Raquel Lopes

Bio: Raquel Lopes is an academic researcher. The author has contributed to research in topics: European union. The author has an hindex of 3, co-authored 3 publications receiving 58 citations.

Low cost microfluidic device for partial cell separation: Micromilling approach

Abstract: Several studies have already demonstrated that it is possible to perform blood flow studies in microfluidic systems fabricated by using low-cost techniques. However, most of these techniques do not produce microchannels smaller than 100 microns and as a result they have several limitations related to blood cell separation. Recently, manufacturers have been able to produce milling tools smaller than 100 microns, which consequently have promoted the ability of micromilling machines to fabricate microfluidic devices able to perform separation of red blood cells (RBCs) from plasma. In this work, we show the ability of a micromilling machine to manufacture microchannels with dimensions down to 30 microns. Additionally, we show for the first time the ability of the proposed microfluidic device to enhance the cell-free layer close to the walls, leading to perform partial separation of RBCs from plasma.

In vitro blood flow and cell-free layer in hyperbolic microchannels: Visualizations and measurements

Abstract: Red blood cells (RBCs) in microchannels has tendency to undergo axial migration due to the parabolic velocity profile, which results in a high shear stress around wall that forces the RBC to move towards the centre induced by the tank treading motion of the RBC membrane. As a result there is a formation of a cell free layer (CFL) with extremely low concentration of cells. Based on this phenomenon, several works have proposed microfluidic designs to separate the suspending physiological fluid from whole in vitro blood. This study aims to characterize the CFL in hyperbolic-shaped microchannels to separate RBCs from plasma. For this purpose, we have investigated the effect of hyperbolic contractions on the CFL by using not only different Hencky strains but also varying the series of contractions. The results show that the hyperbolic contractions with a Hencky strain of 3 and higher, substantially increase the CFL downstream of the contraction region in contrast with the microchannels with a Hencky strain of 2, where the effect is insignificant. Although, the highest CFL thickness occur at microchannels with a Hencky strain of 3.6 and 4.2 the experiments have also shown that cells blockage are more likely to occur at this kind of microchannels. Hence, the most appropriate hyperbolic-shaped microchannels to separate RBCs from plasma is the one with a Hencky strain of 3.

Blood Flow Visualization and Measurements in Microfluidic Devices Fabricated by a Micromilling Technique

Abstract: The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/ 2215/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER). DP acknowledge the PhD scholarship SFRH/BD/89077/2012, and P.C. Sousa acknowledges the fellowship SFRH/BPD/75258/ 2010, all attributed by FCT.

Microfluidic‐Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications

Abstract: Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high-efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label-free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor-intensive steps of labeling molecular signatures of cells. In general, microfluidic-based cell sorting approaches can separate cells using "intrinsic" (e.g., fluid dynamic forces) versus "extrinsic" external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label-free microfluidic-based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic-based cell separation methods are discussed.

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

Abstract: 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.

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

Abstract: 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.

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

Abstract: 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.