Auzmendi Jerónimo A, Smoler Mariano, Moffatt Luciano
Instituto de Química Física de los Materiales, Medio Ambiente y Energía. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
PLoS One. 2015 Jul 15;10(7):e0133187. doi: 10.1371/journal.pone.0133187. eCollection 2015.
Solutions exchange systems are responsible for the timing of drug application on patch clamp experiments. There are two basic strategies for generating a solution exchange. When slow exchanges are bearable, it is easier to perform the exchange inside the tubing system upstream of the exit port. On the other hand, fast, reproducible, exchanges are usually performed downstream of the exit port. As both strategies are combinable, increasing the performance of upstream exchanges is desirable. We designed a simple method for manufacturing T-junctions (300 μm I.D.) and we measured the time profile of exchange of two saline solutions using a patch pipette with an open tip. Three factors were found to determine the timing of the solution switching: pressure, travelled distance and off-center distance. A linear relationship between the time delay and the travelled distance was found for each tested pressure, showing its dependence to the fluid velocity, which increased with pressure. The exchange time was found to increase quadratically with the delay, although a sizeable variability remains unexplained by this relationship. The delay and exchange times increased as the recording pipette moved away from the center of the stream. Those increases became dramatic as the pipette was moved close to the stream borders. Mass transport along the travelled distance between the slow fluid at the border and the fast fluid at the center seems to contribute to the time course of the solution exchange. This effect would be present in all tubing based devices. Present results might be of fundamental importance for the adequate design of serial compound exchangers which would be instrumental in the discovery of drugs that modulate the action of the physiological agonists of ion channels with the purpose of fine tuning their physiology.
溶液交换系统负责膜片钳实验中药物施加的时间控制。产生溶液交换有两种基本策略。当缓慢交换可以接受时,在出口端口上游的管道系统内进行交换更容易。另一方面,快速、可重复的交换通常在出口端口下游进行。由于这两种策略可以结合,提高上游交换的性能是可取的。我们设计了一种制造内径为300μm的T型接头的简单方法,并使用开口尖端的膜片吸管测量了两种盐溶液交换的时间曲线。发现有三个因素决定溶液切换的时间:压力、行进距离和偏心距离。对于每个测试压力,在延迟时间和行进距离之间发现了线性关系,表明其对流体速度的依赖性,流体速度随压力增加。发现交换时间随延迟呈二次增加,尽管这种关系仍无法解释相当大的变异性。随着记录吸管远离液流中心,延迟时间和交换时间增加。当吸管靠近液流边界移动时,这些增加变得显著。沿边界处的慢速流体和中心处的快速流体之间行进距离的质量传输似乎有助于溶液交换的时间进程。这种效应在所有基于管道的设备中都会存在。目前的结果对于串联化合物交换器的适当设计可能具有根本重要性,这将有助于发现调节离子通道生理激动剂作用的药物,以微调其生理学。