Ypsilantis was associate professor of physics at the University of California, Berkeley, and was instrumental in the founding of the Demokritos Research Center in Athens, Greece.

In 1969, he went to Geneva to work at CERN (Centre European Research Nucleaire), where he met Jacques Séguinot.

In 1977, Ypsilantis and Séguinot proposed the technique later called the Ring Imaging Cherenkov (RICH) counter.

Together with Tord Ekelöf, they introduced this technique for high-energy physics: the first large-scale application was for the DELPHI experiment at LEP.

They later worked in the framework of the LAAS Project on noble-liquid calorimetry and on a very large water neutrino detector based on the fast-RICH technique.