Ultrasmall Chemical Imaging of Cells and Vesicular Release

The long-term goal of this research is to develop analytical chemistry techniques capable of establishing the chain of molecular events associated with (1) neurotransmitter release at the single cell and subcellular level and (2) with cell differentiation and reprogramming. These are incredibly important goals for which there are few analytical chemistry methods that are available and useful. New nanoscale chemical imaging methods for both static cell structures and dynamic processes are under development. First, we are working to develop electrochemical methods beyond state of the art for cell measurements - arrays of ultrasmall electrodes beyond anything done before in terms of small size, number of electrodes (from 7 to 55), and rate of read out. A process to construct 16-electrode arrays that could eventually be extended to 4096 electrodes will also be examined. Electrode-array experiments will be used to spatially map active release sites across the cell surface with unprecedented spatial resolution. Second, a new mass spectrometry imaging approach with combined MALDI and cluster SIMS ion sources is under development. Both C60 cluster bombardment and the Bi3+ source will be used for SIMS. This will combine the best in depth profiling, mass resolution, spatial resolution, sensitivity and range of molecules. The system will be used to investigate membrane changes during exocytosis and during stem cell differentiation and somatic cell reprogramming. Although transcription factors can be applied to direct changes in stem and somatic cells, environmental cues are clearly important (e.g. stem cells cultured with striatal astrocytes become dopamine neurons) and these cues likely involve molecules on cell surfaces. We plan to image these molecular cues. The third goal is to develop an in vitro cell array system using nerve-like cells to model communication between cells. Network activity will be measured with electrochemical-array sensors. A long-term aim is to combine the three goals to develop the means to add and direct replacement cells in an in vitro model of disease.
European Research Council (ERC)

Published: Thu 21 Jun 2012. Modified: Mon 28 Oct 2013