The long term career goal of the PI is to help transform quantitative transport modeling in both lab-on-a-chip and biophysical systems, focusing on electric-field mediated flow and transport processes in microfluidic and bio-electrolytic environments. Two interwoven research projects are pursued within a unified, electrohydrodynamic framework. The first investigates complex electrokinetic flow in on-chip sample preconcentration methods, providing both a generalized prediction capability and fundamental understanding for electrokinetic/electrohydrodynamic phenomena in microfluidic environments. The second studies electroporation-mediated molecular delivery, a technique in which the electric field permeabilizes the cellular membrane, and delivers active agents into the intracellular compartment. By combining modeling and experimental efforts, this project investigates the pertinence of electrokinetic transport in molecular delivery, and the possibility to improve electroporation via parametric optimization. The intellectual merit lies in a generalized model framework that will provide in-depth understanding of a wide range of fundamental phenomena, including multi-dimensional, multi-ion electromigration, the response of cellular membrane to the electric field and cross-membrane transport, among others. In particular, in the second project, the correlation of electroporation-mediated molecular delivery with an electrokinetic mechanism is new and a major innovation. This project will demonstrate that fundamental principles established in engineering contexts can be applied to study transport phenomena in biophysical systems. The broader impacts lie in the applications and the integrated educational efforts. The first project will provide guidelines for the design and optimization of high-performance on-chip assays, and significantly impact the development of microfluidic electrokinetic technologies. The second project contributes to the development of safe and efficient electroporation technology, for both biological research and clinical applications. This work will eventually benefit human health. The educational plans have three overarching themes: enhancing the integration of computational analysis into engineering curriculum, active recruitment of underrepresented minority students into engineering disciplines, and the creation of a true interdisciplinary training environment between Mechanical and Biomedical Engineering. These themes are implemented at the high-school, undergraduate, and graduate levels, and the results will be assessed when possible.
The interaction of electric fields with biological cells is a phenomenon of both great complexity and broad utility. In this NSF-funded program, two particular subjects have been extensively and systematically investigated. The first is electroporation, in which the cell membrane is transiently permeabilized to provide access to the cytoplasm. Active agents such as drug molecules, protein, DNA, and RNA, can be subsequently delivered. Despite extensive research and broad applications in both medicine and research, electroporation is limited by low efficiency and high-degree cell damage in general. This limitation is primarily due to a lack of fundamental understanding and quantitative prediction tools. The outcomes of this program contribute significantly to overcome these limitations. 1) We have developed the first numerical model on the whole-cell level to quantitatively predict electroporation-mediated molecular delivery. 2) Combining our numerical capacity and experimental efforts, we have identified an electrokinetic mechanism governing molecular delivery and transport mediated by electroporation. 3) Via carefully designed and controlled experiments, we have quantitatively mapped out scaling laws for both molecular delivery and cell viability post-pulsation. 4) Combining results from all of above, we have implemented electroporation on a microfluidic platform, with the eventual goal to achieve high-efficiency, high-throughput molecular delivery and transfection. The second is electrodeformation, which refers to the deformation of the cell membrane under the electrostatic forcing resulted from field application. This project is meaningful in that deformation techniques are commonly exploited as means to probe the mechanical properties of biomembranes, so as to correlate with physiological and pathophysiological changes in the cells. The outcomes in this direction are: 1) We have developed a quantitative model to fully predict the deformation and relaxation of vesicles under DC electric fields. Vesicles are cell mimics which are often employed as an ideal model system to study the properties of biomembranes. 2) We have performed experiments to achieve large deformations of vesicles under DC electric fields. 3) More importantly, we have identified a systematic approach to map the mechanical properties of biomembranes with high accuracy and specificity. This last result defines the PI’s research direction for the next few years, hence the impact extends beyond the scope of the current funded program. Twenty-one papers (fifteen published, two submitted, four under preparation) have been produced based on the work supported by this project, including publications in a broad range of prestigious journals such as the Physical Review Letters, the Journal of Fluid Mechanics, Physics of Fluids, Lab on the Chip, and the Biophysical Journal. During the last project year, the PI has outreached to higher educational institutes in Germany (The Max Planck Institutes of Colloids and Interfaces) and China (Peking University) to establish long-term collaborative relations, which enabled his pursuit in additional areas such as functional superhydrophobic surfaces. These collaborations serve as platforms for international academic exchanges and education. The broader impact of the work has included the education of four PhD students, two Master students, and several undergraduates, many of whom are female. The PI also focused on outreach efforts in the summers to middle- and high-school female students through day-long workshops on engineering design and testing based on water guns made from PVC pipes. From 2010 to 2014, the PI served as the Rutgers Chapter President for Sigma Xi, the oldest honor society for scientists and engineers. He has actively used this platform to outreach to middle- and high-school teachers in sciences, and to undergraduate and graduate students who pursue academic and research excellence.
