Rafael Davalos, a Virginia Tech professor of biomedical engineering and mechanics, was studying cancer stem cells, which can cause cancer to recur.
He needed to separate the target cells from a tissue sample but found that existing cell sorting techniques had shortcomings.
“The challenge with most cell sorting techniques is that you need to label [the cells] so they are now technically altered and not in their native state,” he wrote in an email to Cardinal News.
This led Davalos and collaborators to invent and patent a new technology that uses an electrical field to rapidly sort and recover different cell types — without changing them. Faster, less invasive cell sorting could improve the understanding of disease, development of drugs, and selection of the most effective therapies.
To commercialize the technology, Davalos and Leo Harris founded CytoRecovery in 2017. Housed at the Virginia Tech Corporate Research Center, CytoRecovery celebrated its first sale in September, to the University of California, Irvine.
Steve Turner is CytoRecovery’s CEO. ”I was introduced to Rafael and his work when I visited Virginia Tech with my good friend Leo Harris, a VT alum active in VT tech transfer,” he wrote in an email. “Leo formed an LLC and helped finance Dr. Davalos’ research over several years. By late 2017 Leo felt it was ready for commercial development and invited me to form CytoRecovery to develop and bring this revolutionary cell sorting technology to market. Five years later, here we are, on the market.”
Other cell-sorting methods used tags or markers, which change the cells’ behavior. Davalos’s approach sorts the cells based on biophysical properties, leaving the cells untouched and ready for the additional steps such as sequencing or therapeutics testing.
Two Cyto Chips. In the chip on the right, blue colored water indicates the fluid path. The black lines (left chip) and silver lines (right chip) are the electrode channels that connect to a generator to produce an electric field. Randy Walker photo 
Mirror-like wafer is used to etch the Cyto Chips. Randy Walker photo 
Kit includes a Cyto Chip (top), tubing and syringes (green). Cost is $125 to $150. Randy Walker photo
The essential part of the technology is called a Cyto Chip. “Cyto” means cell. But the device does not look or feel like a computer chip.
The Cyto Chip is made of a silicon-based polymer. Approximately 1 1/2 by 1 inch and a quarter-inch thick, it is transparent, rubbery and flexible.
“We call these ‘chips’ because the process for manufacturing microfluidics is very similar to the way they make electronic chips out of silicon,” said Alex Hyler, VP and chief scientific officer.
Microfluidics is the study of, and the technology of, manipulating tiny amounts of fluids, typically with the goal of separating or enriching a sample.
Some people call the device a “lab on a chip,” Hyler said.
A researcher will inject a fluid containing a mixture of different types of cells into the Cyto Chip, perhaps seeking to increase the concentration of tumor cells from a biopsy, or sort a certain type of immune cell.
An electric field in the Cyto Chip differentially attracts certain cells, based on the cells’ biophysical properties such as cell membrane structure or the nucleus size.
Inside each chip is an array of tens of thousands of tiny pillars, Hyler said. The pillars act like magnets, although the field is electric rather than magnetic. The target cells are attracted to the pillars, while other cells pass through the Cyto Chip unaffected.
While many of the initial applications were cancer-related, that’s not the only use of the Cyto Chip.
Tayloria Adams is an assistant professor in the Department of Chemical and Biomolecular Engineering at the University of California, Irvine. Her research concerns mesenchymal stem cells.
“Mesenchymal stem cells can turn into bone, they can turn into fat, they can turn into cartilage cells, they support the immune system, they have a lot of different functionalities,” she said.
“We plan on using the CytoRecovery chip in order to do some sorting of mesenchymal stem cells. And so our goal is, can we sort out subpopulations of cells that may turn into bone, better than cells that would turn into fat?
“And then we could take those subpopulations of cells, and they could be used for clinical purposes. These cells are used in clinical trials to treat a variety of diseases.
“We’ve done some initial cell sorting, and we’re actually about to analyze our results.”
The Cyto Chips are sold as part of a disposable kit, including tubing to feed the cell medium into the chip and recover the enriched sample, for $125-150 per kit depending on the package.
CytoRecovery also sells a custom-designed electrical unit that supplies the necessary voltages and frequencies to attract a wide range of potential target cells. Much of the electronic equipment was developed at the University of Virginia, making CytoRecovery a cross-Commonwealth collaboration.
Greg Feldmann is president of Skyline Capital Strategies, a Roanoke business advisory firm affiliated with law firm Woods Rogers Vandeventer Black. Feldmann helped CytoRecovery with fundraising. “Money from the region has gone into that company, both from angels, as well as funds that I and others have introduced them to,” Feldmann said.
The company has progressed from founder funding, to seed funding from outside parties, to series A funding, Feldmann said. Series A funding is the first round of venture capital financing, in which a company receives funding in exchange for shares.
CytoRecovery’s success in getting to this stage “proves that it can happen in this region,” Feldmann said. “They’ve been through the RAMP program and gotten that experience and help and mentorship. I can’t almost think of any better example in the region of something that has its wellspring in university research, and can move out successfully and get commercialized. It’s just a really good example.”
RAMP, located in Roanoke, is a business accelerator that provides mentoring to technology startups. It was founded in 2017 with funding from GO Virginia, the city of Roanoke, and Virginia Western Community College.
CytoRecovery’s first sale came in the same month that the Biden administration launched its $2 billion National Biotechnology and Biomanufacturing Initiative. “I’m not exactly sure the mechanisms of how they’re implementing that funding,” Hyler said. “But if it is up for grabs, in some form, we will definitely be taking a look.”
CytoRecovery has applied for a National Science Foundation Phase 2 Small Business Innovation Research/Small Business Technology Transfer grant to help develop the next generation Cyto Chip.
In line with President Joe Biden’s goal of securing supply lines, CytoRecovery is committed to manufacturing as close to home as possible, Hyler said. While some parts are sourced overseas, the electronics are manufactured in Roanoke, mechanical parts in Baltimore, and the disposables in Blacksburg.
Brett Malone is president and CEO of the Corporate Research Center. As an example of the kind of field that CytoRecovery could impact, he mentioned cell therapy, which is “basically a way to take your own cells out of your body, re-engineer them, and then put them back in your body so they are smart and know how to fight the cancer that you have.” The CytoRecovery technology “enables those kinds of technologies to move into the clinic faster,” he said.
“We’re really proud to have Alex in the Corporate Research Center, and she’s one of many companies that are helping move this field forward.”