Development of a prototype system for assaying exocytosis from individual cells using using transparent microelectrode arrays

 描述(申请人提供)：细胞通过胞吐作用分泌激素和神经递质。了解胞吐作用是如何调节的以及药物和毒素如何抑制胞吐作用具有广泛的医学意义，因为它有助于开发治疗需要增强递质释放(例如帕金森病)或抑制递质释放(例如治疗痉挛和斜视)的医疗条件。该SBIR项目的总体目标是 是利用微制造技术开发商业设备，可以测试单个细胞中递质的释放速度是现有方法的10-100倍，并且成本更低，从而大大加快生物医学研究的步伐。此外，这些设备将提供全新的功能，例如能够同时对荧光标记的囊泡成像，同时使用下面的透明电化学电极测量同一囊泡的释放。这一第二阶段项目的目标是开发一套健壮、实用、用户友好的硬件和软件原型，供研究界通过以下具体目标使用。目的1.研制可插入定制多道恒电位仪的一次性电化学多电极阵列盒装置。目的2.开发一个数据采集和显示软件应用程序和一个高通量尖峰分析应用程序。Excle Electronics是明尼苏达大学生命科学企业孵化器的所在地，该孵化器提供研究设施和创业支持。ALA Science将与ExoCytronics合作开发原型，然后将其转化为产品，并在第三阶段进行营销。除了神经科学研究领域，这些设备的潜在市场还包括制药业，用于校准肉毒杆菌毒素等药物的剂量，临床市场，用于在不使用实验室动物的情况下执行肉毒杆菌中毒的自动分析，以及国防/国土安全市场，用于通过基于细胞的生物传感器检测神经毒素生物武器。

 DESCRIPTION (provided by applicant): 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.