SBIR Phase I: Optoelectronic Microplates: Disruptive Optical Stimulation Technology for Drug Discovery Screening Assays

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop specialized cell culture plates that can provide dynamic optical stimulation of cells during kinetic ion channel drug screening assays. The proposed cell stimulation technology is expected to improve the efficiency of drug discovery, and lead to more promising drug candidates with a wide range of mechanisms of actions. Since effects of drugs often depend on functional states of drug targets, in vitro high-throughput assays must be able to re-create different functional states during drug screening. Currently, screening assays acquire the data either from one functional state or an ensemble average of heterogeneous states, which is not representative of in vivo settings. The proposed microplate-based cell stimulation technology will help drug discovery companies to introduce more efficient drugs faster while reducing the development costs, because the proposed technology can dynamically "cycle" ion channel drug targets through different functional states while evaluating drug effects in kinetic assays. These minimally-invasive all-optical assays will have increased information content and enhanced predictive values. This SBIR Phase I project proposes to develop nanotechnology-based optoelectronic microplates that can serve as a light-controlled actuator enabling dynamic optical stimulation of cells for all-optical drug screening assays. Current cell stimulation technologies require either genetic modifications of cells (which can affect the drug screening results) or electric-field stimulation (which requires specialized instrumentation and can damage cells). The proposed technology is a non-invasive optical stimulation plate-based platform that can work on genetically and structurally intact cells, and will be compatible with existing screening instruments. The research plan in the material science area covers the development of protocols for deposition of graphene materials and comprehensive characterization of graphene-coated microplates in cell-free and cell-based modes. The biological research plan includes the development of all-optical screening assays that incorporate graphene-coated microplates for enabling optical stimulation. Specifically, the goal is to focus on calcium imaging assays for L-type voltage-gated calcium ion channels that will be "cycled" through different functional states by light illumination using optoelectronic plates. The validation process will include the evaluation of pharmacological effects of known state-dependent calcium channel blockers. It is anticipated that optoelectronic microplates will be compatible with existing cell culture protocols and imaging instrumentation.