SBIR Phase I: A nano-liter 3D cell culture well plate for high-throughput screening

这个小型企业创新研究(SBIR)项目的更广泛影响/商业潜力将是开发一种三维(3D)培养孔板，用作研究和药物发现的高通量筛选(HTS)工具。核心技术是一种新型的井板，它包括微米级的通道和隔间，并将具有以自动和高速方式进行自主介质交换和非侵入性药物加载的能力。该孔板将允许针对3D培养细胞筛选更大的潜在药物候选化合物库。这将使制药公司和筛选中心能够通过提高发现和验证所需的规模和吞吐量来增加发现新候选药物的可能性。该技术还将通过提供一种工具来研究细胞在体内类似环境中的行为，从而增加对细胞的科学理解，这在研究肿瘤球体和探索癌症治疗方法时非常重要。这项SBIR第一阶段项目建议通过将新的微流控技术集成到孔板格式中来开发3D细胞培养工具。3D细胞培养正在成为下一代药物筛选方法，因为它通过在类似体内的环境中培养和研究细胞来提供了解细胞反应的窗口。然而，目前市场上还没有工具可以用HTS的方式来测试3D培养细胞与药物化合物的关系。将制造一个井板的原型，并将研究在肿瘤上进行HTS研究所需的几个重要参数。将确定培养3D肿瘤的均匀性、细胞健康生长所需的培养液体积以及平板对药物化合物进行筛选的有效性等参数。预期微流控孔板将在每个微流控孔中产生统一数量的肿瘤，并产生类似于从当前技术状态的3D细胞培养平台获得的结果。在SBIR第一阶段项目期间开发和验证的专利微流控技术将有助于将3D细胞培养整合到主流药物发现级联中。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of a 3-dimensional (3D) culture well plate to be used as a high-throughput screening (HTS) tool for research and drug discovery. The core technology is a novel well plate that incorporates micron-meter-sized channels and compartments, and will have the ability to perform autonomous media exchange and drug loading non-invasively in an automated and high-speed fashion. The well plate will allow larger libraries of potential drug candidate compounds to be screened against 3D cultured cells. This would enable pharmaceutical companies and screening centers to increase the probability of finding new drug candidates by elevating the scale and throughput necessary for their discovery and validation. The technology also will increase scientific understanding of cells by providing a tool to study their behavior in an in vivo-like environment, which is important when studying tumor spheroids and exploring cancer therapeutics.This SBIR Phase I project proposes to develop a 3D cell culture tool by integrating novel microfluidic technology into a well plate format. 3D cell culture is emerging as the next generation drug screening method, as it provides a window into cellular responses by culturing and studying cells in an in vivo-like environment. Currently, however, there are no tools available in the market for testing 3D cultured cells against drug compounds in an HTS fashion. A prototype of the well plate will be fabricated and several important parameters that are required to conduct HTS studies on tumors will be studied. Parameters such as the uniformity in culturing 3D tumors, volume of media required for healthy cellular growth, and effectiveness of the plate to perform screening of drug compounds will be determined. It is anticipated that the microfluidic well plate will create a uniform number of tumors in each microfluidic well and produce results similar to those derived from the current state of the art 3D cell culture platforms. Proprietary patented microfluidic technology developed and verified during the SBIR Phase I project will help integrate 3D cell culture into the mainstream drug discovery cascade.