Development of a microfluidic device for cell concentration and blood cell-plasma separation

Abstract

This work presents design, fabrication and test of a microfluidic device which employs Fahraeus-Lindqvist and Zweifach-Fung effects for cell concentration and blood cell-plasma separation. The device design comprises a straight main channel with a series of branched channels placed symmetrically on both sides of the main channel. The design implements constrictions before each junction (branching point) in order to direct cells that would have migrated closer to the wall (naturally or after liquid extraction at a junction) towards the centre of the main channel. Theoretical and numerical analysis are performed for design of the microchannel network to ensure that a minimum flow rate ratio (of 2.5:1, main channel-to-side channels) is maintained at each junction and predict flow rate at the plasma outlet. The dimensions and location of the constrictions were determined using numerical simulations. The effect of presence of constrictions before the junctions was demonstrated by comparing the performances of the device with and without constrictions. To demonstrate the performance of the device, initial experiments were performed with polystyrene microbeads (10 and 15 μm size) and droplets. Finally, the device was used for concentration of HL60 cells and separation of plasma and cells in diluted blood samples. The cell concentration and blood-plasma purification efficiency was quantified using Haemocytometer and Fluorescence-Activated Cell Sorter (FACS). A seven-fold cell concentration was obtained with HL60 cells and a purification efficiency of 70 % and plasma recovery of 80 % was observed for diluted (1:20) blood sample. FACS was used to identify cell lysis and the cell viability was checked using Trypan Blue test which showed that more than 99 % cells are alive indicating the suitability of the device for practical use. The proposed device has potential to be used as a sample preparation module in lab on chip based diagnostic platforms.

Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation

“…In active methods, acoustic, electrical or magnetic fields are used to impart sufficient energy for the blood plasma separation, which makes the entire system bulky and complicated20. Although active devices are efficient in terms of purification efficiency, such devices offer lower residence time and throughput21. The passive devices operate based on the principles of hydrodynamic forces and response of cells to various biophysical effects.…”

Potential Point-of-Care Microfluidic Devices to Diagnose Iron Deficiency Anemia

“…To ensure that a device can be used in all diverse environments, including remote regions, plasma separation devices should be autonomous and not require an external power source. In-depth discussions about fluid-flow methods are available in other review papers [ 23 , 34 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

Microsphere-Based Microfluidic Device for Plasma Separation and Potential Biochemistry Analysis Applications

“…Although these devices are simple and low-cost, the porous structure of the cellulose material is easily clogged by blood cells and retains proteins within its network structure [ 3 ]. Microstructures have been fabricated to perform plasma separation based on different mechanisms, such as digital microfluidics [ 11 ], cross-flow pillars [ 12 , 13 ], inertial force-based spiral channels [ 14 , 15 , 16 , 17 ], and the Zweifach–Fung separation technique [ 18 , 19 ]. With the elaborate design of microstructures, these devices can achieve a fast separation rate.…”