BioMicroElectricalMechanical Systems

Flexible parylene neural probes with multilayer microelectrodes

Brain Computer Interface (BCI) is an effective solution to help the patients suffering from serious spinal cord injury by bypassing the damaged spinal cord area and re-establishing the communication between the central nervous system and an external prosthetic device. High performance of the BCI system relies heavily on acquiring neural signals with high fidelity. The method which could acquire signal with highest resolution is to insert intracortial microelectrodes to record from individual neurons or neuron ensembles. Since this strategy is highly invasive, it will induce chronic tissue inflammation which may lead to immune cascade that will eventually wall off the implanted microelectrodes from the neighboring neurons. The stiffness and size of the neural probe are two critical factors affecting the chronic tissue response. The hypothesis that smaller and more compliant neural probes will induce less damage to the brain tissue and in turn mitigated neural tissue response as well as improved chronic stability of the implant has been the impetus for researchers to explore soft polymers as probe substrates and scale down the probe size. Previous research done by our group indicates a parylene based neural probe with width between 30-80 microns would induce no discernible neural tissue response for over 12 weeks. (see the following figure). However, the small width of the probe width will inevitably limit the number of recording sites along the probe, and thus reducing the spatial and temporal resolution of the recorded signal, if conventional two-dimensional patterning approach is adopted. Our group presents a novel strategy of patterning electrodes based on a three-dimensional approach to scale up the number of recording sites with minimum risk of increasing the invasiveness of the neural probe. A microfabrication process was confirmed to be compatible with the new patterning approach. Ongoing studies of probe coating and in vivo studies will help validate its chronic recording capability in the physiological environment.

Representative images of GFAP immunostaining for different devices following 24 weeks implantation. (a) a 30 x 5 um probe coated with a 100 x 100 um E5005(2K) coating showing no discernible gliosis. (b) a 80 x 5 um probe coated with a 100 x 100 um coating showing gliosis. (c) a negative control consisting just of the 100 x 100 um coating (d) a positive control based on probe sizes found in literature of a large probe 320 x 5 um coated with a 350 x 5 um coating displaying a large degree of gliosis. Scale bar: 200 um.



Skin Electroporation

With the rise of genetic medicine, gene transfection has become a topic of interest for the development of therapies ranging from disease treatment to vaccinations. Tissue level electroporation has been explored using surface electrodes and intramuscular electrodes to increase the delivery capability of small molecule drugs directly to the patient. However, the high field strengths needed to create pores in the living cell layers can also cause pain and tissue damage. The use of microelectrodes has been shown to reduce the tissue damage done to different tissues while still allowing delivery of molecules. This project investigates the fabrication process and characterization of microelectrode arrays. Microelectrodes have been shown to deliver lower voltage pulses to more targeted areas in the tissue layers, resulting in less damage to the surrounding tissues. The feature sizes and bioinert materials used to create the microelectrode arrays result in less pain and immune response compared to the intramuscular electrodes.

Single-Cell Level, Feedback Controlled Electroporation

Electroporation is a widely used, safe, non-viral approach to deliver foreign vectors into many different cell types. When a cell is exposed to an electric field of the appropriate strength, the membrane undergoes reversible electrical breakdown, where transient pores form in the membrane, allowing molecular transport into the cell. The controlled intracellular delivery of biomolecules and therapeutics enables the ability to study and engineer fundamental cellular processes and has therefore been a major focus in biomedical research and clinical medicine. This work is a collaborative effort at Rutgers, involving 4 primary investigators (Jeffrey Zahn, David Shreiber, Hao Lin, Jerry Shan), with the primary focus of developing a microfluidic technology for performing controlled single-cell level transfection in a continuous, serial fashion. Recently published work showcases the electroporation platforms capability of electrically detecting the presence of a cell in the electroporation zone, applying a prescribed electric pulse of known strength, and measuring the degree of cell membrane permeabilization (both electrically and optically) in real time. Current work involves the validation of the platform for performing more ‘clinically relevant’ transfections, such as plasmid DNA, with the ultimate goal of developing a platform for performing feedback controlled electroporation, that is independent of the cell-to-cell variability of a given population and across different cell types.




Study of Network Hemodynamics in an Artificial Microvaculature

Consisting of the smallest blood vessels, microvascular networks are responsible for gas and nutrient transfer and the regulation of blood flow in individual organs. When the function of the microcirculation is hindered, major health issues, even death can occur. Blood is such vessels behaves are a suspension made up of primarily highly deformable red blood cells, which are very close in size to the blood vessels. Using microfabricated networks as we aim to study network hemodynamics and micro-dynamic insights of blood flow in simple bifurcations and microvascular networks. The image below is of red blood cells suspended at 25% hematocrit (HCT) in a bifurcating microchannel. Data are anlayzed to determine flow characteristics such as cell velocity, N* vs Q*, and HCT partitioning



Neural Tissue Engineering

Cell/Tissue Culture in Micro-enviorments

Drug addiction is a neurological disorder which alters the mesolimbic dopamine pathway, known for reward processing. Transition to addiction involves synaptic modification that creates transient and long-term pathway changes. Animal models have elucidated many mechanisms of drugs of abuse, but are limited in their ability to model the role of human genetic variants in addiction. We propose a model that recapitulates mesolimbic pathway connections using human induced neurons. A compartmentalized device separates subtype neurons which communicate through microchannels. We hope through this model we can provide insight into the role of polymorphisms in mediating addiction and provide a platform for therapeutic development.



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