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IP.com Disclosure Number: IPCOM000186884D
Publication Date: 2009-Aug-31
Document File: 8 page(s) / 146K

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The IP.com Prior Art Database


The present invention relates, in general, to nanopore sequencing. More specifically, the present invention relates to an on-chip system for nanopore sequencing.

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improved system for nanopore sequencing




The present invention relates, in general, to nanopore sequencing. More specifically, the present invention relates to an on-chip system for nanopore sequencing.

Nanopore sequencing is a method for determining the nucleotide order of a strand of deoxyribonucleic acid (DNA). A typical nanopore is a hole within a biological or synthetic substrate with an internal diameter of approximately the same size as the width of a single, unbranched polymeric molecule. For example, the naturally occurring transmembrane cellular protein - alpha-hemolysin has a limiting aperture at its narrowest point of approximately 15 angstroms. Nanopores can be made from such transmembrane cellular proteins, or chemically modified versions thereof, or fabricated by etching holes in a piece of silicon or other solid substrates.

In accordance with an approach, nanopore sequencing entails measuring current that flows through the nanopore when it is immersed in a conducting fluid. The magnitude of current flowing through the nanopore depends on the size of the nanopore and the dimensions of molecules present within the nanopore during the measurement time. Therefore, when a molecule such as a DNA molecule passes through the nanopore, the magnitude of current alters. The current is also altered if a portion of a DNA molecule, such as a nucleotide subunit of the DNA polymer, is present in the nanopore during the measurement time. The current change can be different in magnitude and duration for different molecules, allowing the differences in the molecules to be distinguished. Thus, when the system enables differentiation between different nucleotides, DNA sequencing can be performed.

The passage of a part of DNA molecule through the nanopore is also commonly known as the occurrence of an ‘event’. The amount by which the magnitude of current changes depends on the whether it is blocked by an A, a C, a G or a T nucleotide. The change in the magnitude of current through the nanopore as the DNA molecule passes through the nanopore represents a direct reading of the DNA sequence. Typically, the current through the nanopores is measured using an external multiplexed sensitive current monitor that samples multiple pores sequentially. The systems used for performing such measurements are cumbersome, large, expensive, and prone to missing short duration events which may lead to erroneous molecular characterization such as impeding accurate sequencing.

The present invention provides an improved on-chip system for nanopore sequencing. The present invention proposes to include a current sensor, an analog to digital converter (ADC), a plurality of counters, and an output buffer at each nanopore site. The current sensor measures the current flowing through the n...