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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.

Severe internal trauma results in millions of hospitalizations each year, including thousands of deaths caused by subsequent multiple organ failure. The majority of these deaths occur within the first 24 h, and thus, rapid diagnosis of internal trauma severity is necessary for immediate treatment. For early organ damage identification, diagnosis in point-of-care settings is crucial for rapid triage and treatment. Recent reports suggest that circulating histones may serve as a biomarker for severe organ damage and the risk of multiple organ failure. Here, we report a point-of-care diagnostic system that utilizes the inherent interactions between histones and DNA for the fluorescence-based detection of histones in whole blood. In the assay, histones within the sample are wrapped by DNA, thus preventing an intercalating dye from binding the DNA and fluorescing. To allow for quantitative fluorescent measurements to be made in a point-of-care setting, we integrate a rapid, automated blood separation step into our assay. Furthermore, we eliminate manual reagent additions using a thermally responsive alkane partition (TRAP), thus making the system sample-to-answer. Finally, we demonstrate the assay in a portable fluorescence reader compatible with a point-of-care environment. We report a limit of detection 112 ng/mL in whole blood, suggesting that our device can be used to rapidly diagnose internal trauma severity and the likelihood of multiple organ failure in near-patient settings.

Blood apheresis technologies are crucial during blood donation and toxin removal. Current purification methods such as leukocytapheresis, erythrocytapheresis, thrombocytapheresis and plasmapheresis primarily rely on centrifugation and membrane filtration to separate blood components. Although established and scaled-up, challenges related to the selectivity and long-term impact of these techniques on blood cells and their constituents remain. Shear generated during extraction may stress blood cells leading to cell damage and initiate the complement cascade causing platelet activation or triggering inflammatory responses. Emerging technologies, including microfluidics and selective adsorption present viable alternatives supporting more selective extraction pathways but extensively rely on novel manufacturing or material developments. This review critically assesses recent progress across apheresis technologies relating to advances in surface science and materials engineering to address operating challenges towards selective removal or extraction of blood components in traditional apheresis technologies such as centrifugation and membrane filtration.

Dynamic and on-site analysis of serum from human blood is crucial, however, state-of-the-art blood-assay methods can only collect single or discrete data of physiological analytes; thus, the online reports of the dynamic fluctuation of key analytes remains a great challenge. Here, we propose a novel separation-sensing membrane by constructing a heterogeneous-nanostructured architecture, wherein a surface nanoporous layer continuously extracts serum, while the biosensing nanochannels underneath dynamically recognise biotargets, thereby achieving a continuous testing of vital clinical indices as blood is drawn. By precisely controlling the pore structure and nanoshape of biosensing crystals, this membrane achieved accurate and online glucose and lactate monitoring in patients with a variety of medical conditions within 1 min, which is one order of magnitude faster than state-of-the-art techniques. Moreover, various kinds of bio-recognisers can be introduced into this membrane to accurately detect glutamate, transaminase, and cancer biomarkers.

Antibodies are important biomarkers in clinical diagnostics in addition to being increasingly used for therapeutic purposes. Although numerous methods for their detection and quantification exist, they predominantly require benchtop instruments operated by specialists. To enable the detection of antibodies at point-of-care (POC), the development of simple and rapid assay methods independent of laboratory equipment is of high relevance. In this study, we demonstrate microfluidic thread-based analytical devices (μTADs) as a new platform for antibody detection by means of bioluminescence resonance energy-transfer (BRET) switching sensor proteins. The devices consist of vertically assembled layers including a blood separation membrane and a plastic film with a sewn-in cotton thread, onto which the BRET sensor proteins together with the substrate furimazine have been predeposited. In contrast to intensity-based signaling, the BRET mechanism enables time-independent, ratiometric readout of bioluminescence signals with a digital camera in a darkroom or a smartphone camera with a 3D-printed lens adapter. The device design allows spatially separated deposition of multiple bioluminescent proteins on a single sewn thread, enabling quantification of multiple antibodies in 5 μL of whole blood within 5 min. The bioluminescence response is independent of the applied sample volume within the range of 5-15 μL. Therefore, μTADs in combination with BRET-based sensor proteins represent user-friendly analytical tools for POC quantification of antibodies without any laboratory equipment in a finger prick (5 μL) of whole blood.

