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In this article, we introduce the importance of blood processing for human consumption while also presenting the methodology of porcine blood membrane separation to plasma and red blood cell fractions, as well as the membrane purification after porcine blood separation. Basic analytical measurements were carried out to investigate the blood product attributes, which relate to technological and nutritional quality depending on the separation parameters. Next, we present how the relevant hydrodynamical parameters were calculated during the experiments. Membrane separation was realized by crossflow microfiltration with pore size of 0.8 μm or 1.2 μm, retentate flow rate of 200 l·h-1 or 300 l·h-1 and with transmembrane pressure of 1 x 105 Pa, 2 x 105 Pa or 3 x 105 Pa. The experimental design was analysed, the parameters of the objective function and effect sizes were estimated and the global minimum of the objective function was successfully identified. The results of this optimization can be applied in practice. The membrane separation parameters were then optimized according to a model based on the observed data. An optimum was detected within the examined factor levels and experimental conditions at the lowest transmembrane pressure and at the highest membrane pore size. [ABSTRACT FROM AUTHOR]

Objectives: Our objectives were to determine the separation characteristics and blood product quality of a gravity‐driven microfiltration blood separation system (HemoClear, The Netherlands). Background: A range of centrifugal blood separation devices, including intraoperative cell salvage devices (cell savers) and apheresis machines, are available to assist in preparing both allogenic and autologous blood products. These devices are expensive to operate and require extensive training. Methods and Materials: Nine whole blood units were collected under standard conditions and analysed for haematological parameters, thromboelastographic properties, platelet morphology and activation, and red blood cell (RBC) deformability and morphology. Three whole blood units were separated by means of the HemoClear device, into a liquid and cellular component. The cellular component was diluted with SAGM and cold stored for 14 days. To simulate cell salvage six whole blood units were diluted with isotonic saline, followed by multiple HemoClear separation rounds. Results: The recovery of both RBCs (100 ± 1.6%) and white blood cells (99 ± 4.5%) after undiluted filtration were very high, while platelet recovery was high (83 ± 3.0%). During the filtration, and cold storage after filtration storage both the non‐deformable RBC fraction and the RBC maximum elongation remained stable. Parameters of thromboelastography indicated that platelets remain functional after filtration and after 7 days of cold storage. In the cell salvage simulation the total protein load in the cellular fraction was reduced by 65 ± 4.1% after one washing round and 84 ± 1.9% after two consecutive washing rounds. Conclusion: The novel blood filter studied effectively separates whole blood into diluted plasma and platelet‐rich RBCs. Moreover, the device effectively washed diluted whole blood, driving over 80% of proteins to the liquid component. [ABSTRACT FROM AUTHOR]

Separation of blood plasma or serum from blood is essential for accurate analysis. Conventional blood separation requires instrumentation, reagents, and large sample volumes, limiting this process to laboratory environments with trained personnel. Full implementation of effective blood separation and analysis on microliter sample volumes for point of care (POC) diagnostics has proven extremely challenging resulting in a growing market demand, with common challenges such as expensive device fabrication processes or devices being comprised of materials which are not easily disposable. We developed a membrane-based wicking microfluidic device which is made using a simple fabrication process. This device uses a unique 3D flow channel geometry, fabricated in a polycaprolactone-filled glass microfiber membrane, to efficiently separate microliter sample volumes of blood. Colorimetric assay chemistries were integrated to demonstrate utility of these devices in POC diagnostics. The devices are capable of separating both fresh and anticoagulant-treated blood at microscale sample volumes (<15.0 μL). Modifications to the base device are also reported herein which increased sample volume capacity and separation efficiency. Integrated colorimetric assay enabled semi-quantitative detection of conjugated bilirubin in real blood samples (1.0–1.5 mg/dL). These blood separation devices, fabricated on polycaprolactone-filled glass microfiber, enabled effective blood plasma (anticoagulant-treated blood) and serum (fresh blood) separation with microscale sample volumes. Sample volume capacity and separation efficiency are customizable for specific applications and devices can be integrated with downstream assay chemistries to develop complete POC devices that offer blood separation and diagnostics at the same time on a single membrane. [ABSTRACT FROM AUTHOR]

In this paper, we report on the development of a microfluidic device, which extracts plasma from low‐volume whole blood (10 μL), and is aimed at integration with microfluidic system for micro analytical systems. The device autonomously separates blood cells and transfers the separated plasma by steady rotation. Based on the original autonomous fluidic control theory, we developed the principle of automatic timed injection of pressurizing medium into the separation chamber. This realizes the transferring of separated plasma from blood separation chamber to the other place, after separating blood cells by centrifugal force. Through the demonstration on a polydimethylsiloxane microfluidic device, we confirmed that the automatic plasma extraction was successfully implemented as designed. The efficiency of separation was evaluated on the basis of the concentrations of blood cells in samples before and after extraction, and the rate of blood cell removal was 98.5%. [ABSTRACT FROM AUTHOR]

