Silicon micromachined devices for in vitro and in vivo studies of neural networks

Citation

Tatic-Lucic, Svetlana (1995) Silicon micromachined devices for in vitro and in vivo studies of neural networks. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/6jhx-9889. https://resolver.caltech.edu/CaltechETD:etd-10262007-104017

Abstract

NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. The design, fabrication and mechanical testing of two new kinds of silicon-micromachined devices for both in vitro and in vivo extracellular stimulation and recording are investigated. The novelty of these devices is a neuron well structure fabricated in a 16-20 [...] thick silicon membrane using a double-sided micromachining technique. The neuron well is a trapezoidal cavity with a gold electrode at the bottom and a mechanical grillwork on the top. Through the grillwork, live embryonic neurons can be implanted, cultured, and then electro-physiologically studied inside the wells. This approach can tremendously improve the reliability and signal-to-noise ratio of extracellular recording of the cultured neurons compared to previous approaches. First, a silicon-micromachined microchip for in vitro studies of cultured neural networks has been developed. The bottom of the neurochip has two different designs. One has a circular silicon-dioxide rim ([...] step height) at the bottom (called dimpled bottom), and the other has only a flat bottom. The dimpled bottom is expected to provide a better mechanical seal between the cultured cell and the gold electrode, which would result in a better signal-to-noise ratio. Physiologically, it has been confirmed that the neuron growth inside the well is independent of the kind of bottom. So far, the neurochips' biocompatibility for up to a week has been demonstrated using both rat hippocampal and superior cervical ganglion (SCG) neuron cells. Next, silicon neuroprobes for in vivo studies of central nervous systems have also been successfully developed. These probes are developed using a modified neurochip technology. The mechanical properties of the neuroprobes are satisfactory, proven in bending, buckling, and even in vivo animal tests. Recently, the neuroprobes have been physiologically tested in rat hippocampus. For the first time, outgrowth of neurites from the cultured neurons inside the wells into the host hippocampus has been observed, which represents the very important evidence for the success of using neuroprobes. In the future, although beyond the scope of this work, a lot more exciting electrophysiological research using these devices should be done. This should lead to further improvement over the prototypes, and finally produce a new generation of working neural prosthetic devices.

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