title: Label-free electrical detection of pyrophosphate generated from DNA polymerase reactions on field-effect devices.
abstract: We introduce a label-free approach for sensing polymerase reactions on deoxyribonucleic acid (DNA) using a chelator-modified silicon-on-insulator field-effect transistor (SOI-FET) that exhibits selective and reversible electrical response to pyrophosphate anions. The chemical modification of the sensor surface was designed to include rolling-circle amplification (RCA) DNA colonies for locally enhanced pyrophosphate (PPi) signal generation and sensors with immobilized chelators for capture and surface-sensitive detection of diffusible reaction by-products. While detecting arrays of enzymatic base incorporation reactions is typically accomplished using optical fluorescence or chemiluminescence techniques, our results suggest that it is possible to develop scalable and portable PPi-specific sensors and platforms for broad biomedical applications such as DNA sequencing and microbe detection using surface-sensitive electrical readout techniques.
authors.affiliation: Integrated Biosystems Lab, Intel Labs, Intel Corporation, 2200 Mission College Blvd., Santa Clara, CA 95054, USA. grace.m.credo@intel.com
authors.forename: Grace M
authors.initials: GM
authors.lastname: Credo
authors.forename: Xing
authors.initials: X
authors.lastname: Su
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.forename: Oguz H
authors.initials: OH
authors.lastname: Elibol
authors.forename: David J
authors.initials: DJ
authors.lastname: Liu
authors.forename: Bobby
authors.initials: B
authors.lastname: Reddy
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Tsai
authors.forename: Brian R
authors.initials: BR
authors.lastname: Dorvel
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Daniels
authors.forename: Rashid
authors.initials: R
authors.lastname: Bashir
authors.forename: Madoo
authors.initials: M
authors.lastname: Varma
mesh_terms: D001483:Base Sequence; D015374:Biosensing Techniques; D002614:Chelating Agents / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D011756:Diphosphates / Q000032:analysis*; D055664:Electrochemical Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry; D012825:Silicon / Q000737:chemistry; D013499:Surface Properties; D014173:Transistors, Electronic
chemical_list: D002614:Chelating Agents; D011756:Diphosphates; D012821:Silanes; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D012825:Silicon