High-Yielding Separation and Collection of Plasma from Whole Blood Using Passive Filtration

Abstract

Lateral flow tests and hand-held analyzers facilitate diagnostic testing in resource limited settings and at the point-of-care. However, many of these devices require sample preparation such as plasma separation to remove cells and isolate the liquid portion of blood. Specifically, the separation of plasma from blood is necessary for routine health assessments such as comprehensive metabolic panels and chronic HIV viral load monitoring. Away from laboratories, this type of processing has been addressed by unconventional, hand-operated centrifuge devices (high volume) or plasma separation membranes (PSM) coupled with lateral flow tests (low volume). Herein, we describe a device that separates and stores plasma from undiluted blood using only passive filtration in less than 10 min. Integrating a PSM with a prefilter and absorbent material yields a 3-fold increase in separation efficiency compared to similar devices using passive filtration. We demonstrate the reproducibility of our device across the physiological range of hematocrits (20−50%) with an average recovered plasma volume of 61.7 ± 2.6 μL. Maximum separation efficiency (53.8%, 65.6 ± 3.9 μL plasma) was achieved for a sample of whole blood (30% hematocrit) in 10 min. We evaluate the purity of our plasma sample by quantitation of hemoglobin and report hemolysis as either minimal (≤5%) or undetectable (≤1%). Specific recovery of human IgG, IFN-γ, and HIV-1 RNA indicate the diagnostic utility of plasma obtained from our device is unchanged compared to plasma obtained via centrifugation. Finally, we demonstrate the use of recovered plasma, applied via "stamping", to successfully conduct a commercial lateral flow immunochromatographic assay for tetanus antibodies. This device platform is capable of producing pure plasma samples from blood to facilitate tests in resource limited settings to improve access to healthcare.

Virus Detection: From State‐of‐the‐Art Laboratories to Smartphone‐Based Point‐of‐Care Testing

“…To eliminate centrifugation steps in sample preparation, plasma separation membranes were mostly employed in lateral flow assays or 3D μ PADs. [ 79 , 80 , 81 , 82 ] Based on size exclusion, blood cells are trapped in the membrane while the plasma is separated and transmitted into the detection zones for detection. In comparison to microfluidic chips, those fully integrated paper‐based devices have the advantages of rapid reaction times, quick readout, ease of use, and low cost.…”

Haemoprocessor: A Portable Platform Using Rapid Acoustically Driven Plasma Separation Validated by Infrared Spectroscopy for Point-of-Care Diagnostics

“…Numerous microfluidic platforms have been proposed to perform either blood cell or plasma separation by both passive and active means [ 6 ]. Passive separation techniques commonly rely on microfabricated pillars, customized geometries [ 7 , 8 ] and porous filtration membranes [ 9 ]. These systems use the size-exclusion principle to separate the corpuscular components of blood to leave out the plasma in a continuous flow system.…”

High-Performance Passive Plasma Separation on OSTE Pillar Forest

“…Guo et al built a blood filter using OSTE synthetic paper, which induced the local agglutination of red blood cells by precoating agglutination antibodies on its surface [17]. Baillargeon et al made a paper microfluidic device by integrating a prefilter, a plasma separation membrane, and absorbent material to yield a high separation efficiency [18]. According to the working principle, passive plasma separation methods including sedimentation, filtration, and hydrodynamic effects have been reviewed in detail in Reference [19].…”