ECIS-based High Throughput Screening Instrumentation

描述（由申请人提供）： 电细胞基质阻抗传感（ECIS）是由应用生物物理学开发的，用于真实的实时研究培养细胞的行为。仪器目前在全世界60多个实验室中使用，测量细胞特性，例如细胞单层的渗透性、细胞迁移和细胞-ECM相互作用。目前的ECIS仪器仅限于低通量研究工作。拟议研究的长期目标是推进ECIS技术，以生产为药物发现的高通量筛选（HTS）量身定制的仪器。如果成功的话，基于ECIS的仪器将在制药行业的细胞检测中得到应用，以帮助评估成千上万的测试化合物，以寻找现代治疗药物。为了实现这一点，必须满足几个研究目标。首先，必须采用新的制造技术在标准96孔培养板中生产ECIS阵列，这是HTS努力的主要形式。接下来，在与制药公司协商后，将定制电子设备，以快速返回有意义的ECIS数据，从而可以快速扫描阵列。最后，必须设计软件来帮助研究人员对仪器收集的大量数据进行分类，以有效地确定感兴趣的化合物。具有测量电极阵列的96孔ECIS板对于该目标是必不可少的;然而，使用当前的阵列制造工艺，这些消耗品将是非常昂贵的。因此，第一阶段研究的重点是测试使用自动化和相对便宜的印刷电路板（PCB）技术的可行性。为了实现这一目标，将测试用于制造PCB阵列的材料和方法的细胞培养相容性、培养条件下的电极稳定性及其产生精确ECIS数据的能力。在第一阶段完成后，将生产原型96孔ECIS板，第二阶段的研究将继续进行，最终开发出用于药物发现的新HTS仪器。

DESCRIPTION (provided by applicant): Electric Cell-substrate Impedance Sensing (ECIS) was developed by Applied Bio Physics to study the behavior of cultured cells in real time. Instruments currently find use in over 60 laboratories world wide measuring cell properties such as permeability of cell monolayers, cell migration and cell-ECM interactions. The current ECIS instrumentation is limited to low throughput research endeavors. The long term objective of the proposed research is to advance the ECIS technology to produce instrumentation tailored for high throughput screening (HTS) for drug discovery. If successful, EClS-based instruments will find use in cellbased assays in the pharmaceutical industry to help evaluate literally tens of thousands of test compounds in the search for modern therapeutic drugs. To achieve this, several research aims must be met. First, new manufacturing techniques must be implemented to produce ECIS arrays in a standard 96 well culture platethe mainstay format of HTS endeavors. Next, in consultation with pharmaceutical companies, electronics will be customized to return meaningful ECIS data in a rapid fashion such that arrays may be quickly scanned. Finally, software must be designed to aid researchers in sorting through the abundance of data the instrument will gather to efficiently pinpoint compounds of interest. The 96 well ECIS plate with its array of measuring electrodes is essential to this goal; however, using current manufacturing processes for arrays, these consumable items would be prohibitively expensive. Accordingly, the focus of the Phase I research is to test the feasibility of using automated and relatively inexpensive printed circuit board (PCB) technology for this purpose. To accomplish this, materials and methods to make PCB arrays will be tested for cell culture compatibility, electrode stability under culture conditions and their ability to yield precise ECIS data. At the completion of Phase I, a prototype 96 well ECIS plate will be produced, and Phase II research will continue culminating in a new HTS instrument for drug discovery.