Abstract: The present disclosure provides computing apparatuses, methods and software for generating random numbers. Data is received from an instrument characterising macromolecules in a sample, the data including measurement event information relating to measurements of individual macromolecules recorded over time. For each measurement event in a sequence of measurement events in the data, an event timing representative of the duration of event or the time passing between consecutive events is determined. This is compared with a comparator value to generate a binary output, and a bit value is determined based on the binary output. Data representative of a random number is generated by assembling a vector of bit values determined from the event timings in sequence. The determined sequence of event timings for the sequence of measurement events represents a source of entropy extracted by the comparison step to generate the random number.