Breaking barriers: exploring mechanisms behind opening the blood-brain barrier.

The blood-brain barrier (BBB) is a selectively permeable membrane that separates the bloodstream from the brain. While useful for protecting neural tissue from harmful substances, brain-related diseases are difficult to treat due to this barrier, as it also limits the efficacy of drug delivery. To address this, promising new approaches for enhancing drug delivery are based on disrupting the BBB using physical means, including optical/photothermal therapy, electrical stimulation, and acoustic/mechanical stimulation. These physical mechanisms can temporarily and locally open the BBB, allowing drugs and other substances to enter. Focused ultrasound is particularly promising, with the ability to focus energies to targeted, deep-brain regions. In this review, we examine recent advances in physical approaches for temporary BBB disruption, describing their underlying mechanisms as well as evaluating the utility of these physical approaches with regard to their potential risks and limitations. While these methods have demonstrated efficacy in disrupting the BBB, their safety, comparative efficacy, and practicality for clinical use remain an ongoing topic of research.

Periodic Rayleigh streaming vortices and Eckart flow arising from traveling-wave-based diffractive acoustic fields.

Recent studies have demonstrated that periodic time-averaged acoustic fields can be produced from traveling surface acoustic waves (SAWs) in microfluidic devices. This is caused by diffractive effects arising from a spatially limited transducer. This permits the generation of acoustic patterns evocative of those produced from standing waves, but instead with the application of a traveling wave. While acoustic pressure fields in such systems have been investigated, acoustic streaming from diffractive fields has not. In this work we examine this phenomenon and demonstrate the appearance of geometry-dependent acoustic vortices, and demonstrate that periodic, identically rotating Rayleigh streaming vortices result from the imposition of a traveling SAW. This is also characterized by a channel-spanning flow that bridges between adjacent vortices along the channel top and bottom. We find that the channel dimensions determine the types of streaming that develops; while Eckart streaming has been previously presumed to be a distinguishing feature of traveling-wave actuation, we show that Rayleigh streaming vortices also results. This has implications for microfluidic actuation, where traveling acoustic waves have applications in microscale mixing, separation, and patterning.

3D Diamond Electrode Array for High-Acuity Stimulation in Neural Tissue.

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.

Hybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing.

Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.

Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip.

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.