Inhibition of clot formation in deterministic lateral displacement arrays for processing large volumes of blood for rare cell capture

Abstract

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.

Microfluidics for simultaneous quantification of platelet adhesion and blood viscosity

“…Considering that the platelets adhered to the collagen film make leukocytes adhere to them under blood flow condition 51 , the level of platelet adhesion measured by the proposed method may be slightly overestimated due to the adhesion of leukocytes. Since leukocytes do not significantly adhere by themselves 52 , we can infer that the degree of overestimation may not be so significant. For more accurate analysis, additional modification of the measurement system, and study on leukocyte adhesion are required in the near future.…”

Isolation of cells from whole blood using shear-induced diffusion

“…Our separation scheme also outperforms existing systems based on cell margination 30 , 31 and cross-flow filtration 32 , 33 and is simpler than DLD 34 , 35 and other 36 , 37 devices. While DLD device from Austin’ group 79 , 80 showed comparable efficiency (~86%) with very high flow rate, their system requires 5–20 times dilution and multiple additives to prevent clogging. Similar dilution factor is also necessary for inertial microfluidic devices regardless of various geometries 39 , 63 , 81 .…”

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches

“…One of the most significant is the clot formation when processing the blood samples. [323]. The clots increase the fluid resistance, capture the cells passing through the post array, and alter the paths of the fluid streamlines.…”