Open microfluidics Microfluidics refers to the flow of fluid in channels or networks with at least one dimension on the micron scale. In open microfluidics, also referred to as open surface microfluidics or open-space microfluidics, at least one boundary confining th ...

can be employed in the multidimensional culturing of cell types for various applications including

organ-on-a-chip An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture, integrated circuit (chip) that simulates the activities, mechanics and physiological response of an entire organ or an organ system, a type of artificial organ. It constitu ...

studies, oxygen-driven reactions,

neurodegeneration A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...

, and other cellular pathways.

Usage and benefits

The use of conventional microfluidic devices for cell studies has already improved upon the

cost effective Cost-effectiveness analysis (CEA) is a form of economic analysis that compares the relative costs and outcomes (effects) of different courses of action. Cost-effectiveness analysis is distinct from cost–benefit analysis, which assigns a monetar ...

ness and sample volume requirement, however using open microfluidic channels adds the benefit of removing

syringe pump A syringe driver, also known as a syringe pump, is a small infusion pump, used to gradually administer small amounts of fluid (with or without medication) to a patient or for use in chemical and biomedical research. Some syringe drivers can both ...

s to drive flow, now governed by

surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension is what allows objects with a higher density than water such as razor blades and insects (e.g. water striders) to f ...

s that drive spontaneous

capillary flow Capillary action (sometimes called capillarity, capillary motion, capillary rise, capillary effect, or wicking) is the process of a liquid flowing in a narrow space without the assistance of, or even in opposition to, any external forces li ...

(SCF), and exposes cells to the surrounding environment.Lee, J. J., Berthier, J., Brakke, K. A., Dostie, A. M., Theberge, A. B., & Berthier, E. (2018). Droplet Behavior in Open Biphasic Microfluidics. ''Langmuir'', ''34''(18), 5358–5366. The miniaturization of this process allows for improved sensitivity, high throughput, and ease of manipulation and integration, as well as dimensions that can be more physiologically relevant. The benefits of both open and closed microfluidic platforms have allowed the option for the combination of the two, where the device is open for the introduction and culturing of cells, and can be sealed prior to analysis.

Design

Cells and

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s can be patterned in microfluidic devices with one of the channel walls exposed in different geometries and designs depending on the behaviors and interactions to be studied, such as

quorum sensing In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...

or co-culturing of several types of cells. A majority of cell culturing has been carried out by introducing the cells in a perfused conditioned medium to simulate the desired cell populations in traditional close-channel microfluidic devices. The challenge to support the cell growth and simultaneously study multiple cell types in a single device with an exposed channel is that the interactions between cells in this medium needs to be controlled since the timing and location of the interactions is critical. This issue can be addressed in several ways including the modification of the device design, using droplet microfluidics, and

cell sorting Cell sorting is the process through which a particular cell type is separated from others contained in a sample on the basis of its physical or biological properties, such as size, morphological parameters, viability and both extracellular and intra ...

.Kaigala, G. V., Lovchik, R. D., & Delamarche, E. (2012). Microfluidics in the “open Space” for performing localized chemistry on biological interfaces. ''Angewandte Chemie - International Edition'', ''51''(45), 11224–11240. Not only does this allow for the ease of manipulating the environment of the cells, but having an open channel wall allows for a better understanding of biological interactions at this interface. Creating designs of microfluidic platforms with different compartments that are isolated and have different dimensions allows for co-culturing of several types of cells. These devices often incorporate droplet formation to encapsulate cells and act as transport and reaction vehicles in two or more immiscible phases, making it possible to carry out numerous parallel analyses using different conditions. Open microfluidics has also been coupled with fluorescence-activated

(FACS) to allow for cells to be contained in individually sorted compartments in an open microfluidic network for culturing in an exposed environment. The exposure of one of the channel walls introduces the issue of evaporation and therefore cell loss, however this issue can be minimized by using droplet microfluidics where the cell-containing droplets are submerged in a

fluorinated In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a chemical compound, compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the prod ...

oil. Although evaporation is a major disadvantage of using an open microfluidic system for cell culturing, the advantages over a closed system include ease of manipulation and access to the cells. For certain applications, such as the study of drug transport and lung function using alveolar epithelium cells, air exposure to is essential for developing the lungs.

