Microfluidics technology is characterized by the manipulation of small volumes of fluids (10-9 to 10-18 liters) in channels with dimensions of tens of micrometers. Certain properties of microfluidic technologies such as rapid sample processing and the precise control of fluids in an assay have made them attractive candidates that may replace traditional cell culture approaches.

Components of A Microfluidics System

A microfluidic system must have the following generic elements.

  • Method to introduce reagents and samples
  • Method for moving and combining these fluids on a chip
  • Devices for detection and analysis

While there are a variety of approaches to manufacturing microfluidic devices, soft lithography of an organosilicon compound called poly-dimethylsiloxane (PDMS) is the standard for cell culture applications. Using this technique, structures of micrometer resolution are molded from a hard master into PDMS. Many advanced microfluidic chips use miniaturized micromechanical membrane valves made from PDMS to efficiently manipulate fluids at the microliter scale. These valves allow exact spatial and temporal control of fluid flow and delivery of media, drugs and signaling factors to live cells.

Microfluidic Cell Culture

Culturing and propagating cells in vitro is an expensive, time consuming and laborious task. With the advent of robotics, time-consuming, manual pipetting steps are eliminated which increase throughput and accuracy.

Recent insights from the emerging fields of quantitative and systems biology underscored the need for analyzing individual cells instead of merely bulk cell cultures. Because of natural cell-to-cell variability in biochemical parameters such as transcript and protein expression levels and the molecular noise, population-averaged bulk assays are often inaccurate or misleading. Hence, dynamic analysis of cells is crucial to understanding how biological systems operate.

In this regard, microfluidic cell culture allows controlling fluid flow in precisely defined geometries and facilitates simultaneous manipulation and analysis starting from a single cell level to larger cell populations and up to tissues cultured on fully integrated and automated chips.

When to Use Microfluidic Cell Culture

  • If cell culture requires long run time with constant monitoring
  • Tracking of cellular responses is necessary
  • Controlled, dynamic microenvironments is desired
  • For very small volumes and runs requiring minimal handling of samples and events

Pros and Cons of Microfluidic Cell Culture

Pros Cons
High degree of control over culture conditions Hydrophobicity and porosity of PDMS results in material loss due to absorption of hydrophobic molecules such as lipids and small molecules
Dose delivery to cells can be measured up to femtoliters To prevent above problem, continual replacement of culture media becomes necessary
Precise control of cell numbers and cell density To prevent above problem, continual replacement of culture media becomes necessary
Allows greater control of cell placement and cell monitoring Toxicity due to PDMS
Ability to culture cells in structures that mimic tissue organization

Applications of Microfluidic Cell Culture

Microfluidic technology is emerging as an invaluable tool that is finding applications in tissue engineering, diagnostics, drug screening, immunology, cancer research and stem cell biology. The following are current or potential applications of Microfluidic cell culture devices.

  • The development of novel bioassays for monitoring patient response to therapy
  • Development of diagnostic assays for biomarker research and disease screening purpose
  • Analytical applications for the production and use of biopharmaceuticals
  • Improvements in the quantification of single cell gene expression, RNA sequencing, or proteomic analysis of selected cells at given time points could contribute to addressing important questions in systems and quantitative biology
  • Controlled recovery of single cells from microfluidic cell culture chips could facilitate integration of analytical methods such as high-throughput qPCR, mass spectrometry, and next generation sequencing
  • There is a potential to widen the use of microfluidic cell culture devices in generating physiologically relevant in vitro scenarios of basic processes such as infection, immune response, and clonal expansion and selection of activated immune cells
  • The culture of intact tissues in microfluidics is possibly the next frontier in microfluidics research
  • Dynamic biochemical and biomechanical manipulation of cells and culture conditions has the potential to generate artificial tissues from dissociated cells

References

  • Mehling, M., Tay, S., (2014). Microfluidic cell culture. Current Opinion in Biotechnology. 25:95–102
  • Masoomeh, T., Kouzani, A. Z., Francis, P. S., Kanwar, J. R., (2013). Microfluidic devices for cell cultivation and proliferation. BIOMICROFLUIDICS2
  • Whitesides, G. M., (2006) The origins and the future of microfluidics. Nature, Vol  442
  • Matsumura T, Tatsumi K, Noda Y, Nakanishi N, Okonogi A, Hirano K, Li L, Osumi T, Tada T, Kotera H., (2014). Single-cell cloning and expansion of human induced pluripotent stem cells by a microfluidic culture device. Biochem Biophys Res Commun
  • Harink B, Gac S. L, van Blitterswijk C, Habibovic P., (2014) Microfluidic platform with four orthogonal and overlapping gradients for soluble compound screening in regenerative medicine research. Electrophoresis
  • Sackmann EK, Fulton AL, Beebe DJ., (2014) The present and future role of microfluidics in biomedical research. Nature  13;507(7491):181-9
  • Kim D, Wu X, Young AT, Haynes CL., (2014) Microfluidics-based in vivo mimetic systems for the study of cellular biology. Acc Chem Res 47(4):1165-73

While microfluidics for cell culture is a valuable technique, it cannot yet be used to produce recombinant proteins. GenScript offers transient and stable mammalian cell expression systems for the production of high quality recombinant proteins. To get a quote for one of these services, click here.

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