Oligomer Array Production via Stochastic Particle Deposition

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Solution Overview

Problem

Current methods for producing high-density oligomer arrays, such as peptide arrays, are limited by the need for precise positioning and multiple coupling cycles, leading to side reactions and low quality, with existing technologies only achieving spot densities of up to 40,000 spots/cm², and require complex and costly devices.

Innovation Solution

A method involving stochastic introduction of particles with molecules into wells on a substrate, where the molecules are released and bound to form oligomers, creating a 3D deposition mask that simplifies the production of ultra-high-density arrays without precise positioning, enabling spot densities of up to 1,000,000 spots/cm² or more using a simple and inexpensive process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If lithographic processes are used to achieve high spot density, then spot density can reach up to 10^6 spots/cm², but the process requires precise positioning and multiple coupling cycles leading to side reactions and low quality

Engineering Contradiction:
Improvespot densityVSAvoidarray quality
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The synthesis process is segmented into discrete well-based reactions rather than continuous lithographic patterning. Each well functions as an independent reaction chamber, eliminating the need for precise positioning between coupling cycles and preventing cross-contamination that causes side reactions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Particles serve as intermediaries that deliver monomers to wells in a controlled manner. These particles enable high spot density by stochastically distributing monomer sources across the array, eliminating the need for precise lithographic positioning while maintaining reaction quality.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If lithographic processes are used to achieve high spot density, then spot density can reach up to 10^6 spots/cm², but complex and costly devices are required

Engineering Contradiction:
Improvespot densityVSAvoidproduction device complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The complex mechanical lithographic positioning system is replaced with a stochastic particle delivery system. Instead of precisely moving reagents to fixed positions, particles randomly distribute monomers across wells, dramatically simplifying the required equipment while achieving comparable or superior spot density.

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

Solution Approach 2:

The system uses self-organizing stochastic processes rather than externally controlled precision mechanisms. Particles naturally distribute themselves across the array through random motion and deposition, eliminating the need for complex positioning devices and reducing overall system complexity.

Inventive Principle:
Principle #25Self-service

3Stability of the object's composition

If multiple coupling cycles are performed for oligomer synthesis, then complete oligomers can be formed, but side reactions increase and synthesis quality decreases

Engineering Contradiction:
Improveoligomer completenessVSAvoidside reactions
Core Design Contradiction:
Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The synthesis is segmented into independent well-based reactions where each well contains a complete set of monomers. This allows multiple coupling cycles to occur in parallel isolation, preventing side reactions between different oligomer chains while ensuring complete oligomer formation in each well.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each well provides a localized reaction environment with controlled chemistry specific to that position. This local quality control ensures that coupling reactions proceed cleanly without interference from adjacent reactions, eliminating side reactions even after multiple coupling cycles.

Inventive Principle:
Principle #3Local quality

Data Source

PatentEP3362463B1Ultrahigh-density oligomer arrays and method of production thereof
Publication Date: 2020.04.29 KARLSRUHER INST FUR TECH
  • EP3362463B1 patent drawingFigure 1
  • EP3362463B1 patent drawingFigure 2~3
  • EP3362463B1 patent drawingFigure 4~6

AI summary

The present invention relates to a method of producing an oligomer array. The invention comprises the steps of: providing a substrate with a multitude of depressions; introducing a first particle with a first molecule into a depression; releasing the first molecule from the first particle; binding the first molecule to a second molecule to form an oligomer, with immobilization of the second molecule in the depression; optionally repeating the steps, wherein at least one of the first particles and/or the first molecules has a detectable marker.