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Blood flow visualization and measurements in microfluidic devices fabricated by a micromilling technique

Publication . Singhal, Jaron; Pinho, Diana; Lopes, Raquel; Sousa, Patrícia C.; Garcia, Valdemar; Schütte, Helmut; Lima, Rui A.; Gassmann, Stefan

The most common and used technique to produce microfluidic devices for biomedical applications is the soft-lithography. However, this is a high cost and time-consuming technique. Recently, manufacturers were able to produce milling tools smaller than 100 μm and consequently have promoted the ability of the micromilling machines to fabricate microfluidic devices capable of performing cell separation. In this work, we show the ability of a micromilling machine to manufacture microchannels down to 30 μm and also the ability of a microfluidic device to perform partial separation of red blood cells from plasma. Flow visualization and measurements were performed by using a high-speed video microscopy system. Advantages and limitations of the micromilling fabrication process are also presented.

2015Journal article

Open access

Cell-free layer analysis in a polydimethysiloxane microchannel: A global approach

Publication . Pinto, Elmano; Faustino, Vera; Pinho, Diana; Rodrigues, Raquel Oliveira; Lima, Rui A.; Pereira, Ana I.

The cell-free layer (CFL) is a hemodynamic phenomenon that has an important contribution to the rheological properti es of blood flowing in microvessels. The present work aims to find the closest function describing RBCs flowing around the cell depleted layer in a polydimethysiloxane (PDMS) microchannel with a diverging and a converging bifurcation. The flow behaviour of the CFL was investigated by using a high-speed video microscopy system where special attention was devoted to its behaviour before the bifurcation and after the confluence of the microchannel. The numerical data was first obtained by using a manual tracking plugin and then analysed using the genetic algorithm approach. The results show that for the majority of the cases the function that more closely resembles the CFL boundary is the sum of trigonometric functions.

2016Journal article

Open access

A passive microfluidic device based on crossflow filtration for cell separation measurements: a spectrophotometric characterization

Publication . Faustino, Vera; Catarino, Susana; Pinho, Diana; Lima, Rui A.; Minas, Graça

Microﬂuidic devices have been widely used as a valuable research tool for diagnostic applications. Particularly, they have been related to the successful detection of different diseases and conditions by assessing the mechanical properties of red blood cells (RBCs). Detecting deformability changes in the cells and being able to separate those cells may be a key factor in assuring the success of detection of some blood diseases with diagnostic devices. To detect and separate the chemically modiﬁed RBCs (mimicking disease-infected RBCs) from healthy RBCs, the present work proposes a microﬂuidic device comprising a sequence of pillars with different gaps and nine different outlets used to evaluate the efﬁciency of the device by measuring the optical absorption of the collected samples. This latter measurement technique was tested to distinguish between healthy RBCs and RBCs chemically modiﬁed with glutaraldehyde. The present study indicates that it was possible to detect a slight differences between the samples using an optical absorption spectrophotometric setup. Hence, the proposed microﬂuidic device has the potential to perform in one single step a partial passive separation of RBCs based on their deformability.

2018Journal article

Open access

A rapid and low-cost nonlithographic method to fabricate biomedical microdevices for blood flow analysis

Publication . Pinto, Elmano; Faustino, Vera; Rodrigues, Raquel Oliveira; Pinho, Diana; Garcia, Valdemar; Miranda, João Mário; Lima, Rui A.

Microfluidic devices are electrical/mechanical systems that offer the ability to work with minimal sample volumes, short reactions times, and have the possibility to perform massive parallel operations. An important application of microfluidics is blood rheology in microdevices, which has played a key role in recent developments of lab-on-chip devices for blood sampling and analysis. The most popular and traditional method to fabricate these types of devices is the polydimethylsiloxane (PDMS) soft lithography technique, which requires molds, usually produced by photolithography. Although the research results are extremely encouraging, the high costs and time involved in the production of molds by photolithography is currently slowing down the development cycle of these types of devices. Here we present a simple, rapid, and low-cost nonlithographic technique to create microfluidic systems for biomedical applications. The results demonstrate the ability of the proposed method to perform cell free layer (CFL) measurements and the formation of microbubbles in continuous blood flow.

2015Journal article

Open access

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

Publication . Faustino, Vera; Catarino, Susana; Lima, Rui A.; Minas, Graça

One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft-lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non-lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples.

2016Journal article

Open access