116 results found
Meng X, O'Hare D, Ladame S, 2023, Surface immobilization strategies for the development of electrochemical nucleic acid sensors., Biosens Bioelectron, Vol: 237
Following the recent pandemic and with the emergence of cell-free nucleic acids in liquid biopsies as promising biomarkers for a broad range of pathologies, there is an increasing demand for a new generation of nucleic acid tests, with a particular focus on cost-effective, highly sensitive and specific biosensors. Easily miniaturized electrochemical sensors show the greatest promise and most typically rely on the chemical functionalization of conductive materials or electrodes with sequence-specific hybridization probes made of standard oligonucleotides (DNA or RNA) or synthetic analogues (e.g. Peptide Nucleic Acids or PNAs). The robustness of such sensors is mostly influenced by the ability to control the density and orientation of the probe at the surface of the electrode, making the chemistry used for this immobilization a key parameter. This exhaustive review will cover the various strategies to immobilize nucleic acid probes onto different solid electrode materials. Both physical and chemical immobilization techniques will be presented. Their applicability to specific electrode materials and surfaces will also be discussed as well as strategies for passivation of the electrode surface as a way of preventing electrode fouling and reducing nonspecific binding.
Freeman DME, Ming DK, Wilson R, et al., 2023, Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes, ACS SENSORS, ISSN: 2379-3694
Trouillon R, Kang D-K, Chang S-I, et al., 2022, Neomycin, but Not Neamine, Blocks Angiogenic Factor Induced Nitric Oxide Release through Inhibition of Akt Phosphorylation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 23
Zhang S, Chen Y-C, Riezk A, et al., 2022, Rapid measurement of lactate in exhaled breath condensate: biosensor optimisation and in-human proof-of-concept, ACS Sensors, Vol: 7, Pages: 3809-3816, ISSN: 2379-3694
Lactate concentration is of increasing interest as a diagnostic for sepsis, septic shock, and trauma. Compared with the traditional blood sample media, the exhaled breath condensate (EBC) has the advantages of non-invasiveness and higher user acceptance. An amperometric biosensor was developed and its application in EBC lactate detection was investigated in this paper. The sensor was modified with PEDOT:PSS-PB, and two different lactate oxidases (LODs). A rotating disk electrode and Koutecky–Levich analysis were applied for the kinetics analysis and gel optimization. The optimized gel formulation was then tested on disposable screen-printed sensors. The disposable sensors exhibited good performance and presented a high stability for both LOD modifications. Finally, human EBC analysis was conducted from a healthy subject at rest and after 30 min of intense aerobic cycling exercise. The sensor coulometric measurements showed good agreement with fluorometric and triple quadrupole liquid chromatography mass spectrometry reference methods. The EBC lactate concentration increased from 22.5 μM (at rest) to 28.0 μM (after 30 min of cycling) and dropped back to 5.3 μM after 60 min of rest.
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.
Ledesma Amaro R, Ouldridge T, O'Hare D, et al., 2022, Synthetic biology and bioelectrochemical tools for electrogenetic system engineering, Science Advances, Vol: 8, ISSN: 2375-2548
Synthetic biology research and its industrial applications rely on deterministic spatiotemporal control of gene expression. Recently, electrochemical control of gene expression has been demonstrated in electrogenetic systems (redox-responsive promoters used alongside redox inducers and electrodes), allowing for the direct integration of electronics with biological processes. However, use of electrogenetic systems is limited by poor activity, tunability and standardisation. In this work we developed a strong, unidirectional, redox-responsive promoter before deriving a mutant promoter library with a spectrum of strengths. We constructed genetic circuits with these parts and demonstrated their activation by multiple classes of redox molecules. Finally, we demonstrated electrochemical activation of gene expression in aerobic conditions using a novel, modular bioelectrochemical device. These genetic and electrochemical tools facilitate the design and improve the performance of electrogenetic systems. Furthermore, the genetic design strategies used can be applied to other redox-responsive promoters to further expand the available tools for electrogenetics.
McLeod J, Stadler E, Wilson R, et al., 2021, Electrochemical detection of cefiderocol for therapeutic drug monitoring, Electrochemistry Communications, Vol: 133, ISSN: 1388-2481
Cefiderocol is a novel siderophore-conjugated β-lactam antibiotic which has been approved for clinical use. It has demonstrated efficacy against infections caused by Gram-negative bacteria, including carbapenem-resistant strains. Novel antibiotics are rarely brought to market and, as such, are ideal candidates for therapeutic drug monitoring which enables optimised dosing across a range of clinical scenarios whilst also reducing the chances of antimicrobial resistance. Here we demonstrate direct electrochemical detection of cefiderocol by oxidation using untreated gold and glassy carbon electrodes as well as multi-walled carbon nanotube (MWCNT)-coated glassy carbon and foamed gold electrodes. Quantification of cefiderocol in the therapeutic range is demonstrated in spiked whole human blood using MWCNT-coated pyrolytic carbon screen-printed electrodes.
