Detecting single-abasic residues within a DNA strand immobilized in a biological nanopore using an integrated CMOS sensor.
In this paper, we demonstrate the application of a novel current-measuring sensor (CMS) customized for nanopore applications. The low-noise CMS is fabricated in a 0.35μm CMOS process and is implemented in experiments involving DNA captured in an α-hemolysin (α-HL) nanopore. Specifically, the CMS is used to build a current amplitude map as a function of varying positions of a single-abasic residue within a homopolymer cytosine single-stranded DNA (ssDNA) that is captured and held in the pore. Each ssDNA is immobilized using a biotin-streptavidin linkage. Five different DNA templates are measured and compared: one all-cytosine ssDNA, and four with a single-abasic residue substitution that resides in or near the ~1.5nm aperture of the α-HL channel when the strand is immobilized. The CMOS CMS is shown to resolves the ~5Å displacements of the abasic residue within the varying templates. The demonstration represents an advance in application-specific circuitry that is optimized for small-footprint nanopore applications, including genomic sequencing.
Department of Computer Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, U.S.A.
Jungsuk
J
Kim
Department of Computer Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, U.S.A.
Raj D
RD
Maitra
Department of Electrical Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, U.S.A.
Ken
K
Pedrotti
Department of Computer Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, U.S.A.
William B
WB
Dunbar
Biomedical instrumentation; CMOS current-measuring sensor; DNA-binding proteins; gene sequencer; nanopore technology; potentiostat; single-molecule science