Deterministic microfluidic ratchet based on the deformation of individual cells

Guo, Qiang; McFaul, Sarah M.; Ma, Hongshen

doi:10.1103/physreve.83.051910

Cited by 54 publications

(71 citation statements)

References 26 publications

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“…Additional advantages of microfluidics analysis include the requirement for small sample volumes, low-cost, and high resolution and sensitivity [35]. To experimentally test a prototype microfluidic RBC deformability device, normal and oxidatively damaged RBC were measured in a small sample of blood donors over several weeks [43,44]. As demonstrated in this study, microfluidics provided reproducible intra-and inter-individual data and demonstrated its utility in detecting oxidatively damaged RBC.…”

Section: Introductionmentioning

confidence: 80%

“…(1) in order to correct for the variation of red cell sizes as well as funnel pore geometries [43,44]. Although the Law of Laplace model has been traditionally applied to micropipette aspiration where a part of the cell membrane is suctioned into a circular orifice, this model makes no assumptions about the geometry of the orifice.…”

Section: Discussionmentioning

confidence: 99%

“…While the design used in the current study (Fig. 1) was a low throughput, individually molded and manually operated device the primary principals (channel geometry and pressure range) are easily applied to an automated, high throughput, microfluidic device that is fully selfcontained [43,44]. Of biological interest, this proof-ofconcept microfluidic device clearly demonstrated a reproducible range for different human donors (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Silicon master molds were initially fabricated using photolithography and the master molds were then replicated on demand using Polydimethylsiloxane (PDMS) via multilayer soft lithography technique as previously described [43,44]. Two molds (noted as control and flow layer molds) were used to fabricate the device out of PDMS (Fig.…”

Section: Microfluidic Fabricationmentioning

confidence: 99%

“…Deformability measurements using microfluidics uses minute amounts of a whole blood or RBC suspension flowing through a funnel-shaped microconstriction [42][43][44]. The threshold pressure required for a sample of RBC to traverse the defined constriction is determined and converted to a quantitative measure (cortical tension; pN/mm) of cellular deformability.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

et al. 2013

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Microfluidic analysis of blood has potential clinical value for determining normal and abnormal erythrocyte deformability. To determine if a microfluidic device could reliably measure intra-and inter-personal variations of normal and oxidized human red blood cell (RBC), venous blood samples were collected from repeat donors over time. RBC deformability was defined by the cortical tension (pN/mm), as determined from the threshold pressure required to deform RBC through 2-2.5 lm funnel-shaped constrictions. Oxidized RBC were prepared by treatment with phenazine methosulphate (PMS; 50 mM). Analysis of the control and oxidized RBC demonstrated that the microfluidic device could clearly differentiate between normal and mildly oxidized (20.13 6 1.47 versus 27.51 6 3.64 pN/mm) RBC. In vivo murine studies further established that the PMS-mediated loss of deformability correlated with premature clearance. Deformability variation within an individual over three independent samplings (over 21 days) demonstrated minimal changes in the mean pN/mm. Moreover, inter-individual variation in mean control RBC deformability was similarly small (range: 19.37-21.40 pN/mm). In contrast, PMS-oxidized cells demonstrated a greater inter-individual range (range: 25.97-29.90 pN/mm) reflecting the differential oxidant sensitivity of an individual's RBC. Importantly, similar deformability profiles (mean and distribution width; 20.49 6 1.67 pN/mm) were obtained from whole blood via finger prick sampling. These studies demonstrated that a low cost microfluidic device could be used to reproducibly discriminate between normal and oxidized RBC. Advanced microfluidic devices could be of clinical value in analyzing populations for hemoglobinopathies or in evaluating donor RBC products post-storage to assess transfusion suitability. Am. J. Hematol. 88:682-689,

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Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Microfluidic Fabricationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

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Microfluidic Label‐Free Hydrodynamic Separation of Blood Cells: Recent Developments and Future Perspectives

Lee

Kim

Yang

2023

Adv Materials Technologies

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The biophysical characteristics and counts of blood cells provide useful information regarding pathological conditions. Therefore, the separation of blood components is a crucial task in biology, clinical diagnosis, therapeutics, and personalized medicine. Recently, microfluidics has gained significant interest as an effective technology for separating target cells from heterogeneous cell populations. Within cellular-scale microchannels, cells of interest are separated based on intrinsic properties, such as size, shape, and deformability, followed by further downstream or off-chip analysis. In this review, microfluidic-based hydrodynamic cell-separation technologies used in label-free approaches by categorizing them according to their key working principles are discussed: i) flow fractionation, ii) deterministic lateral displacement, iii) hydrophoresis, iv) inertial migration, and v) microfiltration. An overview of the major separation mechanisms is provided, and the relative performances and features of these technologies are thoroughly discussed. In addition, future perspectives regarding microfluidic system commercialization and standardization are briefly provided for their widespread use and applications.

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Continuous Flow Deformability‐Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets

Park

Jin

Guo

et al. 2016

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Circulating tumor cells (CTCs) offer tremendous potential for the detection and characterization of cancer. A key challenge for their isolation and subsequent analysis is the extreme rarity of these cells in circulation. Here, a novel label-free method is described to enrich viable CTCs directly from whole blood based on their distinct deformability relative to hematological cells. This mechanism leverages the deformation of single cells through tapered micrometer scale constrictions using oscillatory flow in order to generate a ratcheting effect that produces distinct flow paths for CTCs, leukocytes, and erythrocytes. A label-free separation of circulating tumor cells from whole blood is demonstrated, where target cells can be separated from background cells based on deformability despite their nearly identical size. In doping experiments, this microfluidic device is able to capture >90% of cancer cells from unprocessed whole blood to achieve 10(4) -fold enrichment of target cells relative to leukocytes. In patients with metastatic castration-resistant prostate cancer, where CTCs are not significantly larger than leukocytes, CTCs can be captured based on deformability at 25× greater yield than with the conventional CellSearch system. Finally, the CTCs separated using this approach are collected in suspension and are available for downstream molecular characterization.

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Deterministic microfluidic ratchet based on the deformation of individual cells

Cited by 54 publications

References 26 publications

Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

Microfluidic Label‐Free Hydrodynamic Separation of Blood Cells: Recent Developments and Future Perspectives

Continuous Flow Deformability‐Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets

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