Design Evolution and Performance Study of a Reliable Platelet-Rich Plasma Microdevice

Abstract

Separation and enrichment of platelets from whole blood find numerous applications for biomedical research, dermatology, and transfusion purposes. Therefore, there is a great value in selectively isolating and enriching platelets in plasma from whole blood. The conventional method of centrifugation involves several manual steps and cannot be integrated with point-of-care devices.Here, we present an evolved passive microdevice for the enhanced fold enrichment and separation efficiency of platelets in a platelet-enriched plasma sample. The design steps for arriving at the final design are also presented, as learnings from these early designs helped in evolution of the final microdevice; these early designs can also be used as a reference for further studies. The final proposed microdevice is easy to fabricate, requires less hardware and pumping power than available microdevices, and separates high-quality platelets from a whole blood sample. Our microdevice is able to achieve ∼15-fold platelet enrichment. Several biological tests attest to the high quality of platelets obtained from the microdevice. The performance of the developed microdevice is superior to those of few available microdevices. Our work suggests that passive microdevices can attain or even surpass the performance of active microdevices.

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

“…35,49 This collision allows platelets and some of the RBCs to cross the streamlines and start circulating in the recirculation zone and thereby move into the side daughter channels. 12,35,49 The enhanced collision-induced drift results in the separation of the platelet-enriched plasma in the microdevice while working with the whole blood sample.…”

“…In our previous study 35 where we utilized whole blood (hematocrit 42−43%) samples for the experimentation, we obtained the platelet-enriched plasma with ∼15-fold enrichment of platelets in the plasma above the normal physiological level from the microdevice. In this study, the utilization of the…”

“…This test further confirms that the separation of platelets from the microdevice does not adversely affect the platelet quality. 35 It is evident from the working mechanism of separation that with dilution, cells experience lower wall shear forces as well as forces due to the hydrodynamic collision between the cells. The microscopic images of the outlet sample, as shown in Figure 7, show that 96 ± 1% (n = 3) platelets maintained their shape and size postseparation from the microdevice.…”

“…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.…”