A micropore nanoband electrode array for enhanced electrochemical generation/analysis in flow systems.

Our previous work has established that micron-resolution photolithography can be employed to make microsquare nanoband edge electrode (MNEE) arrays. The MNEE configuration enables systematic control of the parameters (electrode number, cavity array spacing, and nanoelectrode dimensions and placement) that control geometry, conferring a consistent high-fidelity electrode response across the array (, high signal, high signal-to-noise, low limits of detection and fast, steady-state, reproducible and quantitative response) and allowing the tuning of individual and combined electrode interactions. Building on this, in this paper we now produce and characterise a micropore nanoband electrode (MNE) array designed for flow-through detection, where an MNEE edge electrode configuration is used to form a nanotube electrode embedded in the wall of each micropore, formed as an array of pores of controlled size and placement through an insulating membrane of sub-micrometer thickness.

pH-Activated Dissolvable Polymeric Coatings to Reduce Biofouling on Electrochemical Sensors.

Implantable electrochemical sensors that enable the real-time detection of significant biomarkers offer huge potential for the enhancement and personalisation of therapies; however, biofouling is a key challenge encountered by any implantable system. This is particularly an issue immediately after implantation, when the foreign body response and associated biofouling processes are at their most active in passivating a foreign object. Here, we present the development of a sensor protection and activation strategy against biofouling, based on coatings consisting of a pH-triggered, dissolvable polymer, that covered a functionalised electrode surface.

Electrofabrication of large volume di- and tripeptide hydrogels hydroquinone oxidation.

The fabrication of protected peptide-based hydrogels on electrode surfaces can be achieved by employing the electrochemical oxidation of hydroquinone to benzoquinone, liberating protons at the electrode-solution interface. The localised reduction in pH below the dipeptide gelator molecules p initiates the neutralisation, self-assembly and formation of self-supporting hydrogels exclusively at the electrode surface. Previous examples have been on a nanometre to millimetre scale, using deposition times ranging from seconds to minutes.

In vivo application of an implantable tri-anchored methylene blue-based electrochemical pH sensor.

The development of robust implantable sensors is important in the successful advancement of personalised medicine as they have the potential to provide in situ real-time data regarding the status of health and disease and the effectiveness of treatment. Tissue pH is a key physiological parameter and herein, we report the design, fabrication, functionalisation, encapsulation and protection of a miniaturised, self-contained, electrochemical pH sensor system and characterisation of sensor performance. Notably for the first time in this environment the pH sensor was based on a methylene blue redox reporter which showed remarkable robustness, accuracy and sensitivity.

Miniaturisation of a peptide-based electrochemical protease activity sensor using platinum microelectrodes.

Proteases are ideal target biomarkers as they have been implicated in many disease states, including steps associated with cancer progression. Electrochemical peptide-based biosensors have attracted much interest in recent years. However, the significantly large size of the electrodes typically used in most of these platforms has led to performance limitations.

A Dual Killing Strategy: Photocatalytic Generation of Singlet Oxygen with Concomitant Pt Prodrug Activation.

A ruthenium-based mitochondrial-targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of Pt prodrugs into their active Pt counterparts, and drives the generation of singlet oxygen was designed. This dual mode of action drives two orthogonal cancer-cell killing mechanisms with temporal and spatial control. The designed photosensitiser was shown to elicit cell death of a panel of cancer cell lines including those showing oxaliplatin-resistance.

Electrochemical sensing of human neutrophil elastase and polymorphonuclear neutrophil activity.

Human neutrophil elastase (HNE) is a serine protease, produced by polymorphonuclear neutrophils (PMNs), whose uncontrolled production has been associated with various inflammatory disease states as well as tumour proliferation and metastasis. Here we report the development and characterisation of an electrochemical peptide-based biosensor, which enables the detection of clinically relevant levels of HNE. The sensing platform was characterised in terms of its analytical performance, enzymatic cleavage kinetics and cross-reactivity and applied to the quantitative detection of protease activity from PMNs from human blood.

Functionalised microscale nanoband edge electrode (MNEE) arrays: the systematic quantitative study of hydrogels grown on nanoelectrode biosensor arrays for enhanced sensing in biological media.

Nanoelectrodes and nanoelectrode arrays show enhanced diffusion and greater faradaic current densities and signal-to-noise ratios compared to macro and microelectrodes, which can lead to enhanced sensing and detection. One example is the microsquare nanoband edge electrode (MNEE) array system, readily formed through microfabrication and whose quantitative response has been established electroanalytically. Hydrogels have been shown to have applications in drug delivery, tissue engineering, and anti-biofouling; some also have the ability to be grown electrochemically.

