Engineering microfluidic concentration gradient generators for biological applications

Toh, Alicia Guek Geok; Wang, Z. P.; Yang, Chun; Nguyen, Nam‐Trung

doi:10.1007/s10404-013-1236-3

Cited by 158 publications

(103 citation statements)

References 119 publications

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“…For instance, patterning with light-induced release of adhesive constraints (Rolli et al, 2012;Vignaud et al, 2012) has been used to study the transition from static to migratory behaviors. Our understanding of migration along gradients of soluble factors (chemotaxis) has benefited from microfluidics, where gradients of soluble factors that are transverse to the direction of microfluidic flow can be created (Chung and Choo, 2010;King et al, 2016;Li Jeon et al, 2002;Toh et al, 2014). Passive diffusion of a chemoattractant across a porous membrane has also been used to create local gradients in the absence of flow (Dupin et al, 2013).…”

Section: Cell Migrationmentioning

confidence: 99%

How cells respond to environmental cues – insights from bio-functionalized substrates

Ruprecht

Monzo

Ravasio

et al. 2016

Journal of Cell Science

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Biomimetic materials have long been the (he)art of bioengineering. They usually aim at mimicking in vivo conditions to allow in vitro culture, differentiation and expansion of cells. The past decade has witnessed a considerable amount of progress in soft lithography, bioinspired micro-fabrication and biochemistry, allowing the design of sophisticated and physiologically relevant micro-and nanoenvironments. These systems now provide an exquisite toolbox with which we can control a large set of physicochemical environmental parameters that determine cell behavior. Biofunctionalized surfaces have evolved from simple protein-coated solid surfaces or cellular extracts into nano-textured 3D surfaces with controlled rheological and topographical properties. The mechanobiological molecular processes by which cells interact and sense their environment can now be unambiguously understood down to the single-molecule level. This Commentary highlights recent successful examples where bio-functionalized substrates have contributed in raising and answering new questions in the area of extracellular matrix sensing by cells, cell-cell adhesion and cell migration. The use, the availability, the impact and the challenges of such approaches in the field of biology are discussed.

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Section: Cell Migrationmentioning

confidence: 99%

How cells respond to environmental cues – insights from bio-functionalized substrates

Ruprecht

Monzo

Ravasio

et al. 2016

Journal of Cell Science

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“…There are comprehensive review papers in literature that have outlined the development and the variety of flow-based microfluidic devices for bacterial chemotaxis [17][18][19] as well as for general biomedical research. [20][21][22] Here, we summarize a few flow-based microfluidic designs that many of these devices share in common. The simplest design of a microfluidic gradient generator is shown in Figure 1(a), where two streams of fluid, one containing a chemoeffector, join together at a junction.…”

Section: Flow-based Microfluidics Gradient Generators For Bacterimentioning

confidence: 99%

A hybrid microfluidic device for on-demand orientation and multidirectional imaging of C. elegans organs and neurons

et al. 2016

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C. elegans is a well-known model organism in biology and neuroscience with a simple cellular (959 cells) and nervous (302 neurons) system and a relatively homologous (40%) genome to humans. Lateral and longitudinal manipulation of C. elegans to a favorable orientation is important in many applications such as neural and cellular imaging, laser ablation, microinjection, and electrophysiology. In this paper, we describe a micro-electro-fluidic device for on-demand manipulation of C. elegans and demonstrate its application in imaging of organs and neurons that cannot be visualized efficiently under natural orientation. To achieve this, we have used the electrotaxis technique to longitudinally orient the worm in a microchannel and then insert it into an orientation and imaging channel in which we integrated a rotatable glass capillary for orientation of the worm in any desired direction. The success rates of longitudinal and lateral orientations were 76% and 100%, respectively. We have demonstrated the application of our device in optical and fluorescent imaging of vulva, uterine-vulval cell (uv1), vulB1\2 (adult vulval toroid cells), and ventral nerve cord of wild-type and mutant worms. In comparison to existing methods, the developed technique is capable of orienting the worm at any desired angle and maintaining the orientation while providing access to the worm for potential post-manipulation assays. This versatile tool can be potentially used in various applications such as neurobehavioral imaging, neuronal ablation, microinjection, and electrophysiology.

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Section: Flow-based Microfluidics Gradient Generators For Bacterimentioning

confidence: 99%

Perspectives in flow-based microfluidic gradient generators for characterizing bacterial chemotaxis

2016

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Chemotaxis is a phenomenon which enables cells to sense concentrations of certain chemical species in their microenvironment and move towards chemically favorable regions. Recent advances in microbiology have engineered the chemotactic properties of bacteria to perform novel functions, but traditional methods of characterizing chemotaxis do not fully capture the associated cell motion, making it difficult to infer mechanisms that link the motion to the microbiology which induces it. Microfluidics offers a potential solution in the form of gradient generators. Many of the gradient generators studied to date for this application are flow-based, where a chemical species diffuses across the laminar flow interface between two solutions moving through a microchannel. Despite significant research efforts, flow-based gradient generators have achieved mixed success at accurately capturing the highly subtle chemotactic responses exhibited by bacteria. Here we present an analysis encompassing previously published versions of flow-based gradient generators, the theories that govern their gradient-generating properties, and new, more practical considerations that result from experimental factors. We conclude that flow-based gradient generators present a challenge inherent to their design in that the residence time and gradient decay must be finely balanced, and that this significantly narrows the window for reliable observation and quantification of chemotactic motion. This challenge is compounded by the effects of shear on an ellipsoidal bacterium that causes it to preferentially align with the direction of flow and subsequently suppresses the cross-flow chemotactic response. These problems suggest that a static, non-flowing gradient generator may be a more suitable platform for chemotaxis studies in the long run, despite posing greater difficulties in design and fabrication.

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Engineering microfluidic concentration gradient generators for biological applications

Cited by 158 publications

References 119 publications

How cells respond to environmental cues – insights from bio-functionalized substrates

How cells respond to environmental cues – insights from bio-functionalized substrates

A hybrid microfluidic device for on-demand orientation and multidirectional imaging of C. elegans organs and neurons

Perspectives in flow-based microfluidic gradient generators for characterizing bacterial chemotaxis

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