To understand how diseases of the CNS can disrupt functions on the whole, it is imperative to investigate the nature of chemical connectivity between neurons. Perhaps one trillion neurons within the human brain function together through 10(15) synapses, and the probability that many neurons assume unique identities demands chemical analyses that are sensitive to variations from cell to cell. Determination of the molecular composition at the cellular and sub-cellular level is critical to development of an accurate model of the mechanisms by which nerve cells normally communicate and how these mechanisms can become flawed in disease states. The long-term objective of this research program is to exploit capillary electrophoresis with high sensitivity fluorescence detection to perform chemical analyses of single neurons, varicosities, synapses, subcellular compartments, and releasates. Presently, on-site instrumentation is capable of fractionating and detecting as few as 1700 analyte molecules taken from a large scale sample preparation. Analysis of minute real- world samples, however, places stringent limitations on sample manipulations. To facilitate quantitative microscale analyses, fluorescent-tagging procedures must be adapted for on-column labeling of natively non-fluorescent analytes.
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