A thermal block assembly is provided. The assembly can comprise a substrate comprising a first surface configured with a plurality of reaction sites each reaction site configured to contain a biological sample and a sample block comprising a plurality of pedestals configured to thermally modulate the plurality of biological samples wherein each pedestal is thermally coupled to one of the reaction sites. The assembly can further comprise cooling blocks, slots and insulating rings associated with reaction sites each capable of minimizing heat flow between reaction sites. A method for thermally isolating reaction sites is also provided. The method can comprise providing a substrate including a plurality of reaction sites, each reaction site configured to contain a biological sample, providing a sample block comprising pedestals, each pedestal having a dimension substantially equal to a dimension of the reaction site and thermally coupled to the reaction site, thermally isolating the reaction sites with a thermal isolating feature, modulating the temperature of the pedestals through a sequence of temperature and hold times and cooling the reaction sites with cooling blocks.