Publications by authors named "Paul R Stoddart"

Optical fiber Raman and surface-enhanced Raman scattering (SERS) probes hold great promise for in vivo biosensing and in situ monitoring of hostile environments. However, the silica Raman scattering background generated within the optical fiber increases in proportion to the length of the fiber, and it can swamp the signal from the target analyte. While filtering can be applied at the distal end of the fiber, the use of bulk optical elements has limited probe miniaturization to a diameter of 600 µm, which in turn limits the potential applications.

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This study investigates the electrochemical behavior of GelMA-based hydrogels and their interactions with PC12 neural cells under electrical stimulation in the presence of conducting substrates. Focusing on indium tin oxide (ITO), platinum, and gold mylar substrates supporting conductive scaffolds composed of hydrogel, graphene oxide, and gold nanorods, we explored how the substrate materials affect scaffold conductivity and cell viability. We examined the impact of an optimized electrical stimulation protocol on the PC12 cell viability.

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Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as "bionic eyes." However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision.

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Emerging applications of optical technologies are driving the development of miniaturised light sources, which in turn require the fabrication of matching micro-optical elements with sub-1 mm cross-sections and high optical quality. This is particularly challenging for spatially constrained biomedical applications where reduced dimensionality is required, such as endoscopy, optogenetics, or optical implants. Planarisation of a lens by the Fresnel lens approach was adapted for a conical lens (axicon) and was made by direct femtosecond 780 nm/100 fs laser writing in the SZ2080™ polymer with a photo-initiator.

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Surface-enhanced Raman Spectroscopy (SERS) is a powerful optical sensing technique that amplifies the signal generated by Raman scattering by many orders of magnitude. Although the extreme sensitivity of SERS enables an extremely low limit of detection, even down to single molecule levels, it is also a primary limitation of the technique due to its tendency to equally amplify 'noise' generated by non-specifically adsorbed molecules at (or near) SERS-active interfaces. Eliminating interference noise is thus critically important to SERS biosensing and typically involves onerous extraction/purification/washing procedures and/or heavy dilution of biofluid samples.

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Microlens arrays (MLAs) which are increasingly popular micro-optical elements in compact integrated optical systems were fabricated using a femtosecond direct laser write (fs-DLW) technique in the low-shrinkage SZ2080 photoresist. High-fidelity definition of 3D surfaces on IR transparent CaF substrates allowed to achieve ∼50% transmittance in the chemical fingerprinting spectral region 2-5 μm wavelengths since MLAs were only ∼10 μm high corresponding to the numerical aperture of 0.3 (the lens height is comparable with the IR wavelength).

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Neural interfaces are well-established as a tool to understand the behaviour of the nervous system recording and stimulation of living neurons, as well as serving as neural prostheses. Conventional neural interfaces based on metals and carbon-based materials are generally optimised for high conductivity; however, a mechanical mismatch between the interface and the neural environment can significantly reduce long-term neuromodulation efficacy by causing an inflammatory response. This paper presents a soft composite material made of gelatin methacryloyl (GelMA) containing graphene oxide (GO) conjugated with gold nanorods (AuNRs).

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The vision of patients rendered blind by photoreceptor degeneration can be partially restored by exogenous stimulation of surviving retinal ganglion cells (RGCs). Whereas conventional electrical stimulation techniques have failed to produce naturalistic visual percepts, nanoparticle-based optical sensors have recently received increasing attention as a means to artificially stimulate the RGCs. In particular, nanoparticle-enhanced infrared neural modulation (NINM) is a plasmonically mediated photothermal neuromodulation technique that has a demonstrated capacity for both stimulation and inhibition, which is essential for the differential modulation of ON-type and OFF-type RGCs.

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From atomic force microscopy (AFM) experiments, we report a new phenomenon in which the dissolution rate of fused silica is enhanced by more than 5 orders of magnitude by simply pressing a second, dissimilar surface against it and oscillating the contact pressure at low kHz frequencies in deionized water. The silica dissolution rate enhancement was found to exhibit a strong dependence on the pressure oscillation frequency consistent with a resonance effect. This harmonic enhancement of the silica dissolution rate was only observed at asymmetric material interfaces (e.

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Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig).

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Mesenchymal stem cell therapies show great promise in regenerative medicine. However, to generate clinically relevant numbers of these stem cells, significant in vitro expansion of the cells is required before transplantation into the affected wound or defect. The current gold standard protocol for recovering in vitro cultured cells involves treatment with enzymes such as trypsin which can affect the cell phenotype and ability to interact with the environment.

