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

Kerwin Kwek Zeming; Thoriq Salafi; Chia-Hung Chen; Yong Zhang

doi:10.1038/srep22934

Sorting same-size red blood cells in deep deterministic lateral displacement devices

Journal of Fluid Mechanics ◽

10.1017/jfm.2018.829 ◽

2018 ◽

Vol 859 ◽

pp. 433-475 ◽

Cited By ~ 7

Author(s):

Gökberk Kabacaoğlu ◽

George Biros

Keyword(s):

Mechanical Properties ◽

Red Blood Cells ◽

Blood Cells ◽

Lateral Displacement ◽

Flow Direction ◽

Lateral Direction ◽

Deterministic Lateral Displacement ◽

Deformable Particles ◽

Dense Suspensions ◽

A Cell

Microfluidic sorting of deformable particles finds many applications, for example, medical devices for cells. Deterministic lateral displacement (DLD) is one of them. Particle sorting via DLD relies only on hydrodynamic forces. For rigid spherical particles, this separation is to a great extent understood and can be attributed to size differences: large particles displace in the lateral direction with respect to the flow while small particles travel in the flow direction with negligible lateral displacement. However, the separation of non-spherical deformable particles such as red blood cells (RBCs) is more complicated than that of rigid particles. For example, is it possible to separate deformable particles that have the same size but different mechanical properties? We study deformability-based sorting of same-size RBCs via DLD using an in-house integral equation solver for vesicle flows in two dimensions. Our goal is to quantitatively characterize the physical mechanisms that enable the cell separation. To this end, we systematically investigate the effects of the interior fluid viscosity and membrane elasticity of a cell on its behaviour. In particular, we consider deep devices in which a cell can show rich dynamics such as taking a particular angular orientation depending on its mechanical properties. We have found out that cells moving with a sufficiently high positive inclination angle with respect to the flow direction displace laterally while those with smaller angles travel with the flow streamlines. Thereby, deformability-based cell sorting is possible. The underlying mechanism here is cell migration due to the cell’s positive inclination and the shear gradient. The higher the inclination is, the farther the cell can travel laterally. We also assess the efficiency of the technique for dense suspensions. It turns out that most of the cells in dense suspensions do not displace in the lateral direction no matter what their deformability is. As a result, separating cells using a DLD device becomes harder.

Download Full-text

Two-dimensional Simulation of Motion of Red Blood Cells with Deterministic Lateral Displacement Devices

Micromachines ◽

10.3390/mi10060393 ◽

2019 ◽

Vol 10 (6) ◽

pp. 393 ◽

Cited By ~ 2

Author(s):

Yanying Jiao ◽

Yongqing He ◽

Feng Jiao

Keyword(s):

Numerical Simulation ◽

Red Blood Cells ◽

Blood Cells ◽

Lateral Displacement ◽

Two Dimensional ◽

Deterministic Lateral Displacement ◽

Pillar Array ◽

Displacement Mode ◽

Pillar Diameter ◽

Dimensional Simulation

Deterministic lateral displacement (DLD) technology has great potential for the separation, enrichment, and sorting of red blood cells (RBCs). This paper presents a numerical simulation of the motion of RBCs using DLD devices with different pillar shapes and gap configurations. We studied the effect of the pillar shape, row shift, and pillar diameter on the performance of RBC separation. The numerical results show that the RBCs enter “displacement mode” under conditions of low row-shift (∆λ < 1.4 µm) and “zigzag mode” with large row shift (∆λ > 1.5 µm). RBCs can pass the pillar array when the size of the pillar (d > 6 µm) is larger than the cell size. We show that these conclusions can be helpful for the design of a reliable DLD microfluidic device for the separation of RBCs.

Download Full-text

Separation of blood cells with differing deformability using deterministic lateral displacement

Interface Focus ◽

10.1098/rsfs.2014.0011 ◽

2014 ◽

Vol 4 (6) ◽

pp. 20140011 ◽

Cited By ~ 66

Author(s):

David Holmes ◽

Graeme Whyte ◽

Joe Bailey ◽

Nuria Vergara-Irigaray ◽

Andrew Ekpenyong ◽

...

Keyword(s):

Whole Blood ◽

Blood Cells ◽

Lateral Displacement ◽

Measurement Techniques ◽

Cell Stiffness ◽

Deterministic Lateral Displacement ◽

Human Red Blood Cells ◽

Hydrodynamic Behaviour ◽

Novel Approach ◽

Marker Free

Determining cell mechanical properties is increasingly recognized as a marker-free way to characterize and separate biological cells. This emerging realization has led to the development of a plethora of appropriate measurement techniques. Here, we use a fairly novel approach, deterministic lateral displacement (DLD), to separate blood cells based on their mechanical phenotype with high throughput. Human red blood cells were treated chemically to alter their membrane deformability and the effect of this alteration on the hydrodynamic behaviour of the cells in a DLD device was investigated. Cells of defined stiffness (glutaraldehyde cross-linked erythrocytes) were used to test the performance of the DLD device across a range of cell stiffness and applied shear rates. Optical stretching was used as an independent method for quantifying the variation in stiffness of the cells. Lateral displacement of cells flowing within the device, and their subsequent exit position from the device were shown to correlate with cell stiffness. Data showing how the isolation of leucocytes from whole blood varies with applied shear rate are also presented. The ability to sort leucocyte sub-populations (T-lymphocytes and neutrophils), based on a combination of cell size and deformability, demonstrates the potential for using DLD devices to perform continuous fractionation and/or enrichment of leucocyte sub-populations from whole blood.

