Entropic Trapping Nanopillars for Nucleic Acid Linearization

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Solution Overview

Problem

Nanopore and nanochannel systems used for nucleic acid sequencing are prone to clogging due to the small size of the pores and channels, leading to inefficient sample flow and clogging, which limits the sequencing efficiency and requires faster sample and reagent exchange.

Innovation Solution

The implementation of a nanoelectrode system with adjustable tunneling nanoelectrodes and entropic trapping components, such as nanopillars with gap spacings less than 50 nanometers, to linearize and concentrate nucleic acid molecules, allowing for faster flow rates and preventing clogging by creating a detection region with a larger fluid channel and entropic trapping components that guide the biopolymer towards the detection area.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If nanopore and nanochannel systems are used for nucleic acid sequencing, then detection precision is improved, but the system is prone to clogging due to small pore size

Engineering Contradiction:
Improvedetection precisionVSAvoidclogging resistance
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The system divides the fluid path into multiple segments: a large-volume fluidic channel for sample introduction and a small-volume nanochannel for detection. This segmentation allows the sample to be processed in stages, preventing clogging while maintaining detection precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A fluidic channel acts as an intermediary between the sample source and the nanochannel detection region. This intermediary channel with larger volume and dimensions prevents direct contact between bulk sample and the fragile nanopore, reducing clogging risk while enabling precise detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If the fluidic channel volume is large relative to nanopore flow capacity, then sample exchange is efficient, but flow rate through the nanopore is limited

Engineering Contradiction:
Improvesample volumeVSAvoidflow rate
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

The system separates the fluid path into a large-volume fluidic channel for efficient sample exchange and a small-volume nanochannel for high-speed detection. This segmentation allows each component to optimize its function without compromising the other.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system transitions from a single-channel design to a multi-dimensional fluid path where sample can be introduced through the larger fluidic channel and then directed into the nanochannel for detection. This dimensional transition enables both efficient sample exchange and high flow rate through the nanopore.

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

3Manufacturing precision

If nanopillars with small gap spacing are used for entropic trapping, then linearization is improved, but device complexity increases

Engineering Contradiction:
Improvelinearization precisionVSAvoiddevice complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The nanopillars with specific gap spacing are placed only in the detection region where linearization is needed, rather than throughout the entire fluidic channel. This localized approach improves linearization precision while minimizing the increase in device complexity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The entropic trapping components are positioned upstream of the detection region to pre-linearize the biopolymer before it reaches the nanopore. This preliminary action ensures proper orientation and linearization without requiring complex real-time adjustment mechanisms during detection.

Inventive Principle:
Principle #10Preliminary 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

This solution enhances the sequencing efficiency by preventing clogging, allowing for faster sample exchange and improved detection of nucleic acid sequences, enabling more accurate and efficient sequencing of biopolymers.

Implementation Method 1

a first entropic trapping component and second entropic trapping component disposed in or adjacent to the nanochannel, wherein (i) the first entropic trapping component is operable to linearize the biopolymer upon flow of the biopolymer through the first entropic trapping component

Methodology Applied
Scientific EffectEntropic trapping:

Data Source

PatentUS10413903B2Devices, systems and methods for linearization of polymers
Publication Date: 2019.09.17 OSAKA UNIVERSITY
  • US10413903B2 patent drawing
  • US10413903B2 patent drawing
  • US10413903B2 patent drawing

AI summary

The present disclosure provides methods and structures for systems which can linearize and capture a nucleic acid molecule (e.g., DNA) for re-measurement of the nucleic acid molecule or other polymer prior to detection of the polymer. The structures may allow for quick exchange between different samples or other reagents.