Adamson David N, Mustafi Debarshi, Zhang John X J, Zheng Bo, Ismagilov Rustem F
Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.
Lab Chip. 2006 Sep;6(9):1178-86. doi: 10.1039/b604993a. Epub 2006 Jul 27.
This paper reports a method for the production of arrays of nanolitre plugs with distinct chemical compositions. One of the primary constraints on the use of plug-based microfluidics for large scale biological screening is the difficulty of fabricating arrays of chemically distinct plugs on the nanolitre scale. Here, using microfluidic devices with several T-junctions linked in series, a single input array of large (approximately 320 nL) plugs was split to produce 16 output arrays of smaller (approximately 20 nL) plugs; the composition and configuration of these arrays were identical to that of the input. This paper shows how the passive break-up of plugs in T-junction microchannel geometries can be used to produce a set of smaller-volume output arrays useful for chemical screening from a single large-volume array. A simple theoretical description is presented to describe splitting as a function of the Capillary number, the capillary pressure, the total pressure difference across the channel, and the geometric fluidic resistance. By accounting for these considerations, plug coalescence and plug-plug contamination can be eliminated from the splitting process and the symmetry of splitting can be preserved. Furthermore, single-outlet splitting devices were implemented with both valve- and volume-based methods for coordinating the release of output arrays. Arrays of plugs containing commercial sparse matrix screens were obtained from the presented splitting method and these arrays were used in protein crystallization trials. The techniques presented in this paper may facilitate the implementation of high-throughput chemical and biological screening.
本文报道了一种制备具有不同化学成分的纳升塞阵列的方法。基于塞的微流控技术在大规模生物筛选应用中的一个主要限制是难以在纳升尺度上制造具有不同化学成分的塞阵列。在此，使用具有多个串联T型接头的微流控装置，将一个大的（约320纳升）塞的单个输入阵列进行拆分，以产生16个较小的（约20纳升）塞的输出阵列；这些阵列的组成和配置与输入阵列相同。本文展示了如何利用T型接头微通道几何结构中塞的被动分裂，从单个大体积阵列中产生一组对化学筛选有用的较小体积输出阵列。提出了一个简单的理论描述，将分裂描述为毛细管数、毛细管压力、通道两端的总压差以及几何流体阻力的函数。通过考虑这些因素，可以在分裂过程中消除塞的聚结和塞-塞污染，并保持分裂的对称性。此外，采用基于阀和基于体积的方法实现了单出口分裂装置，用于协调输出阵列的释放。通过所提出的分裂方法获得了包含商业稀疏矩阵筛选的塞阵列，并将这些阵列用于蛋白质结晶试验。本文提出的技术可能有助于高通量化学和生物筛选的实施。
