We created two kinds of microfluidic chips based on the crossflow filtration principle which can be more effective than conventional types in the area of avoiding clogging or jamming. Simple filter microchip for rapid separation of plasma and viruses from whole blood the harvard community has made this article openly available. The separation method developed in this work can be applied to various onchip stationary filtrations of rbc for pointofcare clinical diagnostics. Separation and collection of wbc and rbc, starting from a sample of whole blood, are the required steps for the subsequent clinica and basic research assays. Various sized silica beads were packed inside a microchannel using a slurrybump pattern that prevented the beads from passing through the microchannel. The plasma separation was based on both crossflow filtration and sedimentation of red blood cells in the microchannels. In addition, flow rate and voltage effects on extraction efficiency are also evaluated. Integrated lateral flow device for flow control with blood separation and biosensing veronica betancur 1, jianbo sun 2. The straight channels are designed to permit the inertial migration effect and to concentrate the blood cells, while the curve channels allow the dean flow to further classify the blood cells based on the cell sizes. Rapid isolation of wbcs directly from whole blood is a prerequisite for any integrated immunoassay platform designed for examining wbc phenotypes and functions. A capillary dielectrophoretic chip for realtime blood cell separation from a drop of whole blood. Sep 17, 2012 lastly, we investigated the onchip recovery of hiv particles, which have diameters ranging from 110 to 146 nm,29 from whole blood spiked with hiv or from hivinfected patient blood samples. Implementing blood separation, one of the key steps of blood analysis, on labonachip devices has long been a major research focus. Although various microfluidicbased blood cell separation or plasma extraction techniques have been demonstrated, to the best of our knowledge.
Video related to research article appearing in lab on a chip. The final hbv concentration of the sample was 10 4 10 6 copies ml1. Efficient separation of cellular populations from whole blood is an essential preparatory step for many biological and clinical assays 1. Background the use of centrifugationbased approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of whole blood into distinct red blood cell rbc, platelet, and plasma products. This paper describes a novel design of an outofplane microvalve that enables high performance of whole blood separation on labonacd centrifugal devices. Pdf a plasma separating biochip is demonstrated using a capillarydriven contactless dielectrophoresis method with low voltage 1 v and high. With its ability to perform rapid, biocompatible, labelfree, contactfree, and continuousflow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role. Outofplane microvalves for whole blood separation on lab. The device can separate plasma from whole blood and quantify plasma proteins in a single step.
Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels the dielectrophoresis dep phenomenon is used to separate platelets directly from diluted whole blood in microfluidic channels. One of the key research fields involves the separation and detection of circulating tumor cells ctc because of their suggested important role in early cancer. The disadvantage of this process is that the patients must have assays performed at the hospital or laboratory where the separation facility is located. Place the centrifuge tube in the centrifuge machine and run it at 3000 rpm for 10 minutes. The chip has 10 switchback curve channels, which are connected by straight channels. This paper presents a novel high throughput blood plasma separation microfluidic chip, which with just a single droplet of undiluted human blood 5l can separate more than 0. Current clinical methods for the separation of whole blood into blood cells and cellfree plasma are currently based on large facility equipment, such as centrifuges. Downloaded by university of cincinnati on 21082014 16. Dielectrophoretic separation of platelets from diluted. The present study presents a design for microfluidic chips with different.
Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for on chip genomic analysis. Micromachines free fulltext highthroughput white blood. To the best of our knowledge, there is not an existing on chip virus isolation technology that does not use complex fluidic pumps. Microfluidic chip for plasma separation from undiluted human whole. Highthroughput and cloggingfree microfluidic filtration. Beadpacked microchannel, blood plasma separator, onchip filtration, pointofcare testing introduction for practical implementation of biochips in poct clinical diagnostics, onchip. The plasma separation membrane needs to be trimmed and put in a close contact with the underneath microstructures in the plasma separation cp. The bloodplasma separator with beadpacked microchannel has successfully separated plasma from the whole blood without haemolysis of rbcs. This highthroughput, cloggingfree, and highly integrated platform holds. To the best of our knowledge, there is not an existing onchip virus isolation technology that does not use complex fluidic pumps. Simultaneous separation, metering, and dilution of plasma.
We describe a microfluidic technique for separation of particles and cells and a device that employs this technique to separate white blood cells wbc from whole human blood. Mar 28, 2014 video related to research article appearing in lab on a chip. On chip pretreatment of whole blood by using mems technology the microfabrication technology has stimulated a plurality of lab on a chip research for biomedical researchers and health care practitioners to manipulate and analyze complex biological fluids at the nano and microliter scale. Into dry clean centrifuge tube, pipette 15 ml of whole blood v1. Integrated separation of blood plasma from whole blood for microfluidic paperbased analytical devices x.
