1 Product Development and Supply-Discovery Supply, GlaxoSmithKline, Upper Providence, PA, USA.
2 Drug Design and Selection-Screening Profiling & Mech Biology US, GlaxoSmithKline, Upper Providence, PA, USA.
SLAS Technol. 2019 Jun;24(3):245-255. doi: 10.1177/2472630318820017. Epub 2019 Feb 6.
Recent advancements in science and engineering are revolutionizing our understanding of an individual's disease, and with this knowledge we are gaining an increasingly sophisticated understanding of how discovery can be transformed to deliver personalized medicines. To reach this future state, we must reengineer our approach to enable the use of more relevant human cellular models earlier in the drug discovery process. Stem cells and primary human cells represent more disease-relevant models than immortalized cell lines; however, due to both availability and cost, their use is limited in lead generation activities. Miniaturization of cellular assays below microtiter plate volumes will enable the use of more relevant cells in screening, but this would require a change in how test molecules are introduced to the biology. With these shifting paradigms, Discovery Supply teams at GlaxoSmithKline (GSK) are modernizing our sample handling approaches. Various emerging technologies such as microarrays, nanowells, and microfluidic devices could bring fundamental changes in conventional sample handling support as we transition from microtiter plates to well-less platforms. The discussion here is exploratory in nature and reviews ongoing proof-of-concept experiments. Our ultimate goal is to industrialize the sample management platforms to support future miniaturized biological assay systems.
近年来，科学和工程领域的进步正在彻底改变我们对个体疾病的认识，随着对这方面知识的深入了解，我们对如何将发现转化为个性化药物的理解也在不断提高。为了实现这一未来目标，我们必须重新设计我们的方法，以便在药物发现过程的早期就能够使用更相关的人类细胞模型。干细胞和原代人类细胞比永生化细胞系更能代表疾病相关模型；然而，由于可用性和成本的原因，它们在先导化合物生成活动中的使用受到限制。将细胞测定的微型化降低到微孔板体积以下，将使更多相关细胞能够用于筛选，但这需要改变测试分子引入生物学的方式。随着这些不断变化的范例，葛兰素史克（GSK）的发现供应团队正在使我们的样品处理方法现代化。各种新兴技术，如微阵列、纳米孔和微流控设备，可能会在我们从微孔板向无孔平台过渡时，给传统的样品处理支持带来根本性的变化。这里的讨论具有探索性，回顾了正在进行的概念验证实验。我们的最终目标是使样品管理平台实现工业化，以支持未来的小型化生物测定系统。
