Automated leukocyte processing by microfluidic deterministic lateral displacement

Civin, Curt I.; Ward, Tony; Skelley, Alison M.; Gandhi, Khushroo; Lee, Zendra Peilun; Dosier, Christopher R.; D'Silva, Joseph; Chen, Yu; Kim, Min Jung; Moynihan, James; Chen, Xiaochun; Aurich, Lee; Gulnik, Sergei V.; Brittain, George C.; Recktenwald, Diether; Austin, Robert H.; Sturm, James C.

doi:10.1002/cyto.a.23019

Cited by 45 publications

(50 citation statements)

References 27 publications

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“…Moreover, recent advances in DLD show its ability to sort particles based on their shapes, deformability, and electrical properties. Due to the high sensitivity of the separation with a resolution limit of 20 nm [11,12], DLD has been widely used to sort, concentrate, and isolate many biological particles including circulating tumor cells [13], white blood cells [14], red blood cells (RBCs) [15], stem cells Fig. 1 a Overview of the working range of passive microfluidics techniques.…”

Section: Introductionmentioning

confidence: 99%

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

2019

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HIGHLIGHTS• A well-organized and thorough discussion on the fundamental principles and recent progress in deterministic lateral displacement (DLD) is provided.• The most updated designs and applications of DLD techniques for particle separation and detection are reviewed.• The current limitations of DLD and its potential solutions for clinical and commercial applications are discussed.ABSTRACT The separation and detection of particles in suspension are essential for a wide spectrum of applications including medical diagnostics. In this field, microfluidic deterministic lateral displacement (DLD) holds a promise due to the ability of continuous separation of particles by size, shape, deformability, and electrical properties with high resolution. DLD is a passive microfluidic separation technique that has been widely implemented for various bioparticle separations from blood cells to exosomes. DLD techniques have been previously reviewed in 2014. Since then, the field has matured as several physics of DLD have been updated, new phenomena have been discovered, and various designs have been presented to achieve a higher separation performance and throughput. Furthermore, some recent progress has shown new clinical applications and ability to use the DLD arrays as a platform for biomolecules detection. This review provides a thorough discussion on the recent progress in DLD with the topics based on the fundamental studies on DLD models and applications for particle separation and detection. Furthermore, current challenges and potential solutions of DLD are also discussed. We believe that a comprehensive understanding on DLD techniques could significantly contribute toward the advancements in the field for various applications. In particular, the rapid, low-cost, and high-throughput particle separation and detection with DLD have a tremendous impact for point-of-care diagnostics.

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Section: Introductionmentioning

confidence: 99%

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

2019

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“…In recent years, more and more targets for detection on diagnostic chips have been investigated. Some salient examples thereof are circulating tumor cells (CTC) of various types of cancer [1,[36][37][38], rare cells (e.g., sickle-cell variants of red blood cells) [39,40], parasites, like Plasmodium falciparum [1,7,10,11,[13][14][15][21][22][23]36,[41][42][43][44][45][46][47][48][49][50] and Trypanosoma spp. [8,44,[51][52][53][54][55][56][57] and even plant pathogens [26,58], as well as-after cells have been lysed-subcellular infection markers (e.g., DNA, RNA fragments) [10,11,22,43,[59][60][61][62].…”

Section: What We Can Detectmentioning

confidence: 99%

“…This asymmetric flow separated different particles according to their diameter. In the 15 years since this empirical description of a phenomenon, additional aspects of DLD have been developed and have broadened its applications: the continuous separation of particles, cancer [3,95,96], healthy blood cells [40,97], infected RBCs [98], yeast [99], bacteria [24], fungal spores [100] and subcellular particles like DNA [101], and virus capsids [102]. Additionally, antibody-coated DLD arrays have been used for non-invasive prenatal diagnosis of circulating fetal cells in samples of their mother's blood [60].…”

Section: Dielectrophoresis (Dep)mentioning

confidence: 99%

Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

Hochstetter

2020

Micromachines

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In the last three decades, microfluidics and its applications have been on an exponential rise, including approaches to isolate rare cells and diagnose diseases on the single-cell level. The techniques mentioned herein have already had significant impacts in our lives, from in-the-field diagnosis of disease and parasitic infections, through home fertility tests, to uncovering the interactions between SARS-CoV-2 and their host cells. This review gives an overview of the field in general and the most notable developments of the last five years, in three parts: 1. What can we detect? 2. Which detection technologies are used in which setting? 3. How do these techniques work? Finally, this review discusses potentials, shortfalls, and an outlook on future developments, especially in respect to the funding landscape and the field-application of these chips.

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“…A question that remains largely unexplored is the effect of blood hematocrit on the performance for sorting and detection of particles suspended in blood. Successful and reliable separation of particles from whole blood has only been achieved for large cells, such as WBCs [34,35] and circulating tumor cells (CTCs) [36][37][38][39]. This is possible because the targeted cells are significantly larger than RBCs, which do not appear to strongly disturb the trajectories of WBCs and CTCs.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Particle Sorting in Concentrated Erythrocyte Suspensions

et al. 2019

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An important step in diagnostics is the isolation of specific cells and microorganisms of interest from blood. Since such bioparticles are often present at very low concentrations, throughput needs to be as high as possible. In addition, to ensure simplicity, a minimum of sample preparation is important. Therefore, sorting schemes that function for whole blood are highly desirable. Deterministic lateral displacement (DLD) devices have proven to be very precise and versatile in terms of a wide range of sorting parameters. To better understand how DLD devices perform for blood as the hematocrit increases, we carry out measurements and simulations for spherical particles in the micrometer range which move through DLD arrays for different flow velocities and hematocrits ranging from pure buffer to concentrated erythrocyte suspensions mimicking whole blood. We find that the separation function of the DLD array is sustained even though the blood cells introduce a shift in the trajectories and a significant dispersion for particles whose diameters are close to the critical size in the device. Simulations qualitatively replicate our experimental observations and help us identify fundamental mechanisms for the effect of hematocrit on the performance of the DLD device.

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Automated leukocyte processing by microfluidic deterministic lateral displacement

Cited by 45 publications

References 27 publications

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

Microfluidic Particle Sorting in Concentrated Erythrocyte Suspensions

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