Microchip-based Plasma Separation from Whole Blood via Axial Migration of Blood Cells

Aota, Arata; Takahashi, Susumu; Mawatari, Kazuma; Tanaka, Yo; Sugii, Yasuhiko; Kitamori, Takehiko

doi:10.2116/analsci.27.1173

Cited by 14 publications

(15 citation statements)

References 38 publications

(47 reference statements)

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“…adhesive into the ring-shaped structure and the major aim was to prevent leakage during the filtration process. Compared to other microfluidic chips, [2][3][4][5][6][7][8][9][10][11][12][13][19][20][21] the onsite blood filtration could be realized with this device by inserting the tip of the plastic syringe into this device. The bonding technique, two-step injection and curing of UV adhesive, would ensure an efficient filtration process and no leakage would happen during the filtration process.…”

Section: Discussionmentioning

confidence: 99%

“…The microchannels in that chip were fabricated on glass substrates and bonded to a Cyclopore membrane using a stainless steel holder. 11 This device takes advantage of axial migration to separate plasma from whole blood and reportedly prevents hemolysis and cell clogging. In experiments, the device was able to separate 65% of plasma in 200 ll of whole blood.…”

Section: Microfiltration Based On Integrating Filters Within Micromentioning

confidence: 99%

“…Microfluidic devices can even be integrated with other components toward a lab-on-a-chip (LOC). Blood analysis [2][3][4][5][6][7][8][9][10][11][12][13] involves separating blood plasma from whole human blood to prevent blood cells from affecting final assay results. The conventional approach for plasma separation involves fitting commercial centrifuge tubes with a filter to separate the blood plasma from the whole human blood; however, the centrifugal forces induced by high speed rotation are difficult to be realized on microfluidic platforms.…”

Section: Introductionmentioning

confidence: 99%

“…Fax: 886-2-27376460. chips. [7][8][9][10][11] Examples of the different microfiltration approaches are described over subsequent paragraphs.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood

Chen

Young

2016

Biomicrofluidics

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In this study, we developed a fully thermoplastic microfiltration chip for the separation of blood plasma from human blood. Spiral microchannels were manufactured on a PMMA substrate using a micromilling machine, and a commercial polycarbonate membrane was bonded between two thermoplastic substrates. To achieve an excellent bonding between the commercial membrane and the thermoplastic substrates, we used a two-step injection and curing procedure of UV adhesive into a ring-shaped structure around the microchannel to efficiently prevent leakage during blood filtration. We performed multiple filtration experiments using human blood to compare the influence of three factors on separation efficiency: hematocrit level (40%, 23.2%, and 10.9%), membrane pore size (5 lm, 2 lm, and 1 lm), and flow rate (0.02 ml/min, 0.06 ml/min, 0.1 ml/min). To prevent hemolysis, the pressure within the microchannel was kept below 0.5 bars throughout all filtration experiments. The experimental results clearly demonstrated the following: (1) The proposed microfiltration chip is able to separate white blood cells and red blood cells from whole human blood with a separation efficiency that exceeds 95%; (2) no leakage occurred during any of the experiments, thereby demonstrating the effectiveness of bonding a commercial membrane with a thermoplastic substrate using UV adhesive in a ring-shaped structure; (3) separation efficiency can be increased by using a membrane with smaller pore size, by using diluted blood with lower hematocrit, or by injecting blood into the microfiltration chip at a lower flow rate. Published by AIP Publishing. [http://dx

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Section: Discussionmentioning

confidence: 99%

Section: Microfiltration Based On Integrating Filters Within Micromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Fax: 886-2-27376460. chips. [7][8][9][10][11] Examples of the different microfiltration approaches are described over subsequent paragraphs.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood

Chen

Young

2016

Biomicrofluidics

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“…36,37 However, because of the large number of methods available for its rapid and precise quantification, CRP detection is still an appealing technique for clinicians and has consequently been largely applied in lab-on-a-chip devices. [38][39][40] Aota et al proposed for example a passive plasma separation device and validated it with microELISA analysis of CRP levels. 40 A blood filtering membrane was also proposed in conjunction with a protein capture strategy to detect CRP levels.…”

Section: Proteinsmentioning

confidence: 99%

Micro-scale blood plasma separation: from acoustophoresis to egg-beaters

2013

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Plasma is a rich mine of various biomarkers including proteins, metabolites and circulating nucleic acids. The diagnostic and therapeutic potential of these analytes has been quite recently uncovered, and the number of plasma biomarkers will still be growing in the coming years. A significant part of the blood plasma preparation is still handled manually, off-chip, via centrifugation or filtration. These batch methods have variable waiting times, and are often performed under non-reproducible conditions that may impair the collection of analytes of interest, with variable degradation. The development of miniaturised modules capable of automated and reproducible blood plasma separation would aid in the translation of lab-on-a-chip devices to the clinical market. Here we propose a systematic review of major plasma analytes and target applications, alongside existing solutions for micro-scale blood plasma extraction, focusing on the approaches that have been biologically validated for specific applications.

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Gravitational field-flow fractionation integrated with chemiluminescence detection for a self-standing point-of-care compact device in bioanalysis

Casolari

Mirasoli

Zangheri

et al. 2013

Analyst

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A "Point-Of-Care-Testing" (POCT) system relies on portable and simply operated self-standing analytical devices. To fulfill diagnostic requirements, the POCT system should provide highly sensitive simultaneous detection of several biomarkers of the pathology of interest (multiplexing) in a short assay time. One of the main unsolved issues in POCT device development is the integration of pre-analytical sample preparation procedures in the miniaturized device. In this work, an integrated POCT system based on gravitational field-flow fractionation (GrFFF) and chemiluminescence (CL) detection is presented for the on-line sample pre-analytical treatment and/or clean-up and analysis of biological fluids. As a proof of principle for the new GrFFF-CL POCT system, the automatic on-line analysis of plasma alkaline phosphatase activity, a biomarker of obstructive liver diseases and bone disorders, starting from whole blood samples was developed. The GrFFF-CL POCT system was able to give quantitative results on blood samples from control and patients with low sample volume (0.5 μL) and reagent consumption, short analysis time (10 minutes), high reproducibility and with a linear range of 50-1400 IU L(-1). The system can be easily applied to on-line prepare plasma from whole blood for other clinical biomarkers and for other assay formats, based on immunoassay or DNA hybridization.

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Microchip-based Plasma Separation from Whole Blood via Axial Migration of Blood Cells

Cited by 14 publications

References 38 publications

Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood

Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood

Micro-scale blood plasma separation: from acoustophoresis to egg-beaters

Gravitational field-flow fractionation integrated with chemiluminescence detection for a self-standing point-of-care compact device in bioanalysis

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