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

SBIR第1阶段项目旨在提供技术，以解决开发有效和安全药物的高成本问题。 将一种新药推向市场通常需要筛选100种？利用细胞、组织和动物模型对数千种化合物进行功效和毒性研究，最终选择一种将在临床试验中进行测试的先导化合物。 这一过程可能需要数年时间，数十亿美元，在更糟糕的情况下，由于安全问题，导致化合物在临床试验中失败。 微流体技术和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流动通道复杂性的组织培养装置。 与具有前所未有的灵敏度的光学传感器相结合，可以构建保持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。 该技术平台提供了高灵敏度的药物对人体组织影响的解析，从而降低了动物试验的成本以及将有毒药物带入临床试验和市场的风险。 此外，该技术将影响个性化医疗领域，在那里药物可以在个人身上进行测试。自身的肿瘤或组织，以及环境健康。 测量体外细胞对药物化合物的反应对于在昂贵的体内动物和临床试验之前鉴定候选药物的毒性作用至关重要。为了满足这一需求，正在开发用于真实的保持和评估活检组织的仪器。 该技术利用微流体技术优化组织活力和功能的维持，并利用光电技术以前所未有的灵敏度测量氧摄取。射流由气体压力驱动，避免了对笨重泵的需求，并且通道通过3D打印制造，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临床试验的先导化合物，估计首次人体试验的剂量，并支持向FDA申请。 在第1阶段SBIR提案中，我们将为合同研究项目和制药公司的beta测试建造2台96通道交钥匙仪器。低容量（8通道）系统的功能先前已演示过。 这笔资金将支持扩大系统的吞吐量，并支持其他操作模式。该仪器将用于合同研究和直接销售给制药行业内的药物发现大市场。

This SBIR Phase 1 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 1 SBIR proposal we will build 2 96-channel turnkey instruments for a contract research program and for beta testing by pharmaceutical companies. The functionality of a low-capacity (8-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.