SBIR Phase II: Ion Mobility Spectrometer for Macromolecular Analysis

这个小企业创新研究（SBIR）二期项目的更广泛的影响/商业潜力将是开发一种分析仪器，用于检测蛋白质生产各个阶段的蛋白质变化。高度工程化治疗蛋白的生产已经超过了分析测定的发展，以保证药物的有效性、纯度和保质期。制造过程中的一个关键控制参数是蛋白质构象；目前，这很难用商业上可用的技术来监测。该项目的目标是为制造商提供新一代分析技术，使他们能够识别批次之间的差异。该技术还提供了有关产品稳定性的信息，因此制造商可以保证其产品的更长的保质期，无论储存条件如何。预计该工具将在从发现到大规模生产和配方到发布前认证的所有阶段提高功效。该SBIR二期项目旨在通过分析技术的商业化来改善生物治疗药物的生产，该技术为快速QC/QA评估蛋白质构象提供了一种新的度量标准。确定蛋白质构象的黄金标准是x射线晶体学，这是一项耗时的技术，需要高质量的晶体和高能物理设备来产生相干x射线。所提出的高灵敏度台式离子迁移谱仪可以检测蛋白质横截面积的微小变化，并检测微小的构象变化。这提供了在发现过程中，当只有微克数量的重组表达蛋白可用时，确定蛋白质稳定性的能力。该过程还表明蛋白质在纯化过程中受到pH值变化后是否会重新折叠，因此可用于确定长期保质期的挑战。该仪器将首次用于证明，离子迁移率将产生生物制造蛋白质质量的高可重复性和生物相关测量。该奖项反映了美国国家科学基金会的法定使命，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 II project will be the development of an analytical instrument to detect protein changes across all stages of protein production. The production of highly-engineered therapeutic proteins has outpaced the development of analytical assays to guarantee effectiveness, purity, and shelf life of the drug. A key control parameter during manufacturing is protein conformation; currently, this is difficult to monitor with commercially available technology. The goal of this project is to provide manufacturers with a new generation of analytical technology that allows them to identify variations between batches. This technology also provides information about product stability so manufacturers can guarantee a longer shelf life for their products, regardless of storage conditions. It is anticipated that this instrument will increase efficacy at all stages, from discovery through scaled-up production and formulation to pre-release certification.This SBIR Phase II project aims to improve biotherapeutic drug production through the commercialization of analytical technology that provides a new metric for the rapid QC/QA assessment of the conformation of proteins. The gold standard for determining protein conformation is x-ray crystallography - a time-consuming technique that requires high quality crystals and a high-energy physics facility to produce coherent x-rays. The proposed highly sensitive bench-top ion mobility spectrometer detects small variations in the cross-sectional area of a protein and detects small conformational changes. This provides a capability to determine protein stability during discovery when only microgram quantities of recombinantly expressed proteins are available. This process also indicates if a protein refolded after it was subjected to a pH change during purification, and thus it may be used to identify challenges to long-term shelf life. This instrument will be used to demonstrate that for the first time, ion mobility will produce highly-reproducible and biologically relevant measurements of the quality of biomanufactured proteins.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.