SU-8 bonding protocol for the fabrication of microfluidic devices dedicated to FTIR microspectroscopy of live cells

Abstract

Here we present a new bonding protocol for SU-8 negative tone photoresist that exploits the chemical modifications induced in the resin by exposure to 254 nm (UVC) light. Fourier Transform Infrared microspectroscopy (μ-FTIR) was used to carry out a thorough study on the chemical processes and modifications occurring within the epoxy resin by exposure to 365 nm and 254 nm light. In particular, we established that UVC light promotes the opening of the epoxy rings bypassing the post-exposure bake. The possibility to promote a further activation of the resin, already patterned with standard UV lithography, was exploited to produce closed microfluidic devices. Specifically, we were able to fabricate fluidic chips, characterized by broadband transparency from mid-IR to UV and long term stability in continuous flow conditions. CaF2 was used as substrate, coated by sputtering with a nanometric silicon film, in order to make surface properties of this material more suitable for standard fabrication processes with respect to the original substrate. The fabricated microfluidic chips were used to study by μ-FTIR the biochemical response of live breast cancer MCF-7 cells to osmotic stress and their subsequent lysis induced by the injection of deionized water in the device. μ-FTIR analyses detected fast changes in protein, lipid and nucleic acid content as well as cytosol acidification.

Lab-on-a-chip devices: How to close and plug the lab?

“…One important problem of patterned and cured SU-8 for adhesive bonding is that highly cross-linked SU-8 does not give good bonding quality if bonded at low temperatures. Recently, Mitri et al addressed this issue and developed a SU-8 bonding protocol that involves the exposure of patterned SU-8 layers to 254 nm light for opening the residual epoxy rings in the resin thereby promoting milder temperature and pressure requirements for bonding [105]. Several companies, including microLIQUID (Spain) and miniFAB (Australia), provide microfluidic chip manufacturing services for SU-8 processing.…”

Microfluidic approaches to synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy of living biosystems

“…This method allowed microstructures like channels and reservoirs to be added to the cell chamber [85,86] or to change the material surface properties [87,88] while giving more precise control of the spacer thickness. The fabrication approach further allowed development of devices that were either thermo-mechanically or chemically sealed [59, 63] instead of being clamped together.…”

“…Imaging live cells can reduce some of the artifacts of fixation [59] and real-time FTIR measurements on living biological systems (Figure 2 ) are crucial to unravel how their chemical composition evolves with time [43]. This can give insights into many problems of biological or medical interest including metabolic processes [60,61], development [51], and real-time responses to treatment or changing environmental conditions [62,63]. Jamin et al [46] performed the first synchrotron-based FTIR measurements of live cells in 1998.…”

Capillary liquid bridge soft lithography for micro-patterning preparation based on SU-8 photoresist templates with special wettability

“…[18][19][20] Though it presents some advantages in the aspects of controlling the droplet geometry, effectively locating the droplet and accurately distributing the aqueous solution to the hydrophilic zone, 21,22 the disadvantages are obvious from their complicated fabrication processes and the nonreusable templates. For the last two decades, the SU-8 photoresist materials have been developed and widely used in electronic industries such as microuidic control, microelectronics machining and chip packaging, [23][24][25] which is mainly attributed to their unique features including their good light transmittance, mechanical property, chemical stability, thermal resistance and biological compatibility. An outstanding advantage is that the micro-congurations with high aspect ratio are easily obtained via simple lithography.…”