Nanopore Device for Molecular Recapture and Trapping

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Solution Overview

Problem

Current methods for DNA sequencing and molecular analysis using solid state nanopores lack understanding and control of DNA capture and translocation dynamics, limiting the ability to characterize single molecules effectively.

Innovation Solution

A nanopore device configuration with fluidic reservoirs and a control system that allows for multiple translocations and recaptures of molecules, enabling detailed analysis of molecular behavior by controlling the conditions at the nanopore and reservoirs, and applying forces to study molecular dynamics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a solid state nanopore is used for DNA sequencing and molecular analysis, then single molecule characterization capability is improved, but understanding and control of DNA capture and translocation dynamics deteriorates

Engineering Contradiction:

Improvesingle molecule characterization capabilityVSAvoidcontrol of DNA capture and translocation dynamics

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent introduces an intermediary control system that mediates between the nanopore and the DNA molecules. This system uses controllable forces (electrical, magnetic, or optical) applied through reservoirs to regulate DNA capture and translocation dynamics, providing the needed control while maintaining single molecule characterization capability

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs parameter changes by dynamically adjusting physical conditions (such as electric field strength, fluid flow rates, or temperature) in the reservoirs to control DNA translocation. This allows precise manipulation of capture and translocation dynamics while preserving the ability to characterize single molecules

Inventive Principle:

Principle #35Parameter changes

2Loss of information

If DNA molecules are threaded through a nanopore for base-by-base analysis, then DNA sequencing capability is improved, but understanding of molecular interaction dynamics at the nanopore deteriorates

Engineering Contradiction:

ImproveDNA sequencing capabilityVSAvoidmolecular interaction dynamics at the nanopore

Core Design Contradiction:

Loss of informationVSDifficulty of detecting and measuring

Solution Approach 1:

The patent implements feedback mechanisms where the translocation process itself provides information about molecular interactions. By controlling and monitoring the forces applied during translocation and measuring the resulting signals, the system generates feedback that reveals interaction dynamics while maintaining sequencing capability

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent ensures continuous useful action by maintaining controlled translocation conditions throughout the process. The continuous application of controllable forces and continuous monitoring of translocation events provides ongoing information about molecular interactions without interrupting the sequencing process

Inventive Principle:

Principle #20Continuity of useful action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables precise manipulation and characterization of molecules, allowing for improved sequencing and analysis of DNA, including spatial trapping and real-time monitoring of molecular interactions, thereby overcoming limitations in existing nanopore technologies.

Implementation Method 1

an electric field or other driving force causes translocation of the DNA from, e.g., a source reservoir of ionic solution through the nanopore to a collection reservoir of ionic solution

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS8273532B2Capture, recapture, and trapping of molecules with a nanopore

Publication Date: 2012.09.25 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

In a molecular analysis system, there is provided a structure including a nanopore and first and second fluidic reservoirs. The two reservoirs are fluidically connected via the nanopore. A detector is connected to detect molecular species translocation of the nanopore, from one of the two fluidic reservoirs to the other of the two fluidic reservoirs. A controller is connected to generate a control signal to produce conditions at the nanopore to induce the molecular species to re-translocate the nanopore at least once after translocating the nanopore. This enables a method for molecular analysis in which a molecular species is translocated a plurality of times through a nanopore in a structure between two fluidic reservoirs separated by the structure.