Multiplexed Aptamer Selection via Single-Volume Biomolecule Library

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Solution Overview

Problem

Current methods for generating functional biomolecules, such as aptamers, are inefficient in identifying multiple target molecules simultaneously, requiring multiple rounds of SELEX and extensive resources, and lack a high-capacity, multiplexed identification process.

Innovation Solution

A method involving a diverse library of biomolecules, including nucleic acids and peptides, is contacted with multiple targets in a single reaction volume, where non-binding members are washed out, and binding members are marked and isolated using identifiers, allowing for simultaneous identification and amplification of multiple target-specific biomolecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple rounds of SELEX are performed to identify multiple target molecules, then binding affinity to targets is improved, but time and resource consumption increase significantly

Engineering Contradiction:
Improvebinding affinityVSAvoidtime consumption
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent combines multiple SELEX processes into a single multiplexed identification process. Multiple target molecules are simultaneously presented to the biomolecule library in one reaction volume, allowing parallel selection of aptamers for multiple targets in a single experiment rather than performing separate SELEX rounds for each target.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a universal identification system that can handle multiple different target molecules simultaneously. The system uses a common library of biomolecules and a unified workflow (contact, wash, mark, isolate) that works across diverse targets, eliminating the need for target-specific optimization of each SELEX process.

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

2Reliability

If multiple rounds of SELEX are performed to identify multiple target molecules, then binding affinity to targets is improved, but resource consumption increases

Engineering Contradiction:
Improvebinding affinityVSAvoidresource consumption
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent combines multiple SELEX processes into a single multiplexed identification process. Multiple target molecules are simultaneously presented to the biomolecule library in one reaction volume, allowing parallel selection of aptamers for multiple targets in a single experiment rather than performing separate SELEX rounds for each target.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent employs a wash step that removes non-binding biomolecules while retaining binding members. This efficient separation and recovery process allows the binding members to be isolated and amplified without requiring extensive resources, as only the relevant binding interactions are maintained through the process.

Inventive Principle:
Principle #34Discarding and recovering

3Measurement precision

If traditional SELEX methods are used to identify multiple targets, then specificity to individual targets is maintained, but the identification process becomes complex and time-consuming

Engineering Contradiction:
Improvetarget specificityVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the identification process into distinct functional steps: contact (exposure to multiple targets), wash (removal of non-binding members), mark (identification of binding members), and isolate (separation of bound biomolecules). This segmentation simplifies the overall process by making each step straightforward while enabling multiplexed identification across multiple targets simultaneously.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a universal identification system that can handle multiple different target molecules simultaneously. The system uses a common library of biomolecules and a unified workflow (contact, wash, mark, isolate) that works across diverse targets, eliminating the need for target-specific optimization of each SELEX process.

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

4Reliability

If multiple rounds of SELEX are performed to identify multiple target molecules, then binding affinity to targets is improved, but physical space requirements increase

Engineering Contradiction:
Improvebinding affinityVSAvoidphysical space
Core Design Contradiction:
ReliabilityVSArea of stationary object

Solution Approach 1:

The patent combines multiple SELEX processes into a single multiplexed identification process. Multiple target molecules are simultaneously presented to the biomolecule library in one reaction volume, allowing parallel selection of aptamers for multiple targets in a single experiment rather than performing separate SELEX rounds for each target.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent nests multiple target molecules within a single reaction volume, allowing simultaneous processing of multiple targets in the same physical space. This nesting approach enables the system to handle multiple targets without proportionally increasing the physical footprint of the experimental setup.

Inventive Principle:
Principle #7Nested doll (Nesting)

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 significantly reduces time, expense, and physical space required, enabling efficient generation and identification of biomolecules with high affinity to multiple targets, improving the multiplexed identification process and reducing the complexity of target binding.

Implementation Method 1

Aptamers are typically characterized by binding to their target molecules via non-Watson-Crick (i.e. non-hybridization) mechanisms, such as by intermolecular forces resulting from the secondary or tertiary structure of the aptamer

Methodology Applied
Scientific EffectNon-covalent binding: Van der Waals Force

Data Source

PatentUS20240110237A1Functional ligands
Publication Date: 2024.04.04 BASE PAIR BIOTECH
  • US20240110237A1 patent drawing
  • US20240110237A1 patent drawing
  • US20240110237A1 patent drawing

AI summary

The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules.