Open multi-culture platform for simple and flexible study of multi-cell type interactions.

The study of multi-cell-type (MCT) interactions has the potential to significantly impact our understanding of tissue and disease biology. Such studies require innovative culture tools for unraveling the contributions of each cell type. Micro- and macro-scale platforms for MCT culture each have different advantages and disadvantages owing to their widely different capabilities, availability, and ease-of-use. However, as evidenced in the literature, there are very few examples of MCT studies and culture platforms, suggesting both biological and technical barriers. We have developed an open multi-culture platform to promote more rapid progress by integrating advantages of both micro- and macro-scale culture devices. The proposed open multi-culture platform addresses technical barriers by allowing easy customization, independent control of basic physical culture parameters, and incorporation of multiple culture modalities (e.g., 2D, 3D, transwell, and spheroid). The design also permits the user to obtain independent endpoints for each culture region. We demonstrate use of the platform in two example studies where we evaluated how cell ratio and cell types influence the response of triple negative breast cancer cells to heat damage and Hedgehog signaling. We also show that the platform can improve soluble factor transport between cell types compared to compartmentalized macro- and micro-scale alternatives. Last, we examine current and future challenges of the platform. We envision simple, yet flexible and customizable, platforms such as this will be important for advancing in vitro study of tissue and tumor biology.

Razor-printed sticker microdevices for cell-based applications.

Tape-based razor-printing is a flexible and affordable ultra-rapid prototyping approach for microscale device fabrication. However, integration of this prototyping approach into cell-based assay development has been limited to proof of principle demonstrations. This is in large part due to lack of an established or well-characterized option for biocompatible adhesive tape. Without such an option, integration of these areas will remain unexplored. Therefore, to address this critical hurdle, we characterized microscale devices made using a potentially biocompatible double-sided adhesive, ARCare 90106. We validated tape-based device performance against 96-well plates and PDMS microdevices with respect to cell viability, hydrophobic small molecule sequestration, the potential for leaching compounds, use in fluorescence microscopy, and outgassing (bubble formation). Results supported the tape as a promising tool for future cell-based assay development. Therefore, we subsequently demonstrated specific strengths enabled by the ultra-rapid (<1 h per prototype) and affordable (∼$1200 cutting plotter, <$0.05 per prototype) approach. Specifically, data demonstrate the ability to integrate disparate materials for advanced sticker-device functionality such as bonding of polystyrene devices to glass substrates for microscopy applications, inclusion of membranes, and incorporation of different electrospun biomaterials into a single device. Likewise, the approach allowed rapid adoption by uninitiated users. Overall, this study provides a necessary and unique contribution to the largely separate fields of tape-based razor-printing and cell-based microscale assay development by addressing a critical barrier to widespread integration and adoption while also demonstrating the potential for new and future applications.