中文摘要：在监管机构的激励下，生物制品商正在从质量测试框架(在生产后对产品进行广泛测试)向质量设计甚至质量控制框架过渡。这就需要强大的分析工具和传感器，在生产过程中测量关键过程变量和/或产品质量属性，最好是在线测量。因此，对监测技术的需求正在迅速增长。基于表面等离子体共振（SPR）的生物传感器可以在开发先进的生物过程监测和控制策略方面发挥作用。SSR技术已经广泛用于探测研究环境中溶液种类与传感器表面固定化伙伴的结合行为，但已开发其实时、无标记检测结合的能力用于目标监测，并有望在不久的将来实现。本文综述了SPR在生物过程监测三个领域中的应用：生物治疗剂生产监测、疫苗监测及细菌和污染物检测。这些应用主要利用SPR测量溶液种类浓度的能力，也可以进行动力学分析，并可用于产品质量评估。随后讨论了SPR在监测中的局限性，以及如何通过硬件和SPR响应建模的最新进展应对这些局限性：主要通过多检测点仪器解决吞吐量限制问题，而新型防污材料可以缓解非特异性结合效应。细胞生长和代谢监测的方法很多，但产品监测主要是后验的。基于SPR的生物传感器显示出从早期生产到下游加工的产品监测工具的潜力，为更有效的生产控制铺平了道路。然而，还需要更多的工作来促进或消除样品预处理的需要，并优化实验方案。
外文摘要：Biomanufacturers are being incited by regulatory agencies to transition from a quality by testing framework, where they extensively test their product after their production, to more of a quality by design or even quality by control framework. This requires powerful analytical tools and sensors enabling measurements of key process variables and/or product quality attributes during production, preferably in an online manner. As such, the demand for monitoring technologies is rapidly growing. In this context, we believe surface plasmon resonance (SPR)-based biosensors can play a role in enabling the development of improved bioprocess monitoring and control strategies. The SPR technique has been profusely used to probe the binding behavior of a solution species with a sensor surface-immobilized partner in an investigative context, but its ability to detect binding in real-time and without a label has been exploited for monitoring purposes and is promising for the near future. In this review, we examine applications of SPR that are or could be related to bioprocess monitoring in three spheres: biotherapeutics production monitoring, vaccine monitoring, and bacteria and contaminant detection. These applications mainly exploit SPR's ability to measure solution species concentrations, but performing kinetic analyses is also possible and could prove useful for product quality assessments. We follow with a discussion on the limitations of SPR in a monitoring role and how recent advances in hardware and SPR response modeling could counter them. Mainly, throughput limitations can be addressed by multi-detection spot instruments, and nonspecific binding effects can be alleviated by new antifouling materials. A plethora of methods are available for cell growth and metabolism monitoring, but product monitoring is performed mainly a posteriori. SPR-based biosensors exhibit potential as product monitoring tools from early production to the end of downstream processing, paving the way for more efficient production control. However, more work needs to be done to facilitate or eliminate the need for sample preprocessing and to optimize the experimental protocols.
外文关键词：surface plasmon resonance (SPR)；bioprocess；monitoring；biosensor；quality by design (QbD)；process analytical technology (PAT)；biotherapeutics production；vaccines production
作者：Gaudreault, J；Forest-Nault, C；De Crescenzo, G；Durocher, Y；Henry, O
作者单位：Polytech Montreal；Natl Res Council Canada
期刊名称：PROCESSES
期刊影响因子：2.753
出版年份：2021
出版刊次：11
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