Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore vision partially and remain insufficient to enable patients to conduct everyday life independently. The visual acuity of the artificial vision is limited by various factors from both engineering and physiological perspectives. To overcome those issues and further enhance the visual resolution of retinal prostheses, a variety of retinal prosthetic approaches have been proposed, based on optimization of the geometries of electrode arrays and stimulation pulse parameters. Other retinal stimulation modalities such as optics, ultrasound, and magnetics have also been utilized to address the limitations in conventional electrical stimulation. Although none of these approaches have been clinically proven to fully restore the function of a degenerated retina, the extensive efforts made in this field have demonstrated a series of encouraging findings for the next generation of retinal prostheses, and these could potentially enhance the visual acuity of retinal prostheses. In this article, a comprehensive and up-to-date overview of retinal prosthetic strategies is provided, with a specific focus on a quantitative assessment of visual acuity results from various retinal stimulation technologies. The aim is to highlight future directions toward high-resolution retinal prostheses.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Purpose: The blood–retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS–BRB modulation can offer a novel method for targeted retinal therapy. Methods: AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure. Results: FUS–BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage. Conclusions: This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases. Translational Relevance: Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.

Neural interfaces, which enable the recording and stimulation of living neurons, have emerged as valuable tools in understanding the brain in health and disease, as well as serving as neural prostheses. While neural interfaces are typically based on electrical transduction, alternative energy modalities have been explored to create safe and effective approaches. Among these approaches, optical methods of linking neurons to the outside world have gained attention because light offers high spatial selectivity and decreased invasiveness. Here, we review the current state-of-art of optical neural interfaces and their clinical applications. Optical neural interfaces can be categorized into optical control and optical readout, each of which can be divided into intrinsic and extrinsic approaches. We discuss the advantages and disadvantages of each of these methods and offer a comparison of relative performance. Future directions, including their clinical opportunities, are discussed with regard to the optical properties of biological tissue.

We present an AC-coupled modular 16-channel analog frontend with 1.774 fJ/c-s∙mm² energy- and area-product for a multichannel recording of broadband neural signals including local field potentials (LFPs) and extracellular action potentials (EAPs). To achieve such a small area- and energy-product, we employed an operational transconductance amplifier (OTA) with local positive feedback, instead of a widely-used folded cascode OTA (FC-OTA) or current mirror OTA for conventional neural recordings, while optimizing the design parameters affecting performance, power, and area trade-offs. In addition, a second pole was strategically introduced in the LNA to reduce the noise bandwidth without an in-channel low-pass filter. Compared to conventional works, the presented method shows better performance in terms of noise, power, and area usages. The performance of the fabricated 16-channel analog frontend is fully characterized in a benchtop and an in vitro setup. The 16-channel frontend embraces LFPs and EAPs with 4.27 μV_rms input referred noise (0.5–10 kHz) and 53.17 dB dynamic range, consuming 3.44 μW and 0.012 mm² per channel. The channel figure of merit (FoM) of the prototype is 147.87 fJ/c-s and the energy-area FoM (E-A FoM) is 1.774 fJ/c-s∙mm².

Increasing the proximity of microelectrode arrays (MEA) to targeted neural tissues can establish efficient neural interfaces for both recording and stimulation applications. This has been achieved by constructing protruding three-dimensional (3D) structures on top of conventional planar microelectrodes via additional micromachining steps. However, this approach adds fabrication complexities and limits the 3D structures to certain shapes. We propose a one-step fabrication of MEAs with versatile microscopic 3D structures via “microelectrothermoforming (μETF)” of thermoplastics, by utilizing 3D-printed molds to locally deform planar MEAs into protruding and recessing shapes. Electromechanical optimization enabled a 3D MEA with 80 μm protrusions and/or recession for 100 μm diameter. Its simple and versatile shaping capabilities are demonstrated by diverse 3D structures on a single MEA. The benefits of 3D MEA are evaluated in retinal stimulation through numerical simulations and ex vivo experiments, confirming a threshold lowered by 1.7 times and spatial resolution enhanced by 2.2 times.