Section 5.2.6.1. Pycnometry

Pycnometry measures the density of a liquid by weighing a calibrated volumetric flask before and after it is filled with the liquid. To measure a crystal's density, the pycnometer is first calibrated and weighed, and then the crystal sample, from which all external liquid has been removed, is introduced. The pycnometer is now reweighed, thus determining the crystal's weight. Next, liquid of known density is added, and the pycnometer is reweighed. The crystal volume is derived from the difference in volumes of the pycnometer with and without the crystal present. The method requires direct measurement of the crystal's weight, yet it is difficult to make microbalances with sensitivity and accuracy limits better than about 0.01 mg. Micropycnometry methods have been developed to determine mineral densities with as little as 5 mg of material (Syromyatnikov, 1935), but typical macromolecular crystals are 1000 times smaller than that.