Asymmetrical Deterministic Lateral Displacement Gaps for Dual Functions of Enhanced Separation and Throughput of Red Blood Cells

Abstract

Deterministic lateral displacement (DLD) method for particle separation in microfluidic devices has been extensively used for particle separation in recent years due to its high resolution and robust separation. DLD has shown versatility for a wide spectrum of applications for sorting of micro particles such as parasites, blood cells to bacteria and DNA. DLD model is designed for spherical particles and efficient separation of blood cells is challenging due to non-uniform shape and size. Moreover, separation in sub-micron regime requires the gap size of DLD systems to be reduced which exponentially increases the device resistance, resulting in greatly reduced throughput. This paper shows how simple application of asymmetrical Deterministic lateral displacement (DLD) method for particle separation in microfluidic devices has been extensively used for particle separation in recent years since it was first published by Huang et al.1,2 Due to its high resolution and robust separation, DLD has shown versatility for a wide spectrum of applications for sorting of microparticles such as parasites 3 , blood cells [4][5][6][7] , circulating tumor cells 8,9 , bacteria 7,10 , spores 11 , and more recently, nanoparticle separation 12 and DNA isolation 13,14 . While the DLD empirical model is well established in current research, its scope is restricted to spherical particles, cylindrical pillars and uniform gap-size across all adjacent pillars 15 . Thus, it has been challenging to separate non-spherical particles such as red blood cells (RBCs), bacteria and DNA. Many groups have worked on changing pillar shapes and device gaps to effectively separate these particles 16,17 . However, this will greatly increase fabrication complexity and restrict throughput by reducing gap-sizes in a DLD pillar array.The DLD method uses rhombic or rotated square pillar arrays to redirect fluid laminar flow streams and each array arrangement would have a distinctive critical separating diameter. Particle larger than the critical cut-off diameter (D c ) will be displaced laterally from its flow from the sample streamline while smaller particles flow unhindered in the pillar array by flowing within the fluid streamlines. Based on current DLD empirical model, DLD separation cut-off size and resolution depends on the array rotation angle or slant and lateral gap-size between pillars 6 : ε = .. D g 1 4(1) c 0 48

On the design of deterministic dielectrophoresis for continuous separation of circulating tumor cells from peripheral blood cells

“…In addition, it has been recently shown by Zeming et al. that utilizing asymmetrical gaps for DLD device enhanced the separation of red blood cells without restricting the throughput significantly . However, DLD faces major design challenges such as inability to sort cells with similar size and unpredictability of the device performance at high throughputs due to flow‐induced cell deformation .…”

Guidance and Self‐Sorting of Active Swimmers: 3D Periodic Arrays Increase Persistence Length of Human Sperm Selecting for the Fittest

“…In the microfluidics realm, there are many surface designs decorating channels in various ways,35 including deterministic lateral displacement methods for separation of particles36, 37 and blood cells 38. To understand sperm motility in such complex geometries, many hydrodynamic models have been developed at different scales;35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 however, to the best of our knowledge, no models exist that can bridge the necessary time and length scales to allow the modeling of clinically relevant microfluidic ARTs and improve their design parameters.…”

“…To understand sperm motility in such complex geometries, many hydrodynamic models have been developed at different scales;35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 however, to the best of our knowledge, no models exist that can bridge the necessary time and length scales to allow the modeling of clinically relevant microfluidic ARTs and improve their design parameters. Here, we designed a filter‐like microfluidic path using multiscale computer simulations in conjunction with experiments and examined how this artificial path of pillars interact with known descriptive and functional characteristics of human sperm, including sperm motility, morphology, DNA integrity, and methylome status.…”

On-chip sample preparations for Point-of-Care cellular analysis of blood

“…Therefore, blood samples with a high cell concentration need to be diluted prior to processing. Because DLD is designed for separating rigid and spherical particles, another challenge of efficient blood cell separation lies in the non-spherical shape and deformability of RBCs [27].…”