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This paper describes an easy-to-handle technique for creating curved, millimetrically scaled polymeric structures in order to develop in vitro cell culture devices for biologically relevant applications. For the master mold in this study, the authors used UV-activated photocurable polydimethylsiloxane (PDMS). This product can readily be used to create millimetrically scaled pattern molds by controlling droplet contact angles during deposition onto a flexible paper-based substrate that has been prepatterned with ink/wax. Resultant desired patterns can be transferred onto thermocurable PDMS as arrays of wells for biological applications. By combining photocurable and thermocurable PDMS manufacturing processes, this approach endows PDMS-based structures with unique controllability in terms of size, pattern, and curvature. Providing such features enhances the biocompatibility and practicality of devices so manufactured in that they mimic the natural topography of the extracellular matrix. Additionally, three-dimensional cell culturing and immunofluorescent staining can be demonstrated on this biomimetic platform. This manufacturing method takes only several minutes to complete and does not require complicated facilities in order to fabricate PDMS-based biomedical devices. We believe that this method would be very useful for rapid, economical fabrication of cell-focused assay platforms, which would be particularly useful in resource-limited settings.

This paper describes the development of physically and/or chemically modified chitosan membranes to probe cellular behaviors and molecular-level structural responses of NIH-3T3 fibroblasts (normal cells) and Ha-ras-transformed cells (abnormal cells) adhered onto these modified membranes. To prepare chitosan membranes with nanometrically scaled physical features, we have demonstrated an inexpensive and easy-to-handle method that could be easily integrated with IC-based manufacturing processes with mass production potential. These physically or chemically modified chitosan membranes were examined via scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and water contact angle measurement, in order to gain a better understanding of chitosan membrane surface characteristics including surface morphology, stiffness, functional groups, and surface hydrophobicity/hydrophilicity. NIH-3T3 fibroblasts and their Ha-ras-transformed progeny were cultured on these modified chitosan membranes. After 12, 24 and 48 h of culture, these cells were investigated to decipher cellular behaviors. We found that NIH-3T3 fibroblasts and their Ha-ras-transformed progeny exhibited distinct structurally based responses attributable to chitosan membrane surface chemical or physical properties that we demonstrate as possibly applicable, for drug screening applications. Secondarily, but crucially to this study, we developed a chitosan-based micropatterning procedure that allowed us to re-arrange mammalian cells (i.e., HeLa cells in this study, for cancer drug screening) at the desired locations (with a single-cell array format). This procedure was based on cell affinity to different surface topographies of chitosan membranes that we prepared. This cell-based patterning approach has the potential for use in a wide range of applications including use as a promising platform for drug discovery, cytotoxicity studies, functional genomics, and investigations of cellular microenvironment. We believe that this study would provide further understanding of naturally derived biomaterials, lay the foundation for broadening the applications of chitosan, and facilitate the development of new biomedical devices (i.e., artificial stents, implantable artificial tissues, and sustainable implantable biosensors) with unique cell–material interface properties and characteristics, such as in vitro cell culture and diagnostic platforms.

A simple and efficient polydimethylsiloxane microlens is made through controlling surface interactions, which can be integrated into soft lithographic systems. Lenses are created by controlling the solid-liquid interface between a droplet of liquid polydimethylsiloxane and a polymer substrate. By altering the surface characteristics, we control the contact angles of the droplet, which creates defined diameters and magnifications of these lenses. Furthermore, we demonstrate the ability to integrate these devices into culture systems enabling real-time magnified biological imaging in both aqueous and nonaqueous environments. This method has potential applications in fields including functional biomimetic microlenses, optical trapping, and endoscopy.