Cells secrete hormones and neurotransmitter via exocytosis. Understanding how exocytosis is regulated and how pharmaceuticals and toxins inhibit exocytosis is of broad medical significance because it aids in developing approaches to treat medical conditions where release of transmitter needs to be enhanced (e.g., Parkinson's disease) or inhibited (e.g., to treat spasms and strabismus). The overall goal of this SBIR project is to use microfabrication technology to develop commercial devices that can assay release of transmitter from individual cells 10- 100 fold faster and cheaper than current approaches and thereby greatly accelerate the pace of biomedical research. In addition, the devices will provide entirely novel capabilities such as the ability to simultaneously image a fluorescently labeled vesicle while measuring release from the same vesicle with an underlying transparent electrochemical electrode. The goal of this Phase II project is to develop a set of robust, practical, user-friendly hardware and software prototypes ready for use by the research community through the following Specific Aims.
Aim 1. Develop disposable electrochemical multi-electrode array cassette devices that plug into a custom multi-channel potentiostat.
Aim 2. Develop a data acquisition and display software application and a high-throughput spike analysis application. Exocytronics is resident in the MU Life Sciences Business Incubator, which offers both research facilities and entrepreneurial support. ALA Scientific will work with ExoCytronics to develop prototypes, and then turn them into products and market them during Phase III. In addition to the neuroscience research community, potential markets for the devices include the pharmaceutical industry to calibrate the dosage of pharmaceuticals such as BoTox, a clinical market to perform automated assays of botulism without the use of laboratory animals and a defense / homeland security market to detect neurotoxin bioweapons with cell-based biosensors.
The goal of this project is to develop robust and easy-to-use products that can assay secretion of hormones and neurotransmitter from individual cells 10- 100 fold faster and cheaper than current approaches. The devices will greatly accelerate the pace of medical research to understand how pharmaceuticals alter cell secretion. Other applications include calibrating the potency of pharmaceuticals used to treat neurological disorders, automated assays of food poisoning without the use of laboratory animals and improved detection of neurotoxin bioweapons.
| Gillis, Kevin D; Liu, Xin A; Marcantoni, Andrea et al. (2018) Electrochemical measurement of quantal exocytosis using microchips. Pflugers Arch 470:97-112 |
| Balaji Ramachandran, Supriya; Gillis, Kevin D (2018) A matched-filter algorithm to detect amperometric spikes resulting from quantal secretion. J Neurosci Methods 293:338-346 |
| Ghosh, Jaya; Liu, Xin; Gillis, Kevin D (2013) Electroporation followed by electrochemical measurement of quantal transmitter release from single cells using a patterned microelectrode. Lab Chip 13:2083-90 |
