Organic semiconductor distributed feedback (DFB) lasers are of interest as external or chip-integrated excitation sources in the visible spectral range for miniaturized Raman-on-chip biomolecular detection systems. However, the inherently limited excitation power of such lasers as well as oftentimes low analyte concentrations requires efficient Raman detection schemes. We present an approach using surface-enhanced Raman scattering (SERS) substrates, which has the potential to significantly improve the sensitivity of on-chip Raman detection systems. Instead of lithographically fabricated Au/Ag-coated periodic nanostructures on Si/SiO2 wafers, which can provide large SERS enhancements but are expensive and time-consuming to fabricate, we use low-cost and large-area SERS substrates made via laser-assisted nanoreplication. These substrates comprise gold-coated cyclic olefin copolymer (COC) nanopillar arrays, which show an estimated SERS enhancement factor of up to ∼ 10(7). The effect of the nanopillar diameter (60-260 nm) and interpillar spacing (10-190 nm) on the local electromagnetic field enhancement is studied by finite-difference-time-domain (FDTD) modeling. The favorable SERS detection capability of this setup is verified by using rhodamine 6G and adenosine as analytes and an organic semiconductor DFB laser with an emission wavelength of 631.4 nm as the external fiber-coupled excitation source.
The success of labs- and organs-on-chips as transformative technologies in the biomedical arena relies on our capacity of solving some current challenges related to their design, modeling, manufacturability, and usability. Among present needs for the industrial scalability and impact promotion of these bio-devices, their sustainable mass production constitutes a breakthrough for reaching the desired level of repeatability in systematic testing procedures based on labs- and organs-on-chips. The use of adequate biomaterials for cell-culture processes and the achievement of the multi-scale features required, for in vitro modeling the physiological interactions among cells, tissues, and organoids, which prove to be demanding requirements in terms of production. This study presents an innovative synergistic combination of technologies, including: laser stereolithography, laser material processing on micro-scale, electroforming, and micro-injection molding, which enables the rapid creation of multi-scale mold cavities for the industrial production of labs- and organs-on-chips using thermoplastics apt for in vitro testing. The procedure is validated by the design, rapid prototyping, mass production, and preliminary testing with human mesenchymal stem cells of a conceptual multi-organ-on-chip platform, which is conceived for future studies linked to modeling cell-to-cell communication, understanding cell-material interactions, and studying metastatic processes.
In this report, we present a new method for generating a high-density (2D) droplet array using double-layered polydimethylsiloxane (PDMS) templates containing honeycomb microwells. Without external flow control, a dropleton-template (DOT) was created by utilizing capillary forces associated with the interfacial tension between the aqueous and oil phases. The DOT process involved three simple steps: (1) vacuum-assisted filling of microwells; (2) excess water removal; and (3) covering the droplet array with oil. To demonstrate the concept of the DOT, we generated spherical water droplets 147, 191, 238, 326 and 405 μm in diameter from corresponding microwells with lengths of 200, 300, 400, 600 and 800 μm, respectively and a height of 76 μm (up to ~1 0,000 droplets on a template 25 × 25 mm). Two important factors, including the aspect ratio (height-to-length ratio) of the microwell and the interfacial tension of the two phases, were investigated to understand how those factors affect the shape of the droplets ('sphere' or 'dome'). All the droplets were spherical up to an aspect ratio of 0.55. The droplets were dome-shaped for aspect ratios above 0.82. For a 1 mM sodium dodecyl sulfate (SDS) solution, the use of mineral oil (which had the highest interfacial tension studied) produced spherical droplets, but dome-shaped droplets were produced by corn oil and oleic acid.
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