While working at IBM he was part of the initial team of ten programmers who created FORTRAN, and later suggested the use of electron beam lithography for the fabrication of X-ray Fresnel zone plates.
Although the key to most direct methods still in use today, Sayre did not share the 1985 chemistry Nobel prize awarded for their discovery.
It is also around this time that Sayre, inspired by Claude Shannon's recent work, suggested in a short paper that the crystallographic phase problem could be solved more easily if one could measure intensities at a higher density than imposed by Bragg's law.
Back in United States, David Sayre worked on structure determination of a carcinogen molecule in the lab of Peter Friedlander at the University of Pennsylvania in Philadelphia.
He suggested to use the newly developed electron beam lithography apparatus at IBM to produce Fresnel zone plates, a type of X-ray lens now widely used in Synchrotron facilities.