Apparatus and Method for Detecting Genetic Mutations and Single Nucleotide Polymorphisms

Abstract

A method and means of identifying nucleic acid oligomers is disclosed. A sample is split into parts and the parts are flowed through chromatography columns containing nucleic acid oligomer probes bound to a binding medium. Analyte oligomers are transiently hybridized to complementary probe oligomers during chromatography. Detection and analysis of oligomer peaks is used to identify the oligomers contained in the sample.

1 . An apparatus for identifying nucleic acid mutations comprising;
 an inlet for accepting a sample of target nucleic acid oligomer comprising at least one target sequence;
 where the target sequence is also known to exist in mutated form; 
   a dividing means connected to the inlet;   at least two chromatography columns, comprising an inlet end and an outlet end, connected to the dividing means;
 where each inlet end of each column is separately connected to the dividing means; 
 where each column comprises binding medium;
 where the binding medium comprises probe nucleic acid oligomers bound to a solid support; 
 
 where a first column comprises binding medium comprising probe oligomers that are complementary to the at least one target sequence; 
 where a second column comprises binding medium comprising probe oligomers that are complementary to a mutated form of the at least one target sequence; 
 where the rates of hybridization and dissociation of the target oligomers and the probe oligomers is about the same; 
   a detection apparatus connected to the outlet ends of the columns;   and an analysis apparatus connected to the detection apparatus.   
     
     
         2 . The apparatus of  claim 1  further comprising at least a third column;
 where the third column comprises binding medium comprising probe oligomers that are complementary to a sequence differing from the at least one target sequence and differing from the mutated form of the at least one target sequence.   
     
     
         3 . The apparatus of  claim 1  wherein the ratio of the rate of hybridization to the rate of dissociation is between about 35:65 and about 65:35. 
     
     
         4 . The apparatus of  claim 1  where the probe oligomers are covalently attached to the binding medium. 
     
     
         5 . The apparatus of  claim 1  where the probe oligomers are non-covalently attached to the binding medium. 
     
     
         6 . The apparatus of  claim 1  where the target oligomers comprise DNA. 
     
     
         7 . The apparatus of  claim 1  where the target oligomers further comprise a label.