In traditional biological research, cells are cultured in static petri dishes and drug testing relies heavily on animal models—a process that is time-consuming, costly, and often fails to accurately mimic the human body's true microenvironment. However, the emergence of microfluidics technology and its derivative, organ-on-a-chip (OOC), over the past two decades has revolutionized this approach by enabling precise manipulation of fluids, cells, and biochemical signals at the micrometer scale, effectively creating "miniaturized versions of human physiological functions" in vitro. At the heart of this paradigm shift in life sciences lies an unassuming material—polydimethylsiloxane (PDMS), a type of liquid silicone rubber—renowned for its unique physicochemical properties and hailed as the "cornerstone material" indispensable to this field.

1. Why Has PDMS Become the 'Gold Standard' for Microfluidics?

Since Harvard University's Whitesides group first systematically applied PDMS to create microchannels around 2000, it has rapidly become dominant in the microfluidics domain due to five core advantages:

Superior optical transparency (transmittance >90%) allows for real-time observation of cell behavior using high-resolution microscopy (bright-field, fluorescence, confocal) without dismantling the chip.

Excellent elasticity and reversible sealing: With a Shore hardness of approximately 40A–80A, PDMS facilitates easy demolding of complex three-dimensional microstructures and forms reversible seals with glass or silicon substrates, making replacement or cleaning straightforward.

Breathability supporting cellular respiration: PDMS exhibits high permeability to oxygen and carbon dioxide (O₂ diffusion coefficient ≈2.4×10⁻⁵ cm²/s), allowing adherent cells to survive long-term without additional gas supply, far surpassing other plastics like PMMA and PC.

Surface functionalization capability: Through oxygen plasma treatment, PDMS surfaces can be rendered hydrophilic from hydrophobic and grafted with biomolecules such as collagen, fibronectin, and peptides to guide cell adhesion and differentiation.

Rapid prototyping: Soft lithography involves pouring liquid PDMS onto a photoresist (e.g., SU-8) master mold, curing it at 60–80°C for one hour to produce high-fidelity microchannels (accuracy down to 1–10 μm) at low cost and short cycle times.

2. Key Applications in Organ-on-a-Chip

Organ chips aim to simulate specific organ microphysiological functions, such as lung breathing, intestinal absorption, and blood-brain barrier screening. PDMS plays multiple roles here:

Constructing dynamic microenvironments: A dual-layer PDMS chip with an intermediate porous membrane allows separate perfusion of "blood" and "air" in upper and lower channels; applying vacuum-induced negative pressure causes periodic stretching of the membrane to mimic alveolar breathing movements. Such "lung chips" can precisely evaluate nanoparticle toxicity or viral infection mechanisms.

Integrating multi-tissue interfaces: By placing hepatocytes, cardiomyocytes, endothelial cells in different chambers connected via microfluidic channels, the entire process from intestinal absorption through liver metabolism to cardiac toxicity can be simulated. PDMS's biocompatibility ensures minimal interference between tissues, with signaling mediated solely through fluid media.

Embedding sensors and actuators: Incorporating flexible electrodes into PDMS enables real-time monitoring of myocardial electrical activity, while integrating pneumatic actuators controls flow path switching for automated drug delivery. Its elasticity supports millions of cycles without failure.

3. Limitations and Solutions

Despite its numerous advantages, PDMS faces challenges in advanced applications:

表格

Problem Impact   Solution

Hydrophobicity leading to small molecule adsorption Drug concentration distortion, especially for lipophilic compounds  Surface coating with Pluronic F-127, PVA, or silanization modification

Swelling in organic solvents     Channel deformation, experimental failure    Limit ethanol use to <30% or develop fluorinated PDMS

Batch-to-batch variability Poor reproducibility   Use high-purity, pre-mixed commercial PDMS (e.g., Dow Corning Sylgard 184)

Non-degradability     Unsuitable for implantable long-term studies      Explore PDMS/hydrogel composites or transient silicon-based materials

4. Frontier Developments

3D-printed PDMS: Breaking free from traditional planar limitations to construct vascular networks, glomeruli, and other three-dimensional structures.

Body-on-a-Chip: Integrating more than ten organ modules on a PDMS platform to predict whole-body pharmacokinetics.

Patient-specific chips: Combining induced pluripotent stem cell (iPSC) technology with patient-specific cells and PDMS chips for personalized drug screening.

5. Ethical and Industrial Impact

Organ chips are progressively replacing certain types of animal experiments, with the European Union incorporating them into cosmetic safety assessment systems. The FDA has also launched a "tissue chip program" to expedite new drug approvals. All these advancements owe their origins to the soft, transparent, and malleable PDMS chip—an inert substance that provides the most realistic stage for understanding life.

Conclusion

On a PDMS chip measuring just millimeters across, what flows isn't merely microliters of fluid but humanity's humble exploration of life's complexity. It allows cells to thrive in biomimetic environments, drugs to undergo preliminary trials before human application, and disease mechanisms to reveal themselves under controlled conditions. As the silent backbone of microfluidics and organ-on-a-chip, silicone rubber, with its flexibility, supports a quiet yet profound revolution in life sciences. Here, every pulse of microfluid represents a solid step toward future medicine.


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