Parallel DNA Detection via 2D Nanopore Membranes

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Solution Overview

Problem

Conventional solid-state nanopores face challenges such as significant thermal conformational DNA fluctuations, fast translocation rates, and undesirable interactions with DNA, hindering the development of effective genome sequencing devices, particularly in simultaneous detection of multiple DNA strands in multipore systems.

Innovation Solution

A novel device utilizing an array of 2D nanopore membranes with graphene or transition metal dichalcogenide membranes, employing all-atom molecular dynamics simulations and electronic transport calculations to model the double-pore system as a parallel resistor circuit, enabling simultaneous detection of multiple DNA strands through transverse sheet current measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional solid-state nanopores are used for DNA detection, then the device structure is simple and manufacturing is easier, but the detection precision is limited due to fast translocation rates and thermal conformational fluctuations

Engineering Contradiction:
Improvedetection precisionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention divides the detection system into multiple independent nanopores arranged in an array, where each pore can detect DNA strands independently. This segmentation allows simultaneous detection of multiple DNA molecules, improving overall detection precision and throughput while maintaining relatively simple individual pore structures

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from single-pore detection to a two-dimensional array of nanopores, adding spatial dimensionality to the detection system. This enables parallel detection across multiple pores, significantly enhancing measurement precision and capacity without proportionally increasing device complexity

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Productivity

If multiple DNA strands are detected simultaneously in multipore systems, then productivity increases, but crosstalk effects and detection accuracy deteriorate

Engineering Contradiction:
Improvedetection throughputVSAvoiddetection accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

Each nanopore in the array operates as an independent detection unit with its own readout circuit, segmenting the detection signal sources. This isolation prevents crosstalk between simultaneously detected DNA strands in different pores, maintaining detection accuracy while enabling high-throughput parallel detection

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces individually addressable readout circuits as intermediaries between each nanopore and the detection system. These intermediaries isolate and independently process signals from each pore, preventing signal crosstalk while enabling simultaneous measurement of multiple DNA strands

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If solid-state nanopores are used instead of biological nanopores, then stability and robustness improve, but undesirable interactions with DNA and fast translocation rates persist

Engineering Contradiction:
ImprovestabilityVSAvoiddetection precision
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The invention modifies the physical and chemical parameters of the nanopore system, including pore size, material composition, and surface properties, to optimize DNA interaction. By adjusting these parameters, the system maintains the stability of solid-state nanopores while reducing unwanted interactions and slowing translocation rates for improved detection precision

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If 2D nanopore membranes with graphene or TMD are used, then detection sensitivity increases, but device complexity and manufacturing difficulty increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmanufacturing ease
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention employs graphene and TMD materials that provide multiple functions simultaneously: they form the nanopore membrane structure, provide the detection interface, and enable electronic readout capabilities. This multi-functionality reduces the need for additional components, offsetting manufacturing complexity with integrated design benefits

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

This approach allows for high detection sensitivity and concurrent detection of multiple DNA strands, overcoming the limitations of conventional systems by leveraging the tunability of graphene nanopore membranes and reducing crosstalk effects, thus advancing the potential for rapid biomolecule detection and genome sequencing.

Implementation Method 1

detection of a DNA molecule translocating through a graphene nanopore by monitoring the variations of the ionic blockade current

Methodology Applied
Scientific EffectIonic blockade current: Electrical Resistance

Implementation Method 2

employing all-atom molecular dynamics simulations and electronic transport calculations to model the double-pore system as a parallel resistor circuit

Methodology Applied
Scientific EffectElectrical resistance: Electrical Resistance

Data Source

PatentUS11099170B2Parallel DNA detection by solid-state multi-pore systems and associated methods
Publication Date: 2021.08.24 THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
  • US11099170B2 patent drawing
  • US11099170B2 patent drawing
  • US11099170B2 patent drawing

AI summary

Aspects of the subject disclosure may include, for example, an apparatus comprising: a dielectric substrate; a plurality of membranes positioned upon the dielectric substrate, wherein each of the plurality of membranes has a first side and a second side, wherein each of the plurality of membranes has a pore disposed therein, wherein each pore extends through each respective membrane from the first side of the respective membrane to the second side of the respective membrane, wherein each pore is associated with a corresponding hole that extends through the dielectric substrate, and wherein each of the plurality of membranes is not in direct contact with any other of the plurality of membranes; and a plurality of electrode pairs, wherein each of the plurality of electrode pairs is in contact with a single respective one of the plurality of membranes. Additional embodiments are disclosed.