Flow focusing through gels as a tool to generate 3D concentration profiles in hydrogel-filled microfluidic chips

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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A 3D hydrodynamic flow-focusing device for cell sorting

Microfluidics and Nanofluidics ◽

10.1007/s10404-021-02425-y ◽

2021 ◽

Vol 25 (3) ◽

Author(s):

Xiaofei Yuan ◽

Andrew Glidle ◽

Hitoshi Furusho ◽

Huabing Yin

Keyword(s):

Cell Sorting ◽

Control Strategies ◽

Three Dimensional ◽

Hydrodynamic Flow ◽

Proof Of Concept ◽

Flow Focusing ◽

Hydrodynamic Focusing ◽

Cell Handling ◽

Fluid Flow Control ◽

High Degree

AbstractOptical-based microfluidic cell sorting has become increasingly attractive for applications in life and environmental sciences due to its ability of sophisticated cell handling in flow. The majority of these microfluidic cell sorting devices employ two-dimensional fluid flow control strategies, which lack the ability to manipulate the position of cells arbitrarily for precise optical detection, therefore resulting in reduced sorting accuracy and purity. Although three-dimensional (3D) hydrodynamic devices have better flow-focusing characteristics, most lack the flexibility to arbitrarily position the sample flow in each direction. Thus, there have been very few studies using 3D hydrodynamic flow focusing for sorting. Herein, we designed a 3D hydrodynamic focusing sorting platform based on independent sheath flow-focusing and pressure-actuated switching. This design offers many advantages in terms of reliable acquisition of weak Raman signals due to the ability to precisely control the speed and position of samples in 3D. With a proof-of-concept demonstration, we show this 3D hydrodynamic focusing-based sorting device has the potential to reach a high degree of accuracy for Raman activated sorting.

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The Lagrangian kinematics of three-dimensional Darcy flow

Journal of Fluid Mechanics ◽

10.1017/jfm.2021.362 ◽

2021 ◽

Vol 918 ◽

Author(s):

Daniel R. Lester ◽

Marco Dentz ◽

Aditya Bandopadhyay ◽

Tanguy Le Borgne

Keyword(s):

Three Dimensional ◽

Darcy Flow

Abstract

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3D Culture Systems for Exploring Cancer Immunology

Cancers ◽

10.3390/cancers13010056 ◽

2020 ◽

Vol 13 (1) ◽

pp. 56

Author(s):

Allison A. Fitzgerald ◽

Eric Li ◽

Louis M. Weiner

Keyword(s):

Immune Cell ◽

Three Dimensional ◽

3D Culture ◽

3D Models ◽

Therapeutic Benefit ◽

Cancer Immunology ◽

Microfluidic Chips ◽

Murine Models ◽

Human Immune System ◽

Culture Systems

Cancer immunotherapy has revolutionized cancer treatment, spurring extensive investigation into cancer immunology and how to exploit this biology for therapeutic benefit. Current methods to investigate cancer-immune cell interactions and develop novel drug therapies rely on either two-dimensional (2D) culture systems or murine models. However, three-dimensional (3D) culture systems provide a potentially superior alternative model to both 2D and murine approaches. As opposed to 2D models, 3D models are more physiologically relevant and better replicate tumor complexities. Compared to murine models, 3D models are cheaper, faster, and can study the human immune system. In this review, we discuss the most common 3D culture systems—spheroids, organoids, and microfluidic chips—and detail how these systems have advanced our understanding of cancer immunology.

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Bifurcation Characteristics of Flows in Rectangular Sudden Expansion Channels

Volume 1: Symposia, Parts A and B ◽

10.1115/fedsm2005-77098 ◽

2005 ◽

Cited By ~ 2

Author(s):

Francine Battaglia ◽

George Papadopoulos

Keyword(s):

Reynolds Number ◽

Laminar Flow ◽

Critical Reynolds Number ◽

Three Dimensional ◽

Reynolds Numbers ◽

Expansion Ratio ◽

Sudden Expansion ◽

Two Dimensional ◽

Effective Expansion ◽

Three Dimensional Simulations

The effect of three-dimensionality on low Reynolds number flows past a symmetric sudden expansion in a channel was investigated. The geometric expansion ratio of in the current study was 2:1 and the aspect ratio was 6:1. Both experimental velocity measurements and two- and three-dimensional simulations for the flow along the centerplane of the rectangular duct are presented for Reynolds numbers in the range of 150 to 600. Comparison of the two-dimensional simulations with the experiments revealed that the simulations fail to capture completely the total expansion effect on the flow, which couples both geometric and hydrodynamic effects. To properly do so requires the definition of an effective expansion ratio, which is the ratio of the downstream and upstream hydraulic diameters and is therefore a function of both the expansion and aspect ratios. When the two-dimensional geometry was consistent with the effective expansion ratio, the new results agreed well with the three-dimensional simulations and the experiments. Furthermore, in the range of Reynolds numbers investigated, the laminar flow through the expansion underwent a symmetry-breaking bifurcation. The critical Reynolds number evaluated from the experiments and the simulations was compared to other values reported in the literature. Overall, side-wall proximity was found to enhance flow stability, helping to sustain laminar flow symmetry to higher Reynolds numbers in comparison to nominally two-dimensional double-expansion geometries. Lastly, and most importantly, when the logarithm of the critical Reynolds number from all these studies was plotted against the reciprocal of the effective expansion ratio, a linear trend emerged that uniquely captured the bifurcation dynamics of all symmetric double-sided planar expansions.

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Time evolution of laminar flow over a three-dimensional backward-facing step

International Journal for Numerical Methods in Fluids ◽

10.1002/(sici)1097-0363(19991030)31:4<721::aid-fld897>3.0.co;2-b ◽

1999 ◽

Vol 31 (4) ◽

pp. 721-745 ◽

Cited By ~ 5

Author(s):

T.P. Chiang ◽

Tony W.H. Sheu

Keyword(s):

Laminar Flow ◽

Time Evolution ◽

Three Dimensional ◽

Backward Facing Step

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Heat Transfer for Laminar Flow in Spiral Ducts of Rectangular Cross Section

Journal of Heat Transfer ◽

10.1115/1.1857950 ◽

2005 ◽

Vol 127 (3) ◽

pp. 352-356 ◽

Cited By ~ 20

Author(s):

Michael W. Egner ◽

Louis C. Burmeister

Keyword(s):

Heat Transfer ◽

Nusselt Number ◽

Laminar Flow ◽

Cross Section ◽

Rectangular Cross Section ◽

Three Dimensional ◽

Radius Of Curvature ◽

Dean Number ◽

Aspect Ratios ◽

Small Pitch

Laminar flow and heat transfer in three-dimensional spiral ducts of rectangular cross section with aspect ratios of 1, 4, and 8 were determined by making use of the FLUENT computational fluid dynamics program. The peripherally averaged Nusselt number is presented as a function of distance from the inlet and of the Dean number. Fully developed values of the Nusselt number for a constant-radius-of-curvature duct, either toroidal or helical with small pitch, can be used to predict those quantities for the spiral duct in postentry regions. These results are applicable to spiral-plate heat exchangers.

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