Detection of minimal amounts of DNA by electron microscopy using simplified spreading procedures

Electron microscopic examination of nucleic acids requires the use of special spreading techniques. The classical method was developed by Kleinschmidt and Zahn in 1959. Modifications of this method increased sensitivity to allow detection of a total amount of about 1 x 10(-3) micrograms of single-stranded DNA and 2 x 10(-5) micrograms of double-stranded DNA. Here we describe two rapid and simple procedures increasing sensitivity by 1-2 orders of magnitude to visualize at least 1 x 10(-5) micrograms of single- and/or double-stranded DNA.