Single-cell sorting by function is now possible because of nanotechnology.

For nearly 40 years, pharmaceutical companies have utilized genetically modified cells as miniature drug factories. These cells can be engineered to release chemicals that can be utilized to treat cancer and autoimmune diseases like arthritis.

A new approach for quickly sorting single, living cells in a typical laboratory setup may benefit efforts to develop and produce new biologic medicines. A UCLA-led research team recently showed the capacity to choose cells based on what type they are and which compounds—and how much of those compounds—they secrete using minuscule, bowl-shaped hydrogel containers called “nanovials.” The findings were reported in the journal ACS Nano.

The technique has the potential to boost basic biology studies as well.

With this technology, the scientific community can gain new insights into key biological processes that represent a significant portion of our protein-coding genes, said Dino Di Carlo, the study’s corresponding author and the Armond and Elena Hairapetian Professor of Engineering and Medicine at UCLA Samueli School of Engineering. “I consider the single cell to be biology’s quantum limit. The nanovial is the Petri dish’s progression to the fundamental limit of one cell. “

“”With this technology, the scientific community can uncover new insights into key biological processes that represent a huge fraction of our protein-coding genes. I think of the single cell as the quantum limit of biology. The nanovial is the evolution of the Petri dish to that fundamental limit of one cell.”

Dino Di Carlo

Di Carlo, who is also a member of UCLA’s California NanoSystems Institute and the UCLA Jonsson Comprehensive Cancer Center, believes that employing nanovials allows scientists to overcome the limits of other devices for quantifying cell secretions.

The more usual method employs a grid of tiny plastic containers known as a microwell plate, but it lacks the nanovial’s capacity to sort single cells, and current technology typically requires weeks for enough cells to grow to detect secretions. The second option is a multimillion-dollar apparatus found in only a few dozen labs globally that can sort live cells and measure the secretions of 10,000 cells every trial.

Nanovials, in comparison to that instrument, may be used to undertake considerably bigger screenings—in the millions of cells—at a fraction of the relative cost—less than one cent per cell, versus $1 or more per cell using the present standard.

Nanovials are so small that 20 million of them would be required to fill a teaspoon. They are tailored to capture specific types of cells and can be supplemented with molecules that adhere to a cell’s secretions and glow in different colors. Because nanovials are constructed of a hydrogel—a polymer that can hold nearly 20 times its weight in water—they provide a wet environment that is akin to the natural habitats of cells.

In the study, researchers looked at cells that had been genetically modified to release a specific antibody medication. They picked cells that secreted the most of that antibody using nanovials and a common analytical device called a flow cytometer, and then expanded those cells into colonies that produced more than 25% more of the medication than colonies that had not been carefully selected.

According to Di Carlo, the capacity to make antibody therapeutics with that increased efficiency might lower medication production costs by a similar percentage.

The researchers also demonstrated the ability to detect rare antibody-secreting cells that bonded exclusively to a target molecule, as well as the DNA sequence information of the released antibody. That experiment, which was crucial in the discovery of novel antibody medicines, took only one day; standard approaches would take weeks.

The researchers are presently employing nanovials to examine immune cells known as T cells, which are used in cell treatments as well as to investigate hitherto unknown biological processes. Partillion Bioscience, a startup company situated on the UCLA campus at CNSI’s Magnify incubator, is similarly built on nanovial technology.

The paper’s co-first author and co-founder and president of Partillion, who obtained a doctorate from UCLA in 2020, said “We are enthusiastic to see the impact nanovials will have on biological research now that they are available for anyone to utilize.”

The paper’s other co-first author is Robert Dimatteo, who will receive his doctorate from UCLA in 2021. Other UCLA co-authors include recently graduated doctoral students Maani Archang, Sohyung Lee, and Kyung Ha; current doctoral students Mark van Zee, Doyeon Koo, Michael Mellody, and Shreya Udani; assistant project scientist Allison Sharrow; James Eichenbaum, who recently graduated with a bachelor’s degree; and professors Andrea Bertozzi and Robert Damoiseaux. Johns Hopkins University and the University of Houston are among the other writers.

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