Abstract

Separating the particles from the liquid component of sample solutions is important for several microfluidic-based sample preparations and/or sample handling techniques, such as plasma separation from whole blood, sheath-free flow focusing, particle enrichment etc. This paper presents a microfluidic in-flow decantation technique that provides the separation of particles from particle-free fluid while in-flow. The design involves the expansion of sample fluid channel in lateral and depth directions, thereby producing a particle-free layer towards the walls of the channel, followed by gradual extraction of this particle-free fluid through a series of tiny openings located towards one-end of the depth-direction. The latter part of this design is quite crucial in the functionality of this decantation technique and is based on the principle called wee-extraction. The design, theory, and simulations were presented to explain the principle-of-operation. To demonstrate the proof-of-principle, the experimental characterization was performed on beads, platelets, and blood samples at various hematocrits (2.5%–45%). The experiments revealed clog-free separation of particle-free fluid for at least an hour of operation of the device and demonstrated purities close to 100% and yields as high as 14%. The avenues to improve the yield are discussed along with several potential applications.

Highlights

  • Microfluidics, in its immense potential to offer miniaturization, cost-effectiveness, precision, automation, and the use of ultra-small quantities of samples, is rapidly expanding into areas of health-care, water treatment, soil testing, biomedical research, chemical and biological sciences

  • In several applications involved in these areas, separation of suspended particles from the sample fluid is a must as a pre-preparatory step for further investigation/research

  • As most of the research in microfluidics is oriented towards health-care, the foregoing discussion presents the importance and latest developments of separation process in this area

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Summary

Introduction

Microfluidics, in its immense potential to offer miniaturization, cost-effectiveness, precision, automation, and the use of ultra-small quantities of samples, is rapidly expanding into areas of health-care, water treatment, soil testing, biomedical research, chemical and biological sciences. To use such a device for blood cell (particle size ranges from 2 μm to 30 μm) separation and focusing requires fabricating the pillars with a spacing smaller than 2 μm while keeping the height of the pillar (and channel) large enough to accommodate the largest particle (30 μm), which is highly difficult to achieve using regular techniques of photolithography and soft lithography This pillar design limits its applicability to only rigid particles and could not answer the problem of clogging due to the uncontrolled fluid flow through the pillar gaps. The principle of operation of this technique was demonstrated using beads (5 μm), platelets, and blood of various particle concentrations (hematocrits) This novel proposed technique in combination with any simple technique to fabricate a 3D flow focusing device that uses external-sheath fluid [22] can be used to develop a sheath-free flow cytometer that meets the needs of blood-cell based tests. The following sections present the theory and principle of operation, simulation and experimental results along with their consequent implications

Theory and Principle of Operation
Simulations
Experimental Procedure
Results and Discussion
Findings
Enhancing the Yield through Multiplexing
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