Current analytical techniques do not permit detection of isotopes when a ratio of 1000 to 1 atoms of equal mass but different atomic number are present along with other isotopes of the same element at an excess of 10¹⁴ atoms. Such capabilities would be useful in neutrino detection, geochemical dating, and other investigations. Detection problems in general and a possible laser solution being developed at Los Alamos National Laboratory are discussed in this paper. Photoionization mass spectrometry and laser-induced fluorescence detection of mass selected ions are two complementary approaches to the detection problem. The former approach is being developed at Oak Ridge National Laboratory, while the latter is being developed at Los Alamos. In the Los Alamos approach, a state of the art mass spectrometer is used in its conventional mode, and ions are detected by laser-induced fluorescence as they exit the mass spectrometer.