Chemical Arrays Cleavable Linkers Solution Phase Diversity

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Solution Overview

Problem

Current chemical array technologies face limitations in generating diverse product molecules from initial chemical arrays, particularly in efficiently producing distinct biopolymers like nucleic acids and polypeptides through cleavage and reaction processes.

Innovation Solution

The method involves subjecting surface-immobilized first moieties on a chemical array to cleavage conditions to produce solution-phase moieties, which are then reacted with additional agents to generate a mixture of product molecules. This includes using cleavable linkers and enzymatic activities to produce nucleic acids or polypeptides, allowing for the creation of diverse molecular products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If surface-immobilized first moieties are subjected to cleavage conditions to produce solution phase moieties, then diverse product molecules can be generated, but the complexity of the process increases

Engineering Contradiction:
Improvediversity of product moleculesVSAvoidprocess complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The chemical array is divided into multiple features with different compositions (nucleic acids, proteins, small molecules) arranged in a predetermined configuration. Each feature can be independently cleaved and reacted to produce specific product molecules, enabling diversity while maintaining process manageability through modular organization

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The first moieties are pre-immobilized on the solid support in specific configurations before cleavage. This preliminary arrangement allows for controlled release and subsequent reaction with reactants to generate diverse products systematically, reducing the complexity of generating diversity de novo

Inventive Principle:
Principle #10Preliminary action

2Productivity

If cleavable linkers are used to immobilize first moieties on the solid support, then product molecules can be efficiently released into solution phase, but the manufacturing complexity increases

Engineering Contradiction:
Improveefficiency of product releaseVSAvoidmanufacturing complexity
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The cleavable linkers are designed with specific chemical properties (base-labile or acid-labile) that allow controlled cleavage under defined conditions. This parameter-based control enables efficient product release while simplifying manufacturing through standardized cleavage protocols rather than complex custom procedures

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If enzymatic activities are used as reactants to produce product molecules, then specific and diverse products can be generated, but the process time increases

Engineering Contradiction:
Improvespecificity of product generationVSAvoidprocess time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The chemical array serves as a template or master copy that directs the generation of multiple product molecules through enzymatic reactions. The immobilized first moieties are copied or replicated into solution phase products, enabling specific and diverse product generation while reducing the need for multiple separate reaction setups, thereby optimizing time

Inventive Principle:
Principle #26Copying

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 enables the production of a plurality of distinct product molecules with known compositions, suitable for various applications, including nucleic acid and polypeptide synthesis, by effectively cleaving and reacting surface-immobilized biopolymers to produce a mixture of nucleic acids or polypeptides with specific sequences and quantities.

Implementation Method 1

subjecting an array of a plurality of features each including first moieties immobilized on a surface of a solid support via a cleavable domain having a cleavable region to conditions sufficient to cleave the cleavable linker and generate a solution phase composition of said first moieties

Methodology Applied
Scientific EffectChemical cleavage: Chemical Bonding

Implementation Method 2

the one or more reactants comprises an enzymatic activity, as is found in an enzymatic reaction system, such as a template dependent polymerase reaction system

Methodology Applied
Scientific EffectEnzymatic reaction: Enzyme

Data Source

PatentUS10017879B2Chemical arrays and methods of using the same
Publication Date: 2018.07.10 AGILENT TECHNOLOGIES INC

AI summary

Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.