The objective of this proposal is to develop biocompatible microsystems that will seamlessly interface with neural systems. Neurons communicated using both electrical and chemical signals. Microelectromechanical systems (MEMS) will be developed that mimic this cellular communication at biological spatial and temporal scales. Integration of microelectrodes and microfluidics into a single platform allows multi-channel bi-directional interaction with cells and tissue at a level of sophistication not possible with existing instrumentation. These microsystems will incorporate polymers that have been demonstrated to elicit minimal bioreactivity and biofouling. To achieve these objectives, my research group will develop the following tools:
Develop active, multi-channel microfluidic systems for spatially and temporally precise delivery and sampling of biological fluids, nutrients, and drugs Develop stable, long-term, and biocompatible polymer devices with appropriate passivation and isolation of electrodes for support of cells and tissue slices Integrate electrical and microfluidic elements for localized dual-mode stimulation and recording from dissociated cells and intact tissue slices These tools will advance scientific discovery in cellular biology and neuropharmacology. Additionally, they will enable new techniques for advancing neuroengineering and tissue engineering which include:
Dual-mode in vitro sensing of biological processes in neural cells and tissue slices Localized biofeedback based on biological cues for controlled and sustained growth In vitro studies on axonal growth and guidance in cells, tissue, and co-cultures Implantable dual-mode microsystems for in vivo investigation of neural injury and repair
INTELLECTUAL MERIT The central nervous system is the most complex biological system and arguably the most important. It is also the most difficult system to interface with. This CAREER plan will develop sophisticated dual-mode tools to enable investigation and manipulation of local neural microenvironment conditions. Such capability is not possible with the current state-of-the-art. The intellectual merit lies in the development of new tools that advance our knowledge of the cause-effect relationship between electrical and chemical signals in neurons communication. This microsystems interface technology will also be applied to other biological systems. The ultimate goal is to develop novel biomedical implants that provide bi-directional electrical and chemical cues for re-growing neural circuits and restoring lost neural functions.
BROADER IMPACT Injuries to the central nervous system (e.g. traumatic brain injury, spinal cord injury, and stroke) result in devastating lifelong physical disabilities in millions of Americans and are presently incurable conditions. This research will enable new understanding of neural injury and lead to new treatments that promote neural repair. The direct benefits to society include the alleviation human suffering and reduction in health care costs. Integrated research and education activities are planned for the University of Southern California (USC) and its surrounding communities with emphasis in increased participation by females and minorities.
The major goals of this research program were to design, fabricate, and demonstrate microdevices that distribute fluids in tiny amounts to neuronal cells and tissues. The purpose of this work is to develop better engineered interfaces to these cells and tissues to enable a deeper understanding of chemical events happening at the cellular scale and push the envelope towards improved medical implants that treat neurologica deficits arising from injury or disease. Towards this end, our group developed microfabricated devices using biocompatible polymer technologies and demonstrated their operation and utility in benchtop experiments with neuronal cells and tissues. In the process of developing these devices, we also developed additional devices that led to engineered interfaces that can interact using mechanical or optical means instead of chemical or electrical means. This further broadens our ability to "talk" to cells at an appropriate length scale and opens the door to many opportunities to expand our understanding of neuroscience and further enhance our ability to develop devices to treat deficits of the nervous system. This project involved the participation of diverse groups of faculty, teachers, and students. Three PhD students were trained and graduated. Many undergraduate and high school students participating in carrying out the research plan and some shared co-authorship on technical publications resulting from the work. In addition to technical training, many students benefitted from the educational products resulting from this work. These include novel educational assessment instruments focused on biomedical microdevices, a textbook used by university students on biomedical microdevices, and simple laboratory experiments relating to microfabrication that can be carried out in settings with minimal access to laboratory facilities. The rich set of educational and outreach activities included student participation in science fairs and international conferences, introduction of new microfabrication and -engineeirng materials to high school classrooms, international research experiences, and mentoring.
