2. Methods of study (1) While the electron microscope(EM) had been known for many years, the invention of the negative-staining technique in 1959 revolutionized studies on virus structure In negative-contrast EM virus particles are mixed with a heavy metal solution(e.g. sodium phosphotungstate磷钨酸盐) and dried onto a support film.The stain provides an electron-opaque background against which the virus can be visualized Negative-staining techniqueWhile the electron microscope (EM) had been known for many years, the invention of the negative-staining technique in 1959 revolutionized studies on virus structure. In negative-contrast EM, virus particles are mixed with a heavy metal solution (e.g. sodium phosphotungstate磷钨酸盐) and dried onto a support film. The stain provides an electron-opaque background against which the virus can be visualized。 2. Methods of study（1） Negative-staining technique