Biomedical microfluidic devices by using low-cost fabrication techniques: A review.

Techniques, such as micropipette aspiration and optical tweezers, are widely used to measure cell mechanical properties, but are generally labor-intensive and time-consuming, typically involving a difficult process of manipulation. In the past two decades, a large number of microfluidic devices have been developed due to the advantages they offer over other techniques, including transparency for direct optical access, lower cost, reduced space and labor, precise control, and easy manipulation of a small volume of blood samples. This review presents recent advances in the development of microfluidic devices to evaluate the mechanical response of individual red blood cells (RBCs) and microbubbles flowing in constriction microchannels. Visualizations and measurements of the deformation of RBCs flowing through hyperbolic, smooth, and sudden-contraction microchannels were evaluated and compared. In particular, we show the potential of using hyperbolic-shaped microchannels to precisely control and assess small changes in RBC deformability in both physiological and pathological situations. Moreover, deformations of air microbubbles and droplets flowing through a microfluidic constriction were also compared with RBCs deformability.

/pdf/deformation-of-red-blood-cells-air-bubbles-and-droplets-in-3gagtn0w34.pdf

Deformation of Red Blood Cells, Air Bubbles, and Droplets in Microfluidic Devices: Flow Visualizations and Measurements.

We present a two-phase model for microcirculation that describes the interaction of plasma with red blood cells. The model takes into account of typical effects characterizing the microcirculation, such as the Fahraeus-Lindqvist effect and plasma skimming. Besides these features, the model describes the interaction of capillaries with the surrounding tissue. More precisely, the model accounts for the interaction of capillary transmural flow with the surrounding interstitial pressure. Furthermore, the capillaries are represented as one-dimensional channels with arbitrary, possibly curved configuration. The latter two features rely on the unique ability of the model to account for variations of flow rate and pressure along the axis of the capillary, according to a local differential formulation of mass and momentum conservation. Indeed, the model stands on a solid mathematical foundation, which is also addressed in this work. In particular, we present the model derivation, the variational formulation, and its approximation using the finite element method. Finally, we conclude the work with a comparative computational study of the importance of the Fahraeus-Lindqvist, plasma skimming, and capillary leakage effects on the distribution of flow in a microvascular network.

/pdf/a-computational-model-for-microcirculation-including-2x4d7y7kyu.pdf

A computational model for microcirculation including Fahraeus-Lindqvist effect, plasma skimming and fluid exchange with the tissue interstitium.

The loss of the red blood cells (RBCs) deformability is related with many human diseases, such as malaria, hereditary spherocytosis, sickle cell disease, or renal diseases. Hence, during the last years, a variety of technologies have been proposed to gain insights into the factors affecting the RBCs deformability and their possible direct association with several blood pathologies. In this work, we present a simple microfluidic tool that provides the assessment of motions and deformations of RBCs of end-stage kidney disease (ESKD) patients, under a well-controlled microenvironment. All of the flow studies were performed within a hyperbolic converging microchannels where single-cell deformability was assessed under a controlled homogeneous extensional flow field. By using a passive microfluidic device, RBCs passing through a hyperbolic-shaped contraction were measured by a high-speed video microscopy system, and the velocities and deformability ratios (DR) calculated. Blood samples from 27 individuals, including seven healthy controls and 20 having ESKD with or without diabetes, were analysed. The obtained data indicates that the proposed device is able to detect changes in DR of the RBCs, allowing for distinguishing the samples from the healthy controls and the patients. Overall, the deformability of ESKD patients with and without diabetes type II is lower in comparison with the RBCs from the healthy controls, with this difference being more evident for the group of ESKD patients with diabetes. RBCs from ESKD patients without diabetes elongate on average 8% less, within the hyperbolic contraction, as compared to healthy controls; whereas, RBCs from ESKD patients with diabetes elongate on average 14% less than the healthy controls. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to assess blood cells deformability due to the huge progress in image processing and high-speed microvisualization technology.

/pdf/a-microfluidic-deformability-assessment-of-pathological-red-3lb6xq8n7r.pdf

A Microfluidic Deformability Assessment of Pathological Red Blood Cells Flowing in a Hyperbolic Converging Microchannel

Red blood cells radial dispersion in blood flowing through microchannels: The role of temperature

SUMMARY The current study proposes an automatic method for the segmentation and tracking of red blood cells flowing through a 100-� m glass capillary. The original images were obtained by means of a confocal system and then processed in MATLAB using the Image Processing Toolbox. The measurements obtained with the proposed automatic method were compared with the results determined by a manual tracking method. The comparison was performed by using both linear regressions and Bland–Altman analysis. The results have shown a good agreement between the two methods. Therefore, the proposed automatic method is a powerful way to provide rapid and accurate measurements for in vitro blood experiments in microchannels. Copyright © 2012 John Wiley & Sons, Ltd.

/pdf/automatic-tracking-of-labeled-red-blood-cells-in-11ctwllf44.pdf

Automatic tracking of labeled red blood cells in microchannels.

The current study proposes an automatic method for the segmentation and tracking of red blood cells (RBCs) flowing through a 100 μm glass capillary. The measurements obtained with the proposed automatic method are compared with a manual tracking method using nonlinear optimization techniques.

/pdf/a-comparison-between-a-manual-and-automatic-method-to-3f927j52fh.pdf

A Comparison between a Manual and Automatic Method to Characterize Red Blood Cell Trajectories

Image analysis is extremely important to obtain crucial information about the blood phenomena in microcirculation. The current study proposes an automatic method for segmentation and tracking red blood cells (RBCs) flowing through a 100 μm glass capillary. The original images were obtained by means of a confocal system and then processed in MatLab using the Image Processing Toolbox. The automatic measurements with the proposed automatic method are compared with a manual tracking method performed by ImageJ. The comparison of the two methods is performed using a statistical Bland–Altman analysis. The numerical results have shown a good agreement between the two methods. Additionally, no significant difference was found between the two methods and as a result the proposed automatic method is demonstrated to be a rapid and accurate way to track RBCs in microchannels.

/pdf/tracking-red-blood-cells-in-microchannels-a-comparative-2uarzrfnqo.pdf

Tracking Red Blood Cells in Microchannels: A Comparative Study Between an Automatic and a Manual Method

The study of the red blood cells (RBCs) flowing in microvessels and microchannels is very important to provide a better understanding on the blood rheological properties and disorders in microvessels [1-5]. In this kind of study, the image analysis is an essential part to obtain crucial information about the blood rheology. However, most of the data analysis procedures have been executed manually [1-3] which is an extremely time consuming task especially with a large amount of data. Additionally, manual tracking methods can also introduce user errors into the data. Hence, it is important to develop image analysis methods able to get the data automatically. The main purpose of this work is to develop an approach able to track the RBCs with x and y coordinates automatically. To accomplish it we tested filtering, segmentation and feature extraction functions available in MatLab.

/pdf/an-automatic-method-to-track-red-blood-cells-in-1dk7s7uyhv.pdf

Fernando Gayubo

Papers

Automatic tracking of labeled red blood cells in microchannels.

A Comparison between a Manual and Automatic Method to Characterize Red Blood Cell Trajectories

Tracking Red Blood Cells in Microchannels: A Comparative Study Between an Automatic and a Manual Method

An automatic method to track red blood cells in microchannels