SBIR Phase I: High-throughput injectability screening of high concentration protein formulations by multiplexed microfluidic quartz resonators

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力推动了一种新型的药物输送。基于蛋白质的药物（生物制剂）由于其活性的高特异性和通常低水平的副作用而变得更受欢迎。生物制剂治疗多种疾病，影响数百万患者的生活，全球收入超过100 B美元。患者更喜欢并遵守生物制剂的注射版本，因为注射快速，并且可以在家中给药，而不像IV输注需要持续几个小时的诊所访问。然而，许多生物制剂的开发和利用受到阻碍，因为它们是粘稠的液体，无法通过注射使用。该项目开发的技术将作为早期筛选，以确定潜在的注射用药物制剂的适用性，从而实现新药的输送。该SBIR I期项目将通过提供蛋白质制剂粘度的早期筛选来增加可注射的蛋白质基治疗剂的数量。在配方开发的早期进行粘度测量目前是不可能的，因为现有的粘度计需要大量的材料。因此，新的蛋白质制剂的可注射性无法测试，直到开发出大量的材料，通常在临床前研究的后期阶段。该项目将创建一个高通量粘度计，每次测试只需要滴液，用于配方优化;它将确定在同一基板上多路复用微流体石英传感器以实现同时粘度测量的可行性。具体而言，在该项目中，1）将开发用于多路复用传感器的电子器件，2）将使用分析和有限元模型设计多路复用传感器，以及3）这些设计将通过微加工执行。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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) Phase I project advances a new type of drug delivery. Protein-based drugs (biologics) have become more popular due to their high specificity of activity and generally low level of side effects. Biologics treat many conditions, impact lives of millions of patients, and have a global revenue of over $100 B. Patients prefer and comply with injectable versions of biologics because injections are rapid and make home-administration possible, unlike IV infusions that require clinic visits lasting several hours. However, the development and utility of many biologics is hampered by their inability to be used via injections because they are thick liquids. The technology developed in this project will act as an early-stage screening to determined the suitability of potential drug formulation for injection, enabling delivery of new drugs.This SBIR Phase I project will increase the number of injectable protein-based therapeutics by providing early screening of protein formulation viscosity. Viscosity measurements early in formulation development are currently not possible because the existing viscometers require high material volumes. Therefore, injectability of new protein-based formulations cannot be tested until significant amounts of material are developed, typically at late stages of preclinical research. This project will create a high-throughput viscometer that requires only drops for each test, for formulation optimization; it will determine the feasibility of multiplexing microfluidic quartz sensors on the same substrate to achieve simultaneous viscosity measurements. Specifically, in this project, 1) the electronics for the multiplexed sensors will be developed, 2) the multiplexed sensors will be designed using analytical and finite element models, and 3) these designs will be executed by microfabrication. Finally, the multiplexed microfluidic quartz sensors will be tested by analyzing relevant formulations simultaneously.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.