Extensional flow-based microfluidic device: deformability assessment of red blood cells in contact with tumor cells

Faustino, Vera; Pinho, Diana; Yaginuma, T.; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Lima, Rui

doi:10.1007/s13206-014-8107-1

Cited by 42 publications

(35 citation statements)

References 24 publications

(26 reference statements)

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“…To address these issues, microfluidic tools have recently been explored as a strategy to measure cellular structural and mechanical properties with a rapidity that may be better suited to drug discovery and clinical application (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Although these approaches have indeed massively improved measurement throughput and reduced operator skill/bias issues relative to traditional measurements, the extraction of cell mechanical properties (e.g., elastic modulus) remains challenging, primarily due to complex viscous forces that severely complicate analysis of deformations.…”

Section: Introductionmentioning

confidence: 99%

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

Guillou

Dahl

Lin

et al. 2016

Biophysical Journal

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The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.

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Section: Introductionmentioning

confidence: 99%

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

Guillou

Dahl

Lin

et al. 2016

Biophysical Journal

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“…1,2 It is widely used to fabricate microfluidic devices to perform blood cells separation [3][4][5][6] and deformability analysis, 7,8 to culture endothelial cells, [9][10][11] and to investigate several flow phenomena happening in microvessels. [12][13][14] In the last years, the production of monodisperse particles with this inert elastomer has stimulated great interest of researchers because of their potential applications, especially in biomedicine.…”

Section: Introductionmentioning

confidence: 99%

Generation of micro-sized PDMS particles by a flow focusing technique for biomicrofluidics applications

et al. 2016

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Polydimethylsiloxane (PDMS), due to its remarkable properties, is one of the most widely used polymers in many industrial and medical applications. In this work, a technique based on a flow focusing technique is used to produce PDMS spherical particles with sizes of a few microns. PDMS precursor is injected through a hypodermic needle to form a film/reservoir over the needle's outer surface. This film flows towards the needle tip until a liquid ligament is steadily ejected thanks to the action of a coflowing viscous liquid stream. The outcome is a capillary jet which breaks up into PDMS precursor droplets due to the growth of capillary waves producing a micrometer emulsion. The PDMS liquid droplets in the solution are thermally cured into solid microparticles. The size distribution of the particles is analyzed before and after curing, showing an acceptable degree of monodispersity. The PDMS liquid droplets suffer shrinkage while curing. These microparticles can be used in very varied technological fields, such as biomedicine, biotechnology, pharmacy, and industrial engineering. V C 2016 AIP Publishing LLC.

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“…For example, hydrodynamic pressure-based interrogation (e.g., inertial microfluidics 17–20 , and real-time deformability cytometry 21 ), and physical constraint-based interrogation ( e.g. , single micropore 22, 23 and microchannel 24–27 , and arrayed microchannels 28–34 ). Despite success in the qualitative characterization of Pf -iRBCs deformability properties, a high throughput quantitative parasitemia measurement at the single cell level has yet to be developed.…”

Section: Introductionmentioning

confidence: 99%

High-throughput and label-free parasitemia quantification and stage differentiation for malaria-infected red blood cells

Yang

Chen

Miao

et al. 2017

Biosensors and Bioelectronics

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This work reports a high throughput and label-free microfluidic cell deformability sensor for quantitative parasitemia measurement and stage determination for Plasmodium falciparum-infected red blood cells (Pf-iRBCs). The sensor relies on differentiating the RBC deformability (a mechanical biomarker) that is highly correlated with the infection status. The cell deformability is measured by evaluating the transit time when each individual RBC squeezes through a microscale constriction (cross-section ~5μm×5μm). More than 30,000 RBCs can be analyzed for parasitemia quantification in under 1 min with a throughput ~500 cells/s. Moreover, the device can also differentiate various malaria stages (ring, trophozoite, and schizont stage) due to their varied deformability. Using Pf-iRBCs at 0.1% parasitemia as a testing sample, the microfluidic deformability sensor achieved an excellent sensitivity (94.29%), specificity (86.67%) and accuracy (92.00%) in a blind test, comparable to the gold standard of the blood smear microscopy. As a supplement technology to the microscopy and flow cytometry, the microfluidic deformability sensor would possibly allow for label-free, rapid and cost-effective parasitemia quantification and stage determination for malaria in remote regions.

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Extensional flow-based microfluidic device: deformability assessment of red blood cells in contact with tumor cells

Cited by 42 publications

References 24 publications

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

Generation of micro-sized PDMS particles by a flow focusing technique for biomicrofluidics applications

High-throughput and label-free parasitemia quantification and stage differentiation for malaria-infected red blood cells

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