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Hybrid Neural Microsystems

Every task performed by the nervous system requires networks of many neurons. Yet, the vast majority of neurophysiology research to date has employed single microelectrodes to probe or influence the activity of a single neuron. Attempts to study ensembles of neurons using microelectrode arrays are also limited by the fact that these are better suited to study 2-D neural cultures as compared to 3-D neural cultures, which are more anatomically similar to living tissue and therefore can provide more biologically relevant information. Figures 1 A, B and 2 A, B help to visually compare 3-D and 2-D cultures.

3-D cell culture schematic 3-D cell culture photomicroscopy 
2-D cell culture schematic 2-D cell culture photomicroscopy

Figure1: 3-D (A) and 2-D (B) cell cultures

The research focus of this thrust area primarily includes, but is not limited to, developing novel bioengineering solutions for the creation of a 3-D Micro-fluidic/electronic Neural Interface System. In this area we are interested in developing methodologies for making microfabrication materials such as SU-8 and SLA polymers more biocompatible. We use these materials for constructing arrays of micromachined towers that incorporate microelectrodes and microfluidic channels and then test these devices for their ability to support and functionally connect with 3-D neural cultures (See Figure 2).

Figures 2: Microstructures with microfluidics ports only are seen in A), microelectrodes only are seen in B), and a complex 3-D network of columns and beams (without microfluidics and microelectrodes) are seen in C), live neurons stained green around micro-towers which appear as black circular regions (indicated by white arrows) are seen in D).

We are simultaneously investigating the applicability of different polymeric scaffolding materials for integration within this 3-D device towards achieving a more anatomically similar neural tissue architecture (See Figure 4).

Figures 4: A neuronal cell body is seen embedded in a 3-D polymeric scaffold of Matrigel in A), and another neuron is seen on a 2-D surface coated with Matrigel in B).

We plan to eventually use these systems as test beds for conducting controlled experiments to advance the knowledge of the functionality and the traumatic disruption of 3-D neural circuits and networks. This will help us understand more comprehensively the functioning of neural tissue, for example, its response to traumatic brain injury or biochemical insults.

BRP website link:

http://www.neuro.gatech.edu/brp/

Relevant Publications

  • Vernekar, V.N., Cullen, D.K., Fogleman, N., Choi, Y., García, A.J., Allen, M.G., Brewer, G.J., LaPlaca, M.C. SU-8 2000 rendered cytocompatible for neuronal bioMEMS applications. J Biomed Mater Res A. Epub, Apr 22, 2008
  • Choi, Y., McClain, M.A., LaPlaca M.C., Frazier A.B., Allen M.G.. Three dimensional MEMS microfluidic perfusion system for thick brain slice cultures. Biomed Microdevices 9(1):7-13. 2007
  • Yoonsu Choi, Richard Powers, Varadraj Vernekar , Bruno Frazier, MichelleLaPlaca, "High aspect Ratio SU-8 Structures for 3-D Culturing of Neurons," ASME-MEMS 2003.