Kim YongTae, Kuczenski Brandon, LeDuc Philip R, Messner William C
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Lab Chip. 2009 Sep 7;9(17):2603-9. doi: 10.1039/b822423d. Epub 2009 Jun 8.
Existing microfluidic systems can control local chemical environments by directing the interface between laminar flowing streams for applications ranging from subcellular stimulation to fuel cells. However, conventional flow modulation methods have not yet provided a robust and reliable way to dynamically control laminar flow interfaces for very long time periods. Such control is important in biological investigations, since response times for living cells and tissues can be as long as several days. Here, we describe a novel long-term, high-speed approach that employs modulation of fluidic resistance and fluidic capacitance between a fluid reservoir and a microfluidic network with feedback control to enable long-term dynamic control of a microfluidic interface in time and space. Our method involves constricting a narrow tube through a pinching approach to modulate fluidic resistance while also controlling a small variable reservoir in the fluidic network through a squeezing approach to modulate fluidic capacitance. We designed a well-tuned proportional-integral-derivative (PID) controller for the closed-loop control system that resulted in control of pressure for short-term (2 s) and long-term (15 h) experiments. Further, we integrated a pressure-based feedback control approach into this method, which enables both long-term spatiotemporal control of our microfluidic interface at frequencies greater than 1 Hz and a reservoir capacity to enable experiments for longer than 60 days. This long-term and high-speed control is not possible with standard microfluidic laboratory practices. Our system has a diversity of potential applications including long-term cellular studies in cancer metastasis or embryonic development.
现有的微流控系统可以通过引导层流之间的界面来控制局部化学环境,其应用范围涵盖从亚细胞刺激到燃料电池等领域。然而,传统的流量调制方法尚未提供一种强大而可靠的方式来长时间动态控制层流界面。这种控制在生物学研究中很重要,因为活细胞和组织的响应时间可能长达数天。在这里,我们描述了一种新颖的长期、高速方法,该方法通过反馈控制来调节流体储液器和微流控网络之间的流体阻力和流体电容,从而能够在时间和空间上对微流控界面进行长期动态控制。我们的方法包括通过挤压方法收缩细管来调节流体阻力,同时通过挤压方法控制流体网络中的一个小可变储液器来调节流体电容。我们为闭环控制系统设计了一个经过良好调谐的比例积分微分(PID)控制器,该控制器在短期(2秒)和长期(15小时)实验中实现了压力控制。此外,我们将基于压力的反馈控制方法集成到该方法中,这使得我们能够在频率大于1Hz的情况下对微流控界面进行长期时空控制,并且具有一个储液器容量,能够进行超过60天的实验。标准的微流控实验室操作无法实现这种长期和高速控制。我们的系统有多种潜在应用,包括癌症转移或胚胎发育方面的长期细胞研究。