This disclosure provides methods for producing a sample of subcellular organelles, particularly nuclei, from a tissue. In some embodiments, this disclosure provides a method of processing a tissue sample involves performing enzymatic/chemical disruption of tissue in a chamber to produce disrupted tissue comprising released cells and/or nuclei and debris; separating the released cells and/or nuclei from the debris therein; and moving the released cells and/or nuclei. In some instances, the method comprises mechanical disruption of the tissue sample.