Cell pinball: phenomenon and mechanism of inertia-like cell motion in a microfluidic channel

Microfluidic devices are used extensively in the development of new in vitro cell culture models like organs-on-chips. A typical feature of such devices is the patterning of biological hydrogels to offer cultured cells and tissues a controlled three-dimensional microenvironment. A key challenge of hydrogel patterning is ensuring geometrical confinement of the gel, which is generally solved by inclusion of micropillars or phaseguides in the channels. Both of these methods often require costly cleanroom fabrication, which needs to be repeated even when only small changes need be made to the gel geometry, and inadvertently expose cultured cells to non-physiological and mechanically stiff structures. Here, we present a technique for facile patterning of hydrogel geometries in microfluidic chips, but without the need for any confining geometry built into the channel. Core to the technique is the use of laminar flow patterning to create a hydrophilic path through an otherwise hydrophobic microfluidic channel. When a liquid hydrogel is injected into the hydrophilic region, it is confined to this path by the surrounding hydrophobic regions. The various surface patterns that are enabled by laminar flow patterning can thereby be rendered into three-dimensional hydrogel structures. We demonstrate that the technique can be used in many different channel geometries while still giving the user control of key geometric parameters of the final hydrogel. Moreover, we show that human umbilical vein endothelial cells can be cultured for multiple days inside the devices with the patterned hydrogels and that they can be stimulated to migrate into the gel under the influence of trans-gel flows. Finally, we demonstrate that the patterned gels can withstand trans-gel flow velocities in excess of physiological interstitial flow velocities without rupturing or detaching. This novel hydrogel-patterning technique addresses fundamental challenges of existing methods for hydrogel patterning inside microfluidic chips, and can therefore be applied to improve design time and the physiological realism of microfluidic cell culture assays and organs-on-chips.

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Cell Motion in a Two-Stream Microfluidic Channel

Journal of Medical Devices ◽

10.1115/1.3135194 ◽

2009 ◽

Vol 3 (2) ◽

Author(s):

J. Hanna ◽

T. B. Darr ◽

A. Hubel ◽

C. Mata ◽

E. K. Longmire ◽

...

Keyword(s):

Microfluidic Channel ◽

Microfluidic Channels ◽

Flow Conditions ◽

Cell Recovery ◽

Average Cell ◽

Gravitational Settling ◽

Cryoprotective Agents ◽

Cell Motion ◽

Velocity Region ◽

Number Of Cells

Microfluidic channels have been proposed as a method for removal of cryoprotective agents from cell suspensions [Fleming, Longmire, and Hubel, J. Biomech. Eng. 129, 703 (2007)]. The device tested consists of a rectangular cross section channel of 500 μm depth, 25 mm width, and 160 mm length, through which a cell suspension and wash stream flow in parallel. Cryoprotective agents diffuse from the cell stream to the wash stream and the wash stream is discarded. The washed cell stream is then ready for use. This device must be capable of removing 95% of the dimethyl sulfoxide (DMSO) from the cell stream with minimal cell losses. Our previous studies have demonstrated our ability to remove DMSO [Mata, Longmire, McKenna, Glass, and Hubel, Microfluid. Nanofluid. 5, 529 (2008)]. The next phase of the investigation involves characterizing the influence of flow conditions on cell motion through the device. To that end, Jurkat cells (lymphoblasts) in a 10% DMSO solution were flowed through the microfluidic channel in parallel with a wash stream composed of phosphate buffered saline solution (PBS). Average cell stream velocities were varied from 0.94 to 8.5 mm/s (Re 1.7 to 6.0). Cell viability at the outlet was high, indicating that cells are not damaged during their passage through the device. Gravitational settling caused an accumulation of cells near the bottom of the channel, where flow velocities are low. Cell settling leads results in an initial transient period for cell motion through the device. For the initial portion of cells flowing through the device, cells tend to accumulate in the device until a critical device population time is reached. Cell recovery (number of cells out of the device divided by the number of cells input to the device) is high (90–100%) after the device has been fully populated. For a single stage device with average cell stream velocities of ⩾6 mm/s, cell recovery was 90–100%. As more stages are added to the device, the population time for the device increases. Gravitational settling of cells also leads to a time-varying cell concentration from the input syringe to the inlet of the channel, as well as cell losses due to cells remaining in the horizontally-oriented syringe. Reorienting the syringes to a vertical position eliminates these losses. Cell motion within the channel can be modulated by the flow conditions used. For sufficiently high Reynolds numbers, the Segre-Silberberg effect [Segre and Silberberg, J. Fluid Mech. 14, 115 (1962)] can be used to move cells from the low velocity region of the cell stream to a higher velocity region thereby reducing the transient portion of processing the cells and improving overall recovery of cells through the device.

