A microscopic image of donut-shaped microparticles, made from silica nanoparticles through vortex ring freezing.  [Duo An/Cornell University]
A microscopic image of donut-shaped microparticles, made from silica nanoparticles through vortex ring freezing. [Duo An/Cornell University]

A summer intern made an accidental discovery while working at Cornell University. Rather than simply exclaim “D’oh,” he made a mental note of the phenomenon he stumbled upon. Then, years later, still at Cornell, the young researcher realized that his accidental discovery—hydrogel donuts—might satisfy all sorts of cravings in biotechnology.

The young researcher, Duo An, is currently a doctoral student in the laboratories of Dan Luo, Ph.D., and Minglin Ma, Ph.D., both of the Department of Biological and Environmental Engineering at Cornell. When he was a summer intern, An was making nanoclay hydrogels, injecting one solution into another to create a gel. But during one particular procedure, instead of direct injection, he dripped one solution into another. When the first solution entered the second, it created vortex-ring particles.

Eventually, it occurred to An that the vortex-ring particles, or tiny donuts, could be more useful than anyone might have imagined, especially if they contained, well, a filling—not a fruit filling, as in a donut for human consumption, but a filling that would help the hydrogel donuts “hit the spot” in biotechnology applications as varied as cell encapsulation, three-dimensional cell culture, and cell-free protein production.

These possibilities were outlined in an article that appeared August 4 in the journal Nature Communications. The article, “Mass Production of Shaped Particles Through Vortex Ring Freezing,” describes how stable hydrogel or solid microparticles of a defined shape can be produced through a gelation or precipitation process. (“Freezing” in the article’s title may be read as “gelation.”)

According to the article, which was contributed by a group of scientists led by Drs. Luo and Ma, controlling the shape and speed of a fluid spray, as well as the speed of the chemical reaction within the spray’s droplets, could yield different structures.

“During its formation, the fluid experiences a rich variety of intriguing geometrical intermediates from spherical to toroidal,” wrote the article’s authors. “Here we show that these constantly changing intermediates can be ‘frozen’ at controlled time points into particles with various unusual and unprecedented shapes.”

The Cornell researchers exploited their electrospraying technique to mass produce inorganic and organic particles, with their sizes well controlled from hundreds of microns to millimeters. Multitudes of vortex ring-derived particles (VRPs) were produced, up to 15,000 rings per minute, then frozen at precise time points.

“Guided further by theoretical analyses and a laminar multiphase fluid flow simulation, we show that this freezing approach is applicable to a broad range of materials from organic polysaccharides to inorganic nanoparticles,” the authors continued. “Moreover, compartmentalization and ordered-structures composed of these novel particles are all achieved, creating opportunities to engineer more sophisticated hierarchical materials.”

Dr. Ma admitted that the concept of using a doughnut-shaped encapsulation hadn't occurred to him, but made perfect sense: “We knew the concept that a doughnut shape is better, but we never thought of making it until we saw it [from An].”

An advantage of the doughnut-shaped encapsulation over a spherical-shaped one is shorter diffusion distance—the distance the encapsulated particle must travel to escape the capsule—while at the same time maintaining a relatively large surface area.

This concept could pave the way for other as-yet-unknown applications of vortex ring freezing, according to Dr. Luo. For example, the Cornell scientists employed nanoclay hydrogel donut-microVRPs to encapsulate DNA molecules for improved cell-free protein production. The group’s previous work had shown that the bulk nanoclay hydrogel protects DNA from DNase and hence enhances the cell-free protein production yield. Compared with a bulk nanoclay hydrogel, the donut-microVRP have a much higher surface area for mass transfer and are therefore ideal for protein production applications.

“Our hope is that this type of material in these shapes can be used much more extensively in other labs for whatever they're trying to do,” noted Dr. Luo. “There is a whole field devoted to just particles, but by default, they are all thinking in terms of spherical particles. Hopefully, this will add to that field of study.”