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Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11127-32. doi: 10.1073/pnas.1205004109. Epub 2012 Jun 25.

Rapid hybridization of nucleic acids using isotachophoresis.

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Mechanical Engineering, Stanford University, 440 Escondido Mall, Stanford, CA 94305, USA.


We use isotachophoresis (ITP) to control and increase the rate of nucleic acid hybridization reactions in free solution. We present a new physical model, validation experiments, and demonstrations of this assay. We studied the coupled physicochemical processes of preconcentration, mixing, and chemical reaction kinetics under ITP. Our experimentally validated model enables a closed form solution for ITP-aided reaction kinetics, and reveals a new characteristic time scale which correctly predicts order 10,000-fold speed-up of chemical reaction rate for order 100 pM reactants, and greater enhancement at lower concentrations. At 500 pM concentration, we measured a reaction time which is 14,000-fold lower than that predicted for standard second-order hybridization. The model and method are generally applicable to acceleration of reactions involving nucleic acids, and may be applicable to a wide range of reactions involving ionic reactants.

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