Biology subjects

Reiche, C. F.

Publications and source records attributed to Reiche, C. F..

5 recordsLinked to original sources

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

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↗

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

In vivo Monitoring of Glucose using Ultrasound-induced Resonance in Implantable Smart Hydrogel Microstructures

A novel glucose sensor is presented that uses smart hydrogels as a biocompatible implantable sensing element, which completely eliminates the need for any implanted electronics and uses an external conventional medical-grade ultrasound transducer for readout. The readout mechanism makes use of resonance absorption of ultrasound waves in glucose-sensitive hydrogels. Changes in in vivo glucose concentration in the interstitial tissue lead to swelling and de-swelling of the gels which in turn lead to changes in resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that is correlated with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, co-located implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference, using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens the path towards future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.

bioengineering↗