Download Full-text

Large Particle Separation From Non-Newtonian Slurries Using Bump Arrays

10.1115/fedsm2021-65904 ◽

2021 ◽

Author(s):

Leonard F. Pease ◽

Judith Ann Bamberger ◽

Carolyn A. Burns ◽

Michael J. Minette

Keyword(s):

Nuclear Waste ◽

Blood Cells ◽

Large Particle ◽

Lateral Displacement ◽

Particle Separation ◽

Small Particle Size ◽

Small Particles ◽

Deterministic Lateral Displacement ◽

Significant Difference ◽

Large Particles

Abstract Here we evaluate the performance of bump arrays to separate large particles from non-Newtonian slurries with Bingham and Cross rheology. Bump arrays in deterministic lateral displacement devices separate large particles from small particles using arrays of staggered posts. Large particles, defined as those with radii larger than the distance between the edge of a post and the stagnation streamline from the next downstream post, must bump toward one side of the device, whereas particles smaller than this distance slalom from entrance to exit without net lateral displacement. Although these devices have been used to separate a wide variety of large particles from blood cells to sand, partition of large particles from non-Newtonian fluids remains unexplored. Yet, an important set of modestly concentrated slurries, including Hanford nuclear waste, displays non-Newtonian rheology. Here we evaluate the influence of non-Newtonian rheology on the large-small particle size cutoff in bump arrays using a model that explores the influence of yield stresses, ratios of zero and infinite shear viscosities, and Cross’s exponent under strictly laminar well-developed conditions. Surprisingly, we find that viscosity ratios and Cross’s exponent make no significant difference on the particle cutoffs between large particles that bump and small particles that slalom around the posts from entrance to exit. In contrast, we find that yield stresses do significantly affect the size cutoff. As the yield stress increases, velocity profiles become more plug like lowering the size cutoff. For nuclear waste separations where removing large particles is a priority, increasing yield stresses is conservative.

Download Full-text

Hemoglobin crystals of the red blood cells in the human renal cortex: electron microscopic observations of the renal lithiasis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100083266 ◽

1978 ◽

Vol 36 (2) ◽

pp. 480-481

Author(s):

Kosuke Ueda ◽

Hiroto Washida ◽

Nakazo Watari

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Renal Cortex ◽

Uranyl Acetate ◽

Osmic Acid ◽

Renal Lithiasis ◽

Electron Microscopic ◽

Hemoglobin C ◽

First Case ◽

Ultrathin Sections

IntroductionHemoglobin crystals in the red blood cells were electronmicroscopically reported by Fawcett in the cat myocardium. In the human, Lessin revealed crystal-containing cells in the periphral blood of hemoglobin C disease patients. We found the hemoglobin crystals and its agglutination in the erythrocytes in the renal cortex of the human renal lithiasis, and these patients had no hematological abnormalities or other diseases out of the renal lithiasis. Hemoglobin crystals in the human erythrocytes were confirmed to be the first case in the kidney.Material and MethodsTen cases of the human renal biopsies were performed on the operations of the seven pyelolithotomies and three ureterolithotomies. The each specimens were primarily fixed in cacodylate buffered 3. 0% glutaraldehyde and post fixed in osmic acid, dehydrated in graded concentrations of ethanol, and then embedded in Epon 812. Ultrathin sections, cut on LKB microtome, were doubly stained with uranyl acetate and lead citrate.

Download Full-text

Densitometric Identification of Primitive Erythroblasts After Reaction With Diaminobenzidine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072083 ◽

1973 ◽

Vol 31 ◽

pp. 328-329

Author(s):

John A. Trotter

Keyword(s):

Red Blood Cells ◽

Analytical Method ◽

Blood Cells ◽

Guinea Pigs ◽

Specific Protein ◽

Visual Examination ◽

Hemoglobin Synthesis ◽

Peroxidatic Activity ◽

Small Density

Hemoglobin is the specific protein of red blood cells. Those cells in which hemoglobin synthesis is initiated are the earliest cells that can presently be considered to be committed to erythropoiesis. In order to identify such early cells electron microscopically, we have made use of the peroxidatic activity of hemoglobin by reacting the marrow of erythropoietically stimulated guinea pigs with diaminobenzidine (DAB). The reaction product appeared as a diffuse and amorphous electron opacity throughout the cytoplasm of reactive cells. The detection of small density increases of such a diffuse nature required an analytical method more sensitive and reliable than the visual examination of micrographs. A procedure was therefore devised for the evaluation of micrographs (negatives) with a densitometer (Weston Photographic Analyzer).

Download Full-text

Scanning electron microscopy of erythrophagocytosis by Entamoeba histolytica trophozoites

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012480x ◽

1992 ◽

Vol 50 (1) ◽

pp. 880-881

Author(s):

Victor Tsutsumi ◽

Adolfo Martinez-Palomo ◽

Kyuichi Tanikawa

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Red Blood Cells ◽

Entamoeba Histolytica ◽

Causative Agent ◽

Blood Cells ◽

Protozoan Parasite ◽

Complex Phenomenon ◽

Great Capacity ◽

Scanning Electron

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis in man. The trophozoite or motile form is a highly dynamic and pleomorphic cell with a great capacity to destroy tissues. Moreover, the parasite has the singular ability to phagocytize a variety of different live or death cells. Phagocytosis of red blood cells by E. histolytica trophozoites is a complex phenomenon related with amebic pathogenicity and nutrition.

Download Full-text

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162132 ◽

1990 ◽

Vol 48 (3) ◽

pp. 914-915

Author(s):

D.J.P. Ferguson ◽

A.R. Berendt ◽

J. Tansey ◽

K. Marsh ◽

C.I. Newbold

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Umbilical Vein ◽

Cell Types ◽

Amelanotic Melanoma ◽

Cytoplasmic Process ◽

Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Download Full-text