PDMS in biology research and more precisely PDMS biocompatibility is an important parameter in many fields of nowadays biology research as microfluidics and lab-on-a-chip is of choice to study various aspects of organ on a chip.
From a technological point of view, the ability to make microfluidic devices in a few hours, without the need for clean room equipments, remains very attractive for research teams beginning in microfluidics.
Crosslinked PDMS block
Additionally PDMS shows numerous advantages coming from its intrinsic properties:
PDMS presents many advantages for biological studies. Some of them are summarised below:
Using PDMS in biology research also has some drawbacks:
Despite those limitations, PDMS microfluidic devices are widely used for cell studies and will probably be used more and more for researches in cell biology.
It is then necessary to understand the effects of microscale environment to integrate the results obtained in microfluidic devices with biological experiments obtained using traditional methods.
Biological results obtained in microfluidic devices have already been of great interest for cell biology but the careful understanding of condition changes generated by miniaturization and properties of PDMS will lead to a better understanding of those results.
There are significant differences in proliferation, glucose consumption, gene expression patterns and mitosis defects between traditional well plates and PDMS micro cell culture. Paguirigan & al used In-Cell western (ICW), which allows to quantify protein expression changes, to show differences signaling pathway activation and protein expression levels between experiments in PDMS microsystems and traditional in-vitro experiments [7]. These studies also show significant inhibition of mouse fibroblast proliferation with 3 times higher glucose consumption. Observations in PDMS microchannel show smaller amounts of cells performing division and show several different cell cycle progression problems with a lot of arrest in S/G2 phase.
One explanation of this difference in behavior could be that microscale culture generally increases the cell volume density (cell by unit of medium) compared to multiwall plates leading to more rapid waste products accumulation and medium consumption. But using higher concentration media has little impact on proliferation; suggesting that the volume density is not the predominating factor [7].
Main reasons for these differences between macro and micro scaled culture systems could be:
Uncrosslinked low molecular weight polymer may also leach from the polymer to the medium and monomer could interact with hydrophobic parts of the cell membrane. Absorption of media components into PDMS, particularly hydrophobic molecules. Hydrophobic growth factors or lipids from the cell culture medium can migrate into the PDMS bulk. This loss of lipids, which is a source of energy for cells, in PDMS may explain the increase in glucose consumption.
One solution to overcome those problems is to perform cell culture with a proper renewal of cell medium which allows evacuation of wastes and renewal of nutriments.
Indeed, Leclerc & al showed that, in the case no media change, glucose and albumin concentrations within the device drop after three days, leading to cells death; but a renewal of media leads to constant albumin and glucose concentrations and long term cells viability [6].
Most of the microfluidic cell culture systems presented before included convective or diffusive medium renewal, depending on the application. Nevertheless, this method may thus not be sufficient for studies like cell signaling studies and determination of drug dose-response where precise molecules amounts absorbed or produced by the cell are crucial. In those cases, medium non-renewal and PDMS absorption could strongly bias the results.
Concerning medium gas composition, since PDMS is permeable to gas, this material allows enough O2 renewal by diffusion through a PDMS wall for cell culture.
Leclerc & al showed that gas diffusion through PDMS walls of 200 µm is sufficient for long term culture of hepatocarcinoma [6]. However, many publications cited before in this review described cell proliferation and growth for weeks. All of them used a medium renewal system to allow proper cells growth for long term experiments.
This review has shown that PDMS in biology research and more precisely PDMS biocompatibility is of importance in many fields of nowadays biology research as microfluidics and lab-on-a-chip is of choice to study the effect of various parameters such as flow rate, and the resulting shear stress on cell growth or bacteria proliferation in a microchannel.
PDMS biocompatibility has been proven over the years. Nevertheless, it remains very dependent upon its environment (time, humidity, temperature) which can be detrimental for experimental reproducibility. It is possible to perform relevant biological studies in PDMS microsystems when taking into account limitations of this technology. Additional studies will be required to identify which kind of results obtained in such kind of microsystems will be exploitable and in which conditions. Instead of trying to correct intrinsic characteristics of PDMS like its surface chemistry, some laboratories develop and test new polymers which could allow same technological potentialities than PDMS with better chemical properties. For more detailed critical information on PDMS as a material for microfluidic devices, one can read [8].
For more reviews about microfluidics, please visit our other reviews here: «Microfluidics reviews». The photos in this article come from the Elveflow® data bank, Wikipedia or elsewhere if specified. Article written by Guilhem Velvé Casquillas and Timothée Houssin and revised by Lauren Durieux.
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