Sorting cells by size, shape and deformability

Beech, Jason P.; Holm, Stefan; Adolfsson, Karl; Tegenfeldt, Jonas O.

doi:10.1039/c2lc21083e

Cited by 236 publications

(262 citation statements)

References 15 publications

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“…[11] In all cases, the variation in the trajectories after passing around a single obstacle is much smaller than the radius of the capsule, a c . Hence, by merely driving the capsules through a narrow gap (between the obstacle and the duct-walls) it is not possible to gener- ate large enough differences between their trajectories to separate them.…”

Section: Modelsmentioning

confidence: 99%

“…[5] In recent times, several microfluidic devices have been fabricated to detect biophysical markers and to sort cells accordingly. [4,[6][7][8][9][10][11] The challenge in this field lies in designing clever geometries that allow for an efficient sorting. Mircofluidic devices possess the unique ability to sort cells by deformability because they operate by balancing the elastic stresses of the cell against the fluid stresses.…”

Section: Introductionmentioning

confidence: 99%

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A microfluidic device to sort capsules by deformability: a numerical study

et al. 2014

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Guided by extensive numerical simulations, we propose a microfluidic device that can sort elastic capsules by their deformability. The device consists of a duct embedded with a semi-cylindrical obstacle, and a diffuser which further enhances the sorting capability. We demonstrate that the device can operate reasonably well under changes in the initial position of the the capsule. The efficiency of the device remains essentially unaltered under small changes of the obstacle shape (from semi-circular to semi-elliptic cross-section). Confinement along the direction perpendicular to the plane of the device increases its efficiency. This work is the first numerical study of cell sorting by a realistic microfluidic device.

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Section: Modelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A microfluidic device to sort capsules by deformability: a numerical study

et al. 2014

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“…However, both methods are time and labor intensive (tens of cells per hour), posing challenges for examining large populations of cells to either obtain statistically valid conclusions or identify rare sub-populations. Recent advances in micro-/nano-fabrication technologies have opened up a range of new mechanophenotyping technologies that can measure deformations of tens to hundreds of cells per second [11][12][13][14][15][16][17][18][19] . We recently reported a technology, called deformability cytometry, in which a cross-slot microfluidic channel is employed to generate a hydrodynamic extension zone where individual cells are exposed to uniform hydrodynamic stress and deformed 20 .…”

Section: Introductionmentioning

confidence: 99%

High-throughput physical phenotyping of cell differentiation

et al. 2017

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In this report, we present multiparameter deformability cytometry (m-DC), in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives. m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters. Parameters extracted from videos include size, deformability, deformation kinetics, and morphology. We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells, mesenchymal stem cells, neural stem cells, and their derivatives compared to size and deformability alone. In addition, we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation. This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner. Ultimately, such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.

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“…For example, cells can be sorted based on size, shape, deformability, density, optical and electrical properties. [6][7][8][9][10] Dielectrophoresis (DEP) is a useful separation method that offers label-free isolation of cells based on geometrical and electrical properties of cells in microfluidic devices. In contrast to some capture-based techniques, the cells remain viable and can be taken off-chip for further analysis.…”

Section: Introductionmentioning

confidence: 99%

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

et al. 2016

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We designed a new microfluidic device that uses pillars on the same order as the diameter of a cell (20 lm) to isolate and enrich rare cell samples from background. These cell-scale microstructures improve viability, trapping efficiency, and throughput while reducing pearl chaining. The area where cells trap on each pillar is small, such that only one or two cells trap while fluid flow carries away excess cells. We employed contactless dielectrophoresis in which a thin PDMS membrane separates the cell suspension from the electrodes, improving cell viability for off-chip collection and analysis. We compared viability and trapping efficiency of a highly aggressive Mouse Ovarian Surface Epithelial (MOSE) cell line in this 20 lm pillar device to measurements in an earlier device with the same layout but pillars of 100 lm diameter. We found that MOSE cells in the new device with 20 lm pillars had higher viability at 350 V RMS , 30 kHz, and 1.2 ml/h (control 77%, untrapped 71%, trapped 81%) than in the previous generation device (untrapped 47%, trapped 42%). The new device can trap up to 6 times more cells under the same conditions. Our new device can sort cells with a high flow rate of 2.2 ml/h and throughput of a few million cells per hour while maintaining a viable population of cells for off-chip analysis. By using the device to separate subpopulations of tumor cells while maintaining their viability at large sample sizes, this technology can be used in developing personalized treatments that target the most aggressive cancerous cells. V C 2016 AIP Publishing LLC. [http://dx

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Sorting cells by size, shape and deformability

Abstract: While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells.

Cited by 236 publications

References 15 publications

A microfluidic device to sort capsules by deformability: a numerical study

A microfluidic device to sort capsules by deformability: a numerical study

High-throughput physical phenotyping of cell differentiation

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

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