Non-thermal cycling for polymerase chain reaction

Abstract

Techniques, systems, and devices are disclosed for non-thermal cycling of polymerase chain reaction (PCR). In one aspect, a method for cycling PCR includes receiving an electrolytic fluid including ions, primers, polymerase enzymes, nucleotides, and a double-stranded nucleic acid in a fluid chamber having a first electrode and a second electrode, applying an electric field across the first and the second electrodes to generate a first pH level of the electrolytic fluid to denature the double-stranded nucleic acid to at least partial single strands, and applying a second electric field across the first and second electrodes to produce a second pH level of the electrolytic fluid, in which the second pH level enables binding of a polymerase enzyme and a primer with a corresponding segment of the single strands.

What is claimed is: 
     
         1 . A device for cycling polymerase chain reaction (PCR), comprising:
 a substrate that is electrically insulating;   a channel formed of an electrically insulative material on the substrate and structured to carry an electrolytic fluid including ions, primers, polymerase enzymes, nucleotides, and a double-stranded nucleic acid;   a first electrode pair and a second electrode pair located in the channel in contact with the electrolytic surface and spaced apart along the channel; and   a circuit electrically coupled to the first and second electrode pairs to apply a first electric field across the first electrode pair to generate a first pH level of the electrolytic fluid, wherein the double-stranded nucleic acid is capable of denaturation to at least partial single strands at the first pH level, and to apply a second electric field across the second electrode pair to generate a second pH level of the electrolytic fluid, wherein the second pH level enables at least one of binding of a polymerase enzyme and a primer with a corresponding segment of the at least partial single strands or synthesis of new complementary nucleic acid strands from the nucleotides using the at least partial single strands.   
     
     
         2 . The device as in  claim 1 , further comprising a third electrode pair located in the channel in contact with the electrolytic surface and spaced apart from the first and the second electrode pairs along the channel,
 wherein the circuit is electrically coupled to the third electrode pair to apply a third electric field across the third pair to generate a third pH level of the electrolytic fluid, wherein the third pH level enables the synthesis of new complementary nucleic acid strands from the nucleotides using the at least partial single strands.   
     
     
         3 . The device as in  claim 1 , further comprising a semi-permeable membrane configured within the interior and along a direction of fluid flow of the channel and being permeable for the ions to traverse the membrane and impermeable  5  to the primers, polymerase enzymes, nucleotides, and double-stranded nucleic acid. 
     
     
         4 . The device as in  claim 3 , wherein the semi-permeable membrane is moveable in a direction substantially perpendicular to the direction of fluid flow. 
     
     
         5 . The device as in  claim 1 , wherein the polymerase enzymes are covalently attached to a surface of at least one of the channel or electrodes.