This device combines the ability to perform plasma separation from human whole blood, control the. Highthroughput white blood cell leukocyte enrichment. Centrifugation of whole blood separates the solid from the supernatant plasma. We have developed a unique, integrated, onchip technology that is capable of isolating exosomes or other types of extracellular vesicles, directly from undiluted wholeblood samples in an automated fashion. However, the logistical complications and potential cellular damage associated with centrifugationapheresis. This real time movie is representative of a typical human blood assay. Siliconbased microfilters for whole blood cell separation. Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for onchip genomic analysis. Selfpowered microfluidic chips for multiplexed protein. An onchip whole bloodplasma separator with beadpacked. Microfluidic vortex enhancement for onchip sample preparation. A microfluidic chip for blood plasma separation using eof control.
The chip was characterized in its ability to filter solutions containing fluorescent beads. Component room should be a separate sanitised room. The movie shows how the air pressure that is generated in the h2o2 fuel reservoir is harnessed to separate plasma from whole blood. Each blood component is used for a different indication. Onchip pretreatment of whole blood by using mems technology ebook. The development of microfilter devices for onchip blood separation utilizing capillary action spans several key disciplines. Biomimetic design of a microfluidic device for autoseparation of leukocytes from whole blood s.
The developed separator provides a new approach to on chip separation of plasmaserum for pointofcare testing poct. A new onchip whole blood plasma separator driven by asymmetric capillary forces. We created a simple microfluidic device that takes advantage of the intrinsic features of blood flow in the microcirculation, such as plasma skimming and leukocyte margination, to separate leukocytes directly from whole blood. Beadpacked microchannel, blood plasma separator, on chip filtration, pointofcare testing introduction for practical implementation of biochips in poct clinical diagnostics, on chip. In particular, for white blood cell separation, the chip recovered 72. We have developed a unique, integrated, on chip technology that is capable of isolating exosomes or other types of extracellular vesicles, directly from undiluted whole blood samples in an automated fashion. Pdf microfluidic chip for plasma separation from undiluted human. Herein we report a microfluidic chip for continuousflow isolation and sorting of wbcs from whole blood with high throughput and separation efficiency. Onestep pathogen specific dna extraction from whole blood on. The separation method developed in this work can be applied to various on chip stationary filtrations of rbc for pointofcare clinical diagnostics. Simple filter microchip for rapid separation of plasma and. Continuousflow microfluidic blood cell sorting for. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99. After blood collection, components should be separated within 5 8 hours.
First step, in the most blood assays is plasma extraction from whole blood. Here, we presented a lab on a chip filter device to isolate plasma and viruses from unprocessed whole blood based on size exclusion without using a micropump. Whole blood is a mixture of various cells, such as red blood cell rbc, white blood cell wbc and so on. Microfluidic chip for plasma separation from undiluted human. A graphical schematic of the microfluidic chip design and sample processing. A portable system for processing donated whole blood into. Technologies for circulating tumor cell separation from. A disposable onchip whole bloodplasma separator, which is able to separate plasma from whole blood by capillary movement through a beadpacked microchannel, has been designed, fabricated and characterized in this work.
The whole blood is collected as 350 ml or 450 ml in doubletriplequadruple or penta bags with cpda1 or additive solution. Results and discussion herein we report a microfluidic chip for continuousflow isolation and sorting of wbcs from whole blood with high throughput and separation efficiency. Pdf blood separation on microfluidic paperbased analytical. Therefore, it is concluded that the proposed microfluidic device is promising for separating wbcs from whole blood without any pretreatment and lysing the wbcs in a continuous and near real. The conventional method for separating the cellular fraction from whole blood is by centrifugation, which requires a laboratory infrastructure. Continuousflow microfluidic blood cell sorting for unprocessed whole blood using surfacemicromachined microfiltration. Recently, more and more researchers are paying attention to onchip whole blood sample pretreatment, which is the focus of this ebook, aiming to form real micro total analysis systems utas for whole blood analysis by integrating blood sample pretreatment and. Blood cells separation and sorting techniques of passive. Microfluidic chip for plasma separation from undiluted. Isolation of exosomes from whole blood by integrating. Microfluidic chip for blood cell separation and collection. The separation strategy is straightforward and the device is easy to manufacture, due to its lack of. Wholeblood sorting, enrichment and in situ immunolabeling.
