Researchers at the University of Virginia School of Engineering and Applied Science have developed cell-tracking software that could enable users to track thousands of fast-moving, often-obscured leukocytes in vivo, the investigators said.
The software, called CellTrek, was developed to monitor and measure how leukocytes move in living tissue, which is an important — although tedious — manual task involved in discovering anti-inflammatory drugs.
According to the researchers, CellTrek cuts through the “noise” surrounding leukocytes so that investigators can rapidly collect accurate data on thousands of cells simultaneously, which can be used to describe the intensity of the inflammatory process they are carrying out.
The software also automates cell collection, thereby reducing the risk of human error. For example, investigators performing manual cell collection may unintentionally introduce bias through the selection of certain cells over others. An effect known as “jitter,” or the sudden image shifts due to the subject’s respiratory and circulatory system, can also introduce error.
According to the UVa. team, CellTrek is faster, less expensive, and more accurate than hand-tracking.
As a result, the team hopes to market the software through a start-up it founded last year called Just-Tracking.
Klaus Ley, director of the Division of Inflammation Biology at the La Jolla [Calif.] Institute for Allergy and Immunology and a co-developer of CellTrek, spoke with CBA News this week about the plans that he and co-developer Scott Acton, a professor of electrical and computer engineering at UVa., have for bringing the CellTrek technology to market.
Can you give me a little background on this technology?
In inflammation, leukocytes need to enter the tissues and they do that by adhering to the blood vessel wall and then transmigrating through the vessel wall into the tissue. The leukocyte does not often have much contrast, unless it has been tagged with a GFP.
In order to better understand the rolling, adhesion, and transmigration into the tissue, it is desirable to track these cells. The tracking software that Acton developed is based on the principle of detecting the cells, then putting a little circle on top of the cell, and then having that circle expand until it hits the border of that cell.
It detects the border of the cell by sensing the contrast there. Once it latches onto the cell, it will follow that cell, even if the cell changes shape a little bit. So it’s an adaptive system.
Older systems that use simpler methods for tracking cells usually fail in cluttered environments where multiple leukocytes are adhering and migrating into the tissue. These leukocytes are often piled on top of one another.
Sometimes it is hard to track individual cells in such a cluttered environment and that is the problem that Dr. Acton has essentially solved.
What was your role in developing the CellTrek software?
I provided the problem. I also helped test the software. Acton had applied similar techniques to other problems like tracking tanks on battlefields, but tackling a biological problem was new to him.
How did you come to work with Acton?
He gave a talk that I attended. During that talk, he showed a video of the Tour de France taken from a helicopter. There were some cyclists in the picture, and they were cycling along a country road. Some of them would even disappear into a little forest and then come out the other side.
He could track them on their moving bicycles from the moving helicopter even though they were obscured. I thought that was pretty cool. If he was able to track stuff like that, I thought he would be able to track leukocytes during the inflammatory process.
What is the next step in this project?
We incorporated a company, Just-Tracking, about a year ago. We are planning to further develop this technology for the scientific community at large, which will require that the software become user-friendly and have more engineering support. We cannot really do this on a collaborative basis.
We give out the software to testers, but the technology is still a little rough, so to speak. You have to really know what you are doing and sometimes it crashes, but it is not at the level that you would expect of a polished, commercial product. That is why we decided that commercializing it is the best way to bring it to the scientific community.
Is it for sale right now, or is it mostly in the hands of testers?
It is mostly in testers’ hands. We are not selling it right now.
Do you have a timeline for commercializing it?
We have a number of investigators nationwide who are using various versions of various aspects of the software. It will be a suite of programs.
Different people track different types of cells that have different types of contrasts, and different types of needs. The investigators may use different types of microscopes and cameras. You can imagine that you need to build a lot of adaptability into the software. Its not like you can send someone a CD and it will work.
Realistically, it may be another year before we have a product that we can bring to market.
How would you further develop and refine CellTrek, and what other related products would you like to develop and market?
The immediate goal is to engineer [CellTrek] so that it becomes user-friendly and robust. As I said, [it is currently being tested] in various laboratories and we are getting valuable feedback from those investigators.
In terms of new products that we are developing, as I said, we envision a suite of programs and new stuff coming out all the time. Our development team is currently very small, so the rate at which new products are developed is rather slow, but we have a product that works with a technique called intravital microscopy and we have another product that works with another technique called flow chamber.