydrogel. Calibration of the sensor was performed to penicillin-G in buffer solution (PBS) and artificial interstitial fluid (ISF). Further calibration of a platinum disc electrode was undertaken using amoxicillin and ceftriaxone. Open-circuit potentials were performed and data analysed using the Hill equation and log(concentration [M]) plots. The microneedle sensor demonstrated high reproducibility between penicillin-G runs in PBS with mean Km (± 1SD) = 0.0044 ± 0.0013 M and mean slope function of log(concentration plots) 29 ± 1.80 mV/decade (r2 = 0.933). Response was reproducible after 28 days storage at 4 °C. In artificial ISF, the sensors response was Km (± 1SD) = 0.0077 ± 0.0187 M and a slope function of 34 ± 1.85 mv/decade (r2 = 0.995). Our results suggest that microneedle array based beta-lactam sensing may be a future application of this AEIROF based enzymatic sensor.
Zhexembekova A, Akhmetova N, Molkenova A, et al., 2017, Thiol-modified activated carbon material for sensor technology, 4th International Conference on Nanomaterials and Advanced Energy Storage Systems (INESS), Publisher: ELSEVIER SCIENCE BV, Pages: 4599-4602, ISSN: 2214-7853
Gandhi SI, Boutelle M, O'Hare D, 2016, A novel electrolytic titrator design - Coating platinum cathodes with an electron sink using Nafion (R) and hexaammineruthenium (III), ELECTROCHEMISTRY COMMUNICATIONS, Vol: 73, Pages: 50-54, ISSN: 1388-2481
Wilson RE, Stoianov I, O'Hare D, 2016, Biofouling and in situ electrochemical cleaning of a boron-doped diamond free chlorine sensor, Electrochemistry Communications, Vol: 71, Pages: 79-83, ISSN: 1873-1902
Biofouling presents a significant obstacle to the long-term use of electrochemical sensors in complex media. Drinking water biofilms reduce performance of sensors by insulating electrode surfaces by inter alia inhibiting mass transport. Boron-doped diamond (BDD) electrodes are relatively resistant to biofouling and inert at high potentials. These qualities can be exploited to create a drinking water quality sensor that resists biofouling to meet performance criteria for longer, and to enable electrochemical cleaning of the sensor surface in situ using high potentials without disconnecting or disassembling the sensor.A purpose-built BDD wall-jet sensor was compared with a glassy carbon (GC) sensor in ability to determine free chlorine, detect biofilm and remove biofilm in situ. It was found that the BDD produced accurate and reliable readings with a 4.86% standard error and a LOD of 0.18 ppm. The BDD could be electrochemically cleaned in situ whereas this was less successful with the GC electrode. The BDD electrode could also detect electroactive pyocyanin, secreted in the biofilm of the drinking water biofilm indicator organism Pseudomonas aeruginosa, potentially enabling biofouling and non-biological fouling such as scaling to be distinguished. Observed changes in flow sensitivity and current-voltage curves that correspond to fouling provide multiple fouling detection methods, resulting in an accurate, sensitive, water quality sensor that can be cleaned without disassembly or replacement of parts and can identify when cleaning is required.
Lee M-H, O'Hare D, Guo H-Z, et al., 2016, Electrochemical sensing of urinary progesterone with molecularly imprinted poly(aniline-co-metanilic acid)s, Journal of Materials Chemistry B, Vol: 4, Pages: 3782-3787, ISSN: 2050-7518
In this work, progesterone is imprinted into poly(aniline-co-metanilic acid) on the working electrode of an electrochemical sensing chip. This sensing chip was used directly to optimize the composition of the imprinting polymer. Poly(aniline-co-metanilic acid) deposited from a 1 : 3 molar ratio of aniline (ANI) : m-aminobenzenesulfonic acid (MSAN) had an imprinting effectiveness which led to a four-fold greater electrochemical response than pure polyaniline. The electrochemical sensing of progesterone had a limit of detection (LOD) less than 1.0 pg mL−1, and the direct electrochemical response was very weak even at high interference concentrations. Results from potential interferents (urea, testosterone, creatinine and 17-β estradiol) are reported. The progesterone levels that were measured in a random urine analysis were compared with those obtained using a commercial ARCHITECT system, and the accuracy of the progesterone concentration was 89.0 ± 5.3% at a concentration of 0.64–5.27 ng mL−1.