Experiments are done with separated human blood decelerated at constant rates to determine the maximum deceleration rate while avoiding remixing of the layers, which have different densities and viscosities. The deceleration rate affects both the stability and separation of particles through sedimentation. The velocity at onset of instability for a constant deceleration rate is experimentally determined for a 12‐cm‐diameter disk. Parameters of cell pack thickness, plasma thickness, and total thickness are investigated experimentally, and the only statistically significant parameter to affect stability is rate of deceleration. The data describe a correlation separating regions of stability and instability. To understand stability in decelerating flow of separated blood plasma and cells, the equations of motion are solved for a two‐layer fluid flow with a moving boundary and free surface. Inclusion of non‐Newtonian rheology of blood predicts large discontinuities in the shear rate, which is proposed as the cause of the interfacial instabilities. © 2019 American Institute of Chemical Engineers AIChE J, 65: 1376–1386, 2019 [ABSTRACT FROM AUTHOR]

Evaluation and diagnosis of blood alterations is a common request for clinical laboratories, requiring a complex technological approach and dedication of health resources. In this paper, we present a microfluidic device that owing to a novel combination of hydrodynamic and dielectrophoretic techniques can separate plasma from fresh blood in a microfluidic channel and for the first time allows optical real-time monitoring of the components of plasma without pre- or post-processing. The microchannel is based on a set of dead-end branches at each side and is initially filled using capillary forces with a 2-μL droplet of fresh blood. During this process, stagnation zones are generated at the dead-end branches and some red blood cells (RBCs) are trapped there. An electric field is then applied and dielectrophoretic trapping of RBCs is used to prevent more RBCs entering into the channel, which works like a sieve. Besides, an electroosmotic flow is generated to sweep the rest of the RBCs from the central part of the channel. Consequently, an RBC-free zone of plasma is formed in the middle of the channel, allowing real-time monitoring of the platelet behavior. To study the generation of stagnation zones and to ensure RBC trapping in the initial constrictions, two numerical models were solved. The proposed experimental design separates up to 0.1 μL blood plasma from a 2-μL fresh human blood droplet. In this study, a plasma purity of 99 % was achieved after 7 min, according to the measurements taken by image analysis. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Blood is the richest source of diagnostic information. The growing interest in point-of-care analytics prompted several attempts to extract plasma from whole blood in simple diagnostic devices. The simplest method of separation is sedimentation. Here we show the first microfluidic system that uses sedimentation to extract plasma from undiluted blood and integrates execution of liquid assays on the extracted material. We present a microfluidic chip that accepts a small sample (27 μL) of whole blood, separates up to 6 μL of plasma, and uses metered volumes of plasma and of reagent (2-chloro-4-nitrophenyl-α-maltotrioside, CNP-G3) for a liquid enzymatic assay. With a custom designed channel, the system separates blood by sedimentation within few minutes of accepting the sample, mixes it with the reagent, and quantifies spectrophotometrically the product of the enzymatic reaction. As a model demonstration, we show a quantitative enzymatic α-amylase assay that is routinely used in diagnosis of pancreas diseases. The paper reports the design and characterization of the microfluidic device and the results of tests on clinically collected blood samples. The results obtained with the microfluidic system compare well to a reference bench-top analyzer. [ABSTRACT FROM AUTHOR]

SUMMARY Background The ErySep system represents an alternative to centrifuge-based whole blood ( WB) separation, using gravity and filtration through hollow-fibres (0·2 µm pore size) to produce red blood cell ( RBC) and plasma components. The aim of this study was to characterise the quality of ErySep RBC and plasma units compared with standard products from WB held overnight. Methods/Materials Two ABO-compatible WB units ( n = 24) were pooled and split to produce matched products. One of the WB units was separated into components using the ErySep system ( ErySep; n = 12), whereas the other units were separated by centrifugation (control; n = 12). RBC units were stored at 2-6 °C and assessed for in vitro quality over 42 days of storage. Plasma was frozen at −30 °C and tested upon thawing. Results Processing WB with the ErySep system took longer than controls. The ErySep RBC units were of an appropriate volume (307 ± 17 mL) and contained sufficient Hb (50 ± 2 g unit−1). ErySep RBC components contained more microparticles relative to controls at expiry. The plasma volume, total protein, coagulation factor activity (fibrinogen, FV, FVIII) and number of microparticles was lower in the ErySep units compared with controls. Conclusion Following overnight hold of WB, the ErySep system was capable of producing RBC components that met specifications. However, the ErySep plasma components did not meet quality specifications. [ABSTRACT FROM AUTHOR]