Background One of the elements that makes up blood safety is automation of processing whole blood into ingredients In 2017, Reveos was installed in Blood Bank in Lodz. By combining the centrifuge function and the press, Reveos provides full automation of the whole blood separation process, minimizing the risk of human error, thus ensuring accuracy and repeatability. The aim is to compare the results of the quality control of ingredients obtained after the blood separation using the Compomat G5, Optipress II and the Reveos system as well as to compare the level of compliance with the recommendations on the quality of blood components contained in the applicable regulations. Materials and methods 150 units were separated into ingredients using above mentioned systems showing choosen parameters. Results Parameters were determined for Compomat, Optipress i Reveos: plasma: volume 260±13ml, 262±14ml i 239±20ml, platelets: 16, 23 i 23x109/l. RBC: volume 286±13ml, 272±13ml i 295±17ml, hemoglobin 55, 51, 58g/unit., hematocrit 59, 58 i 52%, leukocytes 0,6x109/unit., 0,6x109/unit., 0,1x106/unit. Buffy coat volume: 56,6ml i 56,1ml for Compomat i Optipress and interim platelets volume 37,8ml. The platelet content in the above-mentioned components was 0.8, 0.7, 0.66x1011/unit, respectively. Conclusions The comparison of the quality of ingredients after the blood separation showed slight differences in the parameters determined. The main difference concerns the volume of the obtained plasma and red blood cells. Nevertheless, all the ingredients obtained meet rigorous quality control assumptions and separation methods can be successfully used in routine work. The Reveos system allows to obtain qualitatively good ingredients in a one-step process. This reduces staff interference in the whole process, which may result in minimizing errors during processing of the whole blood.

Developing simple, portable, rapid, and easy-to-use diagnostic technologies is essential for point-of-care (POC) blood molecular testing. Integrated microfluidic devices that include the functionalities of blood separation, microfluidic pumping, and molecular detection are desirable for POC testing; however, current technologies still rely on off-chip sample processing or require bulky equipment. We report a fully-integrated microfluidic diagnostic device, i.e., an integrated pneumatic microfluidic circuit (iPC), that can autonomously pump whole blood, continuously sort blood plasma, and readily enable blood plasma proteomic analysis. The iPC contains vacuum pillars as a vacuum source and waste reservoir, as well as microchannels connecting the pillars as a plasma separator or a flow stabilizer. We combined the iPC and a miniaturized fluorescence microscope to create a portable diagnostic platform that enables fluorescence-based biomarker detection. First, we performed systematic parametric studies to establish design rules for determining the transport and distribution of fluid streams in the iPC. We then demonstrated the capability of the iPC-based diagnostic platform by successfully separating blood plasma from microliter quantities of whole blood while simultaneously quantifying thrombin in blood samples using an aptamer beacon within 5 min of sample injection. Our platform holds potential as a rapid, field-deployable, essentially universal diagnostic tool in POC settings.

A microfluidic SERS chip integrated with blood separation and in-situ detection was designed and fabricated for the rapid detection of clinical blood samples. Each functional unit in the microfluidic SERS chip consist of separation-decantation cavity based on centrifugal separation principle, mixing channels and SERS detection chamber built with integrated nano-Au on Ag film microstructure. The serum creatinine was selected as a typical sample to demonstrate the capability of microfluidic SERS chip. It was found that the creatinine SERS characteristic peaks at 678 cm−1 can be effectively identified and the detection limit could be as low as 4.42 × 10−3 μmol mL−1 in water. The blood samples were also tested in microfluidic SERS chip. The whole separation and test process could be completed within 2 min, which is a significant improvement in the field of creatinine detection. The whole blood of six cases clinical blood samples were also tested, and the results were consistent with the enzymatic results. The developed microfluidic SERS chip has advantages including reduction of the required quantity of blood sample, reusable and easy to operate. It is expected to provide a new method for rapid diagnostics.

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 (

This work introduces the procedure of using non-immunoassay distance-based paper analytical devices (dPADs) to accurately measure any traces of the cardiac troponin I (TnI) in whole blood samples without the use of any external blood separation. This enables a rapid clinical diagnosis and the subsequent follow-up in regard to identifying acute myocardial infarction. These dPADs are designed and constructed to accommodate three parts: (1) a blood separation zone that is immobilized with a hemostatic agent, this no longer requires a blood separation membrane for the isolation of the plasma from the blood element, (2) a pretreatment zone, and (3) a detection zone coated with thymol blue. The quantitative TnI level in the whole blood was determined by measuring the blue color length found in the detection zone, which is proportional to the concentration, owing to the dry protein binding principle. Correspondingly, a mere single drop of human whole blood performs adequately within our proposed method. This reduces both the size of the collection process and the sample volumes needed in the respective medical fields. As we cover all of the optimization studies, our dPADs provide an evaluation of the linearity range from 0.025 to 2.5 ng/mL (R2 = 0.9989) of TnI, with a detection limit as low as 0.025 ng/mL by use of an observation just using the naked eye. To validate the clinical utilities of our proposed method, our dPADs were then applied for the detection of TnI in humans using the whole blood sample of 15 volunteers. A great amount of accuracy was required in this assay because there was no significant difference between both methods, with the confidence level being as high as 95%. This technique also showed that the recoveries ranged from 99.40 to 104.27%, with the highest relative standard deviation being at 3.77%. Thus, our proposed dPADs offer more benefits for a rapid TnI determination.

