Microfluidic analysis of red blood cell deformability

Guo, Qiang; Duffy, Simon P.; Matthews, Kerryn; Santoso, Aline T.; Scott, Mark D.; Ma, Hongshen

doi:10.1016/j.jbiomech.2014.03.038

Cited by 96 publications

(73 citation statements)

References 61 publications

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“…Initially, the constriction channel design was used to quantify the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40]. In 2003, Chiu et al, characterized complex behaviors of Plasmodium falciparum infected RBCs using the constriction channels with sizes at 8, 6, 4, and 2 µm in width [23] (see Figure 1a).…”

Section: Constriction Channel Based Mechanical Property Characterizatmentioning

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%

“…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]. When each cell is constrained in a constriction channel, the cellular deformation can be divided into three sections: a leading portion, an internal section contacting the constriction, and a trailing portion (see Figure 6a).…”

Section: Mechanical Modeling Of the Constriction Channel Designmentioning

confidence: 99%

“…[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]. 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: Constriction Channel Based Mechanical Property Characterizatmentioning

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%

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Constriction Channel Based Single-Cell Mechanical Property Characterization

et al. 2015

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“…Therefore, the proposed method could provide useful support in cancer cell analysis thus enabling the realization of an integrated lab-on-chip that allows one to perform both imaging and cytometric analysis. Moreover, this approach well fits the needs of an emerging market interest in realizing lab-on-chip devices that are cheap, disposable, easily transportable and, furthermore, suitable for only one single application, [62][63][64] conversely to bulky traditional bench-top instrumentations.…”

Section: -13mentioning

confidence: 85%

Hydrodynamic self-focusing in a parallel microfluidic device through cross-filtration

et al. 2015

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The flow focusing is a fundamental prior step in order to sort, analyze, and detect particles or cells. The standard hydrodynamic approach requires two fluids to be injected into the microfluidic device: one containing the sample and the other one, called the sheath fluid, allows squeezing the sample fluid into a narrow stream. The major drawback of this approach is the high complexity of the layout for microfluidic devices when parallel streams are required. In this work, we present a novel parallelized microfluidic device that enables hydrodynamic focusing in each microchannel using a single feed flow. At each of the parallel channels, a cross-filter region is present that allows removing fluid from the sample fluid. This fluid is used to create local sheath fluids that hydrodynamically pinch the sample fluid. The great advantage of the proposed device is that, since only one inlet is needed, multiple parallel micro-channels can be easily introduced into the design. In the paper, the design method is described and the numerical simulations performed to define the optimal design are summarized. Moreover, the operational functionality of devices tested by using both polystyrene beads and Acute Lymphoid Leukemia cells are shown. V C 2015 AIP Publishing LLC.

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Converting Red Blood Cells to Efficient Microreactors for Blood Detoxification

Yang

et al. 2016

Advanced Materials

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We report a simple method to convert RBCs into efficient microreactors for important biomedical applications. A commonly used cell membrane permeation agent Triton X-100 (TX) was employed at finely tuned concentrations to punch pores in the membranes and render RBCs highly permeable to substrates while maintaining membrane integrity. Subsequently, low concentration of the fixative agent glutaraldehyde (GA) was used to stabilize the cells and avoid inactivation of the membrane proteins. Atomic force microscopy (AFM) and measurement of Young’s modulus (YM) values clearly demonstrated that the reformed RBCs (Ref-RBCs) retained their size, the biconcave disk-like shape, elasticity, and mechanical flexibility comparable to natural RBCs. Furthermore, Ref-RBCs improve the blood survival time of loaded enzymes, and have high permeability to substrate molecules. By exploiting these properties of Ref-RBCs microreactors, we developed an important biomedical application of blood detoxification. When uric acid (UA) and KCN were used as endogenous and exogenous toxin models, respectively, Ref-RBCs, loaded with the corresponding detoxifying enzymes, showed much faster toxin clearance rates than the unmodified RBCs both in vitro and in an in vivo animal model. Our results suggest that these microreactors, after confirming biocompatibility, would have promising therapeutic applications, especially in blood and liver-related diseases.

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Microfluidic analysis of red blood cell deformability

Cited by 96 publications

References 61 publications

Constriction Channel Based Single-Cell Mechanical Property Characterization

Constriction Channel Based Single-Cell Mechanical Property Characterization

Hydrodynamic self-focusing in a parallel microfluidic device through cross-filtration

Converting Red Blood Cells to Efficient Microreactors for Blood Detoxification

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