Abstract
The fabrication of a large-scale microfluidic mold with 3D microstructures for manufacturing of the conical microwell chip using a combined projection micro-stereolithography (PµSL) 3D printing/CNC micro-milling method for tumor spheroid formation is presented. The PµSL technique is known as the most promising method of manufacturing microfluidic chips due to the possibility of creating complex three-dimensional microstructures with high resolution in the range of several micrometers. The purpose of applying the proposed method is to investigate the influence of microwell depths on the formation of tumor spheroids. In the conventional methods, the construction of three-dimensional microstructures and multi-height chips is difficult, time-consuming, and is performed using a multi-step lithography process. Microwell depth is an essential parameter for microwell design since it directly affects the shear stress of the fluid flow and the diffusion of nutrients, respiratory gases, and growth factors. In this study, a chip was made with microwells of different depth varying from 100 to 500 µm. The mold of the microwell section is printed by the lab-made PµSL printer with 6 and 1 µm lateral and vertical resolutions. Other parts of the mold, such as the main chamber and micro-channels, were manufactured using the CNC micro-milling method. Finally, different parts of the master mold were assembled and used for PDMS casting. The proposed technique drastically simplifies the fabrication and rapid prototyping of large-scale microfluidic devices with high-resolution microstructures by combining 3D printing with the CNC micro-milling method.
Highlights
PDMS has become a successful polymeric substrate material for rapid prototyping owing to its low cost, ease of fabrication, gas permeability, optical transparency, multi-substrate adhesion, chemical inertness, biocompatibility, and ability to form any geometry[6]
Lee et al made a concave microwell chip using a double PDMS casting procedure from the Polymethyl methacrylate (PMMA) mold that was made by a laser carving machine[53]
In a creative and simple method, Kim et al fabricated a concave-bottomed microwell chip using the capillary action of liquid polymer on the pins of a computer CPU, which is achieved without expensive materials or complicated p rocedures[54]
Summary
PDMS has become a successful polymeric substrate material for rapid prototyping owing to its low cost, ease of fabrication, gas permeability, optical transparency, multi-substrate adhesion, chemical inertness, biocompatibility, and ability to form any geometry[6]. The coating layer provides a barrier to the 3D printed material so that the PDMS polymerization is carried out on the surface of the mold, and the PDMS layer can be peeled o ff[4]. Another problem with using a 3D printer in manufacturing microfluidic devices is to achieve the high resolution of construction that many microfluidic applications require. Waldbaur et al used a high resolution DMD-based 3D printer to print a master mold of a tree-based gradient generator chip In this regard, they solved the mentioned problem by translating the projected images; they printed a large layout (3 × 4 cm) with proper r esolution[13]. Mold surface smoothness improved, PDMS was cured on the mold surface and peeled off after curing, and the mold can be reused several times
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