Photograph of a planar multielectrode array (MEA) with integrated electronics. Neurons are cultured in the well and each electronic chips amplifies neuron signals and outputs them through a multiplexer.
The focus of the proposed program of research is to advance the knowledge of the functionality and the traumatic disruption of neural circuits and networks through the development of a set of technologies that facilitates the in-depth study of three-dimensional (3-D) neuronal tissue in vitro. We will create a comprehensive system by combining an array of micromachined towers that incorporate microelectrodes and microfluidic channels: the microfabricated neural interface system (µNIS). These towers will be fabricated on a substrate that will control and process the signals to and from the towers using integrated circuits. The resulting system will enable a new field of neurobiological research, in which the collective properties of 3-D neural circuits can be observed and manipulated with unprecedented detail and precision, and at a level of control not possible in living animals. For example, 3-D cultures that are assembled from dissociated cells form in vivo-like structures, exhibit in vivo-like responses to stimuli, and survival longer than monolayer correlates. In addition, research on cortical slice preparations in vitro is presently limited to thin (~500 µm) cultures that do not include all the layers or lateral dimensions, although the structural organization of the cortex may be the key to its vast information storage and processing capabilities. The µNIS, by incorporating microfluidics for distributed nutrient supply and aeration, will facilitate detailed study of thicker neural cultures and will permit precise stimulation and recording capabilities.
Conceptual drawing of the 3D interfacing system with Fluidic channels (yellow square) & Recording Electrodes (red square)
The proposed project has four specific aims, each of which contains a set of technological developments motivated by biological hypotheses. Aims 1, 2, and 3 each represent a core element of the technical development and will be pursued in a parallel approach: (1) three-dimensional microfabricated structures, (2) microfluidics, and (3) integrated circuitry. Specific Aim 4 represents the culmination of the project through the combination of prior aims and the application to 3-D, simultaneous stimulation and recording of neural tissue.