Deformability based cell margination—A simple microfluidic design for malaria-infected erythrocyte separation

Hou, Han Wei; Bhagat, Ali Asgar S.; Chong, Adrian; Mao, Pan; Tan, Kevin S. W.; Han, Jongyoon; Lim, Chwee Teck

doi:10.1039/c003873c

Cited by 266 publications

(245 citation statements)

References 56 publications

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“…Such an understanding may also impact the application of particles for bioimaging applications, where a low or no margination propensity would help increase the particle circulation time (24). Further, the margination of particles has been successfully exploited to separate cells (e.g., sickle cells) and pathogens (e.g., bacteria and fungi) according to their size and/or stiffness (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Carboni

Bognet

Bouchillon

et al. 2016

Biophysical Journal

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Margination refers to the migration of particles toward blood vessel walls during blood flow. Understanding the mechanisms that lead to margination will aid in tailoring the attributes of drug-carrying particles for effective drug delivery. Most previous studies evaluated the margination propensity of these particles via an adhesion mechanism, i.e., by measuring the number of particles that adhered to the channel wall. Although particle adhesion and margination are related, adhesion also depends on other factors. In this study, we quantified the margination propensity of particles of varying diameters (0.53, 0.84, and 2.11 mm) and apparent wall shear rates (30, 61, and 121 s À1 ) by directly tracking fluorescent particles flowing through a microfluidic channel. The margination parameter, M, is defined as the total number of particles found within the cell-free layers normalized by the total number of particles that passed through the channel. In this study, an M-value of 0.2 indicated no margination, which was observed for all particle sizes in water. In the case of blood, larger particles were found to have higher M-values and thus marginated more effectively than smaller particles. The corresponding M-values at the device outlet were 0.203, 0.223, and 0.285 for 0.53-, 0.84-, and 2.11-mm particles, respectively. At the inlet, the M-values for all particle sizes in blood were <0.2, suggesting that non-fully-developed flow and constriction may lead to demargination. For particle velocities transverse to the flow direction (v y ), all particle sizes showed a larger standard deviation of v y as well as a higher effective diffusivity when the particles were suspended in blood relative to water. These higher values are attributed to collisions between the blood cells and particles, further supporting recent simulation results. In terms of flow rates, for a given particle size, the higher the flow rate, the higher the M-value.

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Section: Introductionmentioning

confidence: 99%

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Carboni

Bognet

Bouchillon

et al. 2016

Biophysical Journal

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“…A number of microfluidic devices have been developed to take advantage of these natural hemodynamics phenomena. Shevkoplyas et al [7] developed a microdevice to isolate WBCs from a blood sample by using the margination effect, whereas Hou et al [8] have very recently proposed a biomimetic separation device to separate normal RBCs from malaria infected RBCs. Other researchers have found several advantages to control and manipulate blood flow in microfluidic devices.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic device for partial cell separation and deformability assessment

2013

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Blood flow in microcirculation shows several interesting phenomena that can be used to develop microfluidic devices for blood separation and analysis in continuous flow. In this study we present a novel continuous microfluidic device for partial extraction of red blood cells (RBCs) and subsequent measurement of RBC deformability. For this purpose, we use polydimethylsiloxane (PDMS) microchannels having different constrictions (25%, 50% and 75%) to investigate their effect on the cell-free layer (CFL) thickness and separation efficiency. By using a combination of image analysis techniques we are able to automatically measure the CFL width before and after an artificial constriction. The results suggest that the CFL width increases with enhancement of the constriction and contributes to partial cell separation. The subsequent measurements of RBCs deformation index reveal that the degree of deformation depends on the constriction geometries and hematocrit after the cell separation module. The proposed microfluidic device can be easily transformed into a simple, inexpensive and convenient clinical tool able to perform both RBC separation and deformability analysis in one single device. This would eliminate the need for external sample handling and thus reducing associated labor costs and potential human errors.

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“…Additionally, Shevkoplyas et al 15 proposed a microfluidic device for assessing RBC deformability in a microchannel network with a topology similar to that of the real microcirculation, and showed that the ability to detect small changes of RBC deformability on the blood flow in a microchannel network may prove a viable clinical instrument in early detection of blood diseases. More recently, Hou et al 6 have proposed a biomimetic separation device to separate normal and malaria infected RBCs.…”

mentioning

confidence: 99%

“…[1][2][3][4][5] The deformability (usually reported as a deformation index, DI) is an important property for the delivery of oxygen to the body and a decrease in RBC deformability can have serious consequences leading to health problems. 5 There are several studies examining the behaviour of RBCs in response to a deforming force (or stress) and demonstrating the clinical relevance of this phenomenon in several blood cell related diseases, such as malaria 4,6 and diabetes mellitus (DM), 5,7,8 in which the deformability is significantly reduced. The capability of the cells to deform has, therefore, the potential to be used as a biophysical marker, without requiring the costly labeling and sample preparation typical of most common biochemical markers.…”

mentioning

confidence: 99%

Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel

et al. 2013

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It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the centerline of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases. V C 2013 AIP Publishing LLC. [http://dx

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Deformability based cell margination—A simple microfluidic design for malaria-infected erythrocyte separation

Cited by 266 publications

References 56 publications

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Direct Tracking of Particles and Quantification of Margination in Blood Flow

A microfluidic device for partial cell separation and deformability assessment

Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel

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