Publications
282 results found
Lo Y, Liang S, Dhillo WS, et al., 2023, Robotic APTamer-Enabled Electrochemical Reader (RAPTER) System for Automated Aptamer-Mediated Electrochemical Analysis., Methods Mol Biol, Vol: 2570, Pages: 271-280
Electrochemical aptamer-based (E-AB) sensors using conformational change-induced electron transfer kinetics are sensitive, reagent-less, and cost-effective tools for molecular sensing. Current advances in this technology can allow continuous drug pharmacokinetic monitoring in living animals (Dauphin-Ducharme et al., ACS Sens 4(10):2832-2837, 2019; Idili et al., Chem Sci 10(35):8164-8170, 2019), as well as automated analysis of hormone pulsatility (Liang et al., Nat Commun 10(1):852, 2019). In this chapter, we provide the methodology for an automated E-AB conformational change-based robotic sensing platform. By using an open-source programmable robotic system, this method can be adapted to a wide range of experimental scenarios.
Phongphut A, Chayasombat B, Cass AEG, et al., 2022, Biosensors Based on Acetylcholinesterase Immobilized on Clay-Gold Nanocomposites for the Discrimination of Chlorpyrifos and Carbaryl, ACS OMEGA, Vol: 7, Pages: 39848-39859, ISSN: 2470-1343
Freeman DME, Cass AEG, 2022, A Perspective on microneedle sensor arrays for continuous monitoring of the body's chemistry, APPLIED PHYSICS LETTERS, Vol: 121, ISSN: 0003-6951
Hassan-Nixon HA, Singh N, Cass AEG, 2022, A sensitive impedimetric immunosensor for the detection of Interleukin-8 in nasal epithelial lining fluid of asthma patients, Biosensors and Bioelectronics: X, Vol: 10
We report the development of a label-free, affinity-based impedimetric biosensor for the quantitative detection of interleukin-8 (IL-8) present in the nasal epithelial lining fluid (NELF). Early diagnosis of IL-8 in NELF samples enables prognosis of inflammatory respiratory disorders including asthma, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. The study involves the fabrication of an electrochemical biosensor by immobilising polyclonal anti-IL-8 antibody on the anti-fouling zwitterionic hydrogel; polycarboxybetaine methacrylate (pCBMA). The immunosensor was characterised using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), vertical scanning interferometry (VSI) and scanning electron microscopy (SEM). Faradaic EIS measurements were conducted to explore the performance of the immunosensor via changes in charge transfer resistance. The sensor exhibited a good analytical performance in the detection and quantification of IL-8 in complex biological media. The biosensor showed a wide range of IL-8 detection, ranging from 55 fM to 55 nM with a 10 fM limit of detection (LOD). The biosensor showed a high selectivity to IL-8 and 90% reproducibility using untreated NELF samples, with 15-min time to result. These results provide a promising potential for multiplexing the cytokine platform for the profiling, diagnosis and clinical signaturing of associated respiratory disorders.
Tortolini C, Cass AEG, Pofi R, et al., 2022, Microneedle-based nanoporous gold electrochemical sensor for real-time catecholamine detection, MICROCHIMICA ACTA, Vol: 189, ISSN: 0026-3672
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- Citations: 2
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.
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
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- Citations: 28
Piersimoni ME, Teng X, Cass AEG, et al., 2020, Antioxidant lipoic acid ligand-shell gold nanoconjugates against oxidative stress caused by α-Synuclein aggregates, Nanoscale Advances, Vol: 2, Pages: 5666-5681, ISSN: 2516-0230
Gold nanoparticle is becoming a promising platform for the delivery of drugs to treat neurodegenerative diseases. Parkinson’s disease, associated with the aggregation of α-synuclein, is a condition that results in dysfunctional neuronal cells leading to their degeneration and death. Oxidative stress has been strongly implicated as a common feature in this process. The limited efficacy of the traditional therapies and the development of associated severe side effects present an unmet need for preventive and adjuvant therapies. The organosulfur compound lipoic acid, naturally located in the mitochondria, plays a powerful antioxidative role against oxidative stress. However, the efficacy is limited by its low physiological concentration, and the administration is affected by its short half-life and bioavailability due to hepatic degradation. Here we exploited the drug delivery potential of gold nanoparticles to assemble lipoic acid, and administered the system to SH-SY5Y cells, a cellular model commonly used to study Parkinson’s disease. We tested the nanoconjugates, termed GNPs-LA, under an oxidative environment induced by gold nanoparticle/α-synuclein conjugates (GNPs-α-Syn). GNPs-LA were found to be biocompatible and capable of restoring the cell damage caused by high-level reactive oxygen species generated by excessive oxidative stress in the cellular environment. We conclude that GNPs-LA may serve as a promising drug delivery vehicle conveying antioxidant molecules for the treatment of Parkinson’s disease.
