A POROUS MEMBRANE-INTEGRATED PMMA MICROFLUIDIC DEVICE FOR RELIABLE CYTOTOXICITY TESTS

다국어 초록 (Multilingual Abstract)

High-throughput microfluidic devices for cytotoxicity screening are currently in high demand because they take much less turnaround time and cost only a fraction to fabricate comparing to the traditional animal testing method. However, most of the previous works have failed to construct a reliable drug testing platform since the largely exploited material - polydimethylsiloxane (PDMS) – absorbs even small hydrophobic molecules, such as anti-cancer drugs. Several previous studies have switched to thermoplastics, including poly(methyl methacrylate) (PMMA), for its inherent impermeability to small molecules. Still, there is no record shown to integrate these resins with polyethylene terephthalate (PETE) track-etched membrane to form a fully compartmentalized chip. This study reports a novel use of (3-glycidyloxypropyl)trimethoxysilane (GLYMO) to achieve an irreversible bonding of PMMA to PETE membranes for developing a drug-testing model. Briefly, the PMMA substrates engraved with microfluidic channels were functionalized with air plasma for 1 min and assembled with a 5% GLYMO - coated PETE membrane, followed by clamping and heating in an oven at 100 °C for 2 min. The fabricated device endured up to 135kPa in gauge pressure and 1.97 × 10^7 kg m^-2 in shear force before showing any signs of liquid leakage. Drug testing efficacy was successfully validated as human lung adenocarcinoma cells showed more reliable cytotoxicity results for vincristine when cultured in the PMMA devices than those in the PDMS counterpart. Overall, our bonding approach was proven to be more advantageous over the fabrication methods using PDMS to construct a highly robust and reliable microfluidic device for promising pharmaceutical drug screening applications.

목차 (Table of Contents)

• I. Introduction-----------------------------------------------------------------------------------------11
• II. Materials and method----------------------------------------------------------------------------- 12
• 2.1 Microfluidic channel design and fabrication----------------------------------------------12
• 2.2 Chemical bonding strategy------------------------------------------------------------------14
• 2.3 Cell culture------------------------------------------------------------------------------------16
• 2.4 Bonding strength measurement-------------------------------------------------------------17
• 2.5 Small molecule absorption -----------------------------------------------------------------17
• 2.6 Cytotoxicity testing of drug-----------------------------------------------------------------18
• Statistical analysis---------------------------------------------------------------------------------18
• III. Results and discussion ---------------------------------------------------------------------------19
• 3.1 Bonding strategy and experimental validation-------------------------------------------19
• 3.2 Bonding strength evaluation----------------------------------------------------------------23
• 3.3 Cell culture and cytotoxicity testing of drug----------------------------------------------25
• IV. Conclusion-----------------------------------------------------------------------------------------29
• V. Reference ------------------------------------------------------------------------------------------30
• VI. Acknowledgment ---------------------------------------------------------------------------------31