STTR Phase II: The BaroFuse, a Microfluidic Multichannel Measurement of Tissue Oxygen Consumption For Drug Testing

STTR 第二阶段：BaroFuse，一种用于药物测试的组织耗氧量微流体多通道测量

• 批准号: 1853066
• 负责人: Daniel Cook
• 金额: $ 75万
• 依托单位: EnTox Sciences, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1853066&HistoricalAwards=false
• 关键词: STTR; Phase; II; BaroFuse; Microfluidic

This STTR Phase 2 project is aimed at providing technology to address the high costs of developing effective and safe drugs. Bringing a new drug to market typically involves screening 100's of thousands of compounds for efficacy and toxicity utilizing cell, tissue and animal models to ultimately select a lead compound that will be tested in clinical trials. This process can take years, billions of dollars, and in the worse case leads to compounds that fail during clinical trials due to safety concerns. Advances in microfluidics and 3D-printing have enabled the construction of tissue culture devices with nearly unlimited numbers of tissue chambers and flow channel complexity. Combined with optical sensors with unprecedented sensitivity, instrumentation can be built that maintain large numbers of biopsied tissue samples, while assessing the effects of exposure of the tissue to libraries of drugs. This technological platform provides resolution of drug effects on human tissue with high sensitivity thereby reducing the cost of animal testing and the risk of bringing toxic drugs to clinical trials and the market. In addition, the technology will impact the fields of personalized medicine, where drugs could be tested on an individual's own tumor or tissue, and environmental health.Measuring in vitro cellular responses to pharmaceutical compounds is critical for identifying toxic effects of candidate drugs prior to costly in vivo animal and clinical testing. To address this need, instrumentation to maintain and assess biopsied tissue in real time is being developed. The technology utilizes microfluidics for optimal maintenance of tissue viability and function, and optoelectronics to measure oxygen uptake with unprecedented sensitivity. The fluidics are driven by gas pressure, circumventing the need for unwieldy pumps, and the channels are fabricated by 3D printing, allowing for nearly unlimited numbers of chambers and flow channel complexity. The technological platform will aid in the selection of lead compounds for clinical trials, estimation of doses for first-in-human tests, and support applications to the FDA. In this Phase 2 STTR proposal, the company will build two 96-channel turnkey instruments for a contract research program and for beta testing by pharmaceutical companies. The functionality of a low-capacity (16- channel) system has been previously demonstrated. The funding will support scaling up the throughput of the system as well as enabling additional modes of operation. The instrumentation will be used for contract research and for direct sales to the large market of drug discovery within the pharmaceutical industry.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.

STTR 第二阶段项目旨在提供技术来解决开发有效且安全药物的高成本问题。将新药推向市场通常需要利用细胞、组织和动物模型筛选数百种化合物的功效和毒性，最终选择将在临床试验中进行测试的先导化合物。这个过程可能需要数年、数十亿美元，在最糟糕的情况下，会导致化合物因安全问题而在临床试验中失败。微流体和 3D 打印的进步使得能够构建具有几乎无限数量的组织室和复杂流道的组织培养装置。与具有前所未有的灵敏度的光学传感器相结合，可以构建能够保存大量活检组织样本的仪器，同时评估组织暴露于药物库的影响。该技术平台能够以高灵敏度解析药物对人体组织的影响，从而降低动物试验成本以及将有毒药物带入临床试验和市场的风险。此外，该技术还将影响个性化医疗领域（可以在个体自身的肿瘤或组织上测试药物）以及环境健康领域。在进行昂贵的体内动物和临床测试之前，测量体外细胞对药物化合物的反应对于识别候选药物的毒性作用至关重要。为了满足这一需求，正在开发实时维护和评估活检组织的仪器。该技术利用微流体技术来最佳维持组织活力和功能，并利用光电技术以前所未有的灵敏度测量摄氧量。流体由气压驱动，避免了对笨重泵的需求，并且通道是通过 3D 打印制造的，允许几乎无限数量的腔室和流道复杂性。该技术平台将有助于选择用于临床试验的先导化合物、估计首次人体试验的剂量以及支持向 FDA 的申请。在第二阶段 STTR 提案中，该公司将为合同研究项目和制药公司的 beta 测试建造两台 96 通道交钥匙仪器。先前已演示了低容量（16 通道）系统的功能。这笔资金将支持扩大系统的吞吐量以及启用其他操作模式。该仪器将用于合同研究和直接销售给制药行业内的大型药物发现市场。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。