A constriction channel based microfluidic system enabling continuous characterization of cellular instantaneous Young's modulus

Luo, Yi; Chen, D.Y.; Zhao, Yang; Wei, Chao; Zhao, Xiaoting; Yue, Wentao; Long, Rong; Wang, Jian Bin; Chen, J.

doi:10.1016/j.snb.2014.05.028

Cited by 63 publications

(49 citation statements)

References 45 publications

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“…The first key progress is the capability of translating raw parameters such as entry time into intrinsic mechanical markers such as instantaneous Young's modulus or cortical tension [35,46,47]. These raw mechanical parameters depend on cell sizes and experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

“…To address this issue, a few studies have been conducted to model the cellular entry process into the constriction channel which can translate these raw parameters into intrinsic cellular mechanical parameters such as Young's Modulus and Cortical Tension [35,36,[45][46][47]51,52]. Ma et al, are pioneers in this field and they used a Newtonian liquid drop to model a RBC where the cell deformability is indicated by a persistent cortical tension of the cell membrane (see Figure 6) [35,46].…”

Section: Mechanical Modeling Of the Constriction Channel Designmentioning

confidence: 99%

“…In addition, Theodoly et al, modelled the cellular entry process into the constriction channel with the effects of friction and leakage taken into consideration [51]. As a follow-up study, Chen et al, used a visco-hyperelastic solid to model a tumor cell using ABAQUS based numerical simulations where cell-channel wall frictions were modeled using a simple Coulomb law (see Figure 7) [47]. Both experiments and simulations confirmed the two-stage cellular entry process into the constriction channel: an instantaneous jump into the channel indicated by instantaneous aspiration length followed by a creeping increase in aspiration length which is terminated by transitional aspiration length (see Figure 7a).…”

Section: Mechanical Modeling Of the Constriction Channel Designmentioning

confidence: 99%

“…Although these two approaches are featured with significantly higher throughputs than conventional approaches, they can only collect cellular mechanical parameters (e.g., deformation ratio and elongation index), which remain dependent on cell sizes and experimental conditions (e.g., pressure drop, channel geometry) [17]. [47] Meanwhile, the microfluidic constriction channel is used to quantify the cellular entry and transition process through a micro channel with a cross-sectional area smaller than the dimensions of a single cell, enabling high-throughput single-cell mechanical property characterization [23][24][25][26] (see Table 1). This technique was first used to evaluate the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40], which was then expanded to study the deformability of WBCs [24,41,42] and tumor cells [25,[43][44][45].…”

Section: Introductionmentioning

confidence: 99%

“…This technique was first used to evaluate the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40], which was then expanded to study the deformability of WBCs [24,41,42] and tumor cells [25,[43][44][45]. Leveraging mechanical modeling of the cellular entry process into the constriction channel, the microfluidic constriction channel design can collect size-independent intrinsic biomechanical markers such as cortical tension or Young's modulus [35,[46][47][48].…”

Section: Introductionmentioning

confidence: 99%

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Constriction Channel Based Single-Cell Mechanical Property Characterization

et al. 2015

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This mini-review presents recent progresses in the development of microfluidic constriction channels enabling high-throughput mechanical property characterization of single cells. We first summarized the applications of the constriction channel design in quantifying mechanical properties of various types of cells including red blood cells, white blood cells, and tumor cells. Then we highlighted the efforts in modeling the cellular entry process into the constriction channel, enabling the translation of raw mechanical data (e.g., cellular entry time into the constriction channel) into intrinsic cellular mechanical properties such as cortical tension or Young's modulus. In the end, current limitations and future research opportunities of the microfluidic constriction channels were discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Mechanical Modeling Of the Constriction Channel Designmentioning

confidence: 99%

Section: Mechanical Modeling Of the Constriction Channel Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Constriction Channel Based Single-Cell Mechanical Property Characterization

et al. 2015

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Microfluidic Cytometry for High‐Throughput Characterization of Single Cell Cytoplasmic Viscosity Using Crossing Constriction Channels

et al. 2019

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This article presents an approach of microfluidic flow cytometry capable of continuously characterizing cytoplasmic viscosities of single cells. The microfluidic system consists of a major constriction channel and a side constriction channel perpendicularly crossing each other. Cells are forced to rapidly travel through the major channel and are partially aspirated into the side channel when passing the channel junction. Numerical simulations were conducted to model the time dependence of the aspiration length into the side channel, which enables the measurement of cytoplasmic viscosity by fitting the model results to experimental data. As a demonstration for high‐throughput measurement, the cytoplasmic viscosities of HL‐60 cells that were native or treated by N‐Formylmethionine‐leucyl‐phenylalanine (fMLP) were quantified with sample sizes as large as thousands of cells. Both the average and median cytoplasmic viscosities of native HL‐60 cells were found to be about 10% smaller than those of fMLP‐treated HL‐60 cells, consistent with previous observations that fMLP treatment can increase the rigidity of white blood cells. Furthermore, the microfluidic system was used to process granulocytes from three donors (sample size >1,000 cells for each donor). The results revealed that the cytoplasmic viscosity of granulocytes from one donor was significantly higher than the other two, which may result from the fact that this donor just recovered from an inflammation. In summary, the developed microfluidic system can collect cytoplasmic viscosities from thousands of cells and may function as an enabling tool in the field of single‐cell analysis. © 2019 International Society for Advancement of Cytometry

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Nucleus of Circulating Tumor Cell Determines Its Translocation Through Biomimetic Microconstrictions and Its Physical Enrichment by Microfiltration

Xia

Wan

Hao

et al. 2018

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The mechanism of cells passing through microconstrictions, such as capillaries and endothelial junctions, influences metastasis of circulating tumor cells (CTCs) in vivo, as well as size‐based enrichment of CTCs in vitro. However, very few studies observe such translocation of microconstrictions in real time, and thus the inherent biophysical mechanism is poorly understood. In this study, a multiplexed microfluidic device is fabricated for real‐time tracking of cell translocation under physiological pressure and recording deformation of the whole cell and nucleus, respectively. It is found that the deformability and size of the nucleus instead of the whole cell dominate cellular translocation through microconstrictions under a normal physiological pressure range. More specifically, cells with a large and stiff nucleus are prone to be blocked by relatively small constrictions. The same phenomenon is also observed in the size‐based enrichment of CTCs from peripheral blood of metastatic cancer patients. These findings are different from a popular viewpoint that the size and deformability of a whole cell mainly determine cell translation through microconstrictions, and thus may elucidate interactions between CTCs and capillaries from a new perspective and guide the rational design of size‐based microfilters for rare cell enrichment.

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A constriction channel based microfluidic system enabling continuous characterization of cellular instantaneous Young's modulus

Cited by 63 publications

References 45 publications

Constriction Channel Based Single-Cell Mechanical Property Characterization

Constriction Channel Based Single-Cell Mechanical Property Characterization

Microfluidic Cytometry for High‐Throughput Characterization of Single Cell Cytoplasmic Viscosity Using Crossing Constriction Channels

Nucleus of Circulating Tumor Cell Determines Its Translocation Through Biomimetic Microconstrictions and Its Physical Enrichment by Microfiltration

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