Developing prototype injectability and developability testing system based on microfluidic quartz resonators

SBIR第二阶段提案的目标是采用QATCH的nanovisQ™技术，该技术是一种广泛的 用于测定生物药物可显影性和可注射性的剪切速率范围和小体积粘度计 从概念验证到可部署和可靠的原型。这一目标的动机是， 不断增长的基于蛋白质的生物制药治疗行业（全球市场规模超过100美元）的需求 十亿）。基于蛋白质的治疗剂由于体积而作为高浓度制剂施用。 皮下注射的限制。然而，在这些高水平下增加的蛋白质-蛋白质相互作用 浓度可能导致注射性和可制造性问题，这些问题在早期阶段无法确定 由于传统流变学技术对样品体积的要求很高，因此，这一技术在药物开发中的应用非常有限。通过 开发宽剪切速率范围、低体积粘度计，可以优化蛋白质分子， 可注射性/可制造性和具有更好可显影性的候选物可被选择用于按比例放大。这 该建议是重要的，因为所提出的装置可以在更早的时间评估蛋白质制剂的可注射性。 药物开发比现有技术，从而减少研发的时间和成本， 开发新的，可注射的基于蛋白质的治疗方法。在SBIR第一阶段研究中，QATCH已 成功扩展了nanovisQ™粘度测量的剪切速率范围， 高浓度蛋白质溶液的表征。因此，nanovisQ™现在被定位为 非常适合高浓度蛋白质制剂的粘度测量。在SBIR第二阶段，QATCH是 提出1）开发基于牺牲多晶硅的制造工艺以在石英晶片上构建微流体， 2)为nanovisQ™传感器开发原型控制和数据采集模块。开发可部署和 可靠的nanovisQ™传感器和仪器将是该技术商业化的关键一步。

The objective of this SBIR Phase II proposal is to carry QATCH’s nanovisQ™ technology, which is a wide- shear-rate range and low volume viscometer for determining developability and injectability of biopharmaceutical formulations, from proof-of-concept to deployable, and reliable prototypes. This objective is motivated by the needs of the growing protein-based biopharmaceutical therapeutics industry (with global market size over $100 billion). Protein-based therapeutics are administered as high concentration formulations due to the volume constraints of subcutaneous injections. However, increased protein-protein interactions at these high concentrations can cause injectability and manufacturability issues, which cannot be determined at early stages of drug development due to the high sample volume requirements of conventional rheology techniques. By developing a wide shear rate range, low volume viscometer, protein molecules can be optimized for injectability/manufacturability and candidates with better developability can be selected for scaling-up. This proposal is significant because the proposed device can assess injectability of protein formulations earlier in drug development than existing technology and consequently reduce the time and cost of R&D spent in developing new, injectable protein-based therapeutics considerably. In SBIR Phase I studies, QATCH has successfully extended the shear-rate range of viscosity measurements of the nanovisQ™ for proper characterization of the high concentration protein solutions. As a result, the nanovisQ™ is now positioned to be a good fit for viscosity measurements of high concentration protein formulations. In SBIR Phase II QATCH is proposing to 1) develop a sacrificial poly-Si based fabrication process to build microfluidics on quartz wafers, 2) develop a prototype control and data acquisition module for nanovisQ™ sensors. Developing deployable and reliable nanovisQ™ sensors and instruments will be a key step in commercialization of this technology.