Objective. Retinal prosthetic devices hold great promise for the treatment of retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Through electrical stimulation of the surviving retinal neurons, these devices evoke visual signals that are then relayed to the brain. Currently, the visual prostheses used in clinical trials have few electrodes, thus limiting visual acuity. Electrode arrays with high electrode densities have been developed using novel technologies, including diamond growth and laser machining, and these may provide a more promising route to achieve high visual acuity in blind patients. Approach. Here, we studied the potential spatial resolution of electrical stimulation using diamond electrodes. We did this by labeling retinal ganglion cells in whole mount retina with a calcium indicator in wild-type rats and those with retinal degeneration. We imaged the ganglion cell responses to a range of stimulation parameters, including pulse duration and return electrode configuration. Main results. With sub-retinal stimulation, in which electrodes were in contact with the intact or degenerated photoreceptor layer, we found that biphasic pulses of 0.1 ms phase duration and a local return configuration was the most effective in confining the retinal ganglion cell activation patterns, while also remaining within the safety limits of the materials and providing the best power efficiency. Significance. These results provide an optimized stimulation strategy for retinal implants, which if implemented in a retinal prosthetic is expected to improve the achievable visual acuity.

No abstract

A novel, ultrasound based approach for the dynamic stimulation and promotion of tissue healing processes employing surface acoustic waves (SAW) on a chip is presented for the example of osteoblast-like SaOs-2 cells. In our investigations, we directly irradiate cells with SAW on a SiO2 covered piezoelectric LiNbO3 substrate. Observing the temporal evolution of cell growth and migration and comparing non-irradiated to irradiated areas on the chip, we find that the SAW-treated cells exhibit a significantly increased migration as compared to the control samples. Apart from quantifying our experimental findings on the cell migration stimulation, we also demonstrate the full bio compatibility and bio functionality of our SAW technique by using LDH assays. We safely exclude parasitic side effects such as a SAW related increased substrate temperature or nutrient flow by thoroughly monitoring the temperature and the flow field using infrared microscopy and micro particle image velocimetry. Our results show that the SAW induced dynamic mechanical and electrical stimulation obviously directly promotes the cell growth. We conclude that this stimulation method offers a powerful platform for future medical treatment, e.g. being implemented as a implantable biochip with wireless extra-corporal power supply to treat deeper tissue.

For an optimal implementation of materials, such as, e.g. medical implants in living environments, a thorough characterization of cell adhesion, kinetics and strength is required, as well as a prerequisite e.g. for bone integration. Here we present a miniaturized (~100 μl) lab-on-a-chip implant hybrid system which allows quantification of cell adhesion under dynamic conditions mimicking those of physiological relevance. Surface acoustic waves are excited and used on optical transparent chips to induce micro acoustic streaming and to create a microfluidic shear spectrum ranging from 0 to ~35 s(-1). We demonstrate its potential for a time-efficient, dynamic screening test of new implant materials using a model of an osseointegration with SAOS-2 cells. The upside-down orientation also allows utilization of the micro reactor on non-transparent materials like titanium and diamond-like-carbon (DLC).

Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this study, we systematically investigate cell adhesion under static, dynamic and physiologically relevant conditions employing a lab-on-a-chip system. We screen adhesion of the bone osteosarcoma cell line SaOs-2 on a titanium implant material for pH and temperature values in the physiological range and beyond, to explore the limits of cell adhesion, e.g., for feverish and acidic conditions. A detailed study of different surface roughness Rq gives insight into the correlation between the cells’ abilities to adhere and withstand shear flow and the topography of the substrates, finding a local optimum at Rq = 22 nm. We use shear stress induced by acoustic streaming to determine a measure for the ability of cell adhesion under an external force for various conditions. We find an optimum of cell adhesion for T = 37 °C and pH = 7.4 with decreasing cell adhesion outside the physiological range, especially for high T and low pH. We find constant detachment rates in the physiological regime, but this behavior tends to collapse at the limits of 41 °C and pH 4.

The study of neurons is fundamental for basic neuroscience research and treatment of neurological disorders. In recent years ultrasound has been increasingly recognized as a viable method to stimulate neurons. However, traditional ultrasound transducers are limited in the scope of their application by self-heating effects, limited frequency range and cavitation effects during neuromodulation. In contrast, surface acoustic wave (SAW) devices, which are producing wavemodes with increasing application in biomedical devices, generate less self-heating, are smaller and create less cavitation. SAW devices thus have the potential to address some of the drawbacks of traditional ultrasound transducers and could be implemented as miniaturized wearable or implantable devices. In this mini review, we discuss the potential mechanisms of SAW-based neuromodulation, including mechanical displacement, electromagnetic fields, thermal effects, and acoustic streaming. We also review the application of SAW actuation for neuronal stimulation, including growth and neuromodulation. Finally, we propose future directions for SAW-based neuromodulation.

Innovations in micro-and nanofabrication technologies enable the manufacture of multielectrode arrays for use in neuromodulation and neural recording. Multielectrode arrays make possible medical implants such as pacemakers, deep-brain stimulators, or visual and hearing aids, to treat numerous neural disorders. An optimal neural interface requires a high density of electrodes to precisely record from and stimulate the nervous system while minimizing the overall size of the array. For example, people with retinal degenerative diseases can benefit from retinal prostheses implanted inside the eye. However, at present the visual acuity provided by such implants is well below the threshold for functional vision, mainly due to the limited spatial resolution. In this work, we present a design of 3D nanostructured conductive diamond electrodes, integrated within a polycrystalline diamond housing, offering a high electrode density and count, which simultaneously satisfies spatial resolution and biocompatibility goals. The array is composed of height adjustable pillar electrodes that are 80 μm in diameter and separated by 150 μm. A holistic characterization of the electrodes was performed and the device tested for stimulation performance in a whole-mounted retina. Electrochemical testing showed impedance of 20 kΩ and a wide water window of 2.47 V. The pillar structure allows the distance between the electrodes and the retinal ganglion cells to be reduced which is key to more confined stimulation at lower current levels, leading to potentially higher-acuity stimulation without damaging retinal tissue.

No abstract