Patent ID: 7547533

Claim:
A method for producing an intramolecularly, covalently cross-linked DNA or RNA polymerase for analyte detection, said method comprising the steps of: providing an aqueous mixture comprising a non-cross-linked DNA or RNA polymerase in a dissolved form that specifically binds with the analyte or with a substance bound to the analyte, reacting said non-cross-linked DNA or RNA polymerase with a cross-linking reagent selected from the group consisting of 3-maleimidobenzoyl-N-hydroxysuccinimide ester, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, disuccinimidylsuberate, N-hydroxysuccinimidyl-4-azido-benzoate, and sulfosuccinimidyl-6(4′-amido-2′-nitrophenyl-amido)hexanoate to produce an intramolecularly, covalently cross-linked DNA or RNA polymerase in the absence of detectable intermolecular multimers of the polymerase, and separating unreacted cross-linking reagent from the intramolecularly, covalently cross-linked DNA or RNA polymerase.