High Purity Plasma Extraction

Several diseases, including cancer, can be detected and monitored by analysing biomarkers present in blood plasma. The method of extraction can have a large effect on the purity of the plasma and quality of the resulting analysis. There is therefore a great need for the extraction process to be as efficient as possible.

To learn more about some of the challenges of extracting plasma from blood, and how a recently developed microfluidic device could help overcome some of these, we spoke to Dr. Weihua Li, Senior Professor & Director, Advanced Manufacturing Technologies Research Strength, University of Wollongong.

AM: What are some of the current challenges of extracting plasma from blood?

WL: Centrifugation and filtration are two conventional plasma separation methods, although simple and ubiquitous, they have many limitations. For example, the centrifugation method is time-consuming, labour-intensive and may impair the analytes of interest due to the mechanical stress induced by high speed rotation; in the filtration method, clogging is the most severe problem. 

Recently, microfluidic methods have been extensively explored for blood plasma separation. According to the operating principle, the microfluidic techniques are classified to active and passive methods. Active methods are based on the application of external force fields such as acoustic, dielectrophoretic, and magnetic forces. The active methods face the challenges of low throughput, complexity and auxiliary expensive equipment, although they can provide more precise manipulation of particles or cells. 

Passive methods are based on the microchannel geometrical effects and intrinsic hydrodynamic forces, such as sedimentation, microfiltration, deterministic lateral displacement, hydrophoresis and inertial microfluidics. They are generally simpler, cheaper and more robust. 

Our method belongs to one of the passive methods, but the difference is that instead of using Newtonian fluid in all the current passive methods, we use a viscoelastic fluid to manipulate blood cells in our ECCA channel (straight channel with asymmetrical expansion–contraction cavity arrays), which is a simpler, with ultrahigh purity method. 

AM:  Can you tell us more about the microfluidic device you have recently developed for plasma extraction?

WL: Our developed method is simple, low-cost and offering high purity plasma, which does not have the problem of clogging or impair the analytes. This is attributed to two factors: one is the design of our ECCA channel, which is a straight channel with asymmetrical expansion–contraction cavity arrays; the other is the viscoelastic fluid we used, which is formed by dissolving poly(ethylene oxide) polymer in blood. When the blood cells (RBCs, WBCs, and platelets) flow in ECCA channel under viscoelastic fluid, they are affected by dean-flow-coupled elasto-inertial effects, and can be three-dimensionally focused to a single line and filtrated out from one outlet, thus plasma of high purity can be collected from the other outlet. The following figure is the schematic of plasma extraction using ECCA channel.

AM:  How can this device help to improve the extraction process?

WL: Because of the specific design of the channel, the blood cells are affected by dean-flow-coupled elasto-inertial effects in viscoelastic blood samples, and they can be three-dimensionally focused very well, while the three-dimensionally focusing is relatively difficult to realize in current passive methods in Newtonian fluid without additional assistance. The good focusing performance of the channel provides higher purity of the extracted plasma, and can ensure the more accurate following detection of biomarkers in plasma.

AM: What implications does this have for the future of cancer diagnostics?

WL: Plasma is rich with indicators of various diseases and cancers, such as circulating nucleic acids, metabolites, proteins, or virus, which is why separating plasma from blood is of clinical importance. Sampling blood is a less invasive approach to detect and monitor cancer without having to subject patients to clinical interventions such as biopsies. Besides the primary tumor, circulating nucleic acids or proteins in plasma are also confirmed to associate with cancer, and these biomarkers can also be used as tools to monitor disease or cancer treatment effectiveness in patients. As the accurate detection of these biomarkers and analyte requires the plasma without any interference from other cells, the higher the purity of the plasma, the more accurate the detection of biomarkers.

Further information about the microfluidic device can be found here.

Dr. Weihua Li was speaking to Anna MacDonald, Editor for Technology Networks.