BIOMIMETIC - A biomimetic microdevice for the diagnosis of erythrocytes diseases based on their deformability

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Publications

Microbubble moving in blood flow in microchannels: effect on the cell-free layer and cell local concentration

Publication . Bento, David; Sousa, Lúcia Isabel Teixeira; Yaginuma, Tomoko; Garcia, Valdemar; Lima, Rui A.; Miranda, João Mário

Gas embolisms can hinder blood flow and lead to occlusion of the vessels and ischemia. Bubbles in microvessels circulate as tubular bubbles (Taylor bubbles) and can be trapped, blocking the normal flow of blood. To understand how Taylor bubbles flow in microcirculation, in particular, how bubbles disturb the blood flow at the scale of blood cells, experiments were performed in microchannels at a low Capillary number. Bubbles moving with a stream of in vitro blood were filmed with the help of a high-speed camera. Cell-free layers (CFLs) were observed downstream of the bubble, near the microchannel walls and along the centerline, and their thicknesses were quantified. Upstream to the bubble, the cell concentration is higher and CFLs are less clear. While just upstream of the bubble the maximum RBC concentration happens at positions closest to the wall, downstream the maximum is in an intermediate region between the centerline and the wall. Bubbles within microchannels promote complex spatio-temporal variations of the CFL thickness along the microchannel with significant relevance for local rheology and transport processes. The phenomenon is explained by the flow pattern characteristic of low Capillary number flows. Spatio-temporal variations of blood rheology may have an important role in bubble trapping and dislodging.

2017Journal article

Open access

Técnicas de separação biomimética em microfluídica

Publication . Faustino, Vera; Pinho, Diana; Rodriques, Raquel; Garcia, Valdemar; Lima, Rui A.

A separação e a identificação de células são essenciais em várias aplicações biomédicas, incluindo a biologia celular e os métodos de diagnóstico e terapêuticos. O sangue é um fluido não-Newtoniano contendo inúmeras informações preciosas sobre o estado fisiológico e patológico do corpo humano. No entanto, devido à sua complexidade, existem actualmente poucos métodos de análise precisos. A maioria das técnicas convencionais usadas na separação e contagem de células são dispendiosas e normalmente é necessário usar agentes externos adicionais para identificar as células. As técnicas biomiméticas de separação em microfluídica usam fenómenos microfluídicos, que ocorrem à microescala, para realizar a separação de determinadas células sanguíneas. Estes fenómenos incluem a separação do plasma, a camada livre de células (CLC), a migração dos glóbulos brancos (GBs), também designados por leucócitos, e a lei da bifurcação. Recentemente, vários investigadores têm replicado estes efeitos, que acontecem em ambientes in vivo, em sistemas microfluídicos, ou seja, em ambientes in vitro. Nos microcanais, os glóbulos vermelhos (GVs), devido à sua deformabilidade e ao gradiente de velocidades (às forças de sustentação), tendem a concentrar-se na zona central dos microcanais, enquanto os GBs e os GVs rígidos (tal como, os GVs infectados com malária) tendem a migrar para a CLC que se forma nas zonas próximas das paredes. A lei da bifurcação estabelece, relativamente ao comportamento dos GVs, que em microcanais com bifurcações eles tendem a escolher o microcanal de secção maior.

2013Journal article

Open access

Visualization of red blood cells flowing through a PDMS microchannel with a microstenosis: an image analysis assessment

Publication . Monteiro, Fernando C.; Taboada, Bruna Rafaela Pereira; Lima, Rui A.

The present study aims to assess the motion of red blood cells (RBCs) under both shear and extensional flow using an image based technique. For this purpose, a microchannel having a smooth contraction was used and the images were captured by a standard high-speed microscopy system. An image processing and analyzing method has been developed in the MATLAB environment, to track the RBCs motion. The keyhole model, tested in this study, proved to be a promising technique to track individual RBCs in microchannels.

2014Conference object

Open access

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

Publication . Muñoz-Sánchez, Beatriz N.; Silva, Filipa Silva; Pinho, Diana; Vega, E.J.; Lima, Rui A.

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.

2016Journal article

Open access

Extensional flow-based microfluidic device: deformability assessment of red blood cells in contact with tumor cells

Publication . Faustino, Vera; Pinho, Diana; Yaginuma, Tomoko; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Lima, Rui A.

Red blood cell (RBC) deformability has become one of the important factors to assess blood and cardiovascular diseases. The interest on blood studies have promoted a development of various microfluidic devices that treat and analyse blood cells. Recent years, besides the RBC deformability assessment, these devices are often applied to cancer cell detection and isolation from the whole blood. The devices for cancer cell isolation rely mainly on size and deformability of the cells. However, the examination of deformability of the RBCs mixed with cancer cells is lacking. This study aims at determining the deformation index (DI) of the RBCs in contact with cancer cells using a hyperbolic microchannel which generates a strong extensional flow. The DIs of human healthy RBCs and human RBCs in contact with a tumor cell line (HCT-15, colon carcinoma) were compared by analyzing the flowing RBCs images captured by a high speed camera. The results reveal that the RBCs that were in contact with HCT-15 cells have lower deformability than the normal RBCs.

2014Journal article

Open access