Blood plasma separation is vital in the field of diagnostics and health care. Due to the inherent advantages obtained in the transition to microscale, the recent trend in these fields is a rapid shift towards the miniaturization of complex macro processes. Plasma separation in microdevices is one such process which has received extensive attention from researchers globally. Blood plasma separation techniques based on microfluidic platforms can be broadly classified into two categories. While active techniques utilize external force fields for separation, the passive techniques are dependent on biophysical effects, cell behavior, hydrodynamic forces and channel geometry for blood plasma separation. In general, passive separation methods are favored in comparison to active methods because they tend to avoid design complexities and are relatively easy to integrate with biosensors; additionally they are cost effective. Here we review passive separation techniques demonstrating separation and blood behavior at microscale. We present an extensive review of relevant biophysical laws, along with experimental details of various passive separation techniques and devices exploiting these physical effects. The relative performances, and the advantages and disadvantages of microdevices discussed in the literature, are compared and future challenges are brought about.

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.

In this work, design and experiments on various blood plasma microdevices based on hydrodynamic flow separation techniques is carried out. We study their performance as a function of dependent governing parameters such as flow rate, feed hematocrit, and microchannel geometry. This work focuses on understanding separation phenomena in simple geometries; subsequently, individual simple geometrical parameters and biophysical effects are combined to fabricate hybridized designs, resulting in higher separation efficiencies. The distinctive features of our microfluidic devices are that they employ elevated dimensions (of the order of hundreds of microns), and thereby can be operated continuously over sufficient duration without clogging, while simplicity of fabrication makes them cost effective. The microdevices have been experimentally demonstrated over the entire range of hematocrit (i.e. from Hct 7% to Hct 45%). A high separation efficiency of about (78.34 ± 2.7)% with pure blood is achieved in our best hybrid design. We believe that the theory and experimental results presented in this study will aid designers and researchers working in the field of blood plasma separation microdevices.