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      An optofluidic system with integrated microlens arrays for parallel imaging flow cytometry

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          Abstract

          In recent years, high-speed imaging has become increasingly effective for the rapid analysis of single cells in flowing environments.

          Abstract

          In recent years, high-speed imaging has become increasingly effective for the rapid analysis of single cells in flowing environments. Single cell imaging methods typically incorporate a minimum magnification of 10× when extracting sizing and morphological information. Although information content may be significantly enhanced by increasing magnification, this is accompanied by a corresponding reduction in field of view, and thus a decrease in the number of cells assayed per unit time. Accordingly, the acquisition of high resolution data from wide field views remains an unsolved challenge. To address this issue, we present an optofluidic flow cytometer integrating a refractive, microlens array (MLA) for imaging cells at high linear velocities, whilst maximizing the number of cells per field of view. To achieve this, we adopt an elasto-inertial approach for cell focusing within an array of parallel microfluidic channels, each equipped with a microlens. We characterize the optical performance of the microlenses in terms of image formation, magnification and resolution using both ray-tracing simulations and experimental measurements. Results demonstrate that the optofluidic platform can efficiently count and magnify micron-sized objects up to 4 times. Finally, we demonstrate the capabilities of the platform as an imaging flow cyclometer, demonstrating the efficient discrimination of hB and Jurkat cells at throughputs up to 50 000 cells per second.

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          Most cited references25

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          Continuous inertial focusing, ordering, and separation of particles in microchannels.

          Under laminar flow conditions, when no external forces are applied, particles are generally thought to follow fluid streamlines. Contrary to this perspective, we observe that flowing particles migrate across streamlines in a continuous, predictable, and accurate manner in microchannels experiencing laminar flows. The migration is attributed to lift forces on particles that are observed when inertial aspects of the flow become significant. We identified symmetric and asymmetric channel geometries that provide additional inertial forces that bias particular equilibrium positions to create continuous streams of ordered particles precisely positioned in three spatial dimensions. We were able to order particles laterally, within the transverse plane of the channel, with >80-nm accuracy, and longitudinally, in regular chains along the direction of flow. A fourth dimension of rotational alignment was observed for discoidal red blood cells. Unexpectedly, ordering appears to be independent of particle buoyant direction, suggesting only minor centrifugal contributions. Theoretical analysis indicates the physical principles are operational over a range of channel and particle length scales. The ability to differentially order particles of different sizes, continuously, at high rates, and without external forces in microchannels is expected to have a broad range of applications in continuous bioparticle separation, high-throughput cytometry, and large-scale filtration systems.
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            Tunable nonlinear viscoelastic "focusing" in a microfluidic device.

            In this Letter we describe a novel method for tunable viscoelastic focusing of particles flowing in a microchannel. It is proposed that some elasticity, inherently present in dilute polymer solutions, may be responsible for highly nonuniform spatial distribution of flowing particles across the channel cross section, yielding their "focusing" in the midplane of the channel. A theory based on scaling arguments is presented to explain the lateral migration and is found to be in a very good agreement with the experimental observations. It was found that, in agreement with the theoretical prediction, the particles would have different spatial distribution depending on their size and rheology of the suspending medium. We demonstrate how the viscoelastic focusing can be precisely controlled by proper rheological design of the carrier solution.
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              Microfluidics and point-of-care testing.

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                Author and article information

                Journal
                LCAHAM
                Lab on a Chip
                Lab Chip
                Royal Society of Chemistry (RSC)
                1473-0197
                1473-0189
                November 20 2018
                2018
                : 18
                : 23
                : 3631-3637
                Affiliations
                [1 ]Institute for Chemical and Bioengineering
                [2 ]Department of Chemistry and Applied Biosciences
                [3 ]ETH Zürich
                [4 ]8093 Zürich
                [5 ]Switzerland
                [6 ]Department of Bionano Technology
                [7 ]Hanyang University
                [8 ]Ansan 15588
                [9 ]South Korea
                Article
                10.1039/C8LC00593A
                30357206
                8bd56471-fbb2-44d3-aaf2-9c2481aa0e71
                © 2018

                http://rsc.li/journals-terms-of-use

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