NUCLEIC ACID SEQUENCING BY ELECTROCHEMICAL DETECTION

摘要

Provided herein is technology relating to sequencing nucleic acids and particularly, but not exclusively, to devices, methods, and systems for sequencing-by-synthesis using changes in pH to monitor base addition. In some embodiments the electrochemical hydrogen ion sensor is a microfabricated mixed metal oxide electrode and in some embodiments the electrochemical hydrogen ion sensor is a membrane electrode. Moreover, in some embodiments the device further comprises a reference electrode. Performing the sequencing reaction involves moving solutions and other fluids (e.g., samples, nucleotide solutions, wash solutions) into and out of the reaction vessel. Thus, in some embodiments, the device further comprises a tube or other transport mechanism or pathway attached to the reaction vessel.

主权项

1. A device for determining the sequence of a nucleic acid, the device comprising a reaction vessel configured to contact a hydrogen ion-sensitive electrode with a sample comprising the nucleic acid, wherein the hydrogen ion-sensitive electrode is either:
a) a microfabricated metal oxide electrode comprising:
i) an insulating material sensitive to hydrogen ions; andii) a conductive metal oxide,wherein the microfabricated metal oxide electrode does not exhibit the bulk conductive properties of the conductive metal oxide; or b) a membrane electrode comprising:
i) a photolithographic base layer; andii) a hydrogen ion-sensitive membrane.