Biology subjects

Blair, S.

Publications and source records attributed to Blair, S..

9 recordsLinked to original sources

bioRxiv2025

Electrochemical guided mode resonance biosensor for simultaneous refractive index and electrochemical measurements

A comprehensive miniaturised biosensing platform needs to detect multiple analytes, which often rely on different transduction mechanisms for their detection and quantification. This necessitates the development of multimodal sensors capable of simultaneous measurements without interference between measurement modalities. Guided mode resonance (GMR) biosensors are highly sensitive to refractive index changes and well suited to out-of-plane optical coupling, but have not previously been implemented in a multimodal configuration. Here, we present the electrochemical guided mode resonance (EC-GMR) sensor, a Si3N4 GMR photonic grating integrated with an indium tin oxide (ITO) electrode that enables concurrent optical and electrochemical sensing. Finite difference time domain (FDTD) simulations show that the resonance wavelength of the GMR shifts as a function of ITO thickness and applied bias. These findings are validated experimentally using EC-GMR devices fabricated with a range of ITO thicknesses. We demonstrate that the EC-GMR achieves a refractive index sensitivity of 84.4 nm/RIU while simultaneously measuring the double-layer capacitance. To highlight its multimodal capability, we characterise the optical and electrochemical responses of methylene blue, a widely used redox reporter in biosensing. By integrating photonic and electrochemical modalities in a compact format, the EC-GMR platform provides critical analytical information beyond that which could be obtained from a traditional single-modality sensor. This approach extends the analytical utility of GMR sensors and represents a robust, adaptable solution for diverse biosensing applications, from clinical diagnostics to environmental monitoring.

biophysics↗

bioRxiv2025

Cortical Response to Acute Implantation of the Utah Optrode Array in Macaque Cortex

Optogenetics has transformed the study of neural circuit function, but limitations in its application to species with large brains, such as non-human primates (NHPs), remain. A major challenge in NHP optogenetics is delivering light to sufficiently large volumes of deep neural tissue with high spatiotemporal precision, without simultaneously affecting superficial tissue. To overcome these limitations, we recently developed and tested in vivo in NHP cortex, the Utah Optrode Array (UOA). This is a 10x10 array of penetrating glass shanks, tiling a 4x4mm2 area, bonded to interleaved needle-aligned and interstitial {micro}LED arrays, which allows for independent photostimulation of deep and superficial brain tissue. Here, we investigate the acute biological response to UOA implantation in NHP cortex, with the goal of optimizing device design for reduced insertion trauma and subsequent chronic response. To this goal, we systematically vary UOA shank diameter, surface texture, tip geometry, and insertion pressure, and assess their effects on astrocytes, microglia, and neuronal viability, following acute implantation. We find that UOAs with shanks of smaller diameter, smooth surface texture and round tips cause the least damage. Higher insertion pressures have limited effects on the inflammatory response, but lead to greater tissue compression. Our results highlight the importance of balancing shank diameter, tip geometry, and insertion pressure in UOA design for preserving tissue integrity and improving long-term UOA performance and biocompatibility.

bioengineering↗

bioRxiv2024

A method for focused ultrasound (FUS) neuromodulation with simultaneous electroencephalogram recordings in awake, head-fixed mice with temporal lobe epilepsy

Transcranial focused ultrasound (FUS) may be a promising neuromodulation technology for treating people with epilepsy whose seizures are drug resistant. Prior studies have shown seizure suppression in animal studies using FUS. However, most of these studies were performed in evoked seizure models and not in animal models of epilepsy. Evoked seizure models do not exhibit the pathophysiology of epilepsy and do not exhibit spontaneous recurrent seizures, which define epilepsy. For translation to humans, there is a critical need to determine the specific FUS stimulation parameters that reduce spontaneous recurrent seizures in a chronic disease model of epilepsy. To achieve this goal, we developed and optimized an approach to determine the effects of ultrasonic stimulation on metrics of seizure-like events (SLEs) in awake, head-fixed mice within the intrahippocampal kainate (IHK) mouse model of temporal lobe epilepsy (TLE). A proof-of-principle study demonstrated that two target (bilateral and contralateral to the kainic acid injection site) stimulation conditions and two FUS parameter sets (low and high pressure) could be combined with the ability to simultaneously record hippocampal electroencephalograms. We also provide a method for analysis of the effects of FUS stimulation on the metrics of SLEs (interevent duration, SLE duration, and spike frequency).

