Wicking microfluidic approach to separate blood plasma from whole blood to facilitate downstream assays

Bandara, Gayan C.; Unitan, Linus J.; Kremer, Matthew H.; Shellhammer, Owen T.; Bracha, Shay; Remcho, Vincent T.

doi:10.1007/s00216-021-03420-6

Cited by 4 publications

(15 citation statements)

References 36 publications

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“…Blood clot was activated using APTT and CaCl 2 reagents, and separation was achieved passively through paper filtration and capillary absorption. The assay is useful for different paper-based POCT, serum collection in remote or resource limited areas, emergency and military situations, long-term serum storage, and frequent follow ups …”

Section: Discussionmentioning

confidence: 99%

“…Few studies proposed serum separation using paper or membranes by application of fresh blood. ,, The actual separation of serum rather than plasma and the purity of serum/plasma was not confirmed. Separated plasma or serum bands look similar by the naked eye or under the microscope and can be distinguished only by further testing to confirm clot formation and removal.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies reported serum separation POCTs including using pulling-force spinning top combined with paper-based assay for COVID-19 diagnosis, HYPER technology that utilizes capillary forces, and crossflow filtration for the separation of whole blood combined with paper-based systems for iron and vitamin A detection . A 3D membrane-based microfluidic device of polycaprolactone-filled glass microfiber was used to separate blood plasma/serum and facilitate downstream assays . Blood coagulation screening using nitrocellulose membrane and lateral flow demonstrate RBCs travel distance in a given time is related to the blood clotting time using different CaCl 2 concentrations .…”

Section: Discussionmentioning

confidence: 99%

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Development of Novel Paper-Based Assay for Direct Serum Separation

Al-Tamimi,

El-sallaq,

Altarawneh

et al. 2023

ACS Omega

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Background: Many conventional laboratory tests require serum separation using a clot activator/gel tube, followed by centrifugation in an equipped laboratory. The aim of this study is development of novel, equipment-free, paper-based assay for direct and efficient serum separation. Methods: Fresh blood was directly applied to wax-channeled filter paper treated with clotting activator/s and then observed for serum separation. The purity, efficiency, recovery, reproducibility, and applicability of the assay were validated after optimization. Results: Serum was successfully separated using activated partial thromboplastin time (APTT) reagent and calcium chloride-treated wax-channeled filter paper within 2 min. The assay was optimized using different coagulation activators, paper types, blood collection methods, and incubation conditions. Confirmation of serum separation from cellular components was achieved by direct visualization of the yellow serum band, microscopic imaging of the pure serum band, and absence of blood cells in recovered serum samples. Successful clotting was evaluated by the absence of clotting of recovered serum by prolonged prothrombin time and APTT, absence of fibrin degradation products, and absence of Staphylococcus aureus-induced coagulation. Absence of hemolysis was confirmed by undetectable hemoglobin from recovered serum bands. The applicability of serum separated in paper was tested directly by positive color change on paper using bicinchoninic acid protein reagent, on recovered serum samples treated with Biuret and Bradford reagents in tubes, or measurement of thyroid-stimulating hormone and urea compared to standard serum samples. Serum was separated using the paper-based assay from 40 voluntary donors and from the same donor for 15 days to confirm reproducibility. Dryness of coagulants in paper prevents serum separation that can be re-stored by a re-wetting step. Conclusions: Paper-based serum separation allows for development of sample-to-answer paper-based point-of-care tests or simple and direct blood sampling for routine diagnostic tests.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of Novel Paper-Based Assay for Direct Serum Separation

Al-Tamimi,

El-sallaq,

Altarawneh

et al. 2023

ACS Omega

View full text Add to dashboard Cite

show abstract

“…However, these studies lacked information regarding membrane clogging, RBC leakage, or whether the device can withstand varying hematocrit levels as well as the yield, purity, or hemolysis level of the extracted sera. 79,80 A more direct approach was used by Vemulapati and Erickson in a device named HERMES (high-efficiency rapid magnetic erythrocyte separator), which captures RBCs in whole blood using magnetic beads conjugated to anti-RBC antibodies (Figure 4C). 81 The binding capacity is enhanced by adding an undisclosed aggregation agent that groups RBCs together, therefore allowing the magnetic beads to capture groups of cells instead of individual cells.…”

