SBIR Phase I: 3D Tumor Model Microtechnology for High Throughput Drug Screening

这个小企业创新研究(SBIR)项目的更广泛的影响/商业潜力是开发一个药物发现平台，用于使用3D肿瘤模型技术进行临床前癌症药物测试。这项技术旨在通过增加进入动物试验的候选药物将有效的可能性，来减少与癌症药物的高失败率(~95%)相关的时间和成本。机器人技术将提供一个生物相关的肿瘤模型，以测试临床前阶段的癌症药库，并取代目前使用的2D癌细胞模型。该项目旨在扩大3D肿瘤模型技术的规模，以适应在制药行业测试的大型药库，并验证其是否符合行业标准和客户需求。这项技术将加速将有效的抗癌药物引入市场，供患者使用，并有助于减少癌症每年夺走的50多万人的生命。这项拟议的工作将极大地促进该技术作为临床前癌症药物筛选工具推向市场，因为它展示了该技术的竞争优势和提高癌症药物发现工作的能力。这项SBIR第一阶段项目建议开发和验证用于制药行业高通量癌症药物筛选的3D肿瘤模型技术。尽管人们对3D癌细胞培养产生了广泛的兴趣，但由于现有方法的许多缺点，目前该行业并未使用这些方法。这项拟议的技术提供了一种强大、高通量和成本效益高的方法来产生3D癌细胞培养，用于快速药物筛选，而不是目前可用的。这项工作将在考虑竞争技术的同时，定量评估3D癌细胞培养的可靠性和稳健性，以及癌症药物测试的成本。一个主要目标是使这项技术适应1536微孔平板格式，用于高效的药物筛选，目前市场上还没有这种药物筛选，并在动物实验中验证该技术预测癌症药物反应的能力。这项工作将涉及机器人方案优化、3D培养的一致性成像分析、概念验证癌症药物筛选以及稳健性的统计评估。预计这项工作将展示该技术在药物测试方面的优势能力和速度、行业级的健壮性、与不同癌细胞类型的兼容性、预测动物研究药物反应的能力以及低成本。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a drug discovery platform for preclinical cancer drug testing using a 3D tumor model technology. The technology is designed to reduce time and costs associated with the high failure rate (~95%) of cancer drugs by increasing the likelihood that candidate drugs advancing to animal studies will be effective. The robotic technology will provide a biologically relevant tumor model to test libraries of cancer drugs in the preclinical stage, and replace currently used 2D cancer cell models. This project aims to scale up the 3D tumor model technology to accommodate large drug libraries tested in the pharmaceutical industry, and verify that it meets industry standards and customer needs. The technology will expedite the introduction of effective cancer drugs into the market for patient use, and help reduce the more than half a million of lives that cancer claims annually. The proposed work will significantly facilitate the introduction of the technology into the market as a preclinical cancer drug screening tool by demonstrating its competitive advantages and capabilities to improve cancer drug discovery efforts.This SBIR Phase I project proposes to develop and validate a 3D tumor model technology for high-throughput cancer drug screening in the pharmaceutical industry. Despite widespread interest in 3D cancer cell cultures, existing methods are not currently used in the industry due to their many disadvantages. The proposed technology provides a robust, high-throughput, and cost-effective approach to generate 3D cancer cell cultures for rapid drug screening, beyond what is currently available. This work will evaluate quantitatively the reliability and robustness of 3D cancer cell cultures and costs of cancer drug testing while considering competitive techniques. A major goal is to adapt the technology to a 1536-microwell plate format for highly efficient drug screening, which is not currently available on the market, and validate the capabilities of the technology to predict cancer drug responses in animal studies. This work will involve robotic protocol optimization, imaging analysis of 3D cultures for consistency, proof-of-concept cancer drug screening, and statistical evaluation of robustness. It is anticipated that the work will demonstrate the advantageous capacity and speed of the technology for drug testing, industry-level robustness, compatibility with different cancer cell types, ability to predict animal study drug responses, and low cost.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.