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How the Wistar Flow Cytometry Facility Came to Be

December 5, 2023

Jeffrey Faust keeps a toolbox next to his office. It looks like something you might find in a garage: screwdrivers, Allen wrenches (standard & metric), wire caps, the indispensable duct tape, and so on. But Jeffrey doesn’t tinker with cars or ham radios — his tools are for adjusting and maintaining flow cytometry equipment with six-figure price tags. That doesn’t faze Mr. Faust, though; he’s been doing this for more than 40 years.

Jeffrey Faust, M.B.A., is the Managing Director of The Wistar Institute’s Flow Cytometry Core Facility, where the days are spent sorting, counting, and analyzing cells. Scientists from around the institute — and even beyond; as a Core Facility, the resources here are commercially available to external parties — depend on Jeffrey and his team to turn biology into data that can be interpreted.

Mr. Faust’s domain is strictly all-business: a set of fluorescently lit rooms that would be unassuming if not for the array of massive whirring machinery that gives the facility a space-age aura. Tools, parts, and sets of instructions line the walls, and the monitors attached to the active machines display live feeds of data as it is collected, displayed, and analyzed.

Having started the facility from scratch, Jeffrey has an impeccable command of all things flow cytometry. He first walked through Wistar’s front doors in 1977, fresh out of the University of Pennsylvania with a degree in natural sciences and hoping only for some form of gainful employment during the 70s’ economic malaise. Hired as secretary, the young Jeffrey soon became a lab technician working with mRNA — until his PI unexpectedly and tragically died, and Jeffrey was thrust into the role of lab manager.

In late 1980, Wistar, eager to stay up to date on the latest in scientific instrumentation, purchased its first flow cytometer; the nascent technology was still new to the world of biological research, and Wistar needed someone who could operate it. An offer was made, and Jeffrey Faust was soon enrolled in a three-week training course to understand how the machine worked — Wistar had found its Director of Flow Cytometry.

So what does a flow cytometer do? A flow cytometer aims a laser of a specific wavelength at a steady stream (or flow) of cells that have been stained with a special chemical called a fluorochrome — which, when excited by light of wavelength x, will emit light with wavelength y. When each cell flows through the laser’s path, the fluorochromes emit certain wavelengths of light, which, after going through a series of optical filters, then hit a detector that converts those emissions into electrical pulses. Those pulses are converted into digital signals that are sent to an attached workstation. This process allows flow cytometers to convert thousands and thousands of signals from the flow of raw cells into data that can be visualized and analyzed.

Because different fluorochromes can bind to different parts of a cell, they can be used to measure different properties. Let’s say you want to know how many cells in a given population are alive after a treatment. You can treat the cells with a fluorochrome that’s known to bind to dead cells but not living ones. Then you process the cell population with the flow cytometer, and for every fluorochrome emission signal you see on the screen, you know you have a dead cell. A similar process allows for the precise determination and quantification of antigen expression.

With the advancement of fluorochrome technology over the years, scientists have been able to use this technology to quantify a variety of cell characteristics in bulk populations; if a phenomenon can be tagged with a fluorochrome, then a flow cytometer can measure it. The Wistar Institute Flow Cytometry Facility now has instruments capable of detecting up to 48 total fluorochromes.

Back when Jeffrey Faust installed the very first of Wistar’s flow cytometers, the technology was still very much in its infancy — limited laser wavelengths and even fewer fluorochromes. And while today’s advanced FC equipment is designed with the user in mind, the first-gen flow cytometers were aggressive in their user-unfriendliness; the picture Jeffrey has of the original machine and its computer resembles nothing so much as a knob- and dial-studded sarcophagus and an antique arcade game, respectively.

“We were really just figuring this stuff out ourselves because we were right there at the beginning of this technology,” says Jeffrey, looking back on the history of the facility. “I’d call up someone halfway across the country who used the same machine, and we’d compare notes. Because we had to; otherwise, we weren’t going to make any progress.”

The machines got bigger, faster, and easier to use, but Jeffrey kept current. In his day, he’s worked with scores of scientists — even Nobel Prize winners, including Wistar’s own Dr. Peter Doherty (1996 Nobel Prize Winner, Physiology or Medicine). The discovery of a monoclonal antibody to detect natural killer cells (NK cells) was an early major discovery in the Wistar Flow Cytometry Facility. “There had not been monoclonal antibodies available that targeted NK cells. At the time, Wistar was working to develop and isolate the very first monoclonal antibodies, and we kept noticing this little shoulder in our flow cytometry data. As that lab, which was Trinchieri and Perussia, dug into it, they narrowed the data down — until we realized that they were able to quantify NK cells for the first time.”

In his time as facility director, Jeffrey has managed and hired 16 technicians to assist him in the facility — eight of whom moved on to manage their own facilities in academia and industry. Wistar’s facility continues to grow, with Jeffrey having helped incorporate spectral flow cytometry as well, which uses additional sensitive wavelength detectors to capture full-spectrum flow data across several parameters. To manage the ever-growing demands for flow cytometry data, Mr. Faust and his staff continue to train and assist users, who learn how to process millions and millions of cells a day with the precision necessary to keep the research moving forward accurately and efficiently.

How have the 40+ years affected Mr. Faust? Hardly at all, it seems. The “guts” of his first machine are still in the office, but the real energy of this facility is in its current operations, not its past. Flow-cytometry data, as it’s being collected and graphed, looks like a real-time pointillism piece, both patterned and strangely abstract. To the non-expert, it’s a mesmerizing sight; to Jeffrey Faust, it’s what a good day’s work looks like. “You see that?” he says, pointing to a line on the screen of an instrument in use. “That’s where the dead cells are excluded.” There are seemingly thousands of dots appearing by the second. And the machine — perfectly adjusted and expertly tuned — keeps counting.