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The use of a two layer discontinuous gradient was developed by Freeman et al [27] who started with an isoosmotic solution of 27.6% (w/v) Nycodenz in 3 mM KCl, 0.3 mM CaNa2-EDTA 5 mM Tris-HCl, pH 7.5 (this isoosmotic solution, which was available as NycoPrep 1.15 is no longer produced commercially)