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Flow Boiling Heat Transfer and Two-Phase Flow Pressure Drop in Thin-Rectangular Channels

ASME 2008 6th International Conference on Nanochannels, Microchannels, and Minichannels ◽

10.1115/icnmm2008-62026 ◽

2008 ◽

Author(s):

Yasuo Koizumi ◽

Tomonari Yamada ◽

Hiroyasu Ohtake

Keyword(s):

Heat Transfer ◽

Pressure Drop ◽

Laminar Flow ◽

Flow Boiling ◽

Flow Region ◽

Flow Channel ◽

Phase Flow ◽

Two Phase ◽

Rectangular Channels ◽

Boiling Flow

Heat transfer and pressure drop of single- and two-phase flow in thin-rectangular channels of the width of 10 mm have been examined. The gap clearance δ of the flow channel covered a range from 0.6 mm to 0.1 mm. In the water single-phase flow condition, the narrowness effect came out around δ = 0.37 ∼ 0.35 mm. Below that value, the friction factor became lower than the value of the usual size in the laminar flow region and the transition from the laminar flow to the turbulent flow was delayed. The Nusselt number also showed dependency on the Reynolds number even in the laminar flow region and became lower than the value for the usual size over the whole Reynolds number region. Bubbly flow, slug flow, semi annular flow and annular flow were observed in boiling flow. The flow pattern transition agreed well with the Baker flow pattern map for the usual size. The Martinelli and Nelson method for the two-phase pressure drop of the boiling flow predicted well present experimental results. Boiling was dominant during the forced flow boiling. The heat transfer coefficient of the boiling flow was larger than the value of the usual sized flow channel. The critical heat flux was lower than the value of the usual sized flow channel. The Koizumi and Ueda method predicted well the trend of the critical heat flux of the present experiments.

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Iterative Learning Control of Two-Phase Laminar Flow Interface in Y-Shaped Microfluidic Channel

IEEE Transactions on Control Systems Technology ◽

10.1109/tcst.2018.2854626 ◽

2019 ◽

Vol 27 (6) ◽

pp. 2743-2748 ◽

Cited By ~ 7

Author(s):

Yong Chen ◽

Tao Meng ◽

Yaolei Wang ◽

Kang Wang ◽

Shixin Meng ◽

...

Keyword(s):

Laminar Flow ◽

Iterative Learning Control ◽

Microfluidic Channel ◽

Learning Control ◽

Iterative Learning ◽

Two Phase

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Computational cell analysis for label-free detection of cell properties in a microfluidic laminar flow

The Analyst ◽

10.1039/c6an00295a ◽

2016 ◽

Vol 141 (13) ◽

pp. 4142-4150 ◽

Cited By ~ 5

Author(s):

Alex Ce Zhang ◽

Yi Gu ◽

Yuanyuan Han ◽

Zhe Mei ◽

Yu-Jui Chiu ◽

...

Keyword(s):

Machine Learning ◽

Laminar Flow ◽

Learning Algorithms ◽

Microfluidic Channel ◽

Machine Learning Algorithms ◽

Fluid Mechanic ◽

Cell Analysis ◽

Label Free ◽

Computational Cell ◽

Label Free Detection

This method utilizes machine learning algorithms and fluid mechanic properties of cells in a microfluidic channel to find the compositions of cell mixtures.

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