Nanopore Immunoassay Multiplexing With Ionic Current Tag Readout

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Solution Overview

Problem

Existing methods for detecting biomarkers and molecular interactions are limited in sensitivity, specificity, and cost-effectiveness, particularly in multiplexed assays, and lack the ability to efficiently quantify multiple compounds simultaneously.

Innovation Solution

A method utilizing a nanopore platform with capture and tagged compounds to detect the presence and quantify multiple biomarkers by measuring electronic signal changes from tags entering nanopores, allowing for multiplexed detection and quantitation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional immunological methods (ELISA, RIA, protein arrays) are used for biomarker detection, then the detection can be performed with established protocols, but the sensitivity and cost-effectiveness are insufficient compared to nanopore methods

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcost-effectiveness
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces traditional mechanical/chemical detection systems (ELISA, RIA, protein arrays) with a nanopore-based electronic detection system. The nanopore array with ionic current readout provides single-molecule electronic detection, substituting the mechanical mixing and optical/chemical readout of traditional methods with an electronic measurement platform that achieves higher sensitivity and cost-effectiveness

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from optical/chemical signals in traditional methods to ionic current blockades in nanopores. By measuring the electrical current through the nanopore array and detecting changes when tagged analytes pass through, the system achieves superior sensitivity and quantitation capabilities at lower cost

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If mass spectrometric methods are used for biomarker detection, then high sensitivity can be achieved, but the cost is significantly higher than nanopore methods

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent substitutes the complex and expensive mass spectrometric system with a simpler nanopore-based electronic detection system. The nanopore array provides single-molecule sensitivity through ionic current measurements, achieving comparable or superior detection sensitivity without the high instrumentation and operational costs of mass spectrometry

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs disposable nanopore arrays that can be manufactured at low cost and used for single-use or limited-use detection. This eliminates the need for expensive, maintenance-intensive mass spectrometers while providing sufficient sensitivity for biomarker detection through the disposable nature of the nanopore platform

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Adaptability or versatility

If multiplexed detection of multiple biomarkers is performed using traditional methods, then comprehensive analysis can be achieved, but the complexity and cost increase significantly

Engineering Contradiction:
Improvemultiplexing capabilityVSAvoidassay complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent implements a universal nanopore array platform where different capture compounds can be attached to different nanopores to detect multiple different analytes simultaneously. The same nanopore array structure and ionic current readout method serve multiple detection functions, enabling multiplexed biomarker analysis without requiring separate assays for each target

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

Solution Approach 2:

The patent divides the detection task across multiple nanopores in an array, with each nanopore potentially configured for a specific analyte through attachment of specific capture compounds. This segmentation allows parallel detection of multiple biomarkers in a single experiment, reducing overall assay complexity compared to sequential traditional methods

Inventive Principle:
Principle #1Segmentation

4Productivity

If quantitative detection of multiple compounds is performed simultaneously, then comprehensive biomarker analysis can be achieved, but the measurement precision and specificity become challenging to maintain

Engineering Contradiction:
Improvequantitation throughputVSAvoidquantification accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent attaches specific capture compounds to specific nanopores in the array, creating localized detection zones optimized for specific analytes. Each nanopore-capture compound pair provides specialized binding characteristics, maintaining high specificity and quantification accuracy for each target even when multiple analytes are detected simultaneously across the array

Inventive Principle:
Principle #3Local quality

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

Enhances sensitivity and specificity in detecting and quantifying biomarkers and molecular interactions, offering a cost-effective alternative to existing methods by enabling simultaneous detection of multiple compounds with high precision.

Implementation Method 1

measuring the electronic signal change across the pore resulting from at least one tag of the tagged compound entering the nanopore

Methodology Applied
Scientific EffectIonic current blockade: Electrical Resistance

Data Source

PatentUS12535477B2Single-molecule electronic multiplex nanopore immunoassays for biomarker detection
Publication Date: 2026.01.27 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • US12535477B2 patent drawing
  • US12535477B2 patent drawing
  • US12535477B2 patent drawing

AI summary

The present application discloses novel and inventive methods, apparatuses, and the required molecules to detect compounds (analytes) utilizing antibodies or other protein-binding molecules and nanopore-detectable tags using specially designed nanopores, coupled with ionic current readout, to provide a single molecule electronic detection solution, offering unique opportunities for multiplexing and quantitation.