As good as today’s modern cell culture imaging microscope systems are today, many of these devices are extremely expensive and while they offer some basic controls over temperature, humidity, and nutrient, their ability to precisely control the actual microenvironment of the cells is limited.
Introduction to Microfluidics |
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A New Standard for Cell Culture
Today, all the major microscope manufacturers offer devices built for live-cell imaging. Many of these systems come complete with computerized incubation chambers and microscope stages that allow multilayered integration of key parameters:- Cooling
- Heating
- Environmental gases
- Mineral balance
Microfluidic Control of Assay Environments
The science of Microfluidics started in the printing and inkjet arenas but now as found applications in every major biological and physical science arena. Biologists are examining microfluidic solutions across a wide arena of specialties, including drug discovery and drug delivery, genetics and genetic sequencing challenges such as the typing of single nucleotide polymorphisms, to proteomics, and even to the newly emerging field termed “lab-on-a-chip” solution systems where several different laboratory functions are performed simultaneously.
Biological Microfluidics
Biological microfluidics is an emerging multidisciplinary science that intersects the fields of biotechnology, biochemistry, chemistry, nanotechnology and physics to create devices that control the cell culture microenvironment. Diffusion in a microfluidic environment can be tightly controlled, making addition and removal of cell culture chamber materials (extrinsic factors) much easier.
In Vivo-Like Cell Culture
Microfluidic systems provide many advantages for live cell imaging, including improved cell culture micro-environments. The tight control of fluid flows assists in creating and maintaining more predictive cell cultures, including mixed cultures, 3D and 4D cultures. Current strategies for 3D cell culture include growing cells in hanging drops, in a natural or synthetic 3D matrix on biodegradable polymers in a cross-linked hydrogel or in porous synthetic scaffolds. Even in these advanced platforms, if subjected to static conditions of gas, nutrient medium and waste buildup, they are limited by the inefficient mass transport between the inside and outside of the 3D cell structures. Microfluidic control of microenvironments is being used increasingly to overcome the challenges of mass transport in 3D culture.
Three-dimensional culture and assessment of drug-induced cell death using the CellASIC® ONIX Microfluidic PlatformDownload Application Note
8 Critical cell culture parameters that can be controlled by microfluidics in combination with a closed culture system
| Parameter | Some Effects of Deficient values | Some Effects of Excessive values |
|---|---|---|
| Temperature | Decreased cell response | Increased respiration/ protein damage |
| Oxygen Level | Decreased pH/increased glycolysis | Increased ROS, Membrane damage |
| Growth Factors | Increased apoptosis/ decreased protein synthesis | Increased angiogenesis and cell division |
| Humidity | Increased osmolarity/ cell metabolism / increase oxidative stress | No significant changes |
| pH | Increased Alkalosis and dehydration | Protein and membrane denaturation |
| Osmolarity | Decreased cell division / increased autophagic proteolysis | Increased oxidative stress, DNA breakage, and nutrient digestion |
| Glucose | Decreased autophagy and metabolism | Increased Apoptosis and ROS |
| ECM and Adhesion | Decreased angiogenesis / aberrant differentiation | Increased cell adhesion, chemotaxis, proliferation |