Cell surface charge, net electricity on cell surface, is a promising new biomarker for rare cell detection, cell sorting, and pathology stage monitoring of malignant cell. Cell surface charge pattern also reflects the in situ dynamic status of cell membrane, which is critical for membrane-regulated cell functions such as endocytosis, muscle cell contraction, nutrient transport, T cell activation and insulin release. Recent evidences show that a variety of cell functions including cell aggregation, cell division and cell migration can be modulated by manipulating cell surface charge patterns. Therefore rapid mapping of single cell surface charge patterns will provide a unique and important approach in advancing analysis of cells and regulation of their functions. However, to date rapid mapping of living cell surface charge remains a large challenge owing to lack of robust techniques capable of measurements at the micro and nano scale. Scanning ion conductance microscopy has been used for quantitative cell surface charge mapping. This method employs a single nano pipette to approach the cell surface point by point, resulting in a low efficiency, labor intensive and destructive measurement. The proposed research aims to address this long standing challenge by exploring a universal method for rapid, non-destructive characterization and mapping of cell surface charge. In addition, with educational and outreach activities, the proposed research is poised to enhance the interdisciplinary learning experience for undergraduate, graduate and K-12 students.
The objective of this project is to explore a lab-on-a- chip platform for rapid, non-destructive living cell surface charge mapping. Such a device will 1) foster the breakthrough of discovering new biomarkers for cell identification, sorting and real time monitoring, and 2) greatly advance the knowledge in understanding the roles cell electrical properties play on cell functions. To achieve the objective, the following tasks will be pursued: 1) demonstration of acoustic cell manipulator that will rapidly focus/release individual living cell onto/off the probe surface in a continuous flow, 2) study of an array of nanopores that can accurately map the cell surface charge with high temporal resolution and accuracy, 3) implementation of signal multiplexing that will enable simultaneous measurement of surface charge distributions via a nanopore array, and 4) validation of the platform for rapid cell surface charge mapping using human dermal fibroblasts cells. The use of non-intrusive cell manipulation enables quick focus/release cells onto/off the nanopore array's surface, allowing rapid, high-throughput surface charge mapping in continuous flow. The use of nanopore array in combination with signal multiplexing enables rapid mapping of the cell surface charge characteristics at one time without complex measurement electronics.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
