Determining the presence of particular nucleic acid sequence in a test sample comprises (a) chemically modifying nucleic acids in the test sample to introduce a label or a reactive site that supports their hybridisability. (b) contacting under hybridisation conditions the chemically modified sample nucleic acids (MNA's) with a hybridisable nucleic acid probe (NAP) which either, when the sample nucleic acids have been modified to introduce a label, carries a reactive site, or when the sample nucleic acids have been modified to introduce a reactive site is labelled. (c) contacting the soln. obtd. with an immobilised form of a reactive partner to the reactive site to form a stable bond with the reactive site on the sample nucleic acids or the probe. (d) sepg. the resulting immobilised fraction and (e) determining the presence of the label in the sped. immobilised fraction or a decrease in the label in the remaining soln.
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