Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels

Manbachi, Amir; Shrivastava, Shamit; Cioffi, Margherita; Chung, Bong Geun; Moretti, Matteo; Demirci, Utkan; Yliperttula, Marjo; Khademhosseini, Ali

doi:10.1039/b718212k

Cited by 75 publications

(85 citation statements)

References 44 publications

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“…Recently this approach has been extended and applied to a multi-level stacked substrate, radial flow bioreactor (Park et al, 2008). Recently, it was also demonstrated that the fluid dynamic environment within microgrooves, which varies with groove width, can affect cell localization and retention following cell seeding and prior to their adhesion and culture (Manbachi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Design of well and groove microchannel bioreactors for cell culture

Korin

Bransky

Khoury

et al. 2008

Biotech & Bioengineering

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Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro-wells/grooves bioreactors, in which micro-topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro-groove/micro-well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro-wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 microm depth) and well bioreactors (35 microm depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays.

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Section: Introductionmentioning

confidence: 99%

Design of well and groove microchannel bioreactors for cell culture

Korin

Bransky

Khoury

et al. 2008

Biotech & Bioengineering

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“…First examples of such manipulation harnessed capillary effect, however the development of microfabrication technologies enabled more sophisticated ways of hydrodynamic manipulation of cells and fluid flow. As an example, cells could be aligned to a single line by using sheath flow, this technique is one of many alternative hydrodynamic focusing techniques [1,2].…”

Section: Open Accessmentioning

confidence: 99%

Manipulation of cells’ position across a microfluidic channel using a series of continuously varying herringbone structures

Jung

Hyun

Choi

et al. 2017

Micro and Nano Syst Lett

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Controlling cells' movement is an important technique in biological analysis that is performed within a microfluidic system. Many external forces are utilized for manipulation of cells, including their position in the channel. These forces can effectively control cells in a desired manner. Most of techniques used to manipulate cells require sophisticated set-ups and equipment to generate desired effect. The exception to this is the use of hydrodynamic force. In this study, a series of continuously varying herringbone structures is proposed for positioning cells in a microfluidic channel using hydrodynamic force. This structure was experimentally developed by changing parameters, such as the length of the herringbone's apex, the length of the herringbone's base and the ratio of the height of the flat channel to the height of the herringbone structure. Results of this study, have demonstrated that the length of the herringbone's apex and the ratio of the heights of the flat channel and the herringbone structure were crucial parameters influencing positioning of cells at 100 μl/h flow rate. The final design was fixed at 170 and 80 μm for the length of herringbone's apex and the length of herringbone's base, respectively. The average position of cells in this device was 34 μm away from the side wall in a 200 μm wide channel. Finally, to substantiate a practical application of the herringbone structure for positioning, cells were randomly introduced into a microfluidic device, containing an array of trapping structures together with a series of herringbone structures along the channel. The cells were moved toward the trapping structure by the herringbone structure and the trapping efficiency was increased. Therefore, it is anticipated that this device will be utilized to continuously control cells' position without application of external forces.

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“…The depressed trenches and microtraps serve to shield the cells from flow-induced shear stresses (Figure 1(b)). 48 The perfusion layer consists of one focal channel, adjacent to which are two flanking channels which drive flow into an open chamber containing the cells, and apposed on the other side of the open chamber by a vacuum channel which aspirates the flow (Figures 1(b) and 1(c)). We define the focal and flanking channel openings as "microjets," since the cross-sectional areas of these openings are much smaller than the rest of the connected fluidic channels: 20 lm Â 20 lm for the focal channel and 50 lm Â 50 lm for the flanking channel.…”

Section: A Device Overviewmentioning

confidence: 99%

An open-chamber flow-focusing device for focal stimulation of micropatterned cells

et al. 2016

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Microfluidic devices can deliver soluble factors to cell and tissue culture microenvironments with precise spatiotemporal control. However, enclosed microfluidic environments often have drawbacks such as the need for continuous culture medium perfusion which limits the duration of experiments, incongruity between microculture and macroculture, difficulty in introducing cells and tissues, and high shear stress on cells. Here, we present an open-chamber microfluidic device that delivers hydrodynamically focused streams of soluble reagents to cells over long time periods (i.e., several hours). We demonstrate the advantage of the open chamber by using conventional cell culture techniques to induce the differentiation of myoblasts into myotubes, a process that occurs in 7-10 days and is difficult to achieve in closed chamber microfluidic devices. By controlling the flow rates and altering the device geometry, we produced sharp focal streams with widths ranging from 36 lm to 187 lm. The focal streams were reproducible ($12% variation between units) and stable ($20% increase in stream width over 10 h of operation). Furthermore, we integrated trenches for micropatterning myoblasts and microtraps for confining single primary myofibers into the device. We demonstrate with finite element method (FEM) simulations that shear stresses within the cell trench are well below values known to be deleterious to cells, while local concentrations are maintained at $22% of the input concentration. Finally, we demonstrated focused delivery of cytoplasmic and nuclear dyes to micropatterned myoblasts and myofibers. The open-chamber microfluidic flow-focusing concept combined with micropatterning may be generalized to other microfluidic applications that require stringent long-term cell culture conditions. Published by AIP Publishing. [http://dx

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Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels

Cited by 75 publications

References 44 publications

Design of well and groove microchannel bioreactors for cell culture

Design of well and groove microchannel bioreactors for cell culture

Manipulation of cells’ position across a microfluidic channel using a series of continuously varying herringbone structures

An open-chamber flow-focusing device for focal stimulation of micropatterned cells

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