Liquid biopsy with circulating free DNA (cfDNA) is a recommended alternative method of re-biopsy. Quality control with cfDNA is indispensable for precise examinations, and it is desirable to achieve high-quality cfDNA separation. We investigated two issues: the influence of pre-analytical procedures on cfDNA analysis performed as a routine procedure in a standard clinical laboratory, and the extent of deterioration of cfDNA quality due to long-term storage. Comparisons among blood collection tube types, storage temperatures, and periods of blood separation were performed in terms of cfDNA quantification, cfDNA size distribution, and detection of EGFR mutations. Quality of cfDNA was better with collection tubes containing 3.2% sodium citrate than with those containing EDTA 2K, and was maintained with storage at 4° C for up to 72 h after blood collection, equivalent to results with cell-stabilizing blood collection tubes. Analysis of cfDNA stored for 7 years showed that samples with low allele frequency (AF) deteriorated more readily than samples with high AF. Despite the same storage period and extraction method, AF of plasma stored for 7 years was remarkably lower than that of cfDNA. However, deterioration due to long-term plasma storage was overcome by changing the DNA extraction method from a silica membrane spin column to a cellulose magnetic beads system. These results can guide the establishment of standardized pre-analytical procedures for liquid biopsy with cfDNA.

Interest in developing paper-based devices for point-of-care diagnostics in resource-limited settings has risen remarkably in recent decades. In this paper, we demonstrate what we refer to as “High Yield Passive Erythrocyte Removal” (HYPER) technology, which utilizes capillary forces in a unique cross-flow filtration for the separation of whole blood with performance comparable to centrifuges. As we will demonstrate, state-of-the-art passive blood separation methods implemented in paper-based systems exhibit rapid blood cell clogging on the filtration media or serum outlet and yield only about 10%−30% of the total serum present in the sample. Our innovation results from the inclusion of a differentiation pad, which exploits hydrodynamic effects to reduce the formation of a fouling layer on the blood filtration membrane resulting in more than 60% serum yield with undiluted whole blood as direct input. To demonstrate the effectiveness of the HYPER technology we implement it in a lateral flow system and demonstrate the accurate quantification of vitamin A and iron levels in whole blood samples in 15 minutes.

A disposable microfluidic chip for measuring the impedimetric ratio of blood cells was developed. The undiluted blood sample was separated into erythrocytes and leukocytes in the blood separation microchannel of the chip, and the erythrocytes and leukocytes were then driven into the measurement chambers, respectively. Inside each measurement chamber was an interdigitated electrode (IDE) array acting as a sensor for the impedimetric measurement of the blood cells. On the surface of the IDE array, ZnO nanowires were synthesized to promote the sensitivity of the impedimetric measurement. The experimental result showed that the measured impedance was proportional to the number of blood cells. The IDE array with ZnO nanowires was more sensitive than the IDE without nanowires. We also used freshly drawn venous blood samples from five healthy donors and ten informed and consenting patients for comparison. The impedimetric ratios of the five healthy donors were similar with low standard deviation, indicating that the impedimetric ratio would tend to be a reliable threshold as the indicator of erythrocytes to leukocytes. The impedimetric measurements of all patients were below the threshold. Using impedimetric measurement, the change in leukocytes could be easily monitored.

Apheretic therapies play an important role in the treatment of many diseases, both as first-line treatments and as rescue therapies, after failure or pharmacological toxicity or, again, in patients where a desirable achievement of the therapeutic objective in a short time. Apheretic technologies have evolved at a dizzying pace in recent decades. Therapeutic apheresis is almost always part of a therapeutic plan: therefore, a patient-centered approach to choose the most appropriate treatment, balancing personal preferences, drug interactions, and technological availability, can significantly influence the choice of technology/protocol to be used. If the wide variety of apheretic treatments can offer an increasingly personalized approach to the patient, it can also create an apprehension about the choice of the most appropriate therapy.

This chapter presents current efforts to design smart materials for blood separation, which do not rely on molecular sieving only, but on mechanisms of interactions between the membrane and the blood component to isolate. Although concepts have been introduced, there is more to do than has ever been done on this topic. This chapter stresses the need for a specific combination of materials to separate the component of interest from the bloodstream without inducing blood coagulation. PEGylated, zwitterionic and pseudo-zwitterionic materials can all improve the hemocompatibility of the membrane design. But to perform a smart separation, a charge bias has to be introduced by incorporating charged polymers, or a stimuli-responsive polymer has to be grafted which interactions with the blood component are tuned by environmental conditions. Attention is also given to methods for preparing supporting layers, poly(vinylidene fluoride)-based or polypropylene-based. Finally, examples of reported smart blood separations are scrutinized, including the separation of proteins from whole blood, the development of leukocyte depletion or platelet concentration filters. We end this chapter with an identification of the current challenges to overcome to expand the development of smart membranes for blood separation.

