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In recent years, viscoelastic particle manipulation within microfluidic systems has received much attention due to the ease with which micron-sized objects may be maneuvered and isolated on the basis of size. While several factors, including both fluid and particle properties, regulate the precise locations and trajectories of micron-sized species flowing along a microchannel, the role of channel cross-section shape is critical, since it directly influences the fluid velocity profile and thus the direction and magnitude of hydrodynamic forces. It is therefore surprising that this parameter has not been comprehensively investigated for cell-based separations, especially since most viscoelastic microfluidic systems are only able to efficiently sperate cells over limited size ranges. To address this shortcoming, we present a viscoelastic microfluidic system integrating a triangular cross-section microchannel, for efficient and tunable size-based separations of micron-sized species. We find that particle focusing patterns can be controlled by simple variation of volumetric flow rates, which allows for the efficient separation of particles and cells of variable size. To showcase the efficacy of the approach, we present a size-based separation of various blood components, including white blood cells, platelets, and rare cells. By quantifying the number of particles collected at the outlets, we achieve recovery efficiencies of over 98%. • Viscoelastic particle manipulation is used to separate micron-sized particles. • A triangular cross-section microfluidic channel design is used for particle separation. • Passive separation of different blood components at low blood dilutions. • Size-selective separation of blood components via tunable viscoelastic focusing. [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical abstract fx1 Highlights • Nano-Au on Ag film taken as SERS substrate was prepared in-situ in the detecting chamber for detection. • The serum separated by microchannels was directly injected into the chamber on the designed chip for SERS detection. • The integrated microfluidic SERS chip was applied to detect rapidly the clinical serum creatinine within 2 min. [ABSTRACT FROM AUTHOR]

Excellent detection capability, a simple assay procedure, and easy device acquisition are three key factors to analyze biomarkers for disease diagnosis using a point-of-care device in resource-limited settings or in emergency situations. However, constructing a platform with the simultaneous presence of these factors to sense multiple biomarkers remains a challenge. In the spirit of "frugal science", a simple method is developed by combining a low-cost portable paper centrifuge with surface-enhanced Raman scattering (SERS) immunoassay for sample pretreatment and multiple-cytokine (IL-6, IL-1, and TNF-α) detection. The paper centrifuge can achieve rapid blood separation as a commercial centrifuge and also concentrate sandwich immune composites to generate abundant hot spots, thus enhancing the SERS signal. By analyzing three prospective cytokines (IL-6, IL-1, and TNF-α) closely related to tumors, the combined paper centrifugation–SERS immunoassay method realizes sensitive assays with detection limits down to 0.86, 0.42 and 0.22 pg/mL. Meanwhile, the proposed approach possesses capabilities of specific recognition and accurate quantitative detection for three cytokines in serum. Hence, the constructed multifunctional SERS platform is expected to be applied in the development of decentralized and battery-free diagnostic devices in facility-limited areas and field settings. [Display omitted] • A combined paper centrifugation–SERS immunoassay method is developed. • Paper centrifuge can achieve rapid blood separation as a commercial centrifuge. • Sensitive, quantitative, and specific detection for three cytokines are realized. [ABSTRACT FROM AUTHOR]

This preliminary study aims to understand the mechanism of haemolysis in the process of blood separation in porous membranes in a confined scope. Two typical membranes (polysulfone and glass fibre membranes) were chosen as the representatives for the two different (vertical and lateral) blood separation directions. The wall shear stress (WSS) applied on the RBCs and the effects of the morphology of the pores in the membranes on the integrity of RBCs, were investigated to find the main reason for inducing the release of intracellular components into the plasma occurring as haemolysis. With the evaluation of WSS in the two membranes, it has been found that the impact of WSS is insufficient as a single factor causing haemolysis. Based on the morphology of the internal structures of the two porous membranes characterised by SEM imaging combined with the quantitative analysis on the number of sharp ends in the membranes, it has been shown that haemolysis is mainly caused by the puncture on the RBCs because of the sharp ends of the fibrous structure in the membranes. The membranes having more sharp ends show a higher level of haemolysis. The haemolysis during blood separation has been characterised using UV–vis spectrophotometry. • Sharp ends of fibres in membranes cause haemolysis during blood plasma separation. • Wall shear stress during blood separation using membrane does not cause haemolysis. • Blood flow models are established to estimate wall shear stress in membrane. [ABSTRACT FROM AUTHOR]

Shape-based separation capabilities of a novel pinched flow fractionation device with a tilted sidewall and vertical focusing channels (t-PFF-v) were demonstrated for (1) spherical and disc-shaped polystyrene (PS) particles; (2) platelets (PLT) and red blood cells (RBC); and (3) singlet, doublet, and triplet clusters of disc-shaped PS particles. The tilted sidewalls and vertical focusing channels of the t-PFF-v device allowed us to perform enhanced separation of non-spherical particles. Using this t-PFF-v device with a W p (pinched segment width) of 20 μm and 15 μm, not only spherical (diameter of 2 μm) and disc-shaped (thickness of ∼2 μm, diameter of ∼5.0 μm) PS particles but also PLTs and RBCs from diluted blood were well separated with good separation resolutions (R disc,sphere = 1.40 and R PLT,RBC = 1.28). Additionally, time-lapse images of flowing particles indicated that both disc-shaped PS particles and RBCs are probably having type I orientation in the pinched segment (i.e., leaning against the tilted sidewalls at the pinched segment). Moreover, we observed streamlines of singlet, doublet, and triplet clustered disc-shaped PS particles, which suggested that these clustered particles could be well separated according to their aspect ratio. The doublet or triplet clustered PS particles are probably lay on the floor and rotated at the pinched segment (type II orientation). We believe that this shape-based separation capability achieved by the t-PFF-v device can be utilized for many application areas, such as medical, biological, material and colloidal sciences. [ABSTRACT FROM AUTHOR]

