A HTS assay for voltage-gated ion channel targets

电压门控离子通道靶标的 HTS 测定

• 批准号: 6790321
• 负责人: Janet Kay Robertson
• 金额: $ 19.93万
• 依托单位: MEMBRANE ASSAYS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790321
• 关键词: bioassay; bioengineering /biomedical engineering; biomedical device power system; biomedical equipment development; biotechnology; cell line; computer system design /evaluation; consumable /disposable biomedical equipment; drug discovery /isolation; electrical measurement; electrical property; high throughput technology; ion transport; voltage gated channel

DESCRIPTION (provided by applicant): Membrane Assays, Inc. (MAI) seeks to develop and commercialize a high throughput screening (HTS) assay for voltage-gated ion channel targets. The assay is called the Ion Channel Assay (ICA). The ICA uses an electric field to stimulate voltage-gated ion channels. The cellular response is detected optically using fluorescence technology. The ICA is an enhanced 96-well microwell plate. On the bottom surface of each of the 96 wells are microelectrodes. Cells grown on the bottom of the well make electrical contact with the microelectrodes. When a voltage is applied between the electrodes, the local electrical potential across the cellular membrane is altered triggering a response by the voltage-gated ion channels. The action of a pharmaceutical to block, increase or decrease this response can then be measured. Voltage-gated ion channels play a critical role in such biological processes as the beating of the human heart, the contraction of muscles, and the release of hormones. Therefore, these channels are also important drug targets. No effective manner of rapidly testing the action of a pharmaceutical against a voltage-gated ion channel exists. Traditional patch clamping is too slow and even the new automated patch clamp products, currently in beta testing, do not have the throughput required. The result is missed good drugs. In addition, unknown side-effects of pharmaceuticals on a particular voltage-gated ion channel in the heart, the hERG channel, have led to the removal of 5 drugs from U.S. market. Thus, even if the target molecular of a pharmaceutical is not a voltage-gated ion channel potential new drugs must still be tested against a voltage-gated ion channel, the hERG channel, to uncover side-effects. MAI proposes to develop a critically needed HTS assay for voltage-gated ion channel targets. The assay is easy to use and compatible with equipment currently in place at most large pharmaceutical companies. Phase I funds will be used to manufacture 100, 96-well plate devices. The fabrication of these first 100 devices will verify the technical feasibility of the proposed manufacturing process and provide plates for ongoing biological testing and assay development. Electrical testing will also be performed.

描述（由申请人提供）：Membrane Assays，Inc. (MAI)寻求开发和商业化用于电压门控离子通道靶的高通量筛选（HTS）测定。该试验称为离子通道试验（伊卡）。伊卡使用电场刺激电压门控离子通道。使用荧光技术光学检测细胞反应。伊卡是一种增强型96孔微孔板。在96个威尔斯孔的每个孔的底面上是微电极。在孔底部生长的细胞与微电极电接触。当在电极之间施加电压时，细胞膜上的局部电位被改变，从而触发电压门控离子通道的反应。然后可以测量药物阻断、增加或减少这种反应的作用。 电压门控离子通道在人体心脏跳动、肌肉收缩和激素释放等生物过程中起着关键作用。因此，这些通道也是重要的药物靶点。不存在快速测试药物对电压门控离子通道的作用的有效方式。传统的膜片钳太慢，即使是新的自动膜片钳产品，目前在beta测试，没有所需的吞吐量。结果是错过了好药。此外，药物对心脏中特定电压门控离子通道（hERG通道）的未知副作用已导致5种药物从美国市场下架。因此，即使药物的靶分子不是电压门控离子通道，潜在的新药仍然必须针对电压门控离子通道（hERG通道）进行测试，以发现副作用。 MAI建议开发一种迫切需要的电压门控离子通道靶点的HTS测定法。该检测方法易于使用，与大多数大型制药公司目前使用的设备兼容。第一阶段的资金将用于制造100个96孔板装置。前100件器械的制造将验证拟定制造工艺的技术可行性，并为正在进行的生物学试验和测定开发提供平板。还将进行电气测试。