Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects

Abstract

In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm; such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations.

Extraction of Cell-Free Whole Blood Plasma Using a Dielectrophoresis-Based Microfluidic Device

“…When compared to previously reported active microfluidic BPS methods, our plasma extraction method isolates plasma of ≈100% purity using a much simpler device with more straightforward operation that is better suited to integration with other microfluidic components. Moreover, relative to recently developed microfluidic passive BPS methods, our plasma extractor provides more precise manipulation of blood cells through its tunable operation, with a much shorter channel length for handling undiluted micro volumes of whole blood.…”

“…These methods provide more precise manipulation of particles or cells, although chip structures can be complex. Extensive research has been performed both on passive and active methods and comprehensive reviews have been written that have focused on microfluidic BPS methods . For example, Ni and Xiang have developed a spiral microfluidic device which can efficiently isolate blood plasma from 20‐fold diluted whole blood at a flow rate of 700 µL min −1 , achieving plasma purity of ≈100% and a yield of ≈38.5%.…”

Printed microfluidic filter for heparinized blood

“…Important parameters that influence the flow velocity in passive microfluidics are the surface wettability 57 and the surface roughness. 38,57 Controlling both parameters is essential for designing suitable blood guiding devices, due to the surface interactions with polar and nonpolar groups and also due to the friction factor values. For instance, bovine serum albumin (BSA) adsorbs more easily on highly hydrophobic substrates, decreasing the blood flow velocity.…”

“…Previously, plasma separation inside microfluidic devices was demonstrated using a variety of distinct approaches, including silicon-glass particle separation system based on Zweifach-Fung effect, 25 cross-flow filtration microdevice, 26 microchannel flow-based separation, 27 two-phase plug, 24,28 highly confined microchannels, 29 micro-gap filter, 30 capillary-driven microfluidic device with a planar crossflow filter using surfactant-added Poly(dimethylsiloxane) (PDMS), 31 stand-alone self-powered integrated microfluidic system, 32 Pyrex glass attached to a silicon wafer with microfluidics, 33 capillary force through a bead-packed microchannel, 34,35 elevated-dimension clog-free T-microchannels utilizing the Zweifach-Fung and Fahraeus effects, 36,37 a combination of the Fahraeus effect, bifurcation law, cell-free region, centrifugal action, and constriction-expansion utilized together. 38,39 Common microfabrication methods for miniaturized diagnostic tests in microfluidics devices include photolithography, soft lithography, hot embossing, laser ablation, injection moulding and plasma etching. Nevertheless, to use most of the proposed methods, it is necessary to apply moulds and/or masks to fabricate these devices, which are not ideal for rapid prototyping; they also often use some external equipment to generate fluidic flux like a peristaltic pump or vacuum.…”

Thermopneumatic suction integrated microfluidic blood analysis system

“…Microfluidic technology is considered a promising approach to solve the aforementioned problems. [10][11][12][13] It miniaturizes and integrates most of the laboratory technologies into a single small chip and analyzes small amounts of samples in a short duration. Moreover, its simple operation reduces the complex multistep sample pretreatment procedures and analysis into a single step; therefore, a microfluidic system can be used by individuals without professional training.…”