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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 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer then bonded to an electrically addressable μLED array.In vivoexperiments 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 μLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Optogenetics is a powerful tool for neural control that supports perturbation of specific cell types. The Utah Optrode Array, paired with a µLED array, is an optical stimulation device for precise multi-site light delivery in deep cortical layers. We describe recent developments in the evolution of this device, including methods for improved light coupling and device encapsulation.

There is current demand for pattern programmable devices that can deliver light to deep brain structures for use in optogenetic experiments. Here we introduce a microLED optrode device with 181 individually addressable sites, each with the capability to optogenetically excite thousands of neurons in vivo. The device consists of a 10 x 10 glass microneedle array directly integrated with a custom fabricated microLED device. 100 microLEDs couple to the needle tips for intra-cortical light delivery and 81 microLEDs sit at interstitial points for surface illumination. Light delivery and thermal properties are comprehensively evaluated.

Hepatocellular carcinoma causes considerable mortality and no efficient chemotherapy is available. Novel molecules of plant origin may prove beneficial in the development of therapy of hepatocellular carcinoma. In this study we examined the anticancer effects of Tanshindiol-C (TC) against the hepatocellular carcinoma SNU-4235 cell line.Proliferation rate of the SNU-2435 cells was determined by MTT assay. Apoptosis was confirmed by DAPI and annexin V/PI staining. Cell cycle analysis was performed by flow cytometry. MicroRNA expression was checked by qRT-PCR and protein expression by western blotting. The in vivo evaluation of TC was performed in xenografted mice models.TC inhibited the growth of the SNU-4235 cells and exhibited an IC50 of 20 µM. Investigation of the underlying mechanism revealed that TC triggered apoptotic death of the SNU-4235 cells which was also associated with enhancement of the expression of Bax and decrease in the expression of Bcl-2. TC also caused arrest of the cells in the G2/M phase of the cell cycle and also exerted angiogenitic effects. TC also enhanced the expression of the tumor suppressor microRNA-21, 222 and 31. In vivo evaluation of TC revealed that it could inhibit the tumor weight volume, suggestive of the anticancer potential of TC.In brief, tanshindiol-C exerts anticancer effects on hepatocellular carcinoma by induction of apoptosis and cell cycle arrest, along with inhibiting the angiogenesis and the expression of tumor suppressive microRNAs. TC could also inhibit the growth of the xenografted tumors and hence could prove to be a potential anticancer agent.

We present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite thousands of neurons in vivo , developed with the aim to allow behavioral 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 two-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 site. The device consists of an array of 181 80 μm × 80 μm2 microLEDs, fabricated on a 150-μm-thick GaN-on-sapphire wafer, coupled to a glass needle array on a 150-μm thick backplane. A pinhole layer is patterned on the sapphire side of the microLED array to reduce stray light. Future designs are explored through optical and thermal modeling and benchmarked against the current device.

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 °C. Future designs are explored through optical and thermal modelling and benchmarked against the current device.

Optogenetics is a powerful tool for neural control, but controlled light delivery beyond the superficial structures of the brain remains a challenge. For this, we have developed an optrode array, which can be used for optogenetic stimulation of the deep layers of the cortex. The device consists of a 10×10 array of penetrating optical waveguides, which are predefined using BOROFLOAT® wafer dicing. A wet etch step is then used to achieve the desired final optrode dimensions, followed by heat treatment to smoothen the edges and the surface. The major challenge that we have addressed is delivering light through individual waveguides in a controlled and efficient fashion. Simply coupling the waveguides in the optrode array to a separately-fabricated μLED array leads to low coupling efficiency and significant light scattering in the optrode backplane and crosstalk to adjacent optrodes due to the large mismatch between the μLED and waveguide numerical aperture and the working distance between them. We mitigate stray light by reducing the thickness of the glass backplane and adding a silicon interposer layer with optical vias connecting the μLEDs to the optrodes. The interposer additionally provides mechanical stability required by very thin backplanes, while restricting the unwanted spread of light. Initial testing of light output from the optrodes confirms intensity levels sufficient for optogenetic neural activation. These results pave the way for future work, which will focus on optimization of light coupling and adding recording electrodes to each optrode shank to create a bidirectional optoelectronic interface.

We fabricated a deep optogenetic cortical stimulation device (10×10 glass waveguide array) using wafer dicing, etching and annealing. A µLED array delivers light through individual shanks. A silicon interposer layer with optical vias prevents crosstalk.