Using light and heat, researchers at Duke University developed a technique for manufacturing biocompatible microparticles for potential use in drug delivery, diagnostics, and tissue engineering. According to research scientist Stefan Roberts, the technique is simple enough to be scaled up to make billions of microparticles in just a few minutes. Although the capability to fabricate many complex microparticles already exists, the process usually involves challenging manufacturing techniques such as multiple-emulsion microfluidics or flow lithography. Roberts and his colleague, professor Ashutosh Chilkoti, demonstrated new types of microparticles made with elastin-like polypeptides, a type of disordered protein, and partially ordered proteins. “Disordered proteins are a hot topic in biology, with many researchers trying to discover how proteins without shape can still have a biological purpose,” Roberts said. “An undercurrent of our work is to instead think of these proteins as a materials scientist would and see if we can engineer them for our own biological functions in ways that can’t be achieved with current materials.” By tweaking the temperatures at which the proteins assembled and disassembled, and sweeping back and forth through a range of temperatures at various rates, the researchers showed that they were able to create a suite of microparticle shapes, including porous particles, core-shell and hollow-shell structures, and a tangle of cords dotted with shells that was dubbed “fruits-on-a-vine.” Then, by incorporating photosensitive amino acids, they showed that they could freeze these shapes into solid microparticles with a beam of light. Mixtures of partially ordered proteins (green) and elastin-like polypeptides (blue), a disordered protein, can be used to create a variety of new microparticle architectures including (clockwise from upper left) porous particles, “fruits-on-a-vine” networks, single hollow “vesicle-like” particles, and core-shell networks. Courtesy of Stefan Roberts, Duke University. Each set of parameters simultaneously creates millions of solid, biocompatible microparticles slightly larger than an average cell. It takes only a few minutes, the researchers said, and it all happens in a volume of liquid about the size of a drop of water. “This is a test case for a type of material that is flexible and simple enough to create both commonly used shapes and architectures that aren’t seen using current techniques,” Roberts said. “We’re using new biocompatible materials to create never-before-seen shapes simply by heating, cooling, and shining a light on them.” The research was published in Nature Communications (www.doi.org/10.1038/s41467-020-15128-9).