Sorting and immobilization system for nucleic acids using synthetic binding systems

Abstract

Methods are provided for producing an array of immobilized nucleic acids on an array device. The array device has a plurality of microlocations each having an electrode. At least one of the microlocations has a synthetic addressing unit coupled to the microlocation. The microlocation is the activated, usually by electronically biasing the electrode of the microlocation. The at least one microlocation is then contacted by a conjugate which has a nucleic acid and a synthetic binding unit. The conjugate is then coupled to the microlocation through an interaction between the synthetic binding unit and the synthetic addressing unit. In one embodiment, the synthetic binding unit and synthetic addressing unit may be pRNA, pDNA, or CNA.

1 . A method for producing an array of immobilized nucleic acids on an array device, the method comprising the steps of: 
 providing an array device comprising a plurality of microlocations, wherein at least one microlocation comprises an electrode and a synthetic addressing unit coupled to the at least one microlocation;    activating the at least one microlocation;    contacting the at least one microlocation with a conjugate, wherein the conjugate comprises a nucleic acid and a synthetic binding unit and wherein the synthetic binding unit is capable of binding to the synthetic addressing unit; and    coupling the conjugate to the microlocation through binding of the synthetic binding unit to the synthetic addressing unit.    
     
     
         2 . The method of  claim 1 , wherein the synthetic addressing unit is coupled to at least two microlocations.  
     
     
         3 . The method of  claim 1 , wherein the at least one microlocation is activated by electronic biasing of the electrode.  
     
     
         4 . The method of  claim 1 , further comprising the step of biasing the at least one microlocation to remove unbound conjugate.  
     
     
         5 . The method of  claim 1 , wherein the synthetic binding unit is selected from the group consisting of pRNA, pDNA, and CNA.  
     
     
         6 . The method of  claim 1 , wherein the synthetic addressing unit is selected from the group consisting of pRNA, pDNA, and CNA.  
     
     
         7 . The method of  claim 1 , wherein the synthetic binding unit is connected via the a linkage between the 4′ end of the synthetic binding unit to the 5′ end of the nucleic acid.  
     
     
         8 . The method of  claim 1 , wherein the synthetic binding unit is connected via the a linkage between the 2′ end of the synthetic binding unit to the 3′ end of the nucleic acid.  
     
     
         9 . The method of  claim 1 , wherein the synthetic binding unit is connected via the a linkage between the 4′ end of the synthetic binding unit to the 3′ end of the nucleic acid.  
     
     
         10 . The method of  claim 1 , wherein the synthetic binding unit is connected via the a linkage between the 4′ end of the synthetic binding unit to the 5′ end of the nucleic acid.  
     
     
         11 . The method of  claim 1 , wherein the nucleic acid is selected from the group consisting of deoxyribonucleic acids, ribonucleic acids, and chemically modified nucleic acids.  
     
     
         12 . The method of  claim 1 , wherein the nucleic acid is selected from the group consisting of phosphorothioate nucleic acids, phosphorodithioate nucleic acids, methylphosphonate nucleic acids, 2′-O-methyl RNA, and 2′-fluoro RNA.  
     
     
         13 . The method of  claim 1 , wherein the nucleic acid is selected from the group consisting of peptide nucleic acids (PNA) and locked nucleic acids (LNA).  
     
     
         14 . The method of  claim 1 , wherein the conjugates further comprise at least one labeling moiety.  
     
     
         15 . The method of  claim 14 , wherein the labeling moiety is selected from the group consisting of fluorescent moieties, quencher moieties, visible dye moieties, radioactive moieties, chemiluminescent moieties, biotin moieties, hapten moieties, micro-particles, paramagnetic micro-particles, and enzymatic labeling moieties.  
     
     
         16 . The method of  claim 1 , wherein the synthetic addressing unit is coupled to the at least one microlocation via a biotin/streptavidin interaction.  
     
     
         17 . The method of  claim 1 , wherein the synthetic addressing unit coupled to the at least one microlocation via a covalent bond.  
     
     
         18 . The method of  claim 1 , wherein the at least one microlocation comprises an additional synthetic binding unit coupled to the at least one microlocation.  
     
     
         19 . The method of  claim 1 , wherein the synthetic addressing unit and synthetic binding unit are bound through non-covalent interaction.  
     
     
         20 . The method of  claim 19 , wherein the non-covalent interaction is hydrogen bonding.