From the World of Modern Cell Science, A Long and Sorted Coming-of-Age Story

He considered using valves or gates to divert the portion of a stream carrying a just-detected cell. But it was quickly clear that that could not be done with enough speed. About this time, Fulwyler read a paper by a Stanford engineer, Richard G. Sweet.

Sweet had discovered a way to create a highly ordered stream of droplets by directing liquid through a tube and out of an orifice oscillating about 30,000 times per second. This led to his invention, the inkjet printer.

Fulwyler realized Sweet had "a way to move small amounts of liquid very rapidly," he recalled in an oral history collected by the Smithsonian Institution in 1991. Moreover, Fulwyler said he thought the "small droplets could then be charged and individually deflected," pulled out of a stream that itself had been partitioned into hundreds of pieces.

Combined with a Coulter-like way of detecting the presence of a cell, Fulwyler said he thought he could come up with "a means of moving a cell around." In August 1964, he visited Sweet, borrowed some inkjet devices, returned to Los Alamos and went to work.

"Mack Fulwyler was the inventor of the cell sorter. There is no question about it," said J. Paul Robinson, a professor of immunopharmacology and biomedical engineering at Purdue University.

Fulwyler's original 1965 cell sorter is long gone. But a copy of it, built in 1967 and sold to a researcher at Brown University, was rescued in 2005 by Robinson just before it was going to be dismantled. It is now at Purdue, but Robinson said he has "absolutely no doubt it will end up in the Smithsonian."

The last big contribution was by Leonard A. Herzenberg, a Stanford biochemist and immunologist. Herzenberg visited Los Alamos in the late 1960s and asked Fulwyler to consider adding a fluorescence detector to the cell sorter. "I said fluorescence would make it very useful to biology," he recalled. Many biological substances (including DNA) are fluorescent in certain wavelengths of light. This would be a way to distinguish cells by something other than size.

In fact, Los Alamos researchers were experimenting with fluorescence detectors on the cell sorter. But it was Herzenberg and his collaborators who over the next dozen years perfected the use of fluorescent dyes and monoclonal antibodies to label cells so that even those virtually identical by size and shape could be differentiated and separated.

Fulwyler died in 2001. In 2006, Herzenberg in 2006 won the $450,000 Kyoto Prize, given to those who have "contributed significantly to the scientific, cultural, and spiritual betterment of mankind."

But the story isn't over. Last month, Massachusetts Institute of Technology researchers published a paper in Nano Letters describing a new approach to cell sorting.

Robert S. Langer and his colleagues use nanotechnology to build a surface covered with various molecular receptors, across which they roll cells. The receptors bind and release the cells at different rates, separating them into collectible groups.

Whether this leads to a better mousetrap -- er, cell trap -- remains to be seen.