Ates HC, Roberts JA, Lipman J, et al., 2020, On-Site Therapeutic Drug Monitoring, TRENDS IN BIOTECHNOLOGY, Vol: 38, Pages: 1262-1277, ISSN: 0167-7799
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- Citations: 67
Izzi-Engbeaya C, Abbara A, Cass A, et al., 2020, Using Aptamers as a Novel Method for Determining GnRH/LH Pulsatility, International Journal of Molecular Sciences, Vol: 21, ISSN: 1422-0067
Aptamers are a novel technology enabling the continuous measurement of analytes in blood and other body compartments, without the need for repeated sampling and the associated reagent costs of traditional antibody-based methodologies. Aptamers are short single-stranded synthetic RNA or DNA that recognise and bind to specific targets. The conformational changes that can occur upon aptamer–ligand binding are transformed into chemical, fluorescent, colour changes and other readouts. Aptamers have been developed to detect and measure a variety of targets in vitro and in vivo. Gonadotropin-releasing hormone (GnRH) is a pulsatile hypothalamic hormone that is essential for normal fertility but difficult to measure in the peripheral circulation. However, pulsatile GnRH release results in pulsatile luteinizing hormone (LH) release from the pituitary gland. As such, LH pulsatility is the clinical gold standard method to determine GnRH pulsatility in humans. Aptamers have recently been shown to successfully bind to and measure GnRH and LH, and this review will focus on this specific area. However, due to the adaptability of aptamers, and their suitability for incorporation into portable devices, aptamer-based technology is likely to be used more widely in the future.
Phongphut A, Chayasombat B, Cass AEG, et al., 2020, Clay/au nanoparticle composites as acetylcholinesterase carriers and modified-electrode materials: A comparative study, APPLIED CLAY SCIENCE, Vol: 194, ISSN: 0169-1317
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- Citations: 12
Le TT, Bruckbauer A, Tahirbegi B, et al., 2020, A highly stable RNA aptamer probe for the retinoblastoma protein in live cells, Chemical Science, Vol: 11, Pages: 4467-4474, ISSN: 2041-6520
<p>An RNA G-quadruplex aptamer, specific for the human retinoblastoma protein (RB) and highly stable inside cells, is selected and its application to live cell probing of the protein illustrated.</p>
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
Howells O, Rajendran N, Mcintyre S, et al., 2019, Microneedle array-based platforms for future theranostic applications, ChemBioChem, Vol: 20, Pages: 2198-2202, ISSN: 1439-4227
Theranostics involves finding the biomarkers of a disease, fighting them through site specific drug delivery and following them for prognosis of the disease. Microneedle array technology has been used for drug delivery and extended for continuous monitoring of analytes present in the skin compartment. We envisage the use of microneedle arrays for future theranostic applications. The potential of using combined microneedle array-based drug delivery and diagnostics as part of closed-loop control system for the management of diseases and delivery of precision drugs in individual patients, is reported in this paper.
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
Chabloz N, Wenzel M, Perry H, et al., 2019, Polyfunctionalised nanoparticles bearing robust gadolinium surface units for high relaxivity performance in MRI, Chemistry - A European Journal, Vol: 25, Pages: 10895-10906, ISSN: 0947-6539
The first example of an octadentate gadolinium unit based on DO3A (hydration number q = 1) with a dithiocarbamate tether has been designed and attached to the surface of gold nanoparticles (around 4.4 nm in diameter). In addition to the superior robustness of this attachment, the restricted rotation of the Gd complex on the nanoparticle surface leads to a dramatic increase in relaxivity (r1) from 4.0 mM‐1 s‐1 in unbound form to 34.3 mM‐1 s‐1 (at 10 MHz, 37 °C) and 22 ± 2 mM‐1s‐1 (at 63.87 MHz, 25 °C) when immobilised on the surface. The ‘one‐pot’ synthetic route provides a straightforward and versatile way of preparing a range of multifunctional gold nanoparticles. The incorporation of additional surface units improving biocompatibility (PEG and thioglucose units) and targeting (folic acid) lead to little detrimental effect on the high relaxivity observed for these non‐toxic multifunctional materials. In addition to the passive targeting attributed to gold nanoparticles, the inclusion of a unit capable of targeting the folate receptors overexpressed by cancer cells, such as HeLa cells, illustrates the potential of these assemblies.
Luu T, Liu M, Chen Y, et al., 2019, Aptamer-Based Biosensing with a Cationic AIEgen, Australian Journal of Chemistry, Vol: 72, Pages: 620-620, ISSN: 0004-9425
<jats:p>Fabrication of low-cost biosensing platforms with high selectivity and sensitivity is important for constructing portable devices for personal health monitoring. Herein, we report a simple biosensing strategy based on the combination of a cationic AIEgen (aggregation-induced emission fluorogen), TPE-2+, with an aptamer for specific protein detection. The target protein can displace the dye molecules on the dye–aptamer complex, resulting in changes in the fluorescence signal. Selectivity towards different targets can be achieved by simply changing the aptamer sequence. The working mechanism is also investigated.</jats:p>
Dhillo W, Liang S, Kinghorn A, et al., 2019, Measuring LH Pulsatility in Patients with Reproductive Disorders Using a Novel Robotic Aptamer-Enabled Electrochemical Reader (RAPTER), 35th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 125-126, ISSN: 0268-1161
Bollella P, Sharma S, Cass AEG, et al., 2019, Minimally Invasive Glucose Monitoring Using a Highly Porous Gold Microneedles-Based Biosensor: Characterization and Application in Artificial Interstitial Fluid, CATALYSTS, Vol: 9, ISSN: 2073-4344
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.
