Multiple Myeloma Cell Drug Responses Differ in Thermoplastic vs PDMS Microfluidic Devices

Area of Science:

• Materials Science
• Biomedical Engineering
• Pharmacology

Background:

• Poly(dimethylsiloxane) (PDMS) is widely used for microfluidic devices.
• PDMS is known to absorb hydrophobic molecules, potentially affecting experimental results.
• Accurate drug-material interactions are vital for microfluidic chemosensitivity and resistance assays (CSRAs) in cancer therapy selection.

Purpose of the Study:

• To investigate the absorption of small hydrophobic cancer drugs in PDMS microfluidic devices.
• To assess the impact of drug absorption on cytotoxicity measurements.
• To compare drug absorption and cytotoxicity in PDMS versus other microfluidic materials.

Main Methods:

• Fabrication of microfluidic devices using polystyrene (PS), cyclo-olefin polymer (COP), and PDMS.
• Treatment of multiple myeloma (MM) cells with bortezomib (BTZ) and carfilzomib (CFZ) in the devices.
• Determination of half-maximal inhibitory concentrations (IC50) for each drug-material combination.
• Analysis of drug adsorption and absorption using time-of-flight secondary ion mass spectrometry (ToF-SIMS).

Main Results:

• PDMS devices showed a ~4.3x higher IC50 compared to thermoplastic PS and COP devices.
• ToF-SIMS analysis confirmed significant drug absorption in PDMS (BTZ ~5.0 μm, CFZ ~3.5 μm).
• Drug absorption in PS and COP was considerably lower, in the range of ~100-300 nm.

Conclusions:

• Drug absorption in PDMS microfluidic devices significantly biases cytotoxicity measurements.
• Material selection is critical for the accuracy of microfluidic drug testing platforms.
• Thermoplastic materials like PS and COP are more suitable for applications involving hydrophobic cancer drugs.