A process for measuring a size distribution of a plurality of nucleic acid molecules, the process comprising: labeling the nucleic acid molecules with a fluorescent dye comprising a plurality of fluorescent dye molecules to form labeled nucleic acid molecules, such that a number of fluorescent dyes molecules attached to each nucleic acid molecule is reliably proportional to the number of base pairs in the nucleic acid molecule, the fluorescent dye molecules having a first florescence spectrum; producing, by the labeled nucleic acid molecules, the first florescence spectrum in response to irradiating the labeled nucleic acid molecules at the first wavelength; and detecting the first florescence spectrum to measure the size distribution of the plurality of nucleic acid molecules.
This invention is a method for measuring the size of single nucleic-acid molecules. Measuring the size of nucleic-acid molecules is important in a variety of applications ranging from criminal forensics to clinical diagnostics. The invention advances conventional methods and instruments used to size single nucleic-acid molecules and provides an unprecedented combination of limit of detection, throughput, accuracy, precision, and repeatability. The methods and apparatus can be used in clinical diagnostics.
The measurements exceed the current state of the art for sizing single DNA molecules by a fluorescence measurement in at least three metrics: the minimum fragment size that can be resolved, the precision or uncertainty of the measurement, and throughput.