bioengineering↗

bioRxiv2024

In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity

Optogenetics allows manipulation of neural circuits in vivo with high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models). Here, we have developed, optimised, and tested in vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181 {micro}LEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies. Thinning the combined {micro}LED and needle backplane of the device from 300 {micro}m to 230 {micro}m improved the efficiency of light delivery to tissue by 80%, allowing lower {micro}LED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1{degrees}C. The device was tested in vivo in the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons. It was shown that the strongest optogenetic response occurred in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling - demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential (LFP) activity.

neuroscience↗

bioRxiv2023

Implementation and testing of a biohybrid transitionmicroelectrode array for neural recording and modulation

Recent advances in microtissue engineered neural networks have opened avenues for the fabrication of biohybrid intracortical brain implants. To date, however, the experimental validation of these biohybrid implants has been restricted to singularly positioned electrodes, with the functionality confined to optical neuromodulation and neural recording. We present for the first time a biohybrid transition microelectrode array (TMEA) comprising a 4x4 matrix of biohybrid electrodes. These electrodes are expected to project axons into the brain, thereby establishing synaptic connections for electrical readout and excitation. Our device thus offers a promising pathway to leverage organic, endogenous materials in intracortical implants to enhance their biocompatibility as well as their functionality. In particular with respect to functionality, we assume that the spatiotemporal resolution of recorded neural signals may be significantly increased using this technology owing to the size ratios of these biohybrid microelectrodes compared to abiotic ones. Future investigations will therefore focus on the exploitation of the electrode density to further advance brain-computer interface technology.

neuroscience↗

bioRxiv2023

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 19 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future pain therapy development.

neuroscience↗

bioRxiv2022

An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply in large brains, such as those of non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback projections. To address this unmet need, we have developed the Utah Optrode Array (UOA), a 10x10 glass needle waveguide array fabricated atop a novel opaque optical interposer then bonded to an electrically addressable LED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in monkey cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, simply by varying the number of activated LEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

neuroscience↗

bioRxiv2021

Tbet expression by Tregs is needed to protect against Th1-mediated immunopathology during Toxoplasma infection in mice

T. gondii infection has proven to be an ideal model to understand the delicate balance between protective immunity and immune-mediated pathology during infection. Lethal infection causes a collapse of Tregs mediated by loss of IL-2, and conversion of Tregs to IFN{gamma} producing cells. Importantly, these Tregs highly express the Th1 transcription factor Tbet. To determine the role of Tbet in Tregs, we infected Tbx21f/f-Foxp3YFPCre and control Foxp3YFPCre mice with the type II strain of T. gondii, ME49. The majority of Tbx21f/f-Foxp3YFPCre mice succumb to a non-lethal acute infection. Notably, parasite burden is comparable between Tbx21f/f-Foxp3YFPCre and Foxp3YFPCre control mice. We found that Tbx21f/f-Foxp3YFPCre mice have significantly higher serum levels of proinflammatory cytokines IFN{gamma} and TNF, suggestive of a heightened immune response. To test if CD4+ T cells were driving immunopathology, we treated Tbx21f/f-Foxp3YFPCre mice with anti-CD4 depleting antibody and partially rescued these mice. Broad spectrum antibiotic treatment also improved survival, demonstrating a role for commensal flora in immunopathology in Tbx21f/f-Foxp3YFPCre mice. RNA-seq analysis reinforced that Tbet regulates several key cellular pathways, including chromosome segregation, cytokine receptor activity and cell cycle progression, that help to maintain fitness in Tregs during Th1 responses. Taken together, our data shows an important role for Tbet in Tregs in preventing lethal immunopathology during Toxoplasma gondii infection, further highlighting the protective role of Treg plasticity to self and microbiota.

immunology↗

bioRxiv2018

A multi-site MicroLED Optrode Array for Neural Interfacing

We present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite hundreds of neurons in vivo, developed with the aim to allow behavioural studies in large mammals. The device is a glass microneedle array directly integrated with a custom fabricated microLED device, which delivers light to 100 needle tips and 81 interstitial surface sites, giving 2-level optogenetic excitation of neurons in vivo. Light delivery and thermal properties are evaluated, with the device capable of peak irradiances > 80 mW/mm2 per needle at 50 ms pulse widths with tissue temperature increase less than 1 {degrees}C. Future designs are explored through optical and thermal modelling and benchmarked against the current device.

neuroscience↗