3D organoids using stem cells to study development and disease are now widespread. These models are powerful to mimic in vivo situations but are currently associated with high variability and low throughput. For biomedical research, platforms are thus necessary to increase reproducibility and allow high-throughput screens (HTS). Here, we introduce a microwell platform, integrated in standard culture plates, for functional HTS. Using micro-thermoforming, we form round-bottom microwell arrays from optically clear cyclic olefin polymer films, and assemble them with bottom-less 96-well plates. We show that embryonic stem cells aggregate faster and more reproducibly (centricity, circularity) as compared to a state-of-the-art microwell array. We then run a screen of a chemical library to direct differentiation into primitive endoderm (PrE) and, using on-chip high content imaging (HCI), we identify molecules, including regulators of the cAMP pathway, regulating tissue size, morphology and PrE gene activity. We propose that this platform will benefit to the systematic study of organogenesis in vitro.

Organic semiconductor lasers are of particular interest as tunable visible laser light sources. For bringing those to market encapsulation is needed to ensure practicable lifetimes. Additionally, fabrication technologies suitable for mass production must be used. We introduce allpolymer chips comprising encapsulated distributed feedback organic semiconductor lasers. Several chips are fabricated in parallel by thermal nanoimprint of the feedback grating on 4 wafer scale out of poly(methyl methacrylate) (PMMA) and cyclic olefin copolymer (COC). The lasers consisting of the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq 3 ) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(pdimethylaminostyril)-4H-pyrane (DCM) are hermetically sealed by thermally bonding a polymer lid. The organic thin film is placed in a basin within the substrate and is not in direct contact to the lid. Thus, the spectral properties of the lasers are unmodified in comparison to unencapsulated lasers. Grating periods of 378 nm to 428 nm in steps of 10 nm result in lasing at wavelengths of 622 nm to 685 nm. The operational lifetime of the lasers expressed in number of pulses is improved 11-fold (PMMA) and 3-fold (COC) in comparison to unencapsulated PMMA devices.

Today replication of microstructured parts is state of the art in laboratory and commercial use. Beside the process of injection molding hot embossing enables the accurate replication of polymer structures in a broad variety of thermoplastic polymers even in the nanometer range. Characteristic for the most replication processes dealing with thermoplastic polymers is the use of microstructured mold inserts based on metals. In this paper we describe an alternative to the established mold inserts--the use of so called interstage mold inserts. These interstage mold inserts are replicated in high performance polymers and technical thermoplastics and can be fabricated many times by a previous replication step from a master even in the submicro range. Aspects like suitable material combinations, demolding behaviour, long time stability, production rate, and the quality of structures will be discussed. Because of the high flexibility the process of hot embossing is used for the fabrication of the microstructured interstage mold inserts and their replications.

We introduce actively tunable diffractive optical elements fabricated from shape-memory polymers (SMPs). By utilizing the shape-memory effect of the polymer, at least one crucial attribute of the diffractive optical element (DOE) is tunable and adjustable subsequent to the completed fabrication process. A thermoplastic, transparent, thermoresponsive polyurethane SMP was structured with diverse diffractive microstructures via hot embossing. The tunability was enabled by programming a second, temporary shape into the diffractive optical element by mechanical deformation, either by stretching or a second embossing cycle at low temperatures. Upon exposure to the stimulus heat, the structures change continuously and controllable in a predefined way. We establish the novel concept of shape-memory diffractive optical elements by illustrating their capabilities, with regard to tunability, by displaying the morphing diffractive pattern of a height tunable and a period tunable structure, respectively. A sample where an arbitrary structure is transformed to a second, disparate one is illustrated as well. To prove the applicability of our tunable shape-memory diffractive optical elements, we verified their long-term stability and demonstrated the precise adjustability with a detailed analysis of the recovery dynamics, in terms of temperature dependence and spatially resolved, time-dependent recovery.

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Hot embossing and injection moulding belong to the established plastic moulding processes in microengineering. Based on experimental and theoretical findings, a variety of microstructures have been replicated using these processes. However, beside the technology also the moulding materials their physical and chemical properties determines the process and their parameters. Especially high temperature semicrystalline polymers like PEEK and LCP are well suited for many applications in microfluidics. The moulding of these polymers by hot embossing requires a precise setting of temperatures for successful moulding. The present publication describes the moulding of high performance polymers by hot embossing and thermoforming. The focus is set to the process parameters and the required heating conditions for the replication of microand nanostructured mould inserts. In detail, the process conditions for hot embossing of LCP, PEEK, FEP and PSU will be discussed.

Materials matter in microfluidics. Since the introduction of soft lithography as a prototyping technique and polydimethylsiloxane (PDMS) as material of choice the microfluidics community has settled with using this material almost exclusively. However, for many applications PDMS is not an ideal material given its limited solvent resistance and hydrophobicity which makes it especially disadvantageous for certain cell-based assays. For these applications polystyrene (PS) would be a better choice. PS has been used in biology research and analytics for decades and numerous protocols have been developed and optimized for it. However, PS has not found widespread use in microfluidics mainly because, being a thermoplastic material, it is typically structured using industrial polymer replication techniques. This makes PS unsuitable for prototyping. In this paper, we introduce a new structuring method for PS which is compatible with soft lithography prototyping. We develop a liquid PS prepolymer which we term as "Liquid Polystyrene" (liqPS). liqPS is a viscous free-flowing liquid which can be cured by visible light exposure using soft replication templates, e.g., made from PDMS. Using liqPS prototyping microfluidic systems in PS is as easy as prototyping microfluidic systems in PDMS. We demonstrate that cured liqPS is (chemically and physically) identical to commercial PS. Comparative studies on mouse fibroblasts L929 showed that liqPS cannot be distinguished from commercial PS in such experiments. Researchers can develop and optimize microfluidic structures using liqPS and soft lithography. Once the device is to be commercialized it can be manufactured using scalable industrial polymer replication techniques in PS--the material is the same in both cases. Therefore, liqPS effectively closes the gap between "microfluidic prototyping" and "industrial microfluidics" by providing a common material.

Hot embossing and pulling techniques are presented allowing the fabrication of hierarchical micro- and nano-structures. By utilizing demolding forces we replicate nanopillars with high aspect ratio (AR of 10) and small diameters (200 nm). Furthermore, we draw a dense nanofur either with defined or random design. Introducing a electromechanical sensor system we subsequently fabricated a threefold hierarchical structure. Using these replication techniques tiny hairs for bio-inspired designs can be realized with short cycle times and high scalability.