The UV-nanoimprint lithography(UV-NIL) fabrication of a novel network of micron-sized channels, forming an open channel microfluidic system is described. Details about the complete manufacturing process, from mastering to fabrication in small batches and in high throughput with up to 1200 micro titer plates per hour is presented. Deep insight into the evaluation of a suitable UV-curable material, mr-UVCur26SF is given, presenting cytotoxic evaluation, cell compatibility tests and finally a neuronal assay. The results indicate how the given pattern, in combination with the resist, paves the way to faster, cheaper, and more reliable drug screening.
A high throughput manufacturing process of microfluidic chips based on Roll-to-Roll imprinting is presented. With this procedure, microfluidic patterns can be produced on large area polymer substrates. The subsequent steps of inlet drilling, bonding and electrode printing are set-up on large area processes, too. Overall, this strategy allows highly parallelized processing of large numbers of chips—all costly steps of individual chip handling are avoided. The chips were used for the characterization of inorganic ions for soil nutrient analysis.
Lateral flow tests (LFTs) had a pivotal role in combating the spread of the SARS-CoV-2 virus throughout the COVID-19 pandemic thanks to their affordability and ease of use. Most of LFT devices were based on nitrocellulose membrane strips whose industrial upscaling to billions of devices has already been extensively demonstrated. Nevertheless, the assay option in an LFT format is largely restricted to qualitative detection of the target antigens. In this research, we surveyed the potential of UV nanoimprint lithography (UV-NIL) and extrusion coating (EC) for the high-throughput production of disposable capillary-driven, foil-based tests that allow multistep assays to be implemented for quantitative readout to address the inherent lack of on-demand fluid control and sensitivity of paper-based devices. Both manufacturing technologies operate on the principle of imprinting that enables high-volume, continuous structuring of microfluidic patterns in a roll-to-roll (R2R) production scheme. To demonstrate the feasibility of R2R-fabricated foil chips in a point-of-care biosensing application, we adapted a commercial chemiluminescence multiplex test for COVID-19 antibody detection originally developed for a capillary-driven microfluidic chip manufactured with injection molding (IM). In an effort to build a complete ecosystem for the R2R manufacturing of foil chips, we also recruited additional processes to streamline chip production: R2R biofunctionalization and R2R lamination. Compared to conventional fabrication techniques for microfluidic devices, the R2R techniques highlighted in this work offer unparalleled advantages concerning improved scalability, dexterity of seamless handling, and significant cost reduction. Our preliminary evaluation indicated that the foil chips exhibited comparable performance characteristics to the original IM-fabricated devices. This early success in assay translation highlights the promise of implementing biochemical assays on R2R-manufactured foil chips. Most importantly, it underscores the potential utilization of UV-NIL and EC as an alternative to conventional technologies for the future development in vitro diagnostics (IVD) in response to emerging point-of-care testing demands.
Microfluidic devices have emerged as a pivotal in vitro technology for axon outgrowth studies, facilitating the separation of the cell body from the neurites by geometric constraints. However, traditional microfabrication techniques fall short in terms of scalability for large-scale production, hindering widespread application. This study presents the development of foil-based cell culture chips, made of polyethylene terephthalate and in-house formulated ultraviolet curable liquid resin by high-throughput roll-to-roll (R2R) manufacturing. Here, two microchannel designs were tested to optimize manufacturing quality and assess the neurite outgrowth behavior. The fabricated neuron-foil chips demonstrated biocompatibility and supported neurite outgrowth within microchannels under static cell culture conditions. Furthermore, fluidic flow, oriented either perpendicular or parallel to the microchannel direction, was applied to enhance the biological reproducibility within the neuron-foil chips. These findings suggest that R2R manufacturing offers a promising approach for the high-throughput production of biocompatible microfluidic devices, advancing their potential application in modeling neurological diseases within the biomedical industry.
We present a disposable lab-on-a-chip (LoC) for colorimetric enzyme activity monitoring in solid-state fermentation (SSF) processes. The microfluidic chip structures are fabricated via roll-to-roll (R2R) extrusion coating, which reduces costs and enhances efficiency. The LoC operates on capillary-driven flow microfluidics in which a droplet added at the inlet self-fills the chip by capillary action, reaching the reaction chamber. A capillary pump then removes excess liquid, isolating the detection area where the enzymatic reaction takes place. The selection of the target enzymes (α-amylase and cellulase) was made based on their relevance to the industrial biodetergent production processes. For LoC compatibility, enzymatic assays must deliver a strong signal and must be user-friendly. One-step colorimetric assays meet these criteria by releasing a dye from a substrate through enzymatic action. To make the chip easier to handle, the enzymatic substrates were integrated into its reaction chamber in dryed form. For this purpose, two strategies for integration were tested: drop-casting followed by freeze-drying, and piezoelectric deposition with air-drying. Additionally, storage conditions were optimized to enhance shelf-life and reagent stability. To measure enzymatic activity, a pocket-sized colorimetric reader was developed and adapted to the LoC geometry while an Android app was created to enable smartphone-based control of the reader. Furthermore, validation with commercial enzymes established the limit of detection (LoD), and subsequent tests with SSF samples from an industrial plant confirmed the functionality of the system. The enzymatic activity measurements are completed in under 10 minutes, revealing increasing enzymatic activity as fermentation progresses. In conclusion, the LoC provides a quick and cost-effective solution for detecting α-amylase and cellulase in samples derived from SSF processes.