Abstract
Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC) chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading) inlet and the parallel (in-line) inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies.
Highlights
In vivo cells work properly by responding to their environmental chemical and physical stimuli such as chemical gradients of various growth factors and mechanical interactions with the extracellular matrix (ECM)
As shown in the left panel, a square laminar flow profile appears in the cross-section perpendicular to the flow in the left panel, a square laminar flow profile appears in the cross-section perpendicular to the flow direction
In the right panel, where the cross-section is parallel to the flow direction, the flow velocity direction
Summary
In vivo cells work properly by responding to their environmental chemical and physical stimuli such as chemical gradients of various growth factors and mechanical interactions with the extracellular matrix (ECM). Petri dishes and microplates are commonly used for in vitro cell studies because of their easy operation in cell culture and observation In using such macro-scaled devices, the consumption of reagents and cells is great, and cells grow in a static (non-circulating) environment. To overcome these hurdles, micro-fabricated devices integrated with fluidic components have recently become popular as an alternative platform for cell studies in a more controllable manner. Micro-fabricated devices integrated with fluidic components have recently become popular as an alternative platform for cell studies in a more controllable manner These microfluidic chips are capable of creating a precise micro-environment of chemical and physical stimuli while minimizing the consumption of cells and reagents and maintaining cells in circulating surrounding. They can be made of glass substrates, silicon wafers, polymethylmethacrylate (PMMA) substrates, polyethyleneterephthalate (PET) substrates, or polydimethylsiloxane (PDMS)
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