Facile Patterning of Thermoplastic Elastomers and Robust Bonding to Glass and Thermoplastics for Microfluidic Cell Culture and Organ-on-Chip

Abstract

The emergence and spread of microfluidics over the last decades relied almost exclusively on the elastomer polydimethylsiloxane (PDMS). The main reason for the success of PDMS in the field of microfluidic research is its suitability for rapid prototyping and simple bonding methods. PDMS allows for precise microstructuring by replica molding and bonding to different substrates through various established strategies. However, large-scale production and commercialization efforts are hindered by the low scalability of PDMS-based chip fabrication and high material costs. Furthermore, fundamental limitations of PDMS, such as small molecule absorption and high water evaporation, have resulted in a shift toward PDMS-free systems. Thermoplastic elastomers (TPE) are a promising alternative, combining properties from both thermoplastic materials and elastomers. Here, we present a rapid and scalable fabrication method for microfluidic systems based on a polycarbonate (PC) and TPE hybrid material. Microstructured PC/TPE-hybrid modules are generated by hot embossing precise features into the TPE while simultaneously fusing the flexible TPE to a rigid thermoplastic layer through thermal fusion bonding. Compared to TPE alone, the resulting, more rigid composite material improves device handling while maintaining the key advantages of TPE. In a fast and simple process, the PC/TPE-hybrid can be bonded to several types of thermoplastics as well as glass substrates. The resulting bond strength withstands at least 7.5 bar of applied pressure, even after seven days of exposure to a high-temperature and humid environment, which makes the PC/TPE-hybrid suitable for most microfluidic applications. Furthermore, we demonstrate that the PC/TPE-hybrid features low absorption of small molecules while being biocompatible, making it a suitable material for microfluidic biotechnological applications.

Keywords: microfabrication; microfluidics; organ-on-chip; thermoplastic elastomer.

Figure 1

(A) TPE microfabrication process: (i) A silicon wafer with SU-8 patterns serves as a master for (ii) the negative PDMS mold, which is replicated once more in the form of (iii) the epoxy master mold. Hot embossing using the epoxy mold enables fabrication of (iv) TPE and PC/TPE-hybrid-based microfluidic platforms. (B) Micrographs of features fabricated by hot embossing into TPE and PC/TPE-hybrid as well as the used photomask. A close-up side view shows microstructures in the TPE part of a PC/TPE-hybrid. The full-sized side view image of the PC/TPE-hybrid, additionally showing the transition from TPE to PC, is presented in the supplementary information. Scale bar represents 200 µm. Comparison of feature dimensions between different structures, materials, and the original CAD design. The features have a height of approximately 100 µm. (C) UV-VIS transmittance spectra of TPE, PC, and PC/TPE-hybrid as well as of an Ostemer Crystal clear disc and a PDMS slab for comparison purposes. The inset comprises a photograph of a PC/TPE-hybrid device (left) and a TPE device (right) demonstrating the difference in transparency.

Figure 2

Maximum working pressure (A) non-activated samples and (B) activated samples bonded to different substrates are able to withstand. Day 0 refers to devices tested right after the overnight thermal bonding. Day 7 refers to devices stored for one week submersed in PBS at 37 °C. The star-labeled data points belong to devices that failed due to material deformation, while spheres belong to devices that resulted in delamination from the substrate. Samples labeled with a black circle reached the maximum pressure of the setup without any form of failure. For each condition, three independent experiments were conducted (only for PS, non-activated, day 0: N = 2).

Figure 3

Absorption of rhodamine molecules into PDMS-based and TPE-based microfluidic devices. Average intensity profiles at different time points for chips incubated with (A) rhodamine B, (B) rhodamine 101, and (C) rhodamine 6G solutions. After 72 h of incubation, the solutions were washed out, and the remnant profile was acquired. Micrographs of the channels from day 0 (d0) and from day 3, after washout (d3-wash) are also shown. The scale bars refer to 100 µm. N = 2 for PDMS-rhodamine 6G 72 h and 72 h washout. All others are N = 3.

Figure 4

(A) Schematic depiction of cell culture experimental steps. The PC/TPE-hybrid–glass device is initially coated with type I collagen. Excess collagen is flushed out and followed by HUVEC seeding. The chip is temporarily flipped during cell seeding to ensure cell adhesion to both sides of the channel. (B) Micrographs acquired using phase contrast microscopy show cell attachment and progression of the cell culture from day 1 to day 3 for both substrates (left). (C) Fluorescence microscopy images from the live/dead staining (Hoechst/FDA/PI) on day 3 (left: composite image; right: individual color channels). Scale bars: 100 µm. N = 3.