Fragmentation and labelling with a programmable temperature control module

A system for estimating nucleic acid sequence frequencies, the system comprising:

• a fragmentation reaction chamber in a time and temperature programmable temperature control module;
• a pool of nucleic acids contained in the reaction chamber;
• a fragmentation reaction solution in the reaction chamber, which solution fragments the nucleic acid pool to an extent controlled by a time and temperature programmed into the temperature control module;
• a labeling component that binds a detectable marker to a nucleic acid fragment produced by the fragmentation reaction solution, thereby labeling the nucleic acid fragment;
• one or more target nucleic acid sequences bound to locations on a solid support;
• and,
• a detector adapted to quantitatively detect the labeled nucleic acid fragments at the locations, and to provide a quantitative detection signal;
• whereby the frequency of one or more nucleic acids in the pool of nucleic acids can be estimated from the quantitative detection signal.

A method of labeling nucleic acids, the method comprising:

• programming a time and temperature sequence into a programmable temperature control module;
• fragmenting the nucleic acids with a fragmentation reaction solution in a chamber of the programmable temperature control module;
• inhibiting the fragmentation by raising the chamber to a termination temperature;
• and,
• labeling one or more nucleic acid fragments produced by the fragmentation reaction solution with a detectable marker;
• wherein said raising the chamber to the termination temperature is controlled by the programmed time and temperature sequence, provided by the programming.

A method of providing an estimate of a frequency of a nucleic acid sequence, the method comprising:

• providing pooled nucleic acids comprising two or more different sequences;
• fragmenting the pooled nucleic acids in a time and temperature programmable temperature control module;
• labeling a nucleic acid fragmented in the temperature control module with a detectable marker;
• placing the labeled nucleic acid fragment into a hybridization reaction with two or more target nucleic acids comprising one or more sequences complimentary to the labeled nucleic acid fragment;
• and,
• detecting a labeled nucleic acid fragment which becomes hybridized to at least one of the complimentary target nucleic acid sequences, thereby providing a measure of the sequence frequency in the pooled nucleic acids.