By exploiting the fact that platelets are the smallest. Blood plasma is the medium in which the blood cells red cells, white cells, and platelets are suspended. The microfluidic cell sorting chip leveraged the crossflow filtration. Beadpacked microchannel, bloodplasma separator, onchip filtration, pointofcare testing introduction for practical implementation of biochips in poct clinical diagnostics, onchip. The developed separator provides a new approach to onchip separation of plasmaserum for pointofcare testing poct. Integrated lateral flow device for flow control with blood. We separated viruses, which were 110146 nm in size,29 from whole blood using a microchip with 12. Jun 28, 2018 human plasma is extracted from whole blood without dilution or other complex pre.
A microfluidic chip for blood plasma separation using eof. It operates on microliter samples of whole blood, provides positive, continuous flow selection of. Rapid and safe isolation of human peripheral blood b and t. In about a 3 min period, we have simultaneously separated plasma from human whole blood and metered and diluted the plasma using a microchip with an interchannel microstructure. Lastly, we investigated the onchip recovery of hiv particles, which have diameters ranging from 110 to 146 nm,29 from whole blood spiked with hiv or from hivinfected patient blood samples. The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. Rapid and safe isolation of human peripheral blood b and t lymphocytes through spiral microfluidic channels. Isolation of plasma from whole blood using planar microfilters for lab. We evaluated the effect of pore size on plasma separation using four filter membranes of different pore sizes 0. The conventional method for separating the cellular fraction from whole blood is by centrifugation, which requires a laboratory. Because simpler integrated and more efficient plasma extraction methods that avoid sample dilution are highly desired, the authors develop a simple dielectrophoresis dep.
Biomimetic design of a microfluidic device for auto. Remove the tube, withdraw the liquid layer plasma by pasture pipette and. The whole blood which is a mixture of cells, colloids and crystalloids can be separated into different blood components namely packed red blood cell prbc concentrate, platelet concentrate, fresh frozen plasma and cryoprecipitate. Design and simulation of a microfluidic bloodplasma. Several different techniques are applied for onchip plasma separation from whole blood. Rapid isolation of blood plasma using a cascaded inertial. In addition, the blood cell rejection ratio was further improved to 97. Integrated separation of blood plasma from whole blood for. Simple filter microchip for rapid separation of plasma and viruses from whole blood.
The separation is performed in crossflow in an array of microchannels with a deep main channel and large number of orthogonal, shallow side channels. Here, we presented a labonachip filter device to isolate plasma and viruses from unprocessed whole blood based on size exclusion without using a micropump. Wang, shuqi, dusan sarenac, michael h chen, shihhan huang, francoise f giguel, daniel r kuritzkes, and utkan demirci. Technologies for circulating tumor cell separation from whole. Xing chen onchip pretreatment of whole blood by using mems technology ebook. A microfluidic chip, which can separate and enrich leukocytes from whole blood, is proposed.
Onchip pretreatment of whole blood by using mems technology. The first chip uses continuous deterministic lateral displacement dld with an array of dropletshaped posts with 20 or 32. Using human whole blood, the microfilters have been characterized and compared for their blood handling capacity, wbcs trapping efficiency and rbcs passing efficiency. Onchip pretreatment of whole blood by using mems technology view sample. Labelfree cancer cell separation from human whole blood.
Microfluidic device with integrated porous membrane for cell sorting and separation. A side channel network was used to skim off the plasma from the cellfree layer while all blood cells were kept in the main channel. Metering and diluting operations of the plasma were based on volume control of liquid in the. Jun 19, 2010 the blood plasma separator with beadpacked microchannel has successfully separated plasma from the whole blood without haemolysis of rbcs.
Proteins are the most abundant solid components of plasma, with total protein plasma concentration ranging from 6 to 8 gdl average 7. Cryoprecipitate same storage as ffp cannot be refrozen as ffp once it is separated. Onestep pathogen specific dna extraction from whole blood. Both microbead mixture and undiluted whole blood sample are separated by the platform effectively. A microfluidic device for simultaneous extraction of plasma, red. Blood components and preparation linkedin slideshare. Wholeblood sorting, enrichment and in situ immunolabeling of. Conventional macroscale cell sorting techniques include.
Microfluidic blood plasma separation for medical diagnostics. Outofplane microvalves for whole blood separation on labon. Schematic illustration of the acoustic separation mechanism showing cells beginning to translate from the sidewall to the center of the channel due to axial acoustic forces applied to the cells when they enter the working region of the standing surface acoustic waves. A microfluidic device for continuous white blood cell.
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