PDMS

Polydimethylsiloxane Polydimethylsiloxane (PDMS), also known as dimethylpolysiloxane or dimethicone, belongs to a group of polymeric organosilicon compounds that are commonly referred to as silicones. PDMS is the most widely used silicon-based organic polymer, as its ...

(PDMS) is a common material for open microfluidic devices that introduces additional advantages and disadvantages. The

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a f ...

of small biological molecules from cell culturing samples as well as the release of

oligomers In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...

into the culture medium have both been posed as issues of using PDMS for biological studies, however these can be reduced by adopting pretreatment procedures to create optimal environments. Advantages of using PDMS include the ease of surface modification, low cost, biocompatibility, and optical transparency. In addition, PDMS is an attractive material to use for generating oxygen gradients for cell culturing in studies that involve monitoring ROS governed cellular pathways due to its oxygen permeability. Plastics such as

polystyrene Polystyrene (PS) is a synthetic polymer made from monomers of the aromatic hydrocarbon styrene. Polystyrene can be solid or foamed. General-purpose polystyrene is clear, hard, and brittle. It is an inexpensive resin per unit weight. It is a ...

can be used to create microfluidic devices by embossing and bonding methods,

CNC milling Numerical control (also computer numerical control, and commonly called CNC) is the automated control of machining tools (such as drills, lathes, mills, grinders, routers and 3D printers) by means of a computer. A CNC machine processes a ...

injection molding Injection moulding (U.S. spelling: injection molding) is a manufacturing process for producing parts by injecting molten material into a mould, or mold. Injection moulding can be performed with a host of materials mainly including metals (for ...

, or

stereolithography Stereolithography (SLA or SL; also known as vat photopolymerisation, optical fabrication, photo-solidification, or resin printing) is a form of 3D printing technology used for creating models, prototypes, patterns, and production parts in a lay ...

. Devices created with polystyrene by these methods include microfluidic platforms that integrate several microfluidic systems, creating arrays to study several cell cultures simultaneously. Another type of material that is used for open-microfluidic cell culturing is

paper-based microfluidics Paper-based microfluidics are microfluidic devices that consist of a series of hydrophilic cellulose or nitrocellulose fibers that transport fluid from an inlet through the porous medium to a desired outlet or region of the device, by means of capi ...

. Cell culturing on paper-based microfluidic devices is accomplished either by encapsulating cells in a

hydrogel A hydrogel is a crosslinked hydrophilic polymer that does not dissolve in water. They are highly absorbent yet maintain well defined structures. These properties underpin several applications, especially in the biomedical area. Many hydrogels ar ...

or directly seeding them in stacked

cellulose Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wall ...

filter paper Filter paper is a semi-permeable paper barrier placed perpendicular to a liquid or air flow. It is used to separate fine solid particles from liquids or gases. The raw materials are different paper pulps. The pulp may be made from softwood, hardwo ...

s and the cell culture medium is passively transported to the culture areas.Tao, F. F., Xiao, X., Lei, K. F., & Lee, I. C. (2015). Paper-based cell culture microfluidic system. ''Biochip Journal'', ''9''(2), 97–104. A major advantage of this type of open-microfluidics includes the low cost, the variety of dimensions of porous papers that are commercially available, improved cell viability, adhesion, and migration over tissue culture plates.Ng, K., Gao, B., Yong, K. W., Li, Y., Shi, M., Zhao, X., … Xu, F. (2017). Paper-based cell culture platform and its emerging biomedical applications. ''Materials Today'', ''20''(1), 32–44. In addition, it is an attractive substrate for 3D cell culture devices due to its ability to incorporate essential characteristics such as oxygen and nutrient gradients, fluid flow that can control

, and stacking filter papers with different cells suspended in

to monitor cellular interactions or complex populations.

References

{{reflist Microfluidics Cell culture