Parallel, minimally-invasive implantation of ultra-flexible neural electrode arrays.

OBJECTIVE: Implanted microelectrodes provide a unique means to directly interface with the nervous system but have been limited by the lack of stable functionality. There is growing evidence suggesting that substantially reducing the mechanical rigidity of neural electrodes promotes tissue compatibility and improves their recording stability in both the short- and long-term. However, the miniaturized dimensions and ultraflexibility desired for mitigating tissue responses preclude the probe's self-supported penetration into the brain tissue. APPROACH: Here we demonstrate the high-throughput implantation of multi-shank ultraflexible neural electrode arrays with surgical footprints as small as 200 µm2 in a mouse model. This is achieved by using arrays of tungsten microwires as shuttle devices, and bio-dissolvable adhesive polyethylene glycol (PEG) to temporarily attach a shank onto each microwire. MAIN RESULTS: We show the ability to simultaneously deliver electrode arrays in designed patterns, to adjust the implantation locations of the shanks by need, to target different brain structures, and to control the surgical injury by reducing the microwire diameters to cellular scale. SIGNIFICANCE: These results provide a facile implantation method to apply ultraflexible neural probes in scalable neural recording.

A novel flexible microfluidic meshwork to reduce fibrosis in glaucoma surgery.

PURPOSE/RELEVANCE: Fibrosis and hence capsule formation around the glaucoma implants are the main reasons for glaucoma implant failure. To address these issues, we designed a microfluidic meshwork and tested its biocompatibility in a rabbit eye model. The amount of fibrosis elicited by the microfluidic meshwork was compared to the amount elicited by the plate of conventional glaucoma drainage device. METHODS: Six eyes from 3 New Zealand albino rabbits were randomized to receive either the novel microfluidic meshwork or a plate of Ahmed glaucoma valve model PF7 (AGV PF7). The flexible microfluidic implant was made from negative photoresist SU-8 by using micro-fabrication techniques. The overall size of the meshwork was 7 mm × 7 mm with a grid period of 100 µm. Both implants were placed in the subtenon space at the supratemporal quadrant in a standard fashion. There was no communication between the implants and the anterior chamber via a tube. All animal eyes were examined for signs of infection and implant erosion on days 1, 3, 7, and 14 and then monthly. Exenterations were performed in which the entire orbital contents were removed at 3 months. Histology slides of the implant and the surrounding tissues were prepared and stained with hematoxylin-eosin. Thickness of the fibrous capsules beneath the implants were measured and compared with paired student's t-test between the two groups. RESULTS: The gross histological sections showed that nearly no capsule formed around the microfluidic meshwork in contrast to the thick capsule formed around the plate of AGV PF7. Thickness of the fibrotic capsules beneath the AGV PF7 plate from the 3 rabbit eyes was 90µm, 82µm, and 95 µm, respectively. The thickness at the bottom of fibrotic capsules around the new microfluidic implant were 1µm, 2µm, and 1µm, respectively. The difference in thickness of capsule between the two groups was significant (P = 0.002). No complications were noticed in the 6 eyes, and both implants were tolerated well by all rabbits. CONCLUSION: The microfluidic meshwork elicited minimal fibrosis and capsule formation after 3-months implantation in a rabbit model. This provides promising evidence to aid in future development of a new glaucoma drainage implant that will elicit minimal scar formation and provide better long-term surgical outcomes.

On-chip porous microgel generation for microfluidic enhanced VEGF detection.

Advances in medical diagnostics and personalized therapy require sensitive and rapid measurement of minute amounts of proteins from patients. Standard ELISA is difficult to prepare and involves lengthy protocols. Here we report a novel method using capture antibody immobilized porous poly (ethylene) glycol diacrylate (PEGDA) hydrogel microspheres to enable high sensitivity VEGF detection in arrayed microfluidics. Our technique incorporates antibody encapsulation, trapping, and flow perfusion on a single device. We showed that the convergence of tunable porous hydrogel with efficient microfluidics improved the sensitivity of the assay. The detection limit of this microfluidic porous microgel based assay was 0.9 pg/mL, with only 1+ hour of assay time, demonstrating a novel assay that exceeded conventional technologies in terms of sensitivity and speed.

Balancing oxygen diffusion and convection in spiral microfluidics to mimic radial biological gradients.

Biological gradients are more than linear, one-dimensional phenomena-they often manifest radial geometries superimposed over tissue features and in turn, elicit a spatial response. In wound healing, injury to tissue produces a hypoxic gradient towards the center of the wound, and wound cells respond to this by secreting growth hormones to promote healing. Despite this spatial element in tissue hypoxia, most in vitro hypoxia techniques rely on linear, diffusion-based gradients of limited dimensions. To demonstrate a large area, radial hypoxia gradient, a concentric spiral microfluidics was devised to balance oxygen diffusion against nitrogen convection. The devices were fabricated using only a simple robotic cutter and soft lithography. With these spirals, spatial gradients of 3-15 % oxygen were delivered to fibroblast cells seeded across a gas-permeable membrane to modulate VEGF secretions. This technique opens the door for more studies on hypoxic gradients in wound healing and a number of tissue oxygen applications.