Hansel C, Crowder S, Cooper S, et al., 2019, Nanoneedle-mediated stimulation of cell mechanotransduction machinery, ACS Nano, Vol: 13, Pages: 2913-2019, ISSN: 1936-0851
Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell membrane, revealing that biophysical cues directed to the intracellular space can generate heretofore unobserved mechanosensory responses. These findings highlight the ability of nanoneedles to study and direct the phenotype of large cell populations simultaneously, through biophysical interactions with multiple mechanoresponsive components.
Liang S, Kinghorn AB, Voliotis M, et al., 2019, Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader, Nature Communications, Vol: 10, Pages: 1-10, ISSN: 2041-1723
Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility. Through selective evolution of ligands by exponential enrichment (SELEX), we identify DNA aptamers that bind specifically to LH and not to related hormones. The aptamers are integrated into electrochemical aptamer-based (E-AB) sensors on a robotic platform. E-AB enables rapid, sensitive and repeatable determination of LH concentration profiles. Bayesian Spectrum Analysis is applied to determine LH pulsatility in three distinct patient cohorts. This technology has the potential to transform the clinical care of patients with reproductive disorders and could be developed to allow real-time in vivo hormone monitoring.
Bollella P, Sharma S, Cass AEG, et al., 2019, Minimally-invasive Microneedle-based Biosensor Array for Simultaneous Lactate and Glucose Monitoring in Artificial Interstitial Fluid, ELECTROANALYSIS, Vol: 31, Pages: 374-382, ISSN: 1040-0397
Mie M, Matsumoto R, Mashimo Y, et al., 2019, Development of drug-loaded protein nanoparticles displaying enzymatically-conjugated DNA aptamers for cancer cell targeting, Molecular Biology Reports, Vol: 46, Pages: 261-269, ISSN: 0301-4851
Modification of protein-based drug carriers with tumor-targeting properties is an important area of research in the field of anticancer drug delivery. To this end, we developed nanoparticles comprised of elastin-like polypeptides (ELPs) with fused poly-aspartic acid chains (ELP-D) displaying DNA aptamers. DNA aptamers were enzymatically conjugated to the surface of the nanoparticles via genetic incorporation of Gene A* protein into the sequence of the ELP-D fusion protein. Gene A* protein, derived from bacteriophage ϕX174, can form covalent complexes with single-stranded DNA via the latter's recognition sequence. Gene A* protein-displaying nanoparticles exhibited the ability to deliver the anticancer drug paclitaxel (PTX), whilst retaining activity of the conjugated Gene A* protein. PTX-loaded protein nanoparticles displaying DNA aptamers known to bind to the MUC1 tumor marker resulted in increased cytotoxicity with MCF-7 breast cancer cells compared to PTX-loaded protein nanoparticles without the DNA aptamer modification.
Singh M, Nabavi E, Zhou Y, et al., 2019, Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment, Nanotheranostics, Vol: 3, Pages: 89-102, ISSN: 2206-7418
Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.
Grell M, Dincer C, Le T, et al., 2019, Autocatalytic metallization of fabrics using Si ink, for biosensors, batteries and energy harvesting, Advanced Functional Materials, Vol: 29, Pages: 1-11, ISSN: 1616-301X
Commercially available metal inks are mainly designed for planar substrates (for example, polyethylene terephthalate foils or ceramics), and they contain hydrophobic polymer binders that fill the pores in fabrics when printed, thus resulting in hydrophobic electrodes. Here, a low‐cost binder‐free method for the metallization of woven and nonwoven fabrics is presented that preserves the 3D structure and hydrophilicity of the substrate. Metals such as Au, Ag, and Pt are grown autocatalytically, using metal salts, inside the fibrous network of fabrics at room temperature in a two‐step process, with a water‐based silicon particle ink acting as precursor. Using this method, (patterned) metallized fabrics are being enabled to be produced with low electrical resistance (less than 3.5 Ω sq−1). In addition to fabrics, the method is also compatible with other 3D hydrophilic substrates such as nitrocellulose membranes. The versatility of this method is demonstrated by producing coil antennas for wireless energy harvesting, Ag–Zn batteries for energy storage, electrochemical biosensors for the detection of DNA/proteins, and as a substrate for optical sensing by surface enhanced Raman spectroscopy. In the future, this method of metallization may pave the way for new classes of high‐performance devices using low‐cost fabrics.
Bollella P, Sharma S, Cass AEG, et al., 2019, Microneedle-based biosensor for minimally-invasive lactate detection, BIOSENSORS & BIOELECTRONICS, Vol: 123, Pages: 152-159, ISSN: 0956-5663
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- Citations: 93
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
Maniyam MN, Ibrahim AL, Cass AEG, 2019, Enhanced cyanide biodegradation by immobilized crude extract of Rhodococcus UKMP-5M, ENVIRONMENTAL TECHNOLOGY, Vol: 40, Pages: 386-398, ISSN: 0959-3330
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