An Optically Controlled 3D Cell Culturing System

A novel 3D cell culture system was developed and tested. The cell culture device consists of a microfluidic chamber on an optically absorbing substrate. Cells are suspended in a thermoresponsive hydrogel solution, and optical patterns are utilized to heat the solution, producing localized hydrogel formation around cells of interest. The hydrogel traps only the desired cells in place while also serving as a biocompatible scaffold for supporting the cultivation of cells in 3D. This is demonstrated with the trapping of MDCK II and HeLa cells. The light intensity from the optically induced hydrogel formation does not significantly affect cell viability. 1. Introduction Drug- and cell-based therapies are being explored for many medical conditions [1, 2], including heart disease [3], cancer [4–6], and diabetes [7–9]. However, the process of identifying suitable treatments is long and complicated. The time from drug discovery to Food and Drug Administration approval is usually 10 to 15 years [10], costing from $800 million to $1 billion [11]. Numerous processes contribute to this long lead time, including the testing of drug compounds, drug effects, and drug safety. These tests are conducted in order of increasing complexity: biochemical assays, cell-based assays, animal models, and then clinical trials. It is possible to simplify this testing procedure with improved cell-based assays that could enable the reduction or elimination of animal testing, reducing the time and cost of developing new drugs. Cell-based drug assays can be improved by culturing cells in vitro that remain highly representative of their in vivo counterparts, resulting in more realistic testing results, mitigating the risks and costs associated with testing on live subjects, while accelerating the development process. Recent evidence suggests that 3D cultures are more representative of cellular behavior as compared to 2D cultures [12], as 3D cultures more closely simulate in vivo cellular microenvironments [13]. For example, cancerous cells grown in 3D cultures are more resistant to drugs versus cells in 2D cultures [14, 15]. 3D cultures have been developed where cells are seeded on porous biomaterials [10, 15, 16] or scaffold-like microstructures [17–19]. Integration of these materials in microfluidic systems can facilitate diffusive transfer of nutrients and waste and minimizes the use of materials and reagents, thereby lowering costs and increasing parallelization of culturing and testing [10, 20]. Thus, appropriately designed microdevices can greatly improve the predictive value of