D'Silva Joseph, Austin Robert H, Sturm James C
Department of Electrical Engineering, Princeton University, Princeton, NJ 08540, USA.
Lab Chip. 2015 May 21;15(10):2240-7. doi: 10.1039/c4lc01409j.
Microfluidic deterministic lateral displacement (DLD) arrays have been applied for fractionation and analysis of cells in quantities of ~100 μL of blood, with processing of larger quantities limited by clogging in the chip. In this paper, we (i) demonstrate that this clogging phenomenon is due to conventional platelet-driven clot formation, (ii) identify and inhibit the two dominant biological mechanisms driving this process, and (iii) characterize how further reductions in clot formation can be achieved through higher flow rates and blood dilution. Following from these three advances, we demonstrate processing of 14 mL equivalent volume of undiluted whole blood through a single DLD array in 38 minutes to harvest PC3 cancer cells with ~86% yield. It is possible to fit more than 10 such DLD arrays on a single chip, which would then provide the capability to process well over 100 mL of undiluted whole blood on a single chip in less than one hour.
微流控确定性侧向位移（DLD）阵列已被用于对约100μL血液中的细胞进行分离和分析，然而处理大量血液时会受到芯片堵塞的限制。在本文中，我们（i）证明这种堵塞现象是由传统的血小板驱动的凝血形成所致，（ii）识别并抑制驱动该过程的两种主要生物学机制，以及（iii）描述如何通过更高的流速和血液稀释来进一步减少凝血形成。基于这三项进展，我们展示了在38分钟内通过单个DLD阵列处理14 mL等效体积的未稀释全血，以收获产率约为86%的PC3癌细胞。在单个芯片上可以安装10多个这样的DLD阵列，这样就能在不到一小时的时间内，在单个芯片上处理超过100 mL的未稀释全血。
