Micro and nano-biomimetic structures for cell migration study fabricated by hybrid subtractive and additive 3D femtosecond laser processing

Lab-on-a-chip devices have been intensively developed during the last decade when emerging technologies offered possibilities to manufacture reliable devices with increased spatial resolution. These biochips allowed testing chemical reactions in nanoliter volumes with enhanced sensitivity and lower consumption of reagents. There is space to further consolidate biochip assembling processing since the new technologies attempt direct fabrication in view of reducing costs and time by increasing efficiency and functionalities. Rapid prototyping by ultrafast lasers which induces local modifications inside transparent materials of both glass and polymers with high precision at micro- and nanoscale is a promising tool for fabrication of such biochips. We have developed a new technology by combining subtractive ultrafast laser assisted chemical etching of glasses and additive two-photon polymerization to integrate 3D glass microfluidics and polymer microcomponents in a single biochip. The innovative hybrid "ship-in-a-bottle" approach is not only an instrument that can tailor 3D environments but also a tool to fabricate biomimetic in vivo structures inside a glass microfluidic chip. It was possible to create appropriate environment for cell culturing and to offer robustness and transparency for optical interrogation. Cancer cells were cultivated inside biochips and monitored over short and long periods. With the view of understanding cancer cells specific behavior such as migration or invasiveness inside human body, introduction of different geometrical configurations and chemical conditions were proposed. The cells were found responsive to a gradient of nutrient concentration through the microchannels of a 3D polymeric scaffold integrated inside glass biochip.