Ming DK, Jangam S, Gowers SAN, et al., 2021, Real-time Continuous Measurement of Lactate through a Minimally-invasive Microneedle Biosensor: a Phase I Clinical Study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Five healthy adult participants wore a solid microneedle biosensor on their forearms and undertook aerobic exercise for 30 minutes. The microneedle biosensor quantifies lactate concentrations in interstitial fluid (ISF) within the dermis continuously and in real-time. Outputs were captured as sensor current and compared with lactate concentrations from venous blood and microdialysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The biosensor was well-tolerated. Participants generated a median peak venous lactate of 9.25 mmol/L (Interquartile range, 6.73 to 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 minutes (IQR -4 to 11 minutes) between microneedle and blood lactate measurements.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study provides first-in-human data on use of a minimally-invasive microneedle biosensor for continuous lactate measurement, providing dynamic monitoring. The platform offers distinct advantages to frequent blood sampling in a wide range of clinical settings, especially where access to laboratory services is limited or b
Rawson TM, Wilson RC, O'Hare D, et al., 2021, Optimizing antimicrobial use: challenges, advances and opportunities, NATURE REVIEWS MICROBIOLOGY, Vol: 19, Pages: 747-758, ISSN: 1740-1526
Zaman S, Seligman H, Lloyd FH, et al., 2021, Aerosolised fluorescein can quantify FFP mask faceseal leakage: a cost-effective adaptation to the existing point of care fit test, CLINICAL MEDICINE, Vol: 21, Pages: E263-E268, ISSN: 1470-2118
Colburn AW, Levey KJ, O'Hare D, et al., 2021, Lifting the lid on the potentiostat: a beginner's guide to understanding electrochemical circuitry and practical operation, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 23, Pages: 8100-8117, ISSN: 1463-9076
Gillespie P, Channon RB, Meng X, et al., 2021, Nucleic acid sensing via electrochemical oligonucleotide-templated reactions, BIOSENSORS & BIOELECTRONICS, Vol: 176, ISSN: 0956-5663
Morgan LD, Mohammed A, Patel BA, et al., 2020, Decreased 14-3-3 expression correlates with age-related regional reductions in CNS dopamine and motor function in the pond snail, Lymnaea, EUROPEAN JOURNAL OF NEUROSCIENCE, Vol: 53, Pages: 1394-1411, ISSN: 0953-816X
Lee M-H, Liu K-T, Thomas JL, et al., 2020, Peptide-Imprinted Poly(hydroxymethyl 3,4-ethylenedioxythiophene) Nanotubes for Detection of alpha Synuclein in Human Brain Organoids, ACS APPLIED NANO MATERIALS, Vol: 3, Pages: 8027-8036, ISSN: 2574-0970
Raditya AN, O'Hare D, 2020, Review-Electrochemical Sensor Biofouling in Environmental Sensor Networks: Characterisation, Remediation and Lessons from Biomedical Devices, JOURNAL OF THE ELECTROCHEMICAL SOCIETY, Vol: 167, ISSN: 0013-4651
Chen Y-C, O'Hare D, 2020, Exhaled breath condensate based breath analyser - a disposable hydrogen peroxide sensor and smart analyser, ANALYST, Vol: 145, Pages: 3549-3556, ISSN: 0003-2654
Channon RB, Gillespie P, Nazmul Islam M, et al., 2020, Electrochemical oligonucleotide templated reactions, Pages: 476-477
The biosensing of nucleic acids is an excellent approach for medical diagnosis, however established nucleic acid sensing technologies are typically limited by slow throughput, bulky equipment and the difficulty in achieving trace sensitivity with single nucleotide specificity. Here, we describe the first example of an electrochemical oligonucleotide templated reaction (EOTR). The target nucleic acid acts as a template for two probe-modified peptide nucleic acids. Reaction of the probe heads then generates an electrochemically active adduct. We couple EOTR with a lateral flow assay platform, towards developing a screening test for prostate cancer specific miRNA.
Cass AEG, O'Hare D, Sharma S, 2020, Recent Developments in Continuous Monitoring Diagnostics with Microneedle Arrays, 7th International Conference on the Development of Biomedical Engineering, Publisher: SPRINGER-VERLAG SINGAPORE PTE LTD, Pages: 337-339, ISSN: 1680-0737
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
Background: Enhanced 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.Methods: This 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 Clinical
Cass A, Sharma S, O'Hare D, 2019, Minimally invasive microneedle sensor arrays: New window on the body, ACS Fall National Meeting and Exposition, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
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
Channon RB, Pavagada S, Chang JYH, et al., 2019, Point-of-care nucleic Acid sensors via paper-based oligonucleotide-templated reactions, Pages: 815-816
This paper describes a new and inexpensive approach for specific sensing of endogenous concentrations of miRNAs extracted from blood, based on a fluorogenic oligonucleotide templated reaction (OTR) on a lateral flow assay (LFA). Our method is then applied to develop the first early screening test for Preterm birth.
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, 2018, 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.
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