Section: Microfluidic Devices For Capillary Samples (Plasma/ Serum)mentioning

confidence: 99%

“…It combined the lateral displacement separation technique from Gao et al (Figure A) with an immobilized antibody to create an immunoassay embedded within the device. , The assay was performed within 10 min and demonstrated a serum extraction efficiency of 70% and 99.8% purity, similar to the parameters observed by Gao et al , Other devices also integrated plasma separation membranes and capillary action to filter undiluted whole blood and drive serum into detection zones without using external forces. , Biomarker detection was performed in-chip and validated with spiked samples. However, these studies lacked information regarding membrane clogging, RBC leakage, or whether the device can withstand varying hematocrit levels as well as the yield, purity, or hemolysis level of the extracted sera. , …”

Section: Microfluidic Devices For Sample Preparation Of Undiluted Who...mentioning

confidence: 99%

Emerging Microfluidic Devices for Sample Preparation of Undiluted Whole Blood to Enable the Detection of Biomarkers

et al. 2023

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Blood testing allows for diagnosis and monitoring of numerous conditions and illnesses; it forms an essential pillar of the health industry that continues to grow in market value. Due to the complex physical and biological nature of blood, samples must be carefully collected and prepared to obtain accurate and reliable analysis results with minimal background signal. Examples of common sample preparation steps include dilutions, plasma separation, cell lysis, and nucleic acid extraction and isolation, which are time-consuming and can introduce risks of sample cross-contamination or pathogen exposure to laboratory staff. Moreover, the reagents and equipment needed can be costly and difficult to obtain in point-of-care or resource-limited settings. Microfluidic devices can perform sample preparation steps in a simpler, faster, and more affordable manner. Devices can be carried to areas that are difficult to access or that do not have the resources necessary. Although many microfluidic devices have been developed in the last 5 years, few were designed for the use of undiluted whole blood as a starting point, which eliminates the need for blood dilution and minimizes blood sample preparation. This review will first provide a short summary on blood properties and blood samples typically used for analysis, before delving into innovative advances in microfluidic devices over the last 5 years that address the hurdles of blood sample preparation. The devices will be categorized by application and the type of blood sample used. The final section focuses on devices for the detection of intracellular nucleic acids, because these require more extensive sample preparation steps, and the challenges involved in adapting this technology and potential improvements are discussed.

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Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract

Peng,

Zhou,

Zhang

et al. 2024

Biomicrofluidics

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Bilestones are solid masses found in the gallbladder or biliary tract, which block the normal bile flow and eventually result in severe life-threatening complications. Studies have shown that bilestone formation may be related to bile flow dynamics and the concentration level of bile components. The bile flow dynamics in the biliary tract play a critical role in disclosing the mechanism of bile stasis and transportation. The concentration of bile composition is closely associated with processes such as nucleation and crystallization. Recently, microfluidic-based biosensors have been favored for multiple advantages over traditional benchtop detection assays for their less sample consumption, portability, low cost, and high sensitivity for real-time detection. Here, we reviewed the developments in bile dynamics study and microfluidics-based bile component detection methods. These studies may provide valuable insights into the bilestone formation mechanisms and better treatment, alongside our opinions on the future development of in vitro lithotriptic drug screening of bilestones and bile characterization tests.

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Wicking microfluidic approach to separate blood plasma from whole blood to facilitate downstream assays

Cited by 4 publications

References 36 publications

Development of Novel Paper-Based Assay for Direct Serum Separation

Development of Novel Paper-Based Assay for Direct Serum Separation

Emerging Microfluidic Devices for Sample Preparation of Undiluted Whole Blood to Enable the Detection of Biomarkers

Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract

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