Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore

Abstract

Techniques for controlling the position of a charged polymer inside a nanopore are provided. For example, one technique includes using electrostatic control to position a linear charged polymer inside a nanopore, and creating an electrostatic potential well inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application under 37 CFR §1.53(b) of U.S. application Ser. No. 11 / 670,621 filed Feb. 2, 2007, incorporated by reference herein.FIELD OF THE INVENTION[0002]The present invention relates to polymer characterization and, more particularly, to systems and methods for controlling the position of a charged polymer inside a nanopore.BACKGROUND OF THE INVENTION[0003]Rapid, reliable, and inexpensive characterization of polymers, particularly the sequencing of nucleic acids, has become increasingly important. One potential application of polymer characterization is in the field of personalized medicine. For example, potential benefits of polymer characterization may include treatment of disease by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions. The ability to read individual genomes quickly and economically would be a beneficial...

AI Technical Summary

Benefits of technology

The present invention provides techniques for controlling the position of a charged polymer inside a nanopore. This is achieved through the use of electrostatic control to position the polymer and an electrostatic potential well to control its position. The invention also includes methods for characterizing the polymer and translocating it by one or more monomers. The invention overcomes limitations in existing approaches by controlling the position of a polymer with single monomer accuracy.

Problems solved by technology

However, sequencing by synthesis produces problems such as, for example, slow reagent cycling times (tens of seconds), short read lengths (tens to hundreds of bases) and expensive reagents.

Slow reagent cycling times is a fundamental problem because it results in a need to change chemistry in a flow cell to remove fluorophore from each incorporated base.

However, single nucleotide resolution has not yet been achieved.

Existing approaches using nanopore sequencing cannot resolve a single base, but, rather, require at least a few dozen bases.

Some existing approaches detect events of DNA translocation through a nanopore by measuring sub-millisecond blockades of ionic current through the nanopore but fail to resolve single bases within the translocated molecule.

Despite the ease of obtaining biological nanopores, the difficulties of dealing with unreliable and poorly understood membrane proteins lead many researches to use solid-state nanopores.

In existing approaches, however, repetitive measurements of tunnel current are necessary to provide enough statistics to determine the base type with a high degree of accuracy.

At present, nanopore sequencing is still theoretical, as single nucleotide resolution has not yet been achieved.

One of the possible reasons for such unsuccessful experimental results in existing approaches is that the translocation of DNA through the nanopore is too fast and erratic for current measurement methods to reliably resolve the type of a single nucleotide.

Despite attempts to slow down the translocation speed by optimization of various parameters (for example, electrolyte temperature, salt concentration, viscosity, and the electrical bias voltage across the nanopore), existing approaches have still been unsuccessful in attaining single nucleotide resolution.

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