Patent Number: 6,169,194

Title: High surface density covalent immobilization of oligonucleotide monolayers using a 1-(thiotrifluoroacetato)-11-(trichlorososilyl)-undecane linker

Abstract: Oligonucleotides and other biomolecules are immobilized in high density on solid substrates through covalent forces using either a permanent thioether bond, or a chemoselectively reversible disulfide bond to a surface thiol. Substrates which have hydroxyl groups on their surfaces can be first silanized with a trichlorosilane containing 2-20 carbon atoms in its hydrocarbon backbone, terminating in a protected thiol group. The oligonucleotides or other biomolecules are first connected to a tether consisting of a hydrocarbon or polyether chain of 2-20 units in length which terminates in a thiol group. This thiol may be further modified with a halobenzylic-bifunctional water soluble reagent which allows the conjugate to be immobilized onto the surface thiol group by a permanent thioether bond. Alternatively, the oligonucleotide-tether-thiol group can be converted to a pyridyldisulfide functionality which attaches to the surface thiol by a chemoselectively reversible disulfide bond. The permanently bound oligonucleotides are immobilized in high density compared to other types of thiol functionalized silane surfaces and to the avidin-biotin method.

Inventors: Thompson; Michael (Toronto, Ontario, CA), McGovern; Mark E. (Etobicoke, Ontario, CA)


International Classification: B32B 17/06 (20060101); B32B 17/10 (20060101); C03C 17/34 (20060101); C03C 17/30 (20060101); C03C 17/28 (20060101); C07H 21/00 (20060101); C07F 007/12 (); C07B 309/39 (); G01N 033/552 ()

Expiration Date: 01/02/2018