SBIR Phase II: Ion Mobility Spectrometer for Macromolecular Analysis

小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力将是开发一种分析仪器，以检测蛋白质生产所有阶段的蛋白质变化。高度工程化的治疗蛋白的生产已经超过了分析分析的发展，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进行监测。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。这项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在任何储存条件下都有更长的保质期。预计该仪器将在所有阶段提高疗效，从发现、扩大生产和配方到发布前认证。SBIR第二阶段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，这一分析技术为蛋白质构象的快速QC/QA评估提供了新的衡量标准。确定蛋白质构象的黄金标准是X射线结晶学--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的X射线。拟议的高灵敏度台式离子迁移率光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。当只有微克量的重组表达蛋白质可用时，这提供了在发现过程中确定蛋白质稳定性的能力。这一过程还表明蛋白质在纯化过程中受到pH变化后是否发生折叠，因此可以用来确定对长期货架期的挑战。该仪器将首次被用来证明，离子迁移率将产生高度重复性和生物相关性的生物制造蛋白质质量的测量。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.