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Objective: Infrared light can be used to modulate the activity of neuronal cells through thermally-evoked capacitive currents and thermosensitive ion channel modulation. The infrared power threshold for action potentials has previously been found to be far lower in the in vivo cochlea when compared with other neuronal targets, implicating spiral ganglion neurons (SGNs) as a potential target for infrared auditory prostheses. However, conflicting experimental evidence suggests that this low threshold may arise from an intermediary mechanism other than direct SGN stimulation, potentially involving residual hair cell activity.

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Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal.

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Objective: Compared to electrical stimulation, optogenetic stimulation has the potential to improve the spatial precision of neural activation in neuroprostheses, but it requires intense light and has relatively poor temporal kinetics. We tested the effect of hybrid stimulation, which is the combination of subthreshold optical and electrical stimuli, on spectral and temporal fidelity in the cochlea by recording multiunit activity in the inferior colliculus of channelrhodopsin (H134R variant) transgenic mice.

Approach: Pulsed light or biphasic electrical pulses were delivered to cochlear spiral ganglion neurons of acutely deafened mice, either as individual stimuli or as hybrid stimuli for which the timing of the electrical pulse had a varied delay relative to the start of the optical pulse.

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Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck.

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In infrared neural stimulation (INS), laser-evoked thermal transients are used to generate small depolarising currents in neurons. The laser exposure poses a moderate risk of thermal damage to the target neuron. Indeed, exogenous methods of neural stimulation often place the target neurons under stressful non-physiological conditions, which can hinder ordinary neuronal function and hasten cell death.

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Phenylalanine was the minimalistic and first of numerous nonproteinaceous building blocks to be demonstrated to form amyloid-like fibrils. This unexpected organization of such a simple building block into canonical architecture, which was previously observed only with proteins and peptides, has numerous implications for medicine and supramolecular chemistry. However, the morphology of phenylalanine fibrils and their mechanical properties was never characterized in solutions.

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Objective: The performance of neuroprostheses, including cochlear and retinal implants, is currently constrained by the spatial resolution of electrical stimulation. Optogenetics has improved the spatial control of neurons in vivo but lacks the fast-temporal dynamics required for auditory and retinal signalling. The objective of this study is to demonstrate that combining optical and electrical stimulation in vitro could address some of the limitations associated with each of the stimulus modes when used independently.

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Controlled release is at the forefront of modern bioscience as it aims to address challenges associated with the dosing of drugs within required levels for therapeutic effect. Many materials and approaches can be used to control the release from different reservoirs including nanoparticles, liposomes and hydrogels. Using thermoresponsive hydrogels, near infrared illumination of plasmonic nanoparticles can be used to control the hydrogel through localised surface plasmon resonance heating.

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Controlling the release of bioactive agents has important potential applications in tissue engineering. While microspheres have been investigated to manipulate release rates, the majority of these investigations have been based on delivery into aqueous media, whereas the cellular environment in tissue engineering is more typically a hydrogel scaffold. If drug-loaded microspheres are introduced within scaffolds to deliver biologically active substances in situ, it is crucial to understand how the release rate is influenced by interactions between the microspheres and the scaffold.

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For decades, electrode-tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near-infrared (NIR) light, are explored as alternatives.

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Neurophotonics is an exploding field that spans the intersection of light and neurons for fundamental discovery and clinical translation. Optical technologies have significantly impacted brain research by probing into the mysteries of the brain, modulating brain activity, and improving patient care. Based on a discussion held at the International Conference on Biophotonics 2017, a group of leading researchers brainstormed to identify areas of unmet need in neuroscience and medicine, where biophotonics research could have the highest affect.

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Understanding the detailed functioning and pathophysiology of the brain and the nervous system continues to challenge the scientific community, particularly in terms of scaling up techniques for monitoring and interfacing with complex 3D networks. Nanotechnology has the potential to support this scaling up, where the eventual goal would be to address individual nerve cells within functional units of both the central and peripheral nervous system. Gold nanoparticles provide a variety of physical and chemical properties that have attracted attention as a light-activated nanoscale neuronal interface.

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Nano-textured Au surfaces were prepared on pre-stretched 2D polystyrene (PS) sheets sputtered with different thicknesses of Au. The Au-coated PS was subjected to thermal annealing above the glass transition temperature at ∼150 °C, thus undergoing surface area rescaling via a volume phase transition. The yellow color of the Au changed from the typical mirror-like appearance to a diffusive dark yellow, progressing to dark brown at the smallest feature size, hence, electromagnetic energy was coupled into the substrate.

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