We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 μm/sec and volume rates up to 1 μl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.

The fractionation of small particles in a liquid based on their size in a micropost array by deterministic lateral displacement was recently demonstrated with unprecedented resolution (L. R. Huang, E. C. Cox, R. H. Austin and J. C. Sturm, Science, 2004, 304, 987–990, ). In this paper, we present a model of how the critical particle size for fractionation depends on the micropost geometry, depending specifically on the gap between posts, the offset of posts in one row with respect to another, and whether the fluid is driven by hydrodynamics or by electroosmosis. In general the critical particle diameter is much smaller than the gap, which prevents clogging. The model is supported by data with particles from 2.3 to 22 µm.

We present a continuous-flow microfluidic device that enables cell by cell separation of cells selectively tagged with magnetic nanoparticles. The cells flow over an array of microfabricated magnetic stripes, which create a series of high magnetic field gradients that trap the magnetically labeled cells and alter their flow direction. The process was observed in real time using a low power microscope. The device has been demonstrated by the separation of leukocytes from whole human blood.

Sub-micrometer particles (0.10–1.0 μm) are of great significance to study, e.g., microvesicles and protein aggregates are targets for therapeutic intervention, and sub-micrometer fluorescent polystyrene (PS) particles are used as probes for diagnostic imaging. Focusing of sub-micrometer particles – precisely control over the position of sub-micrometer particles in a tightly focused stream – has a wide range of applications in the field of biology, chemistry and environment, by acting as a prerequisite step for downstream detection, manipulation and quantification. Microfluidic devices have been attracting great attention as desirable tools for sub-micrometer particle focusing, due to their small size, low reagent consumption, fast analysis and low cost. Recent advancements in fundamental knowledge and fabrication technologies have enabled microfluidic focusing of particles at sub-micrometer scale in a continuous, label-free and high-throughput manner. Microfluidic methods for the focusing of sub-micrometer particles can be classified into two main groups depending on whether an external field is applied: 1) passive methods, which utilize intrinsic fluidic properties without the need of external actuation, such as inertial, deterministic lateral displacement (DLD), viscoelastic and hydrophoretic focusing; and 2) active methods, where external fields are used, such as dielectrophoretic, thermophoretic, acoustophoretic and optical focusing. This article mainly reviews the studies on the focusing of sub-micrometer particles in microfluidic devices over the past 10 years. It aims to bridge the gap between the focusing of micrometer and nanometer scale (1.0–100 nm) particles and to improve the understanding of development progress, current advances and future prospects in microfluidic focusing techniques.