[9][10] Additionally, uncured PDMS oligomers can leach into the cell culture media, which can harm the microenvironment.
[22] This technique has demonstrated a stark difference in the sensitivity of the peripheral terminals compared to the neuronal cell body to certain stimuli such as protons.
[22] This gives an excellent example as to why it is so important to study the peripheral terminals in isolation using microfluidic cell culture devices.
[10] Microfluidics also allow for chemical gradients, the continuous flow of fresh media, high through put testing, and direct output to analytical instruments.
[27] Many microfluidic systems employ the use of hydrogels as the extracellular matrix (ECM) support which can be modulated for fiber thickness and pore size and have been demonstrated to allow the growth of cancer cells.
The first report of these types of microfluidic cultures was used to study the toxicity of naphthalene metabolites on the liver and lung (Viravaidya et al.).
Some of the challenges include: imaging of the cells, control of gradients in static models (i.e., without a perfusion system), and difficulty recreating vasculature.
[37] Algae can be incubated, and their growth rate and lipid production can be monitored in a hanging-drop microfluidic system.
[46] Recently, co-culture has become the predominant approach to study the effect of cellular communication by culturing two biologically related cell types together.
[48][49] The more common method is segregated co-culture, where the two cell types are physically separated but can communicate in shared media by paracrine signaling.
[49][50][54][55] The flexibility of microfluidic devices greatly contributes to the development of multi-culture studies by improved control over spatial patterns.
For example, mixed co-culture can be achieved in droplet-based microfluidics easily by a co-encapsulation system to study paracrine and juxtacrine signaling.
[57] When embedded in gels, salivary gland adenoid cystic carcinoma (ACC) cells can be co-cultured with carcinoma-associated fibroblast (CAF) in a 3D extracellular matrix to study stroma-regulated cancer invasion in the 3D environment.
[59] Although closed channel microfluidics (discussed in the section above) offers high customizability and biological complexity for multi-culture, the operation often requires handling expertise and specialized equipment, such as pumps and valves.
[49][53] In addition, the use of PDMS is known to cause adverse effects to cell culture, including leaching of oligomers or absorption of small molecules, thus often doubted by biologists.
[60] Therefore, open microfluidic devices made of polystyrene (PS), a well-established cell culture material, started to emerge.
[60] The advantages of open multi-culture designs are direct pipette accessibility and easy fabrication (micro-milling, 3D printing, injection molding, or razor-printing – without the need for a subsequent bonding step or channel clearance techniques).
[49][53][61][62][63] They can also be incorporated into traditional cultureware (well plate or petri dish) while remaining the complexity for multi-culture experiments.
[49][53][62][63] For example, the "monorail device" which patterns hydrogel walls along a rail via spontaneous capillary flow can be inserted into commercially available 24-well plates.
Being able to provide different environments in a steady, sustainable and precise manner has a significant impact on cell culture research and study.
[65] Multiple microfluidic systems have been designed to control the desired gas concentrations for cell culture.
[67] Poly(methyl pentene) (PMP) may be an alternative material, because it has high oxygen permeability and biocompatibility like PDMS.