Detecting single-abasic residues within a DNA strand immobilized in a biological nanopore using an integrated CMOS sensor

作者：Kim Jungsuk; Maitra Raj D; Pedrotti Ken; Dunbar William B^*

来源：Sensors and Actuators B: Chemical , 2013, 177: 1075-1082.

DOI：10.1016/j.snb.2012.11.027

• Biomedical instrumentation
• CMOS current-measuring sensor
• DNA-binding proteins
• Gene sequencer
• Nanopore technology
• Potentiostat
• Single-molecule science

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 0.35 mu m CMOS process and is implemented in experiments involving DNA captured in an a-hemolysin (alpha-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 similar to 1.5 nm aperture of the a-HL channel when the strand is immobilized. The CMOS CMS is shown to resolves the similar to 5 angstrom 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.

• 出版日期2013-2