Two words sum up the advantages microfluidics offers over traditional cell culture techniques: control and consistency. One of the primary challenges of traditional cell culture techniques is maintaining control over the microenvironment. Doing this requires a lot of monitoring and staff time that could be spent focusing on other productive activities. Microfluidics offers a higher degree of fluid control and automation than traditional cell culture techniques. With appropriately sized channels and chambers that can accommodate biological cells and tissues, microfluidic chips give you precise control over the chemical and physical microenvironment including:

• Convection
• Diffusion
• Reaction
• Flow rate
• Mechanical stimulation
• Electrical stimulation and sensing
• Cell matrix
• pH levels
• Temperature
• Monitoring
• Cell placement
• Cell numbers
• Dose delivery to cells
• Density

Having control over the cellular and biochemical microenvironment is extremely important, especially for stem cell applications. When cells consume culture medium and metabolize, nutrients and oxygen can be monitored and replenished continuously using continuous perfusion systems, and waste can be carried away via fluid flow. Microfluidics can mick the microenvironmental conditions of the desired case study, leading to a more realistic and reliable models and results.

Obviously, cell culture using microfluidic technology is not without some drawbacks, many of which are being addressed in various ways. The primary limitations for adopting microfluidics for cell culture applications are inertia and money. Conventional 2D cell culture methods have been around for more than 100 years and it can be a challenge to get people to adopt new technology, especially one that is more complex to learn initially. Regarding money, while manufacturing microfluidic chips can be relatively inexpensive once designed, switching from a simple 2D cell culture methodology to a more complex 3D microfluidic technology can be costly to set up. In the long run those costs are offset because once designed and implemented, a microfluidic process saves labor time, is scalable and consistent.

While the presence of shear stress on cells can be a key parameter to generate certain microenvironmental conditions (endothelial cells), it could also be an issue, that may be overcome by reducing flow rates, altering channel depths or geometries, incorporating microwells and other techniques. While the technology associated with microfluidic channels, pumps and valves, is always improving, microfluidic chips may not be a good fit for some applications including those with large tissue explants.

Most cell culture chips and micromechanical valves are made from PDMS which is easy to fabricate and exhibits excellent biocompatibility and transparency characteristics (good for fluorescence detection). Other thermoplastic polymers offer promise for specific microfluidic cell culture use cases:

• Polystyrene (PS)
• Polycarbonate (PC)
• Cyclo-olefin polymers and copolymers (COP)
• Polymethyl methacrylate (PCCA)

All of these have various pluses and minuses related to fabrication, oxygen permeability, biological inertness, ease of bonding, autofluorescence and optical clarity. One drawback of PDMS is that is has a tendency to absorb small molecules and thus can be challenging for studying longer term interactions.

Cell culture has traditionally been done in two-dimensional format using flat plastic dishes. This method is inexpensive and simple to understand. However, conducting cell culture in a 2D environment makes it difficult to get a true understanding of how the cells interact with one another and the surrounding 3D extracellular matrix (ECM). When used exclusively for studies, 2D cell cultures may result in misleading data.

Microfluidics supports 2D and 3D environments but the most compelling argument for investing in a microfluidic solution is to replicate 3D “in vivo” cell activity. Microfluidic cartridges work well in a 3D construct since real 3D networks and scaffolds can be created and inserted to regulate fluid flow.

While microfluidics applications for cell culture is becoming more widely adopted in research settings, commercial applications are emerging. One exciting applications is generally referred to as “organ on a chip” and is used to study lung, heart, liver, kidney, gut and other cellular interactions. This field holds commercial promise because of the contributions that it may make to pre-clinical drug research, clinical diagnosis, personalized treatment, regenerative medicine, identifying disease biomarkers and more.