The present invention relates generally to systems and methods for processing a biological sample that result in a physical change, such as reacting two molecules together to form a reaction product or for use in lysing viruses or biological cells for analysis using biological assay systems. As such, the present invention relates both to breaking apart biological species such as viruses and cells, as well as the formation of reactants from one or more reactive species. The sample has a volume in the range from about 1 microliter to 10 milliliters. The sample is processed by applying pressure, and either sonic energy or thermal energy to the sample, wherein the pressure achieved is usually at least 24 atmospheres, and the temperature of the sample is usually raised to at least 50° C.