New Algae Research Tool: The PicoShell

Production of high-energy fats by microalgae may provide a sustainable, renewable energy source that can help tackle climate change. However, microalgae engineered to produce lipids rapidly usually grow slowly themselves, making it difficult to increase overall yields.

UCLA bioengineers have created a new type of petri dish in the form of microscopic, permeable particles that can dramatically speed up research and development timelines of biological products, such as fatty acids for biofuels. Dubbed PicoShells, the picoliter (trillionth of a liter), porous, hydrogel particles can enable more than one million individual cells to be compartmentalized, cultured in production-relevant environments, and selected based on growth and biomass accumulation traits using standard cell-processing equipment.

Proceedings of the National Academy of Sciences recently published a study detailing how PicoShells work and their potential applications.

Animated gif image showing a euglena cell inside a PIcoShell. Credit: Mark van Zee/UCL

PicoShells consist of a hollow inner cavity where cells are encapsulated and a porous outer shell that allows for continuous solution exchange with the external environment so that nutrients, cell-communication molecules, and cytotoxic cellular byproducts can transport freely in and out of the inner cavity. The shell also keeps the small groups of growing cells penned in, allowing researchers to study and compare their behaviors — what they do, how fast they grow, what they produce — to those in other PicoShells.

Researchers can also use this new class of lab tool to grow living, single-cell microorganisms — including algae, fungi, and bacteria — under the same industrial-production conditions, such as in a bioreactor filled with wastewater or an outdoor cultivation pond.

This could shorten R&D-to-commercial production timelines

“PicoShells are like very tiny mesh balloons. The growing cells are effectively fenced in but not sealed off,” said study leader Dino Di Carlo, UCLA’s Armond and Elena Hairapetian Professor in Engineering and Medicine at the UCLA Samueli School of Engineering. “With this new tool, we can now study the individual behaviors of millions of living cells in the relevant environment. This could shorten R&D-to-commercial production timelines for bioproducts from a few years to a few months. PicoShells could also be a valuable tool for fundamental biology studies.”

PicoShells’ permeability can bring the lab to the industrial environment, allowing testing at a sectioned-off area of a working facility. Growth can occur more quickly and cell strains that perform well can be identified and selected for further screening.

According to the researchers, another advantage is that the analysis of millions of PicoShells is automated, since they are also compatible with standard lab equipment used for high-volume cell processing. Massive groups of cells, up to 10 million in one day, can be sorted and organized by certain characteristics.

Continuous analysis could result in ideal sets of cells — ones that are already performing well in the environment with suitable temperature, nutrient composition and other properties that could be used in mass production — in just a few days rather than the several months it would take using current technologies.

The shells can be engineered to burst when the cells inside have divided and grown beyond their peak volumes. Those free cells are still viable and can be recaptured for continued research or further selection. Researchers can also create shells with chemical groups that break down when exposed to a biocompatible reagent, enabling a multifaceted approach to release selected cells.

“If we want to zero in on algae that are the best at producing biofuels, we can use PicoShells to organize, grow and process millions of single algal cells,” said lead author Mark van Zee, a bioengineering graduate student at UCLA Samueli. “And we can do that in machines that sort them using fluorescent tags that light up to signify fuel levels.”

The researchers demonstrated the new tool by growing colonies of algae and yeast, comparing their growth and viability against other colonies grown in water-in-oil emulsions. For the algae, the team found that PicoShell colonies accumulated biomass rapidly while algae did not grow at all in water-in-oil emulsions. Similar results were found in their yeast experiments. By selecting the top growing algae in PicoShells, they could increase the production of chlorophyll biomass by 8% after only a single cycle.

The authors said PicoShells could offer a faster alternative to develop new algae and yeast strains, leading to improved biofuels, plastics, carbon-capture materials and even food products and alcoholic beverages. Further refinements to the technology, such as coating the shells with antibodies, could also lead to developing new types of protein-based medicines.