Evaluation of the Effects of Solvents Used in the Fabrication of Microfluidic Devices on Cell Cultures

Abstract

Microfluidic microphysiological systems (MPSs) or “organs-on-a-chip” are a promising alternative to animal models for drug screening and toxicology tests. However, most microfluidic devices employ polydimethylsiloxane (PDMS) as the structural material; and this has several drawbacks. Cyclo-olefin polymers (COPs) are more advantageous than PDMS and other thermoplastic materials because of their low drug absorption and autofluorescence. However, most COP-based microfluidic devices are fabricated by solvent bonding of the constituent parts. Notably, the remnant solvent can affect the cultured cells. This study employed a photobonding process with vacuum ultraviolet (VUV) light to fabricate microfluidic devices without using any solvent and compared their performance with that of solvent-bonded systems (using cyclohexane, dichloromethane, or toluene as the solvent) to investigate the effects of residual solvent on cell cultures. Quantitative immunofluorescence assays indicated that the coating efficiencies of extracellular matrix proteins (e.g., Matrigel and collagen I) were lower in solvent-bonded COP devices than those in VUV-bonded devices. Furthermore, the cytotoxicity of the systems was evaluated using SH-SY5Y neuroblastoma cells, and increased apoptosis was observed in the solvent-processed devices. These results provide insights into the effects of solvents used during the fabrication of microfluidic devices and can help prevent undesirable reactions and establish good manufacturing practices.

Microfluidics for High Pressure: Integration on GaAs Acoustic Biosensors with a Leakage-Free PDMS Based on Bonding Technology

“…This can be achieved by using of double-sided tape, glues, or solvent bonding [ 52 ]. The bonding of PDMS on different substrates has been reported in the scientific literature [ 36 ], but the solvents used in the bonding process can also strongly influence the growth of cells cultured in the microfluidic devices [ 53 ]. Wu et al used (3-Mercaptopropyl) trimethoxysilane (MPTMS), which was a chemical coupling reagent to modify the surfaces of the noble metals, and PDMS to improve their adhesion [ 54 ].…”

Recent Advances in Thermoplastic Microfluidic Bonding

“…Generally, solvent uptake should be kept low to reduce channel distortion of the microfluidic device during the bonding process. This is controlled by the solvent exposure time; however, it needs to be balanced by the required bonding strength and bonding pressure [ 57 ]. Ng et al proposed controlling the process parameter by using a thermally activated solvent bonding process.…”

“…Ng et al developed a bonding technique to prevent excessive channel clogging and distortion, in which the PMMA substrates were bonded by isopropanol combined with the pre-processing step of pressure and thermal annealing of the PMMA substrates, and a post-processing step of solvent removal by subjecting the chip to a vacuum environment. These pre and post-processing steps produced a chip with better optical clarity, and had strong bonding strength and minimal distortion and clogging of the microchannels [ 57 ].…”

“…For application of the solvent to the substrates, different methods are practiced. The solvent can be spread uniformly on thermoplastics by pipette [ 57 ], or by other methods, such as spray coating [ 72 ], soak method [ 54 ], and spin coating [ 71 ]. Plasma treatment [ 77 ] and UV irradiation [ 72 , 74 ] methods are used to improve the bonding quality.…”

Curved Film Microstructure Arrays Fabricated via Mechanical Stretching

“…However, PDMS-based microfluidic devices are not suited to mass production. Some other polymers are potential alternatives to PDMS, which include polymethyl methacrylate (PMMA), polystyrene (PS), polypropylene (PP), cyclo-olefin polymer (COP), and cyclic olefin copolymer (COC) [11,12].…”