Nanopore Protein Conjugates for Multi-Analyte Capture Rate Sensing

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Solution Overview

Problem

Existing methods for detecting and identifying biologically active components in fluid solutions are often expensive, time-consuming, and prone to errors, and they typically can only analyze one or a few components at a time without determining concentration.

Innovation Solution

Nanopore protein conjugates comprising a nanopore protein monomer and a capture tag, tethered to an analyte ligand, are used to form a nanopore assembly within a membrane, allowing for the detection and concentration determination of multiple analytes by monitoring capture rate changes with a sensing electrode.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If conventional diagnostic methods are used to detect biologically active components, then detection accuracy can be maintained, but the process becomes time-consuming and expensive

Engineering Contradiction:
Improvedetection timeVSAvoiddetection accuracy
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The patent replaces complex mechanical/diagnostic systems with a nanopore-based detection system that uses electrical measurements to detect analytes. The nanopore protein conjugates with capture tags enable direct electrical detection of molecular binding events, eliminating the need for complex laboratory diagnostic equipment and procedures while maintaining detection reliability.

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

Solution Approach 2:

The patent changes the detection parameter from complex multi-step diagnostic measurements to simple electrical current measurements through nanopores. By monitoring ionic current blockades when analytes bind to capture tags on nanopore proteins, the system achieves rapid detection without compromising accuracy, as the electrical signal directly reflects molecular binding events.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional diagnostic methods are used, then comprehensive analysis can be performed, but the complexity increases leading to errors

Engineering Contradiction:
Improvedetection accuracyVSAvoidtest complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the detection function into modular nanopore protein conjugates, each with a specific capture tag for a particular analyte. Multiple such conjugates can be used simultaneously in parallel nanopores to detect multiple analytes independently, simplifying the overall test while maintaining comprehensive analysis capability and reducing errors through modular design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The nanopore detection system serves multiple functions: it can detect various biologically active components (proteins, small molecules, nucleic acids) using different capture tags on the same nanopore platform, perform quantitative concentration measurements, and provide rapid results. This multi-functionality reduces complexity compared to having separate specialized tests for each analyte type.

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

3Adaptability or versatility

If conventional methods are used to analyze multiple components, then comprehensive profiling is achieved, but the cost and time increase significantly

Engineering Contradiction:
Improvemulti-analyte detection capabilityVSAvoidanalysis time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent merges multiple detection capabilities into a single nanopore array system where multiple nanopore protein conjugates with different capture tags are incorporated into the same membrane. This allows simultaneous detection of multiple analytes in parallel, achieving comprehensive multi-analyte profiling in a single experiment rather than requiring separate sequential tests, thereby dramatically reducing analysis time while maintaining versatility.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses identical nanopore protein structures with different capture tags attached, effectively creating functional copies of the detection platform tailored for different analytes. This standardized copying approach enables rapid deployment of multi-analyte detection without developing entirely new systems for each analyte, reducing both time and cost while maintaining comprehensive profiling capability.

Inventive Principle:
Principle #26Copying

4Reliability

If conventional diagnostic tests are performed, then accurate identification is achieved, but significant laboratory resources are required

Engineering Contradiction:
Improveidentification accuracyVSAvoidresource requirement
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs nanopore protein conjugates that can be produced relatively simply and used in disposable sensor chips. The nanopore proteins are expressed in bacterial systems and can be purified and attached to chip surfaces in a straightforward process. These sensor chips can be manufactured at low cost and used single-use or regenerated, significantly reducing laboratory resource requirements while maintaining identification accuracy through the specific capture tag-analyte binding.

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

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

The method enables rapid, efficient, and cost-effective detection and identification of multiple analytes in a fluid solution, with the ability to determine their concentration based on capture rate transitions.

Implementation Method 1

monitoring capture rate changes with a sensing electrode

Methodology Applied
Scientific EffectElectrochemical detection:

Data Source

PatentUS12474321B2Nanopore protein conjugates for detection and analysis of analytes
Publication Date: 2025.11.18 ROCHE DIAGNOSTICS OPERATIONS INC
  • US12474321B2 patent drawing
  • US12474321B2 patent drawing
  • US12474321B2 patent drawing

AI summary

Provided are methods, compositions, and systems for the detection of a target analyte. Also provided are methods, compositions, and systems for determining the concentration one or more target analytes in fluid solution. The compositions include nanopore conjugates in which a nanopore protein monomer is joined to a capture tag. Tethered to the nanopore protein conjugate is an analyte ligand directed to a specific analyte. When a voltage is applied across a nanopore assembly including the nanopore conjugate, the nanopore captures the capture tag at a given capture rate. In the presence of the analyte to the analyte ligand, however, the capture rate of the capture tag changes, thus permitting detection of the analyte by the nanopore assembly. Further, based on the capture rate associated with binding between the analyte and the analyte ligand, the concentration of the analyte can be determined using association/dissociation kinetics.