Studies on microfluidic thread-based analytical devices (μTADs) have been developed for a decade. Threads, made of natural cellulose or synthesized polymer fibres, are manufactured in the form which possesses a large number of capillary gaps for liquid transport, and show differences in structural morphologies and surface chemistry. Threads have been used to design simple thread-based microfluidics with different analytical functions. Due to their low-cost, portability, biocompatibility and ease of integration with other components, threads show a great application basis to fabricate point-of-care μTADs. To date, there are a limited number of published studies on μTADs in contrast to paper-based analytical devices. To facilitate further advances of μTADs, this review summarizes the development of these devices from the aspects of engineering control of capillary flow on threads and biological applications. Particularly, as liquid flow on threads affects the transport and detection efficiencies, strategies of controlling liquid flow on threads are firstly reviewed. This includes thread surface modification, proper thread type selection, and microfluidic channel design. Then various detection methods including colorimetry, fluorescence, electrochemistry and surface-enhanced Raman spectroscopy applied on μTADs are reviewed. The biological applications of μTADs in blood separation and analysis, immunoassay, wearable sensing, as well as compatibility with smartphones for biosensing are also systematically summarized. Finally, the future perspectives of μTADs regarding external collaboration to satisfy the “REASSURED” criteria are proposed. This review is expected to expand understandings of μTAD designs and applications, and to clarify the challenges and future development directions of μTADs.

A novel membrane with heterogeneously functionalized nanocrystal layers was designed to synchronously perform in situ blood separation and sensing for the extraction of pure serum without any blood cells and fibrinogen by size sieving, and simultaneously realizing the electrochemical analysis of various physiological indexes.

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. Graphical Abstract Schematics of a real-time plasma monitoring system based on a Hydrodynamic and direct-current insulator-based dielectrophoresis microfluidic channel.

A fidget spinner, the toy twirled endlessly between the fingers of schoolkids, can act as a makeshift centrifuge and separate blood plasma sufficiently for an HIV test (Anal. Chem. 2018, DOI: 10.1021/acs.analchem.8b04860). For blood tests, red blood cells must be separated from the plasma, usually with a fast-spinning centrifuge, but these are expensive and require electricity to operate, which may not be feasible in resource-limited regions of the world, says Chien-Fu Chen of the Institute of Applied Mechanics at National Taiwan University. Along with Chien-Cheng Chang and colleagues, Chen put human blood spiked with a common HIV-1 diagnostic protein in 50 mm long plastic tubes, sealed them, and taped them to each of the three spinning arms of a commercially available fidget spinner. After spinning the device for 4–7 min, the team separated about 30% of the plasma from the blood sample—with 99% purity. A paper-based HIV test detected the

As the point of care diagnosis devices are becoming ever more popular, this paper suggest a miniaturized testing device from a drop of blood to diagnosis of disease for the global healthcare. The minimal requirements for the POC blood-testing device are blood microsampling, blood separation, immunoassay, and detection and communication of the signals. The microsampling of the blood can be achieved by specialized needle, which can be connected to the microchip or analytical devices. The sampled blood is then separated using either a filter (weir or pillar type), or by the phenomena unique to microfluidic system. The separated blood should then go through sandwich, homogeneous non-competitive, or competitive immunoassay, which can effectively diagnose diverse diseases. Lastly, the device should detect and translate the immune-signals to readable, and clinically significant signals. The development of such device will play a great role for improving healthcare technology.

Appropriate sample collections and quality laboratory techniques are vital to ensure quality data, as results from the analysis of blood/urine/tissue samples are most often part of the primary or secondary outcome measures of a trial. This chapter describes the appropriate blood and urine sample collection, storage and shipment, principles of blood separation, the centrifugation process, plasma and serum sampling, and the consequences of preanalytical issues and nonadherence to protocol or laboratory manual.

This paper describes a novel microfluidic chip, including implementation of serially connected filters for improvement of collection efficiency in blood plasma separation. We have previously reported on a blood plasma separation device, comprising serially connected filters, and its effect on plasma collection efficiency. This paper describes improvement of the device structure for biological blood separation and integration of the filters into a microfluidic chip. Plasma collection into an outer reservoir enables use of the separated plasma in further processing, although the ultimate objective is on-chip analysis of plasma constituents, this is not currently possible. Thus, a collection mechanism for the serially connected filters was also developed and implemented. The device developed in this study was able to extract approximately 4 μL of plasma from 50 μL of non-diluted whole blood into an outer reservoir without critical hemolysis. The successfully miniaturized filter device was able to collect both plasma and un-separated blood into outer reservoirs for further processing and will be a useful separation platform for μTAS applications.

