Non-photolithographic plastic-mold-based fabrication of cylindrical and multi-tiered poly(dimethylsiloxane) microchannels for biomimetic lab-on-a-chip applications

Abstract

To overcome the limitations of conventional lithography for generating cylindrical and multi-tiered microchannels, we demonstrate a facile and alternative route for non-photolithographic fabrication of plastic molds via micro-milling combined with hot embossing. First, semi-cylindrical negative channels were engraved on poly(methylmethacrylate) (PMMA) using a ball mill, and the obtained semi-cylindrical negative channel structure was transferred onto poly(ethyleneterephthalate) (PET) via hot embossing performed at a temperature intermediate between the glass transition temperature (T g ) values of the two thermoplastics. In this way, a positive semi-cylindrical channel structure was formed on the PET without distorting the original patterns on the PMMA. The PET mold with positive structures was then replicated onto poly(dimethylsiloxane) (PDMS) to produce negative semi-cylindrical channels, and by aligning two identical PDMS replicas, a cylindrical microchannel with a completely circular cross section was formed.Second, multi-tiered channel structures were readily obtained by controlling the depths of the microchannels in the micro-milling process. The effectiveness of the fabricated cylindrical and multitiered microchannels was evaluated by constructing a microvascular network and human liver sinusoid structure as proof-of-concept experiments. The simple fabrication and high precision in the resulting structures will pave the way for the construction of disposable biomimetic Lab-on-a-Chip (LOC) platforms with low manufacturing cost in a simple and facile manner feasible for mass production.

Design and mixing performance characterization of a mini-channel mixer with nature-inspired geometries

“…In order to precisely bound this field of biomimetics, Lee (2000) reminds that it consists in microchannels with a cylindrical cross-section mimicking micro-vascular networks from arterioles and venules (8 − 250 µm) to small arteries and small veins (0.25 − 2 mm). As an example, this range of size matches the smallest vessels in the liver which play a critical role in the transportation of a small number of molecules to and from the blood stream, respectively Jang et al (2015). The identified Murray's law has a slightly different exponent in larger vessels closer to the base of arterial trees Huang et al (2009); Tondeur et al (2009).…”

Systematic characterization of cleanroom-free fabricated macrovalves, demonstrating pumps and mixers for automated fluid handling tuned for organ-on-chip applications

“…Furthermore, micromilling of molds is less labor intensive than fabricating molds by the conventional process of photolithography using reflow photoresist, which also requires experience to achieve reproducible results. Although micromilled molds for PDMS macrovalves have already been reported 21 , 38 , the corresponding fabrication methods require a negative mold and double casting of PDMS on PDMS 21 , or a polyethylene terephthalate (PET) casting step 38 . In addition, the dimensions of these rounded channels are limited by the availability of cone-shaped milling tools 21 , 38 .…”

“…Although micromilled molds for PDMS macrovalves have already been reported 21 , 38 , the corresponding fabrication methods require a negative mold and double casting of PDMS on PDMS 21 , or a polyethylene terephthalate (PET) casting step 38 . In addition, the dimensions of these rounded channels are limited by the availability of cone-shaped milling tools 21 , 38 .…”

“…Our proposed method allows us to create a mold with an upstanding structure with any shape (e.g., cylindrical or elliptical) and size (height and width) as desired, without being limited by the shapes and sizes of the ball or cone mills available. Such direct positive molds facilitate and simplify the fabrication process and minimize the potential error caused by PDMS shrinkage compared to the double casting methods 21 , 38 . In summary, the proposed micromilled direct molds for fabricating Quake-style valves allow an easier approach for the commercialization of molds and the multiplexing of PDMS OoCs.…”

Microvessel-on-Chip Fabrication for the In Vitro Modeling of Nanomedicine Transport

“…A minimum channel diameter of 200 μm was reported. 19 More frequently, the well-known temperature reflow process of ridges made on thermoplastic materials has been used. 17,20,21 However, this method offers poor control of the channel cross section.…”