The production of high-energy fats from microalgae can be a sustainable, renewable energy source that can help tackle climate change. However, microalgae that are designed to produce lipids grow rapidly, usually slowly themselves, making it difficult to increase the overall yield.
UCLA bioengineers have created a new type of petri dish in the form of microscopic, permeable particles that can dramatically accelerate research and development (R&D) timelines for biological products, such as fatty acids for biofuels. Baptized PicoShells, picoliters (trillionths of a liter), porous hydrogel particles can allow more than one million individual cells to divide, grow in production-relevant environments, and be selected based on growth and biomass accumulation properties using standard cell therapy equipment. .
Proceedings of the National Academy of Sciences recently published a study describing how PicoShells works and their potential uses.
PicoShells consist of a hollow inner cavity where cells are encapsulated and a porous outer shell that allows continuous solution exchange with the external environment so that nutrients, cell communication molecules and cytotoxic cellular by-products can be freely transported in and out of the inner cavity. The shell also holds the small groups of growing cells inside, allowing researchers to study and compare their behaviors – what they do, how fast they grow, what they produce – with other groups’ behaviors inside different PicoShells.
This new class of laboratory tools allows researchers to grow living, single-celled 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.
“PicoShells are like very small mesh balloons. The growing cells inside them are effectively fenced but not sealed,” said study leader Dino Di Carlo, UCLA’s Armond and Elena Hairapetian, professor of engineering and medicine at UCLA Samueli School of Engineering. “With this new tool, we can now study the individual behavior of millions of living cells in the relevant environment. This can 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 basic biology studies. ”
The permeability of PicoShells can bring the laboratory to the industrial environment, enabling testing in a cut-off area of a work facility. Growth can occur more rapidly, and cell strains that perform well can be identified and selected for further screening.
According to the researchers, another advantage of this new tool is that the analysis of millions of PicoShells is automated, as they are also compatible with standard laboratory equipment used for high-volume cell therapy.
Massive groups of cells, up to 10 million in one day, can be sorted and organized according to specific properties. Continuous analysis can result in ideal sets of cells – those that are already doing well in the environment with the appropriate temperature, nutrient composition and other properties that could be used in mass production – in just a few days instead of the several months it would take to use current technologies.
The shells can be designed to rupture once the cells inside have divided and grown beyond their maximum volume. These free cells are still viable and can be recaptured for further research or further selection. Researchers can also create shells with chemical groups that degrade when exposed to biocompatible reagents, enabling a multifaceted approach to releasing selected cells.
“If we want to focus on algae that are the best at producing biofuels, we can use PicoShells to organize, grow and process millions of single algae cells,” says lead author Mark van Zee, a bioengineering student at UCLA Samueli. “And we can do that in machines that sort them using fluorescent tags that light up to indicate fuel levels.”
Currently, the cultivation and comparison of such microorganisms takes place mostly using traditional laboratory tools, such as microwell plates – cartons that hold several dozen small test tube-like volumes. However, these methods are slow and it is difficult to quantify their effectiveness because it can take weeks or months to grow large colonies for study. Other approaches, such as water-in-oil droplet emulsions, can be used to analyze cells in smaller volumes, but ambient oils prevent free exchange of medium into the water droplets. Even cells or microorganisms that perform well under laboratory conditions may not perform as well once placed in industrial environments, such as bioreactors or outdoor farms. As a result, cell strains developed in the laboratory often do not exhibit the same beneficial characteristic behaviors when transferred to industrial production.
Microwell plates are also limited in the number of experiments that can be performed, resulting in a great deal of trial and error in finding cell strains that work well enough for mass production.
The researchers demonstrated the new tool by growing colonies of algae and yeast, comparing their growth and viability with 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 in water-in-oil emulsions at all. Similar results were found in their yeast experiments. By selecting the fastest growing algae in PicoShells, the researchers were able to increase the production of chlorophyll biomass by 8% after just a single cycle.
The authors said PicoShells could offer a faster alternative to developing new algae and yeast strains, leading to improved biofuels, plastics, carbon capture materials and even foods and alcoholic beverages. Further improvements in technology, such as coating the shells with antibodies, may also lead to the development of new types of protein-based medicines.
Di Carlo, van Zee and co-author Joseph de Rutte Ph.D. ’20, a former member of Di Carlo’s research group, is named inventor on a patent application filed by the UCLA Technology Development Group. The other UCLA writers on paper are Rose Rumyan, Cayden Williamson, Trevor Burnes, Andrew Sonico Eugenio, Sara Badih, Dong-Hyun Lee and Maani Archang. Randor Radakovits of Synthetic Genomics of San Diego is also an author.
Cultivation of algae outside wastewater
Mark van Zee et al., High-throughput selection of cells based on accumulated growth and division using PicoShell particles, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073 / pnas.2109430119
Provided by the University of California, Los Angeles
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