Current gels used in blood separation tubes create an imperfect barrier between the blood components because of their physical and thixotropic nature. As a result, blood components tend to leak into the gel layer or vice versa during transport and storage. To overcome these problems, we demonstrate the use of a UV-curable thixotropic gel composed of a sorbitol-based gelator in a diacrylate oligomer. Initially, the sample is a physical gel composed of weak, non-covalent bonds, and its thixotropic nature allows it to flow under centrifugation and form a barrier between the density-stratified layers of blood. Immediately afterward, the gel is chemically crosslinked by short exposure to UV light for 10–30 s. This results in a rigid, impenetrable barrier that is freeze-thaw stable. The gel is compatible with blood, allowing blood samples to be stored in the tube and analyzed over long times. We believe the present method is a significant advance in the practice of blood analysis for medical purposes.

Therapeutic apheresis refers to a group of related interventions characterized by the use of extracorporeal blood separation in the treatment of disease. The establishment of therapeutic apheresis in modern transfusion practice is due in large part to technological advances such as automation and optimization of equipment and to the formalization of evidence-based guidelines for appropriate use.

A novel device of smart pipette has been suggested to extract and deliver plasma from whole blood in a disposable format. By operating an on-chip disposable micropump, approximately 30 μL of plasma was obtained from 100 μL of whole blood within 5 min without any external equipment for point-of-care blood analysis.

The paper presents numerical analysis in three-dimensional (3D) of a hybrid micro-separator that uses magnetophoresis (MAP) and hydrodynamic forces for blood cells separation. The separation between red blood cells (RBC) and white blood cells (WBC) is done by manipulating the differences of their physical and magnetic susceptibilities. The MAP force is induced from ferromagnetic line fabricated on a glass slide while the hydrodynamic force is obtained by a ‘U’ shape microfluidic channel. The analysis was conducted using finite element software, COMSOL Multiphysics®. The particles trajectories, which represent the actual blood cells' movements on the micro-separator, were profiled and show successful separation between RBCs and WBCs by using the MAP and hydrodynamic forces. This study also provides insights of challenges associated with blood separation towards the realization of better diagnostic devices.

None of the present magnetic separators is capable of achieving the classification of particles according to their magnetic susceptibility. We have developed a new apparatus to attain these magnetic classification goals. In this paper, the design of the continuous-mode large-scale prototype of the magnetic classifier is presented. Many areas of application are foreseen for this device, and we analyse two of them – health sciences and chemical engineering – presenting also some possible application cases within these areas.

The aim of this work is to construct a computational fluid dynamics model capable of simulating the quasitransient process of apheresis. To this end a Lagrangian-Eulerian model has been developed which tracks the blood particles within a delineated two-dimensional flow domain. Within the Eulerian method, the fluid flow conservation equations within the separator are solved. Taking the calculated values of the flow field and using a Lagrangian method, the displacement of the blood particles is calculated. Thus, the local blood density within the separator at a given time step is known. Subsequently, the flow field in the separator is recalculated. This process continues until a quasisteady behavior is reached. The simulations show good agreement with experimental results. They shows a complete separation of plasma and red blood cells, as well as nearly complete separation of red blood cells and platelets. The white blood cells build clusters in the low concentrate cell bed.

Insulin-like growth factor-I (IGF-I) is sensitive to nutritional stress and is reduced in soldiers during stressful field training. Methods have recently been developed to measure IGF-I from filter paper blood spots. Filter paper has advantages over traditional blood sampling in that neither blood separation equipment nor refrigeration is necessary after sample collection. This study determined whether filter paper blood spots collected in a field environment could measure IGF-I and subsequent changes during military operational stress. Thirty-four Marines participating in an 8-day military field exercise characterized by near-continuous physical work (total daily energy expenditure 17-25 MJ/day) and underfeeding (dietary intake 7.0 MJ/day) had blood samples taken on day 0, day 4, and day 8. IGF-I was measured by filter paper blood spot assays from fingertip blood samples and by conventional methods using serum. Correlation and measurement agreement were assessed. Blood spot (Day 0 152 +/- 6 ng mL(-1)Day 4 111 +/- 6 ng mL(-1)Day 8 74 +/- 4 ng mL(-1)) and serum IGF-I (Day 0 412 +/- 10 ng mL(-1)Day 4 258 +/- 14 ng mL(-1)Day 8 203 +/- 13 ng mL(-1)) concentrations declined (p0.05) progressively over the 8-day exercise. Overall, the two methods significantly (p0.05) correlated (r = 0.92); however, the blood spot values were on average 61% lower than serum, but could be used to predict serum values ( +/- 10%). IGF-I is a biomarker of metabolic status. The filter paper blood spot method for IGF-I detected reductions accompanying nutritional stress and may be of potential value for characterizing the IGF-I response when conventional blood sampling methods are not feasible.