Electrodrugs: an electrochemical prodrug activation strategy.

The term electroceutical has been used to describe implanted devices that deliver electrical stimuli to modify biological function. Herein, we describe a new concept in electroceuticals, demonstrating for the first time the electrochemical activation of metal-based prodrugs. This is illustrated by the controlled activation of Pt(iv) prodrugs into their active Pt(ii) forms within a cellular context allowing selectivity and control of where, when and how much active drug is generated.

A Microelectrode Array with Reproducible Performance Shows Loss of Consistency Following Functionalization with a Self-Assembled 6-Mercapto-1-hexanol Layer.

For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses.

Integration of Electrodeposited Ni-Fe in MEMS with Low-Temperature Deposition and Etch Processes.

This article presents a set of low-temperature deposition and etching processes for the integration of electrochemically deposited Ni-Fe alloys in complex magnetic microelectromechanical systems, as Ni-Fe is known to suffer from detrimental stress development when subjected to excessive thermal loads. A selective etch process is reported which enables the copper seed layer used for electrodeposition to be removed while preserving the integrity of Ni-Fe. In addition, a low temperature deposition and surface micromachining process is presented in which silicon dioxide and silicon nitride are used, respectively, as sacrificial material and structural dielectric.

Correction: Impedimetric measurement of DNA-DNA hybridisation using microelectrodes with different radii for detection of methicillin resistant Staphylococcus aureus (MRSA).

Correction for 'Impedimetric measurement of DNA-DNA hybridisation using microelectrodes with different radii for detection of methicillin resistant Staphylococcus aureus (MRSA)' by Poh Quan Li et al., Analyst, 2017, 142, 1946-1952.

Impedimetric measurement of DNA-DNA hybridisation using microelectrodes with different radii for detection of methicillin resistant Staphylococcus aureus (MRSA).

Due to their electroanalytical advantages, microelectrodes are a very attractive technology for sensing and monitoring applications. One highly important application is measurement of DNA hybridisation to detect a wide range of clinically important phenomena, including single nucleotide polymorphisms (SNPs), mutations and drug resistance genes. The use of electrochemical impedance spectroscopy (EIS) for measurement of DNA hybridisation is well established for large electrodes but as yet remains relatively unexplored for microelectrodes due to difficulties associated with electrode functionalisation and impedimetric response interpretation.

Advances in electroanalysis, sensing and monitoring in molten salts.

Microelectrodes have a number of advantages over macroelectrodes for quantitative electroanalysis and monitoring, including reduced iR drop, a high signal-to-noise ratio and reduced sensitivity to convection. Their use in molten salts has been generally precluded by the combined materials challenges of stresses associated with thermal cycling and physical and corrosive chemical degradation at the relatively high temperatures involved. We have shown that microfabrication, employing high precision photolithographic patterning in combination with the controlled deposition of materials, can be used to successfully address these challenges.

Nanoband array electrode as a platform for high sensitivity enzyme-based glucose biosensing.

We describe a novel glucose biosensor based on a nanoband array electrode design, manufactured using standard semiconductor processing techniques, and bio-modified with glucose oxidase immobilized at the nanoband electrode surface. The nanoband array architecture allows for efficient diffusion of glucose and oxygen to the electrode, resulting in a thousand-fold improvement in sensitivity and wide linear range compared to a conventional electrode. The electrode constitutes a robust and manufacturable sensing platform.

Label- and amplification-free electrochemical detection of bacterial ribosomal RNA.

Current approaches to molecular diagnostics rely heavily on PCR amplification and optical detection methods which have restrictions when applied to point of care (POC) applications. Herein we describe the development of a label-free and amplification-free method of pathogen detection applied to Escherichia coli which overcomes the bottleneck of complex sample preparation and has the potential to be implemented as a rapid, cost effective test suitable for point of care use. Ribosomal RNA is naturally amplified in bacterial cells, which makes it a promising target for sensitive detection without the necessity for prior in vitro amplification.

Methylene blue not ferrocene: Optimal reporters for electrochemical detection of protease activity.

