Advances in cell separation: recent developments in counterflow centrifugal elutriation and continuous flow cell separation

Bauer, Johann

doi:10.1016/s0378-4347(98)00308-9

Cited by 62 publications

(36 citation statements)

References 179 publications

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“…Later, in the nineteenth century, the development of tissue-staining techniques allowed the initial characterization the first blood cell populations. Even today, the examination of the peripheral blood film using Wright-Giemsa staining procedures and the full blood count are two of the most basic and yet the most informative investigations performed in hematology (2). Only flow cytometry techniques, available since the 1960s, can rival these in terms of finer details and higher throughput, representing today the golden standard in cell identification and separation.…”

Section: Introductionmentioning

confidence: 99%

Blood-on-a-Chip

Toner

Irimia²

2005

Annu. Rev. Biomed. Eng.

587

451

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Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.

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Section: Introductionmentioning

confidence: 99%

Blood-on-a-Chip

Toner

Irimia²

2005

Annu. Rev. Biomed. Eng.

587

451

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“…The separated compounds can be continuously collected as fractions at the separation channel outlets. FFE has been applied for separations and purifications of complex mixtures [9] containing proteins [10,11], peptides [10,12,13], cells [14], and small ions [15]. FFE was also used as a continuous sample preparation step [16][17][18] for online or offline analytical determinations.…”

Section: Introductionmentioning

confidence: 99%

Microchip free‐flow electrophoresis on glass substrate using laser‐printing toner as structural material

2006

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In this work, a microfluidic free-flow electrophoresis device, obtained by thermal toner transferring on glass substrate, is presented. A microdevice can be manufactured in only 1 h. The layout of the microdevice was designed in order to improve the fluidic and electrical characteristics. The separation channel is 8 microm deep and presents an internal volume of 1.42 microL. The deleterious electrolysis effects were overcome by using a system that isolates the electrolysis products from the separation channel. The Joule heating dissipation in the separation channel was found to be very efficient up to a current density of 8.83 mA/mm(2) that corresponds to a power dissipation per unit volume of running electrolyte of 172 mW/microL. Promising results were obtained in the evaluation of the microdevices for the separation of ionic dyes. The microfluidic device can be used for a continuous sample pretreatment step for micro total analysis system.

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“…One strategy is to eliminate tagging using technologies such as counterflow centrifugal elutriation (CCE) (Bauer, 1999;Donaldson et al, 1997), which separates based on size and density. While this type of technology is powerful in separating cell mixtures with significant difference in sizes as reviewed by Bauer (1999), it does not provide enough resolution to distinguish among blood cell or stem cell mixtures.…”

Section: Introductionmentioning

confidence: 99%

“…While this type of technology is powerful in separating cell mixtures with significant difference in sizes as reviewed by Bauer (1999), it does not provide enough resolution to distinguish among blood cell or stem cell mixtures. Similarly, while dielectrophoretic fractionation techniques can be useful to purify leukocytes from whole blood (Auerswald and Knapp, 2003;Yang et al, 1999), it would not be very effective in isolating CD4 þ T cells from other lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Enrichment using antibody‐coated microfluidic chambers in shear flow: Model mixtures of human lymphocytes

Sin

Murthy

Revzin

et al. 2005

Biotech & Bioengineering

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Isolation of phenotypically-pure cell subpopulations from heterogeneous cell mixtures such as blood is a difficult yet fundamentally important task. Current techniques such as fluorescent activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) require pre-incubation with antibodies which lead to processing times of at least 15-60 min. In this study, we explored the use of antibody-coated microfluidic chambers to negative deplete undesired cell types, thus obtaining an enriched cell subpopulation at the outlet. We used human lymphocyte cell lines, MOLT-3 and Raji, as a model system to examine the dynamic cell binding behavior on antibody coated surfaces under shear flow. Shear stress ranging between 0.75 and 1.0 dyn/cm2 was found to provide most efficient separation. Cell adhesion was shown to follow pseudo-first order kinetics, and an anti-CD19 coated (Raji-depletion) device with approximately 2.6 min residence time was demonstrated to produce 100% pure MOLT-3 cells from 50-50 MOLT-3/Raji mixture. We have developed a mathematical model of the separation device based on the experimentally determined kinetic parameters that can be extended to design future separation modules for other cell mixtures. We conclude that we can design microfluidic devices that exploits the kinetics of dynamic cell adhesion to antibody coated surfaces to provide enriched cell subpopulations within minutes of total processing time.

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Advances in cell separation: recent developments in counterflow centrifugal elutriation and continuous flow cell separation

Cited by 62 publications

References 179 publications

Blood-on-a-Chip

Blood-on-a-Chip

Microchip free‐flow electrophoresis on glass substrate using laser‐printing toner as structural material

Enrichment using antibody‐coated microfluidic chambers in shear flow: Model mixtures of human lymphocytes

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