In this paper, a microfluidic chip inspired by fish gills has been designed and fabricated in order to separate blood cells from serum. This microchip is modeled after fish gills which filter particles from fluids. In this way, the blood passes through a reservoir that contains several parallel rows of filter columns, which perform the filtering action. COMSOL Multiphysics software was used to conduct several simulations to optimize the pressure and velocity parameters of blood entering the microchip, and these parameters were used to determine the appropriate dimensions of the microchip. The simulation results indicate that the microchip is able to completely separate the cells from the serum, assuming a blood flow rate of 134 μl/s. With the help of the proposed filter, blood cells are separated from the plasma after 20 s and the aggregation occurs in the outlet reservoirs. In order to fabricate the microchip, the filter component made of polydimethylsiloxane (PDMS) was bonded to the copper substrate. In this paper a new copper to PDMS bonding process is proposed. Copper was chosen as the substrate because it allows the application of voltage to separate particles through the Dielectrophoresis method. The chemical etching method reinforced with noble metals was used to create micro holes on the silicon wafer, which are used to mold PDMS filters with a diameter of several micrometers. The main reservoir with a depth of 20 µm was created by the wet etching method. The reservoir was coated with silane coating and the oxygen plasma was utilized to bond the PDMS filters and the main reservoir. The copper substrate allows the microchip to be used with other electronic devices and circuits on printed circuit boards. Scanning Electron Microscopy (SEM) was used to observe the silane-coated copper surface, the micro holes on the silicon wafer, and the PDMS pillars. The topography and roughness of the copper surface before and after silane coating was evaluated through Atomic Force Microscopy (AFM). Optical Microscopy (OM) was utilized to observe the separation of the cells from the plasma. The results showed acceptable adhesion between copper and PDMS and good results for serum separation from blood cells. [Display omitted] • Design and simulation of Microfluidic Chip inspiring fish gill geometry. • Ag Assisted Chemical Etching of Si for fabrication of mold of PDMS micro pillars. • Proposing Silane intermediate layer to bond PDMS and copper. • Proposing a process for implementation of microfluidic chips with electronics, all in one. [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]

Abstract: To set up a point-of-care whole-blood immunoassay system, sample preparation and on-chip storage of conjugate reagents are indispensable functional units. Here, we merge these functions into a deposited microbead plug (DMBP) to simultaneously play the roles of a blood filter and a conjugate reagent carrier. The DMBP was easily fabricated by the use of natural deposition of beads without the need of weirs. Conjugate reagents (FITC labeled antibodies used here) were incorporated into the DMBP during the assembly of the DMBP. To demonstrate the ability of the DMBP, we constructed a DMBP-based microfluidic chip and used it for the detection of human IgG (hIgG). The DMBP enabled to remove blood cells from whole blood and provide the pure plasma for the downstream on-chip immunoreactions. The release of reconstituted FITC labeled antibodies from the DMBP was controlled in a passive fashion. Dry FITC labeled antibodies retained at least 81% of their activity after 60 days of storage at the room temperature. The DMBP presented here makes an important step towards the development of the self-contained, integrated, sample-to-answer microfluidic chips for point-of-care diagnostics. [Copyright &y& Elsevier]

Abstract: When aiming a complete microfluidic analysis system for human blood tests the blood plasma separation should be preferably also integrated in the device. The sensitivity of the analysis is significantly affected by the sample quality, so in this work the efficiency of the Zweifach-Fung effect based microfluidic separation systems was characterized. The microstructures were fabricated by simple replication in polydimethylsilixane applying SU-8 photoresist master beside extensive variation of the geometric parameters. [Copyright &y& Elsevier]

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]

Abstract: 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. [Copyright &y& Elsevier]

Accurately monitoring blood glucose in real-time is highly required for diabetes. Utilizing membrane to realize fast separation of a trace of blood is significant for accurately testing blood glucose. In this work, we designed a Janus membrane with thin film composite structure by electrospinning polyurethane (PU) on Ca 3 (PO 4) 2 -coated nylon mesh. This Janus membrane exhibited directional liquid transport performance and liquid wastage reduction during separation through optimizing the surface wettability, pore parameters and asymmetric structures of membrane. When a trace of water with volume as small as 3 μL was dipped on the hydrophobic side with pore size of around 1.1 μm, this water droplet could easily penetrate through the Janus membrane within 2.9 s under only gravity and liquid wastage reduction was achieved at the same time (D 2 /D 1 = 1.27), suggesting an excellent liquid transportation performance. The blood glucose meter integrated with this Janus membrane could efficiently remove red blood cells from 10 μL blood within 7.2 s. As a result, the sensitivity of the blood glucose meter increased by 4.5%. Image 1 • Janus membrane was prepared via phase inversion assisted dip coating process combining electrospining process. • Directional transport of a trace of water with little wastage was realized on this membrane. • The Janus membrane could efficiently remove red blood cells from 10 μL blood within 7.2 s. • The sensitivity of blood glucose meter integrated with the Janus membrane was increased by 4.5%. [ABSTRACT FROM AUTHOR]