Living systems masterfully self-organize in space and time. Many remaining grand challenges in biology and medicine stem from our inability to resolve the underlying molecular-scale phenomena in a complex context such as a multi-component mixture or a cell. We explore precision 3D printing to design and program dynamic biological states far from equilibrium and to explore spatiotemporal self-organization principles in biology that by lack of suitable tools have previously been inaccessible to experimental quantification.
We advance high-resolution microfabrication to create and comprehend biomolecular structure and function across scales. This entails microfluidic chips to map protein solution phase space to optimize protein crystal nucleation and growth as well as in situX-ray diffraction. Ultracompact 3D microfluidics help address sample delivery challenges in high-viscosity extrusion of membrane proteins, as well as time-resolved mix-and-inject serial femtosecond crystallography to record ‘molecular movies’ of macromolecular conformational changes at the atomic scale. High-resolution coaxial gas- and liquid- sheet electrosprays improve transmission rates and reduce background in single particle imaging. Tailored 3D micro-optics promise new opportunities for in situ imaging and spectroscopy of such injection systems in the confined space around the X-ray interaction region.
Applied to synthetic biology, these technologies support the reconstitution of functional biological and biomimetic systems with unprecedented precision and throughput. This includes protein inks to nano-3D- print compartments with the highest achievable functional conformity to sub-cellular structures in vivo, such as a direct 3D printed contractile eukaryotic cell division model. For accurate nanoscale 3D print evaluation, we explore integrated microfluidic workflows for cryo-electron tomographic imaging.
