A capillary flow-driven microfluidic device for point-of-care blood plasma separation

Plasma has significant utility as an input for diagnostics and screening for conditions such as viral infections, cancer, and more. However, plasma is difficult to obtain at the point-of-care, as separation from whole blood is typically carried out via centrifugation. We have designed and optimized a low-cost, simple-to-operate microfluidic device which carries out the separation of plasma from whole blood. The device utilizes depth filtration as its separation mechanism and collects plasma via capillary action, allowing for operation without components that drive flow externally. We first optimized device dimensions and operating parameters and demonstrated consistent separation efficiencies for the samples with hematocrits ranging from 25–65%. The impact of input sample hematocrit percentage on flow rate through the device was also examined, with samples with hematocrits greater than 45% decreasing plasma flow rate. Lastly, we evaluated the ability of this device to produce plasma with a high protein concentration and found no significant difference between protein levels in samples from the device compared to samples produced via centrifugation. This system produced plasma with a maximum separation efficiency of 88.5% and achieved a maximum plasma volume of ∼14 μl from a 50 μl whole blood input. The low cost, simplicity of operation, and high plasma quality associated with this device give it many advantages in a point-of-care setting. This device could be integrated into plasma-based diagnostic workflows to increase access to various types of disease testing and monitoring.

[1]  Eon Soo Lee,et al.  Blood Plasma Self-Separation Technologies during the Self-Driven Flow in Microfluidic Platforms , 2021, Bioengineering.

[2]  Jianchao Cai,et al.  Lucas-Washburn Equation-Based Modeling of Capillary-Driven Flow in Porous Systems. , 2021, Langmuir : the ACS journal of surfaces and colloids.

[3]  Ayush Goyal,et al.  Surface tension measurement of normal human blood samples by pendant drop method , 2020, Journal of medical engineering & technology.

[4]  J. Lamanna,et al.  Direct loading of blood for plasma separation and diagnostic assays on a digital microfluidic device. , 2020, Lab on a chip.

[5]  Nam-Trung Nguyen,et al.  Challenges and perspectives in the development of paper-based lateral flow assays , 2020 .

[6]  Y. Bertrand,et al.  Blood Rheology: Key Parameters, Impact on Blood Flow, Role in Sickle Cell Disease and Effects of Exercise , 2019, Front. Physiol..

[7]  N. Roxhed,et al.  High-Yield Passive Plasma Filtration from Human Finger Prick Blood. , 2018, Analytical chemistry.

[8]  David Juncker,et al.  Capillary microfluidics in microchannels: from microfluidic networks to capillaric circuits. , 2018, Lab on a chip.

[9]  Uddin M Jalal,et al.  Histogram analysis for smartphone-based rapid hematocrit determination. , 2017, Biomedical optics express.

[10]  T. Chandra,et al.  Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation , 2017, Scientific Reports.

[11]  M. Kersaudy-Kerhoas,et al.  Microfluidic blood plasma separation for medical diagnostics: is it worth it? , 2016, Lab on a chip.

[12]  S. Tripathi,et al.  Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects , 2016, Scientific Reports.

[13]  Jasmina Casals-Terré,et al.  Self-driven filter-based blood plasma separator microfluidic chip for point-of-care testing , 2015, Biofabrication.

[14]  Jasmina Casals-Terré,et al.  Hydrodynamic and direct-current insulator-based dielectrophoresis (H-DC-iDEP) microfluidic blood plasma separation , 2015, Analytical and Bioanalytical Chemistry.

[15]  Luke P. Lee,et al.  Hemolysis-free blood plasma separation. , 2014, Lab on a chip.

[16]  Temsiri Songjaroen,et al.  Blood separation on microfluidic paper-based analytical devices. , 2012, Lab on a chip.

[17]  Donald W Cockcroft,et al.  Methacholine test and the diagnosis of asthma. , 2012, The Journal of allergy and clinical immunology.

[18]  S. Shevkoplyas,et al.  Integrated separation of blood plasma from whole blood for microfluidic paper-based analytical devices. , 2012, Lab on a chip.

[19]  C. Chon,et al.  A microfluidic chip for blood plasma separation using electro-osmotic flow control , 2011 .

[20]  Jackson Streeter,et al.  Blood-based diagnostics of traumatic brain injuries , 2011, Expert review of molecular diagnostics.

[21]  M. Madou,et al.  Large-volume centrifugal microfluidic device for blood plasma separation. , 2010, Bioanalysis.

[22]  M. Kersaudy-Kerhoas,et al.  Hydrodynamic blood plasma separation in microfluidic channels , 2009 .

[23]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[24]  A. Undar,et al.  A microfluidic device for continuous, real time blood plasma separation. , 2006, Lab on a chip.

[25]  V. Vandelinder,et al.  Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device. , 2006, Analytical chemistry.

[26]  Marshall Gayton,et al.  Robust scale-up of dead end filtration: impact of filter fouling mechanisms and flow distribution. , 2005, Biotechnology and bioengineering.

[27]  N. Constantine,et al.  HIV testing technologies after two decades of evolution. , 2005, The Indian journal of medical research.

[28]  S. Hawkes,et al.  Mapping the landscape of diagnostics for sexually transmitted infections: key findings and recommendations. , 2004 .

[29]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[30]  Walker Hk,et al.  Hemoglobin and Hematocrit -- Clinical Methods: The History, Physical, and Laboratory Examinations , 1990 .