Guest Editor's Introduction: By 1977, the NCI/IBM 2990 and the Amico Celltrifuge, a conceptually similar instrument that had an identical centrifuge bowl, were being used worldwide. However, a major technical problem remained in that the blood path was still not completely disposable. To overcome this drawback, IBM 2977 was developed. The centrifuge bowl was changed from an axial flow separator to a circumferential flow geometry. The IBM 2997 single-stage channel instrument was first introduced and followed by the dual-stage channel instrument to obtain platelet concentrate with minimum lymphocyte contamination. This paper describes the basic design, operation conditions, and collection performance of the single-stage channel IBM 2977. This paper was printed in Blood, vol 54, page 254–268 (1979) and reprinted here with permission. A single-stage disposable channel and seal that provides for leukocyte and granulocyte collection by continuous-flow cell separation (CFCS) has been designed by the IBM Corporation. This paper describes (1) the separation characteristics of whole blood as it responds to varying gravitational (G) forces and flow rates through the channel; (2) the mechanism by which the buffy coat accumulates and is extracted; (3) the efficiency of extraction; (4) those donor and procedural variables that contribute to the final yield; (5) posttransfusion increment response in patients; and (6) the functional integrity of the cells collected.

This study successfully used the modified fiber membrane to improve the filtration efficiency in the commercial rapid test strip. It can decrease the interference of the optical measurement or human eyes observation which was caused by the red blood cells. Our strategy was that added several modified fiber membranes above the commercial available blood separation area to enhance the filtration efficiency of the red blood cells. The fiber membrane had the specific pore size which can generate the physical barriers to remain the blood cells and used the chemical modification method to decrease the hemolysis and thrombus conditions in the rapid test strip.

A novel noninstrumented technology (ChemTrak AccuMeter) for the quantitative measurement of analytes in biological fluids was reported at the 1990 Oak Ridge Conference (Clin Chem 1990;36:1591-7). This instrument-free technology has been adapted for the quantitative measurement of high-density lipoprotein (HDL). An in situ lipoprotein separation method has been developed and incorporated into the test for HDL determination. The sensitivity of the assay system has been adjusted so that HDL is measured over a clinically significant range of 250 to 1000 mg/L. This compares to a range of 1000 to 4000 mg/L for the total cholesterol in the earlier reported assay. Like the AccuMeter total cholesterol test, the Accumeter HDL test system is self-contained and consolidates blood separation, lipoprotein separation, and specimen measurement into a single step. The test procedure is simple, and the results are accurate.

In recent years, it has been expected that UV light irradiation on PC may prevent HLA-alloimmunization following repeated platelet transfusion. For the purpose to evaluate this technique, we tested the UV light permeability of blood bags and inactivation effect of UV light on lymphocytes in PC.UVB light (280-320nm) permeability of blood bags, available from Japanese mamufactures, was 60% on average. Among them, PVC bag plasticized with DnDP showed most excellent permeability of 73%.In MLR testing, UBV light irradiation at proper doses of 1×104J/m2 was recommended for complete lymphocytes inactivation. Plasma thickness of 16mm and RBC contamination of 4×104μl did not disturb the inactivation effect of UVB light.These data support our conclusion that UVB light irradiation on PC can be performed without changing any present procedures of blood separation, blood bags, PC volume and red cell contamination. UVB light irradiation is simple and inexpensive technique, and so it has a practical usefulness.

This paper presents the challenges encountered in modelling biofluids in microchannels. In particular blood separation implemented in a T-microchannel device is analysed. Microfluids behave different from the counterparts in the microscale and a different approach has been adopted here to model them, which emphasize the roles of viscous forces, high shear rate performance and particle interaction in microscope. A T-microchannel design is numerically analysed by means of computational fluid dynamics (CFD) to investigate the effectiveness of blood separation based on the bifurcation law and other bio-physical effects. The simulation shows that the device can separate blood cells from plasma.

