Robust chemical bonding of PMMA microfluidic devices to porous PETE membranes for reliable cytotoxicity testing of drugs

• Published in: Lab on a chip Vol. 19; no. 21; pp. 376 - 3713
• Main Authors: Nguyen, Thao, Jung, Su Hyun, Lee, Min Seok, Park, Tae-Eun, Ahn, Suk-kyun, Kang, Joo H
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 07.11.2019
• Subjects: Air plasma; Bonding strength; Chemical bonds; Cytotoxicity; Drugs; Engraving; Membranes; Microfluidic devices; Organic chemistry; Polydimethylsiloxane; Polyethylene terephthalate; Polymethyl methacrylate; Silicone resins; Substrates; Thermoplastic resins; Toxicity testing
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/c9lc00338j

Here, we report a simple yet reliable method for bonding poly(methyl methacrylate) (PMMA) to polyethylene terephthalate (PETE) track-etched membranes using (3-glycidyloxypropyl)trimethoxysilane (GLYMO), which enables reliable cytotoxicity tests in a microfluidic device impermeable to small molecules, such as anti-cancer drugs. The porous PETE membranes treated with 5% GLYMO were assembled with microfluidic channel-engraved PMMA substrates after air plasma treatment for 1 minute, followed by heating at 100 °C for 2 minutes, which permits irreversible and complete bonding to be achieved within 1 h. The bonding strength between the two substrates (1.97 × 10 7 kg m −2 ) was robust enough to flow culture medium through the device without leakage even at a gauge pressure of above 135 kPa. For validation of its utility in drugs testing, we successfully demonstrated that human lung adenocarcinoma cells cultured in the PMMA devices show more reliable cytotoxicity results for vincristine in comparison to conventional polydimethylsiloxane (PDMS) devices due to the inherent property of PMMA of it being impervious to small molecules. Given that the current organ-on-a-chip fabrication methods mostly rely on PDMS, this bonding strategy will expand simple fabrication capability using various thermoplastics and porous track-etched membranes, and allow us to create 3D-micro-constructs that more precisely mimic organ-level physiological conditions. A GLYMO-based method enables robust fabrication of PMMA-PETE cell-culturing microfluidic devices, which permits more precise cytotoxicity response to lipophilic drugs.