A computer-implemented method for selecting one or more monoclonal cell colonies using an apparatus having a digital imaging device, the method comprising: loading a sample plate onto the apparatus, the sample plate including a well having a plurality of single cells held in a semi-solid growth medium; capturing, at a first time and using the digital imaging device, a first plurality of vertically spaced-apart images of the well, each image having a different height along a Z axis, such that a volumetric image stack is generated with respect to the well; identifying, based on one or more images of the well captured at a second time substantially later than the first time, a location of one or more candidate colonies of cells; determining, based on the volumetric image stack, a measure of likelihood, for each candidate colony, that the candidate colony is monoclonal, wherein the determining a measure of likelihood comprises: correlating the position of the one or more candidate colonies in the one or more images captured at the second time with the position of a single cell in the images captured at the first time; identifying, from the plurality of single cell locations, single cells that are spaced from all other cells by at least a selected first distance; and limiting potential locations of each candidate colony of cells to locations corresponding to the identified single cells; compiling a pick list of colony coordinates using the measure of likelihood that a colony is monoclonal, and picking the colonies of the pick list using a picking head of the apparatus to isolate at least a portion of the colony. loading a sample plate onto the apparatus, the sample plate including a well having a plurality of single cells held in a semi-solid growth medium; capturing, at a first time and using the digital imaging device, a first plurality of vertically spaced-apart images of the well, each image having a different height along a Z axis, such that a volumetric image stack is generated with respect to the well; identifying, based on one or more images of the well captured at a second time substantially later than the first time, a location of one or more candidate colonies of cells; determining, based on the volumetric image stack, a measure of likelihood, for each candidate colony, that the candidate colony is monoclonal, wherein the determining a measure of likelihood comprises: correlating the position of the one or more candidate colonies in the one or more images captured at the second time with the position of a single cell in the images captured at the first time; identifying, from the plurality of single cell locations, single cells that are spaced from all other cells by at least a selected first distance; and limiting potential locations of each candidate colony of cells to locations corresponding to the identified single cells; compiling a pick list of colony coordinates using the measure of likelihood that a colony is monoclonal, and picking the colonies of the pick list using a picking head of the apparatus to isolate at least a portion of the colony. correlating the position of the one or more candidate colonies in the one or more images captured at the second time with the position of a single cell in the images captured at the first time; identifying, from the plurality of single cell locations, single cells that are spaced from all other cells by at least a selected first distance; and limiting potential locations of each candidate colony of cells to locations corresponding to the identified single cells; compiling a pick list of colony coordinates using the measure of likelihood that a colony is monoclonal, and picking the colonies of the pick list using a picking head of the apparatus to isolate at least a portion of the colony.