Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes

Inglis, David W.; Lord, Megan S.; Nordon, Robert E.

doi:10.1088/0960-1317/21/5/054024

Cited by 79 publications

(72 citation statements)

References 25 publications

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“…The 10 mL/min flow rates presented constitute a 50-fold improvement in flow rate over the herringbone-CTC chip used by Stott et al, 12 a 10 5 -fold improvement over the 10 s of μL/min historical flow rates in DLD arrays 22,28 and a 100-fold improvement over more recent efforts by Inglis 29 and are the fastest reported operation of these devices. With internal velocities exceeding 1 m/s and Reynolds number Re > 40, we confirm that the size-based separation functionality is preserved even outside the low Reynolds number flow regime.…”

confidence: 78%

“…There are several examples in the literature that have demonstrated that cells in blood can be isolated literally free from background cells using DLD arrays with a buffer input. 22,28,29 (2) Although a second clear buffer channel would decrease the background of non-sorted cells greatly, it would not increase the absolute concentration of sorted cells in the output stream.…”

confidence: 99%

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Deterministic separation of cancer cells from blood at 10 mL/min

et al. 2012

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Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters of cancer cells with their associated stroma cells. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement (DLD) arrays. We show here that a DLD array device can isolate CTCs from blood with capture efficiency greater than 85% CTCs at volumetric flow rates of up to 10 mL/min with no effect on cell viability

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confidence: 78%

confidence: 99%

Deterministic separation of cancer cells from blood at 10 mL/min

et al. 2012

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“…[1][2][3][4][5][6][7][8][9][10] It has, in fact, been successfully used in a number of applications, especially for the separation of biological samples. [11][12][13][14][15][16][17][18] Although in most cases DLD is described (and investigated) as a size-based separation technique, it could also separate particles based on shape and flexibility 19,20 and may contribute to the growing field of chiral separation. 21,22 We have shown that a simple model 23,24 that describes the motion of a suspended sphere around an individual obstacle in the DLD array (which we refer to as a particle-obstacle collision) predicts the separation capability of the system.…”

Section: Introductionmentioning

confidence: 99%

Inertia and scaling in deterministic lateral displacement

2013

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The ability to separate and analyze chemical species with high resolution, sensitivity, and throughput is central to the development of microfluidics systems. Deterministic lateral displacement (DLD) is a continuous separation method based on the transport of species through an array of obstacles. In the case of force-driven DLD (f-DLD), size-based separation can be modelled effectively using a simple particle-obstacle collision model. We use a macroscopic model to study f-DLD and demonstrate, via a simple scaling, that the method is indeed predominantly a sizebased phenomenon at low Reynolds numbers. More importantly, we demonstrate that inertia effects provide the additional capability to separate same size particles but of different densities and could enhance separation at high throughput conditions. We also show that a direct conversion of macroscopic results to microfluidic settings is possible with a simple scaling based on the size of the obstacles that results in a universal curve. V C 2013 AIP Publishing LLC.

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“…Passive hydrodynamic separation may be achieved by deterministic lateral displacement (DLD). 1 DLD is a central research focus because it is capable of enriching rare cell populations [1][2][3][4] with highthroughput 2 and promises to improve clinical point-of-care diagnostics. These advantages can only be achieved if the relevant engineering challenges can be overcome.…”

Section: Introductionmentioning

confidence: 99%

Manufacturing and wetting low-cost microfluidic cell separation devices

et al. 2013

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Deterministic lateral displacement (DLD) is a microfluidic size-based particle separation or filter technology with applications in cell separation and enrichment. Currently, there are no cost-effective manufacturing methods for this promising microfluidic technology. In this fabrication paper, however, we develop a simple, yet robust protocol for thermoplastic DLD devices using regulatory-approved materials and biocompatible methods. The final standalone device allowed for volumetric flow rates of 660 ll min À1 while reducing the manufacturing time to <1 h. Optical profilometry and image analysis were employed to assess manufacturing accuracy and precision; the average replicated post height was 0.48% less than the average post height on the master mold and the average replicated array pitch was 1.1% less than the original design with replicated posts heights of 62.1 6 5.1 lm (mean 6 6 standard deviations) and replicated array pitches of 35.6 6 0.31 lm.

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Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes

Cited by 79 publications

References 25 publications

Deterministic separation of cancer cells from blood at 10 mL/min

Deterministic separation of cancer cells from blood at 10 mL/min

Inertia and scaling in deterministic lateral displacement

Manufacturing and wetting low-cost microfluidic cell separation devices

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