Ng SR, Pang H, Chen P, et al., 2015, A Novel Electroactive Polymer for pH-independent Oxygen Sensing, ELECTROANALYSIS, Vol: 27, Pages: 2745-2752, ISSN: 1040-0397
Huang C-Y, O'Hare D, Chao I-J, et al., 2015, Integrated potentiostat for electrochemical sensing of urinary 3-hydroxyanthranilic acid with molecularly imprinted poly (ethylene-co-vinyl alcohol), BIOSENSORS & BIOELECTRONICS, Vol: 67, Pages: 208-213, ISSN: 0956-5663
Leow PL, Chee PS, Patel BA, et al., 2015, A study of the in-column detection performance for chromatography separation, Microfluidics and Nanofluidics, Vol: 19, Pages: 343-349, ISSN: 1613-4990
This paper studies the in-column detection performance for chromatography separation. Numerical modeling was performed to investigate the detection efficiency of the electrodes that are suspended within a packed chromatography column. The results show that the density of the silica beads packed within the channel does not hinder the detection ability of the electrode. The findings have been further validated with experimental works. An 8 in-column electrode array provides the full separation progress traces of the five neurotransmitters and metabolites (adrenalin, dopamine, DOPAC, serotonin and 5-HIAA) within the column. From the in-column detection, better peak resolutions are developed though the separation column as compared to the conventional post-column detection. The whole progress of the separation shows that good separation (R s > 1) can be obtained at E5 (28.7 mm from column inlet), whereas baseline separation could be obtained at E8 (last in-column electrode) with R s ≥ 1.5 within 60 min. The presented results suggest that the packing materials within the column do not obstruct the efficiency of the electrodes but able to produce a good baseline separation detection as compared to conventional post-column detection.
Ng SR, O'Hare D, 2015, An iridium oxide microelectrode for monitoring acute local pH changes of endothelial cells, ANALYST, Vol: 140, Pages: 4224-4231, ISSN: 0003-2654
Lee M-H, O'Hare D, Chen Y-L, et al., 2014, Molecularly imprinted electrochemical sensing of urinary melatonin in a microfluidic system, BIOMICROFLUIDICS, Vol: 8, ISSN: 1932-1058
Kim J-Y, Chang S-I, deMello AJ, et al., 2014, Integration of monolithic porous polymer with droplet-based microfluidics on a chip for nano/picoliter volume sample analysis., Nano Converg, Vol: 1, ISSN: 2196-5404
In this paper, a porous polymer nanostructure has been integrated with droplet-based microfluidics in a single planar format. Monolithic porous polymer (MPP) was formed selectively within a microfluidic channel. The resulting analyte bands were sequentially comartmentalised into droplets. This device reduces band broadening and the effects of post-column dead volume by the combination of the two techniques. Moreover it offers the precise control of nano/picoliter volume samples.
Trouillon R, Williamson ED, Saint RJ, et al., 2012, Electrochemical detection of the binding of Bacillus anthracis protective antigen (PA) to the membrane receptor on macrophages through release of nitric oxide, BIOSENSORS & BIOELECTRONICS, Vol: 38, Pages: 138-144, ISSN: 0956-5663
Bell CG, Anastassiou CA, O'Hare D, et al., 2012, Theoretical treatment of high-frequency, large-amplitude ac voltammetry applied to ideal surface-confined redox systems, ELECTROCHIMICA ACTA, Vol: 64, Pages: 71-80, ISSN: 0013-4686
Kim J-Y, Cho S-W, Kang D-K, et al., 2012, Lab-chip HPLC with integrated droplet-based microfluidics for separation and high frequency compartmentalisation, CHEMICAL COMMUNICATIONS, Vol: 48, Pages: 9144-9146, ISSN: 1359-7345
Trouillon R, O'Hare D, Chang S-I, 2011, An electrochemical functional assay for the sensing of nitric oxide release induced by angiogenic factors, BMB REPORTS, Vol: 44, Pages: 699-704, ISSN: 1976-6696
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
Trouillon R, Kang D-K, Chang S-I, et al., 2011, Angiogenin induces nitric oxide release independently from its RNase activity, CHEMICAL COMMUNICATIONS, Vol: 47, Pages: 3421-3423, ISSN: 1359-7345
Kim J-Y, deMello AJ, Chang S-I, et al., 2011, Thermoset polyester droplet-based microfluidic devices for high frequency generation, LAB ON A CHIP, Vol: 11, Pages: 4108-4112, ISSN: 1473-0197
Trouillon R, O'Hare D, Einaga Y, 2011, Effect of the doping level on the biological stability of hydrogenated boron doped diamond electrodes, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 13, Pages: 5422-5429, ISSN: 1463-9076
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