Electrochemical peptide-based biosensors are attracting significant attention for the detection and analysis of proteins. Here we report the optimisation and evaluation of an electrochemical biosensor for the detection of protease activity using self-assembled monolayers (SAMs) on gold surfaces, using trypsin as a model protease. The principle of detection was the specific proteolytic cleavage of redox-tagged peptides by trypsin, which causes the release of the redox reporter, resulting in a decrease of the peak current as measured by square wave voltammetry.

Enhanced electroanalysis in lithium potassium eutectic (LKE) using microfabricated square microelectrodes.

Molten salts (MSs) are an attractive medium for chemical and electrochemical processing and as a result there is demand for MS-compatible analysis technologies. However, MSs containing redox species present a challenging environment in which to perform analytical measurements because of their corrosive nature, significant thermal convection and the high temperatures involved. This paper outlines the fabrication and characterization of microfabricated square microelectrodes (MSMs) designed for electrochemical analysis in MS systems.

A systematic study of the influence of nanoelectrode dimensions on electrode performance and the implications for electroanalysis and sensing.

Micron resolution photolithography has been employed to make microsquare nanoband edge electrode (MNEE) arrays with reproducible and systematic control of the crucial dimensional parameters, including array element size and spacing and nanoelectrode thickness. The response of these arrays, which can be reproducibly fabricated on a commercial scale, is first established. The resulting characteristics (including high signal and signal-to-noise, low limit of detection, insensitivity to external convection and fast, steady-state, reproducible and quantitative response) make such nanoband electrode arrays of real interest as enhanced electroanalytical devices.

Nanoscale electrode arrays produced with microscale lithographic techniques for use in biomedical sensing applications.

A novel technique for the production of nanoscale electrode arrays that uses standard microfabrication processes and micron-scale photolithography is reported here in detail. These microsquare nanoband edge electrode (MNEE) arrays have been fabricated with highly reproducible control of the key array dimensions, including the size and pitch of the individual elements and, most importantly, the width of the nanoband electrodes. The definition of lateral features to nanoscale dimensions typically requires expensive patterning techniques that are complex and low-throughput.

Comparison of the performance of an array of nanoband electrodes with a macro electrode with similar overall area.

The performance of two electrode architectures with broadly similar overall active electrode areas are examined. The first is an electrode comprising a single contiguous area (a disc) and the second is an electrode in which the cumulative electrode area is dispersed over a wide area as a 50 nm thickness platinum nanoband. A direct comparison of the electrochemical performance of these two electrodes has been made.

Cyclic denaturation and renaturation of double-stranded DNA by redox-state switching of DNA intercalators.

Hybridization of complementary nucleic acid strands is fundamental to nearly all molecular bioanalytical methods ranging from polymerase chain reaction and DNA biosensors to next generation sequencing. For nucleic acid amplification methods, controlled DNA denaturation and renaturation is particularly essential and achieved by cycling elevated temperatures. Although this is by far the most used technique, the management of rapid temperature changes requires bulky instrumentation and intense power supply.

Impedimetric detection of single-stranded PCR products derived from methicillin resistant Staphylococcus aureus (MRSA) isolates.

Using electrochemical impedance spectroscopy (EIS) the sensitive and specific detection of the antibiotic resistance gene mecA has been demonstrated. The gene sequence was obtained from clinical Staphylococcus aureus isolates. Initially a mecA specific probe was selected from hybridisation tests with a 3' and 5' version of a previously published probe sequence.

Development of immunosensors for direct detection of three wound infection biomarkers at point of care using electrochemical impedance spectroscopy.

A method for label-free, electrochemical impedance immunosensing for the detection and quantification of three infection biomarkers in both buffer and directly in the defined model matrix of mock wound fluid is demonstrated. Triggering Receptor-1 Expressed on Myeloid cells (TREM-1) and Matrix MetalloPeptidase 9 (MMP-9) are detected via direct assay and N-3-oxo-dodecanoyl-l-HomoSerineLactone (HSL), relevant in bacterial quorum sensing, is detected using a competition assay. Detection is performed with gold screen-printed electrodes modified with a specific thiolated antibody.

Alkaline phosphatase enzymatic signal amplification for fast, sensitive impedimetric DNA detection.

Enzymatic signal amplification by the deposition of insoluble product on the electrode surface enhances impedimetric DNA detection sensitivity. This work demonstrates a method which gives the required detection sensitivity at significantly reduced enzyme reaction times, and demonstrates the capability for DNA SNP discrimination of biologically relevant sequences. This opens up the prospect of more rapid and relevant multiparameter impedimetric bioassays.