Real-time quantitative polymerase chain reaction (RQ-PCR) has been accepted as integral part of the management of patients with hematologic malignancies. Whereas standardization efforts of RQ-PCR, initiated by Europe Against Cancer (EAC) group, have been gradually widespread in the world, Japanese laboratories use their individual protocol for RQ-PCR analysis. Therefore, we assessed the variability of quantitative results obtained from 4 different laboratories in Japan, including 3 companies and Tohoku University Hospital, using identical peripheral blood or bone marrow samples of patients in chronic myeloid leukemia (CML; n = 11) and acute myeloid leukemia (AML; n = 2). RQ-PCR was designed to quantify the copy numbers of disease-specific fusion chimeras; BCR-ABL (CML) and AML1-ETO (AML). In 5 out of 13 samples, the quantitative results from 4 laboratories varied more than 10 times (up to 712 times). Thus, we next sought to determine factors affecting the variability of RQ-PCR results across laboratories, by sending back RNA and cDNA samples from each company to Tohoku University, and they were further proceed to yield quantitative data. The main difference between companies and Tohoku University was probably due to the difference of blood separation method (Blood lysis or Ficoll-Hypaque). On the other hand, the variability among 4 laboratories was the most noticeable in the PCR step, mainly attributable to the difference of primer/probe sequence among laboratories. In conclusion, our analyses indicate the importance to limit both preanalytical (sample processing) and analytical (RQ-PCR) interlaboratory variability for RQ-PCR protocol, and the need of further efforts on standardization program in Japan.

Gesamtdissertation, Es wurde eine alternative Methode zu Zentrifugation und Hämapherese für die Herstellung von Blutkomponenten entwickelt. Verwendet wurde der bereits in der Hämodialyse eingesetzte Hollow Fiber Filter , dessen Filtereigenschaft auf der Ausnutzung der Schwerkraft beruht. Über die Filtermembran der parallel angeordneten Hohlfasern aus Polypropylen fand bei einer Porengröße von 0,2-0,5 µm die Trennung in Erythrozytenkonzentrat und Plasma statt. Es wurde eine Apparatur konstruiert, die sich aus Teilen des geschlossenen Beutelsystems und dem Hollow Fiber Filter zusammensetzt. Für die Leukozytendepletion wurde ein Leukozytenfilter integriert. Die Erythrozytenkonzentrate sollten einen Hämatokrit von 50-70% aufweisen. Durch das Optimieren der Abstände der Beutel zum Hollow Fiber Filter konnten akzeptable Hämatokritwerte erreicht werden. Für das zweimalige Filtern der Blutkonserve über den HF Filter, einschließlich der Leukozytenfiltration bis zum Erhalten der Blutkomponenten werden durchschnittlich zwischen 45 Minuten (Leukozytenfiltration nach 2. Filtration) und 80 Minuten (Leukozytenfiltration vor 1. Filtration) benötigt. Das gewonnene Erythrozytenkonzentrat zeigt im Durchschnitt ein Volumen von 262 ml ohne additive Lösung und von 322 ml nach der Zugabe von additiver Lösung. Der mittlere Hämatokrit der optimierten Versuche beträgt 71,84 % ohne additive Lösung. Bei Hämatokritwerten von über 72 % konnten nach der Zugabe von additiver Lösung Hämatokritwerte von ca. 54 % bestimmt werden. Das gewonnene Plasmavolumen erreicht einen mittleren Wert von 254 ml. Dieses Verfahren zeichnet sich durch die Verwendung von Materialien aus ,die im klinischen Alltag bereits vorkommen, durch seine Unabhängigkeit von äußeren Energiequellen, ist es prinzipiell überall anwendbar., An alternative method to centrifugation and automatic separation was developed to produce blood components. It was composed an equipment of parts from the closed plastic bag system and the hollow fiber filter , which is normally used for the haemodialysis. The hollow fiber filter consists of a bundle of polypropylene hollow fibers (0,2-0,5 µm pore size) , which separate the whole blood into plasma and a red cell concentrate by using gravity. For the leucoreduction it was integrate a leucocyte filter in the system. The red cell concentrates had to have a haematocrit of 50-70 %. By optimize the distances from the bags to the hollow fiber filter and a second filtration through the hollow fiber filter , it was possible to get an acceptable haematocrit. The mean volume of the red cell concentrate was 262 ml (without additive solution) and 322 ml (with additive solution). By optimising the attempts the mean haematocrit was 71,84% ( without additive solution) and 54 ml ( with additive solution).The mean volume of the plasma was 254 ml. This method used only materials, which occurs in the clinic, it is simple to practise, with a low personal expense and costs. It is independent from electrical devices and can be used principal all over the world.

