Nucleic Acid Aptamer Binding Elements for Reversible Target Detection

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Solution Overview

Problem

Existing binding elements, such as antibodies and engineered protein binders, face challenges with stability, immunogenicity, and high costs, making them unsuitable for therapeutic applications and repeated use, while nucleic acid-based binding elements lack stability and selectivity for multiple-use paradigms in target detection.

Innovation Solution

The development of nucleic acid-based binding elements immobilized on solid supports for repeated regeneration cycles, allowing for reversible detection and quantitation of targets through binding, washing, elution, and regeneration processes, enabling multiple cycles of target binding and release without significant loss of binding capacity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If antibodies or engineered protein binders are used as binding elements, then high selectivity and affinity are achieved, but stability and reusability deteriorate due to molecular complexity and immunogenicity

Engineering Contradiction:
Improveselectivity and affinityVSAvoidstability and reusability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent uses nucleic acid-based binding elements (aptamers) as simplified copies or alternatives to protein binders, achieving similar target binding functionality while eliminating the stability and reusability problems associated with protein structures

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent changes the fundamental material parameter from protein-based to nucleic acid-based binding elements, transforming the chemical composition to achieve both high selectivity and improved stability for repeated use

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If engineered protein binders are used, then small size and ease of synthesis are achieved, but immunogenicity and cost increase, making them unsuitable for therapeutic applications and repeated use

Engineering Contradiction:
Improveease of synthesisVSAvoidimmunogenicity
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent replaces protein binders with nucleic acid-based aptamers that can be synthesized chemically rather than through biological systems, eliminating immunogenicity while maintaining ease of production

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent employs chemically synthesized nucleic acid aptamers that are cost-effective and can be easily replaced or regenerated, eliminating the high cost and immunogenicity issues of protein binders

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

3Reliability

If nucleic acid-based binding elements are used, then cost-effectiveness and reusability are improved, but stability and selectivity deteriorate compared to protein binders

Engineering Contradiction:
ImprovereusabilityVSAvoidselectivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent employs dynamic selection processes (SELEX) to evolve nucleic acid aptamers with high selectivity, allowing the binding elements to adapt and improve their target recognition capabilities through iterative selection and amplification

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent optimizes the nucleic acid sequence parameters through systematic variation and selection, achieving high selectivity and stability combinations that were previously only available from protein binders

Inventive Principle:
Principle #35Parameter changes

4Productivity

If binding elements are used for multiple detection cycles, then detection expense is reduced, but binding capacity and detection accuracy deteriorate due to loss of binding element integrity

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

Solution Approach 1:

The patent implements regeneration protocols that recover and restore the binding capacity of nucleic acid aptamers after each detection cycle, allowing repeated use without significant loss of detection accuracy

Inventive Principle:
Principle #34Discarding and recovering

Solution Approach 2:

The patent maintains continuous binding capacity of the aptamers through proper regeneration and storage conditions, enabling the detection system to operate continuously over many cycles without degradation of performance

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

This approach provides stable, selective, and cost-effective target detection and quantitation over numerous cycles, reducing the expense of detection processes and maintaining the integrity of binding elements for multiple uses.

Implementation Method 1

contacting a sample comprising the target to the binding elements to form a binding element-target complex

Methodology Applied
Scientific EffectMolecular recognition:

Implementation Method 2

detecting the target-binding event with a detector to generate a detection signal

Methodology Applied
Scientific EffectSurface binding detection:

Implementation Method 3

eluting the target from the binding element-target complex in an elution event

Methodology Applied
Scientific EffectElution:

Implementation Method 4

applying a regeneration solution to complete the removal of the target bound to the binding element in a regeneration event

Methodology Applied
Scientific EffectRegeneration:

Data Source

PatentUS10989709B2Methods and systems for detection of target and applications thereof
Publication Date: 2021.04.27 CYTIVA SWEDEN AB
  • US10989709B2 patent drawing
  • US10989709B2 patent drawing
  • US10989709B2 patent drawing

AI summary

A method of recovering a target from a sample is provided. The method of recovering the target follows different steps. The steps include providing a binding element, wherein the binding elements are immobilized on a solid support, adding the sample comprising the target to the binding element to form a binding element-target complex; washing the binding element-target complex; and eluting the target from the binding element-target complex. The system for reversible detection of target in a range from 2 to 1,000,000 bind/release cycles is also provided.