New materials and processes for rapid prototyping of microfluidic chips

In recent years 3D printing has gained a lot of attention for rapid prototyping of microfluidic chips, due to its numerous advantages over established microstructuring methods like glass etching and soft replication in polydimethylsiloxane. Key features of 3D printing include a fully open design space, which is not limited to 2.5D structures. Furthermore, by utilizing support of CAD applications the concept-to-chip time can be drastically reduced. Also, fabrication of microfluidics with 3D printing does not require an additional bonding step, that is mandatory when creating microfluidics from glass or polydimethoxysiloxane (PDMS). Additionally, material properties play a vital role in microfluidics due to the high surface-to-volume ratio. Therefore, controlling material properties is a key to the development of new microfluidic chips. 3D printing allows to process materials with a wide range of properties, while glass etching and soft replication in PDMS are restricted to one material respectively, which makes them stellar in material properties. Still, despite many advantages, after decades 3D printing has not yet replaced conventional methods for microfluidics prototyping on the market. While 3D printing enables the processing of a wide variety of polymeric materials, some polymers with abundant industrial usage are not typically processed. As an example, Fused Deposition Modeling (FDM) is a widespread technology with a wide spectrum of commercially-available thermoplastics. Still, one of the go-to materials for manufacturing microfluidic chips on an industrial scale is polystyrene (PS), which has not been shown for FDM printing of microfluidics yet. As the preferred materials for lab-scale prototyping do not match the materials for mass-marketing, there is a gap between microfluidics development and their industrial fabrication and distribution. This hinders the development of new microfluidic chips, as results from lab-scale are challenging to scale up to industrial level. Therefore, in this thesis we present for the first time FDM fabrication of microfluidic chips from transparent PS. We fabricated a continuous PS filament, which was extruded from commercial PS granules and can be readily 3D printed. We optimized the printing parameters to increase the transparency of the chips. We present PS chips with embedded channels featuring a width down to 300 µm. We demonstrate strategies to increase the transparency further by printing on a commercial PS substrate. Furthermore, we showcase functional chips like Tesla-mixer and mixer cascades. In addition, we conducted cell culture experiments that show a high cell viability of 3D printed PS compared to commercial PS. Following this, another lack in the material selection for microfluidics prototyping is the inaccessibility of high-performance thermoplastics with outstanding thermal and chemical resistance. While many filament types are commercially available, they rarely can withstand common solvents used in organic chemistry, or be operated at temperatures close to or above 100 °C. Therefore, many typical chemical applications for on-chip synthesis are inaccessible for FDM printed microfluidics, limiting the versatility of this technology in the field of chemistry-on-chip. Therefore, we demonstrated for the first time FDM Abstract -iv fabrication of microfluidic chips in PVDF, which shares many typical properties of highly-fluorinated polymers and therefore has a high thermal and chemical resistance, well suited for high-performance applications. We effectively eliminated warping of 3D printed PVDF and optimized the printing parameters to 3D print embedded channels down to a width of 200 µm. As PVDF is a semi-crystalline material with low optical transmission, we demonstrate direct fabrication of microchannels on a glass substrate to allow optical analysis within embedded channels. Solvent-compatibility tests showed a low swelling of 3D printed PVDF compared to PDMS. Furthermore, we printed Tesla-mixer that were perfused with dimethylformamide without structural disintegration. To demonstrate versatility of the FDM technology, we utilized a print-pause-print protocol to fabricate microreactors for heterogeneous catalysis, which were filled while manufacturing with the catalyst. To demonstrate functionality, we conducted the catalytic deprotection of benzaldehyde dimethyl acetal to benzaldehyde with a conversion of more than 99 %. Furthermore, this thesis takes on another challenge within the fabrication of high-resolution microfluidics. Whereas FDM printing offers a low resolution at affordable cost, stereolithography can be used to fabricate high-resolution features, often referred to as microstereolithography. The most widespread µSL-technology for microfluidics prototyping is the projection-based Digital Light Processing (DLP), which can reach resolutions down to the single-digit micron regime. While this resolution is well suited to print embedded channels below a width of 100 µm, the DLP technology inherently restricts the fabrication of chips to a footprint of multiple centimeters. Therefore, even though featuring optics for high-resolution 3D printing, the versatility of many SL 3D printers is limited for microfluidic prototyping. To overcome this, we utilized a laser-based stereolithography instrument equipped with a 405 nm laser, that can switch between a 40 µm and 5 µm beam width and translate along a XY plane of 10 x 10 cm². We optimized a photoresist based on poly(ethylene glycol) diacrylate for high in-plane and out-of-plane resolution. Writing parameters were optimized to decrease the zovercure error to ± 1 µm. We fabricated embedded channels down to a width and height of 21 µm and 30 µm, respectively. Furthermore, we developed strategies to selectively alternate either illumination dose or the beam diameter within a spatially-resolved volume element. Channels with an aspect ratio of 10 or 0.1 were successfully fabricated. Additionally, we showed how the manipulation of the laser focus can be used as a tool to write structures with a custom beam diameter. As a showcase, we fabricated a microfluidic mixer with a minimum channel width of 78 µm and a total length of 7.24 cm.