ECIS-based High Throughput Screening Instrumentation

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.