Separation and Enrichment of Platelets from Whole Blood Using a PDMS-Based Passive Microdevice

Abstract

Separation and enrichment of platelets in blood plasma play a major role in monitoring the human health condition and transfusion purposes. Although centrifugation is frequently employed to achieve platelet separation, recent advancements in the field of cell separation place microfluidic platforms in advantageous positions over the conventional ones. In this work, we report the development of a PDMS-based passive microfluidics device to separate and enrich platelets in blood plasma. The devices were tested with whole blood in a practically relevant flow rate range of 0.2–0.6 mL/min. One of our proposed devices, comprising gradual constriction–expansion, is able to separate and enrich platelets with 8.7-fold enrichment factor, 25.5% purity, and with minimum activation at a flow rate of 0.4 mL/min using whole human blood. The amount of enrichment and purity is found to be sensitive to the ratio of RBCs and WBCs to platelets in the incoming sample. The ability of the microdevice to handle whole blood at a high flow rate, and enrich platelets in plasma with minimal activation, makes the microdevice unique. These results also demonstrate the strong effect of the RBCs and WBCs to platelet ratio on the amount of enrichment and purity that can be obtained from passive microdevices.

Biophysical Phenomenon-Based Separation of Platelet-Poor Plasma from Blood

“…The hydrodynamic collision between RBCs and platelets plays a major role in the isolation of PPP. It is reported in literature as well as observed from our experimental data 12 that an increase in the collision frequency of these cells results in the larger margination of platelets. Further, it is also reported that in the absence of RBCs, no lateral movement of platelets is observed in the microchannel.…”

“…Later, the post-baked wafer was developed to dissolve unhardened SU8 and was hard baked at 110 °C. 12 A master mold prepared via this process was used for the soft-lithography process.…”

“…On the contrary, a passive microdevice does not need any external force, it rather utilizes biophysical laws, geometrical, and hydrodynamic effects for the isolation of target cells. 10,12,20 Several active 23−26 and passive 27−33 microfluidic devices are available in the literature for the isolation of platelets or pure plasma from blood; whereas, only a few microdevices have demonstrated the isolation of a suspension of platelets in the plasma. Among these, most of the reported microdevices are for the enrichment of platelets in the plasma sample 12,34,35 and not for the depletion of platelets.…”

“…36 Thus, there is enough scope to develop a low-cost and reliable microdevice for obtaining PPP from blood. We recently reported the separation of the platelet-enriched plasma from whole blood, 12,35 where platelets were enriched in the plasma above the normal physiological level, whereas, the present study focuses on the separation of PPP consisting of platelets below the normal physiological level (<10,000 platelets/μL) in plasma. Therefore, the scope of the two studies is completely different in that the mechanism of separation and the target sample is entirely different.…”

Hydrodynamic drag reduction of shear-thinning liquids in superhydrophobic textured microchannels

“…Since the velocity slip induced by the entrapped gas pockets on an SH-textured surface reduces the pressure drop, such surfaces alleviate the pumping power requirement in microfluidic devices (Davis and Lauga 2009). However, most of the microfluidic devices operate with non-Newtonian liquids, such as blood (Laxmi et al 2020), mucus (Elberskirch et al 2019), polymeric liquids (Raoufi et al 2019) and even colloidal suspensions (Liu et al 2020). Despite the importance of such non-Newtonian liquids in microfluidics, the hydrodynamic drag reduction of these liquids is rarely investigated in the context of pressure-driven flow through SH-textured micro-channels.…”