ARC Centre for Personalised Therapeutics Technologies, The University of Melbourne, Parkville, VIC, 3010, Australia.
Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Lab Chip. 2022 Mar 15;22(6):1137-1148. doi: 10.1039/d1lc00841b.
Cells and tissues are routinely cultured for biological research with findings being extrapolated to their host organ and tissue function. However, most samples are cultured and studied in unphysiological environments, without temporal variation in the biochemical cues that are ubiquitous . The artificiality of these conditions undermines the predictive value of cell culture studies. We ascribe the prevalence of this suboptimal culture methodology to the lack of practical continuous flow systems that are economical and robust. Here, we design and implement an expandable multiplexed flow system for cell culture superfusion. By expanding on the concept of the planar peristaltic pump, we fabricated a highly compact and multiplexed pump head with up to 48 active pump lines. The pump is incorporated into a custom, open-top superfusion system configured for conventional multi-well culture plates. We then demonstrated the utility of the system for circadian entrainment using a daily cortisol pulse, generating a sustained circadian amplitude that is essential for physiological emulation and chrono-pharmacological studies. The multiplexed pump is complemented by a package of fluidic interconnection and management methods enabling user-friendly and scalable operation. Collectively, the suite of technologies provides a much-needed improvement in physiological emulation to support the predictive value of biomedical and biological research.
细胞和组织通常被培养用于生物学研究，研究结果被推断为其宿主器官和组织的功能。然而，大多数样本都是在非生理环境中培养和研究的，没有时间变化的生化线索是普遍存在的。这些条件的人为性破坏了细胞培养研究的预测价值。我们将这种次优培养方法的普遍存在归因于缺乏经济实惠且坚固耐用的实用连续流动系统。在这里，我们设计并实施了用于细胞培养灌注的可扩展多路复用流系统。通过扩展平面蠕动泵的概念，我们制造了一个高度紧凑和多路复用的泵头，具有多达 48 个活动泵线。该泵被整合到一个定制的、开放式顶置的超流系统中，该系统配置用于常规的多孔板培养。然后，我们使用每日皮质醇脉冲演示了该系统用于昼夜节律同步的实用性，产生了持续的昼夜节律幅度，这对于生理模拟和chrono-pharmacological 研究至关重要。多路复用泵由一套流体连接和管理方法补充，实现了用户友好和可扩展的操作。总的来说，这一系列技术为支持生物医学和生物学研究的预测价值提供了急需的生理模拟改进。
