Since the first microfluidic device was developed more than three decades ago, microfluidics is seen as a technology that exhibits unique features to provide a significant change in the way that modern biology is performed. Blood and blood cells are recognized as important biomarkers of many diseases. Taken advantage of microfluidics assets, changes on blood cell physicochemical properties can be used for fast and accurate clinical diagnosis. In this review, an overview of the microfabrication techniques is given, especially for biomedical applications, as well as a synopsis of some design considerations regarding microfluidic devices. The blood cells separation and sorting techniques were also reviewed, highlighting the main achievements and breakthroughs in the last decades.

https://www.mdpi.com/2072-666X/10/9/593/pdf

Blood cells separation and sorting techniques of passive microfluidic devices: From fabrication to applications

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.

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

Suspensions of healthy and pathological red blood cells (RBC) flowing in microfluidic devices are frequently used to perform in vitro blood experiments for a better understanding of human microcirculation hemodynamic phenomena This work reports the development of particulate viscoelastic analogue fluids able to mimic the rheological and hemorheological behavior of pathological RBC suspensions flowing in microfluidic systems The pathological RBCs were obtained by an incubation of healthy RBCs at a high concentration of glucose, representing the pathological stage of hyperglycaemia in diabetic complications, and analyses of their deformability and aggregation were carried out Overall, the developed in vitro analogue fluids were composed of a suspension of semi-rigid microbeads in a carrier viscoelastic fluid made of dextran 40 and xanthan gum All suspensions of healthy and pathological RBCs, as well as their particulate analogue fluids, were extensively characterized in steady shear flow, as well as in small and large amplitude oscillatory shear flow In addition, the well-known cell-free layer (CFL) phenomenon occurring in microchannels was investigated in detail to provide comparisons between healthy and pathological in vitro RBC suspensions and their corresponding analogue fluids at different volume concentrations (5% and 20%) The experimental results have shown a similar rheological behavior between the samples containing a suspension of pathological RBCs and the proposed analogue fluids Moreover, this work shows that the particulate in vitro analogue fluids used have the ability to mimic well the CFL phenomenon occurring downstream of a microchannel contraction for pathological RBC suspensions The proposed particulate fluids provide a more realistic behavior of the flow properties of suspended RBCs when compared with existing non-particulate blood analogues, and consequently, they are advantageous for detailed investigations of microcirculation

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In vitro particulate analogue fluids for experimental studies of rheological and hemorheological behavior of glucose-rich RBC suspensions

Microfluidic technology is interdisciplinary with a diversity of applications including in food processing The rapidly growing global population demands more advanced technologies in food processing to produce more functional and safer food, and for such processing microfluidic devices are a popular choice This review critically critiques the state-of-the-art designs of microfluidic devices and their applications in food processing, and identifies the key research trends and future research directions for maximizing the value of microfluidic technology Capillary, planar, and terrace droplet generation systems are currently used in the design of microfluidic devices, each with their strengths and weaknesses as applied in food processing, for emulsification, food safety measurements, and bioactive compound extraction Conventional channel-based microfluidic devices are prone to clogging, and have high labor costs and low productivity, and their "directional pressure" restricts scaling-up capabilities These disadvantages can be overcome by using "inside-out centrifugal force" and the new generation continuous flow thin-film microfluidic Vortex Fluidic Device (VFD) which facilitates translating laboratory processing into commercial products Also highlighted is controlling protein-polysaccharide interactions and the applications of the produced ingredients in food formulations as targets for future development in the field

Application of microfluidic technology in food processing

Polydimethylsiloxane (PDMS), due to its remarkable properties, is one of the most widely used polymers in many industrial and medical applications. In this work, a technique based on a flow focusing technique is used to produce PDMS spherical particles with sizes of a few microns. PDMS precursor is injected through a hypodermic needle to form a film/reservoir over the needle's outer surface. This film flows towards the needle tip until a liquid ligament is steadily ejected thanks to the action of a coflowing viscous liquid stream. The outcome is a capillary jet which breaks up into PDMS precursor droplets due to the growth of capillary waves producing a micrometer emulsion. The PDMS liquid droplets in the solution are thermally cured into solid microparticles. The size distribution of the particles is analyzed before and after curing, showing an acceptable degree of monodispersity. The PDMS liquid droplets suffer shrinkage while curing. These microparticles can be used in very varied technological fields, such as biomedicine, biotechnology, pharmacy, and industrial engineering.

/pdf/generation-of-micro-sized-pdms-particles-by-a-flow-focusing-496pgg6jyw.pdf

Generation of micro-sized PDMS particles by a flow focusing technique for biomicrofluidics applications

The interest in the development of blood analogues has been increasing recently as a consequence of the increment in the number of experimental hemodynamic studies and the difficulties associated with the manipulation of real blood in vitro because of ethical, economical or hazardous issues. Although one-phase Newtonian and non-Newtonian blood analogues can be found in the literature, there are very few studies related to the use of particulate solutions in which the particles mimic the behaviour of the red blood cells (RBCs) or erythrocytes. One of the most relevant effects related with the behaviour of the erythrocytes is a cell free layer (CFL) formation, which consists in the migration of the RBCs towards the center of the vessel forming a cell depleted plasma region near the vessel walls, which is known to happen in in vitro microcirculatory environments. Recent studies have shown that the CFL enhancement is possible with an insertion of contraction and expansion region in a straight microchannel. These effects are useful for cell manipulation or sorting in lab-on-chip studies. In this experimental study we present particulate Newtonian and non-Newtonian solutions which resulted in a rheological blood analogue able to form a CFL, downstream of a microfluidic hyperbolic contraction, in a similar way of the one formed by healthy RBCs.

/pdf/particulate-blood-analogues-reproducing-the-erythrocytes-2uwtecsuyj.pdf

Joana Calejo

Papers

Particulate Blood Analogues Reproducing the Erythrocytes Cell-Free Layer in a Microfluidic Device Containing a Hyperbolic Contraction