To add to the traditional method of blood separation by centrifugation, a membrane method has in recent years been coming into wide clinical use in treating autoimmune diseases by plasma exchange. The membrane method which not only is easy but also needs simple equipment has been the focus of attention as a new means to collect blood components, especially plasma.This paper discusses the results of clinical evaluation of the safety and performance of Terumo Corporation's membrane type plasma separator Donor Set GDS-1.As a result, it was demonstrated that 174ml of plasma could be separated from approximately 408ml of blood in a little more than 10min, and that the N-N time from needle insertion to withdrawal was approximately 21min. The laboratory data of the donors were not remarkable after plasma separation, and no adverse effects plasma separation were observed. Accordingly, plasmapheresis by this system may be considered to be for practical purpose adequately safe. The activation of the coagulation, fibrinolysis and complement systems was so slight that biocompatibility was considered satisfactory.This system which separates plasma from the blood by gravity is high of clinical use for its safety and procedural simplicity.

Most clinical chemistry tests are performed on cell-free serum or plasma. Therefore micro assay devices for blood tests require integrated on-chip microfluidics for separation of plasma or serum from blood. This is achieved by a new blood separation technique based on a microchannel bend structure developed within the collaborative microtele-biochip (/spl mu/TBC) project co-funded by the German Ministry for education and research (BMBF). Different prototype polymer chips have been manufactured with an UV-LIGA process and hot embossing technology. The separation efficiency of these chips has been determined with samples of human whole blood as well as diluted blood samples. The results show different separation efficiencies up to 90% for blood cells and plasma depending on microchannel geometry as well as cell concentration. As compared to present microfluidic devices for the separation of blood cells like filters or filtration by diffusion the microchannel bend is an integrated on-chip blood separation method, which combines the advantages of rapid separation times and a simple geometry.

We propose a MEMS device which integrates a dielectrophoretic blood separation technique with a cytometer and pump for use in low cost blood analysis. Our technical analysis focuses on fluid flow, blood modeling for electrical systems and the dielectrophoresis and cytometry methods. Simulation results of the flow, separation and cytometry are presented.

A blood analysis chip including a power-free micro blood separator capable of separating cells-free plasma from whole blood using a specially designed sub-micron structure and electrochemical electrodes for glucose sensing is developed. Preliminary tests show the possibility of the presented chip.

Healing and fusion in challenging bone grafting procedures is not guaranteed using the gold standard of autogenous iliac crest bone, and clinicians are increasingly interested in tissue engineering solutions using cells and signaling factors to enhance both overall success rate and time to fusion. The potential role in wound repair from application of cytokines contained in platelets was initially described more than 20 years ago. A rapid, simple preparation method to perioperatively separate and collect the platelet-rich fraction was developed a decade later, expanding the potential range of clinical applications. Numerous additional point-of-care techniques have since been introduced, potentially providing a cost-effective alternative to single recombinant proteins. As with many emerging technologies, clinicians are confronted with a frequently conflicting array of largely anecdotal claims for clinical utility. With a focus on structural bone graft repair, this chapter will present the therapeutic basis for clinical use of topically applied autogenous growth factor preparations and summarize existing experimental and application-specific clinical outcomes reports. Keywords: blood separation; platelets; growth factors; tissue regeneration; orthopedics

In this paper, we confirmed that clogging does not happen in short time and inline type separate efficiency is higher than stagger type. The mechanical micro blood separator can be a good candidate for bio sample separation devices. In future, we will observe the influence of micro structures geometry on clogging and separation performance will be clarified. And we will design micro structures geometry for clogging reduction and separation performance improvement. In this paper, we confirmed that clogging does not happen in short time and inline type separate efficiency is higher than stagger type. The mechanical micro blood separator can be a good candidate for bio sample separation devices. In future, we will observe the influence of micro structures geometry on clogging and separation performance will be clarified. And we will design micro structures geometry for clogging reduction and separation performance improvement

The Axial Separation Module (ASM™), which separates whole-blood specimens serially in Axial Process Containers (APC™), was evaluated for clinical performance at the University of Virginia Health Sciences Center (UVA HSC) in a community-based outpatient laboratory (North Ridge Clinic). We hypothesized that moving the task of blood separation to point of care would reduce specimen turnaround time within the main laboratory. Blood drawn into an APC was separated in the ASM at point of care at the North Ridge Clinic. Blood drawn into a Vacutainer Tube™was separated in a conventional centrifuge at the main laboratory. Turnaround time was calculated for the “chem 17” test from files stored in our laboratory information system. Blood serially separated at point of care yielded turnaround time savings for specimens originating from the North Ridge Clinic. Average turnaround time decreased by 24%. Phlebotomists found no appreciable workload increase from incorporating the ASM as a point-of-care blood separation device. Phlebotomists also found that they could immediately detect hemolysis. We concluded that serial separation at point of care reduces specimen turnaround time at the main laboratory. The ASM/APC was found to be better suited for point-of-care blood separation than a conventional centrifuge. We speculate that immediate blood separation has the potential to improve the quality of analytical results.