The flux of small molecules and ions at the surface of cells carries important information that is communicated both internally to the cell and externally to neighboring cells. Examples of such important cellular flux in biology include neurotransmitter release and reuptake in neurons, glucose transport for adapted cell metabolism in cancer cells, and ion flux in plant gravity sensing during development. No method currently exists that can quantify the spatial map and dynamics of true cellular flux and biomolecule gradients from many single cells in a chip format. This project will apply recent advances and expertise in nano/microelectronics, mathematical modeling, and biosensors to create such a technology. The outcome of the work will be an on chip platform technology that can be replicated for a wide range of cellular systems to answer basic biological questions regarding cellular flux that cannot be answered today. For example, a freshly resected tumor could be rapidly analyzed to examine how a drug candidate affects glucose metabolism of the heterogeneous cell population or neurotransmitter dynamics could be integrated with electrical activity information to better understand information processing of neuronal networks during learning and memory.
The flux and resulting concentration gradients of small molecules and ions at the surface of cells carry important information that is communicated both internally to the cell and externally to neighboring cells. Self-referencing biosensors are currently the best method for quantifying cellular flux dynamics, but this method is limited to measurements at one location in space on one cell at a time. In addition, this method is not portable and cannot be used for sensing in remote locations such as on space missions, in environmental monitoring, or in high throughput biomedical applications. No method currently exists that can quantify the spatial map and dynamics of true cellular flux and biomolecule gradients from single cells in a chip format. The overall objective of this work is to create a technology for the spatial and temporal mapping of biomolecule gradients and flux at the level of single cells by creating 1D and 2D arrays of individually addressable nano/microscale electrochemical sensors. The proposal develops and integrates novel solutions to the technical challenges of creating such a device including synchronous detection to overcome noise limitations, a field-programmable approach to reduce the need for precision alignment between sensors and cells, electrode addressable biofunctionalization to achieve high spatial resolution of bio-recognition layers and multi-analyte sensing, and a mathematical framework to design and optimize electrode arrays considering both the biological signal and sensor function in space and time. Importantly each of these technical advances has application beyond flux sensing and applies more broadly to the field of nano-biosensing. The end result of the work will be an on-chip platform technology that can be replicated for a wide range of cellular systems.
This award is being made jointly by two Programs- (1) Nano-Biosensing, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate), and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).
