High-throughput injectability screening of high concentration protein formulations by microfluidic quartz resonators

SBIR Direct第二阶段提案的目标是采用QATCH的nanovisQ™技术， 宽剪切速率范围和小体积粘度计，用于测定 从单次检测传感器到高通量和自动化格式，这 目的是由不断增长的基于蛋白质的生物制药治疗工业的需求所推动的（具有 全球市场规模超过3000亿美元）。基于蛋白质的治疗剂以高浓度给药 由于皮下注射的体积限制，然而，增加蛋白质-蛋白质 在这些高浓度下的相互作用可导致高粘度并妨碍可注射性和可制造性。 现有的粘度计消耗大量的样品，这妨碍了早期评估，并且仍然具有 高蛋白质和后期的时间成本。通过开发高通量、自动化、宽剪切速率范围， 低容量粘度计、蛋白质分子和制剂可针对可注射性/可制造性进行优化 更早，成本更低，风险更小。这一提议意义重大，因为提议的设备可以开始评估 在药物开发的早期，蛋白质制剂的可注射性， 与现有技术相比，配方速度更快，材料更少，从而减少了时间和成本 的研发花费在开发新的，可注射的蛋白质为基础的治疗相当。作为初步研究， QATCH展示了适用于蛋白质制剂的宽剪切速率和低样品体积粘度计， 测试格式。此外，QATCH显示，来自4个传感器的4个同时测量值（间距为9 mm） 在同一石英毛坯上可以精确地实现。因此，nanovisQ™现在定位为6x 4 用于高浓度蛋白质配方的传感器矩阵和自动粘度计。在SBIR第二阶段QATCH 建议1）开发具有扩展剪切速率粘度测量的4传感器阵列， 2）开发用于高通量系统的6x 4传感器矩阵， 环境控制和自动送样能力。开发高通量和 自动化低样品体积粘度计是走向商业化的关键一步，因为低样品体积 和高通量是药物开发组的两个最重要的参数。

The objective of this SBIR Direct 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 single-test sensors to high-throughput and automated format. This objective is motivated by the needs of the growing protein-based biopharmaceutical therapeutics industry (with global market size over $300 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 high viscosity and prevent injectability and manufacturability. Existing viscometers consume high volumes of sample, which prevents early-stage assessment and still have high protein and time costs at later stages. By developing a high-throughput, automated, wide shear rate range, low volume viscometer, protein molecules and formulations can be optimized for injectability/manufacturability earlier with less cost and risk. This proposal is significant because the proposed device can start assessing injectability of protein formulations earlier in drug development, perform this test in a higher number of formulations faster and with less material than existing technologies and consequently reduce the time and cost of R&D spent in developing new, injectable protein-based therapeutics considerably. As preliminary studies, QATCH demonstrated wide-shear-rate and low sample volume viscometers for protein formulations in single- test format. In addition, QATCH showed that 4 simultaneous measurements from 4 sensors with 9 mm spacing on the same quartz blank can be achieved accurately. As a result, the nanovisQ™ is now positioned to be a 6x4 sensor matrix and automated viscometer for high concentration protein formulations. In SBIR Phase II QATCH is proposing to 1) develop 4-sensor arrays with extended shear-rate viscosity measurements to serve high- concentration protein formulations 2) develop 6x4 sensor matrix for the high-throughput system with environmental control and the automated sample delivery capability. Developing a high-throughput and automated low-sample volume viscometer is a key step towards commercialization since low-sample volume and high-throughput are two most important parameters for drug development groups.