Rapid prototyping of integrated biochips for on-demand 3D cell culture

The future of research in biology and medicine depends on modular tridimensional cell culture platforms with suitable on-demand geometries that can imitate any cell-specific environment with micron-size features. A high level of control of physico-chemical properties of the substrates is critical, as mechanotransduction signals are passed to the cells that sense their environment. The possibility to pattern nanoscale geometries on chip are also leading to better culture results. All these biomimicry parameters influence the cells phenotype, structure and behavior and are now opening new perspectives in 3D cell culturing for basic biology, medicine and drug testing applications. However, this growing need for on-demand 3D platforms is currently limited by two factors: the specificity of the commercial biochips is not suitable for many cell types and the high cost of technology used to design and fabricate custom-made substrates. In this work, we present the application of a simple, low-cost alternative technique enabling the rapid fabrication of on-demand, custom-made biochips for cell culture with micron-scale resolution. We developed a process that enables the use of low-power, low-cost lasers to etch on-demand micropatterns in transparent biopolymers, circumventing the need for high power lasers or photolithography. We also report the integration of embedded electronics for in situ monitoring or actuation and microchannels on chip. We also succeeded in producing localized carbon nanodomains that are enhancing cell cultures and allowing regionalization in 3D cell culture platforms.