Detecting mutation in nucleic acid, by contacting nucleic acid with colloidal solution containing three types of nanoparticles bonded to nucleic acids

摘要

A colloidal solution containing a first number of nanoparticles bonded to a first target nucleic acid (A), a second number of nanoparticles bonded to a second target nucleic acid (B) and a third number of nanoparticles bonded to a third target nucleic acid (C) is contacted with the acid in order to form nanoparticle aggregates, then a phase separation is carried out to form a gel phase and a dilute phase and then the concentration of the second or third nanoparticles in the gel or dilute phase is measured and compared with a phase diagram for a suspension of the colloidal solution and nucleic acid. A method for detecting at least one first mutation in a nucleic acid with at least two parts comprises the following steps: (1) providing a colloidal solution containing a first number of nanoparticles bonded to a first target nucleic acid (A) having a sequence complimentary to the sequence in the part of the acid, a second number of nanoparticles bonded to a second target nucleic acid (B) having a sequence complimentary to the sequence of the second part of the acid and a third number of nanoparticles bonded to a third target nucleic acid (C) having a sequence complimentary to the sequence of a first mutation in the second part of the acid; (2) contacting the acid with the colloidal solution under conditions chosen so that the first nanoparticles become coupled to the second or third nanoparticles in order to form first-second (AB) or first-third (AC) aggregates and subjecting the solution to a phase separation in order to form a gel phase with an increased concentration of second nanoparticles compared with the third nanoparticle concentration and a dilute phase with a reduced concentration of second nanoparticles compared with the third nanoparticle concentration; (3) measuring the concentration of the second or third nanoparticles in the gel or dilute phase; (4) producing a phase diagram for a suspension of the colloidal solution and nucleic acid; (5) comparing the concentrations measured in step (3) with the phase diagram; and (6) determining whether the mutation is present or not on the basis of this comparison. An independent claim is also included for the colloidal solution.