Abstract: The plasma separation rate is enhanced significantly, as much as 8 times faster for whole blood, by simple change of the channel geometry in a rotating disc. It was enhanced in the channels with narrower channel widths and larger tilt angles with respect to the radial direction but independent of the channel depth or spin direction. A modified Ponder-Nakamura-Kuroda (PNK) theory could nicely fit all of the experimental data to a linear line, which data were obtained from spinning discs with various channel designs and blood samples with broad hematocrit range. To the best of our knowledge, this is the first investigation of geometry effects on the particle separation rate on a rotating disc and it will potentially contribute to the further performance enhancement of centrifugal microfluidic devices. [Copyright &y& Elsevier]

Blood, a complex biological fluid, comprises 45% cellular components suspended in protein rich plasma. These different hematologic components perform distinct functions in vivo and thus the ability to efficiently fractionate blood into its individual components has innumerable applications in both clinical diagnosis and biological research. Yet, processing blood is not trivial. In the past decade, a flurry of new microfluidic based technologies has emerged to address this compelling problem. Microfluidics is an attractive solution for this application leveraging its numerous advantages to process clinical blood samples. This paper reviews the various microfluidic approaches realized to successfully fractionate one or more blood components. Techniques to separate plasma from hematologic cellular components as well as isolating blood cells of interest including certain rare cells are discussed. Comparisons based on common separation metrics including efficiency (sensitivity), purity (selectivity), and throughput will be presented. Finally, we will provide insights into the challenges associated with blood-based separation systems towards realizing true point-of-care (POC) devices and provide future perspectives. [ABSTRACT FROM AUTHOR]

Abstract: A major requirement for the development of point-of-care tests for the detection of disease analytes is the need to separate plasma from whole blood in an efficient and rapid manner. Furthermore, the separated plasma must be able to elute efficiently the analyte of interest and serve effectively as a physical matrix to deliver the equivalent of neat plasma for downstream diagnostic analysis. Additionally, many applications require the use of heat shock to liberate immunocomplexed antigen found in the collected plasma. A membrane-based filter method is reported for rapid and efficient collection of plasma from a whole blood sample that is compatible with heat shock. Using pediatric human immunodeficiency virus as an example, this device elutes 100% of the input p24 core antigen post-collection and enables heat shock of plasma samples identical to neat plasma treatment. [Copyright &y& Elsevier]

Abstract: This paper presents a microfluidic device that can separate and extract blood plasma from several microliters of blood without external mechanical driving sources such as a centrifugal machine and a syringe pump. This device consists of a main-channel, many side-channels, a reservoir, and two electrodes. After blood was automatically injected into the main-channel by capillary force, blood cells blocked the side-channel entrances and prevented blood plasma from entering them. Next, when AC voltage application between the two electrodes separated blood into cells and plasma by dielectrophoresis (DEP), cells were removed from the side-channel entrances. This permitted plasma to be injected into the side-channels connecting to the reservoir. Experiments using diluted blood samples (dilution 1:9) showed that blood cell removal and blood plasma extraction were affected by channel geometry and magnitude/frequency of applied AC voltage. In case of applied AC voltage of 10V and 1MHz, blood cells were removed by about 97%, and blood plasma of about 300nL was extracted from 5μL blood. Moreover, we found that optimal dimension of the side-channels for blood plasma extraction is 5μm wide and 2μm deep. [Copyright &y& Elsevier]

The aim of this study was to assess the separation of whole blood into red cells and plasma by using the Sangofer® device, which is a gravity-fed, hollow-fibre system. The components would then be compared with those produced by the use of more elaborate technical equipment. Ten whole-blood units were leucoreduced by using a WBF2 filter and immediately separated into red cells and plasma by using the Sangofer® blood-separation device. Red cells were stored in additive solution and tested on days 1 and 42. The plasma was assayed for levels of various coagulation factors and for markers of both coagulation and complement activation. The red-cell parameters were similar to those obtained when routine centrifugation methods were used. The filter did not cause haemolysis. Levels of plasma factor VIII and factor XI were lower than those seen in routinely produced leucoreduced plasma units but there was no evidence of activation of the coagulation and complement systems. The Sangofer® device is simple and straightforward to use and eliminates the need for both centrifugation and automated separation steps during the processing of whole blood into red cells and plasma components. Minor changes are required to make the procedure easier to incorporate into routine use. [ABSTRACT FROM AUTHOR]