Polymer Array Mask Design for Synthesis Error Reduction

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Solution Overview

Problem

The existing methods for manufacturing microarrays, such as those used in DNA and RNA sequence analysis, face challenges in minimizing the Hamming distance between adjacent polymers to reduce synthesis errors and enhance accuracy, efficiency, and cost-effectiveness, particularly for applications requiring chips with no spaces between features.

Innovation Solution

The method involves creating mask sets that minimize the 'Border Length' by ensuring all adjacent polymers differ by at most one subunit through insertions, deletions, or translocations, allowing for the synthesis of arrays with error-correcting capabilities and precise placement of polymers on a substrate, enabling the generation of arrays with thousands to millions of unique polymers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional microarray manufacturing methods are used, then production can be performed, but the Hamming distance between adjacent polymers cannot be minimized, leading to increased synthesis errors

Engineering Contradiction:
Improvesynthesis accuracyVSAvoidpolymer placement precision
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by pre-designing mask sets with specific geometric patterns (e.g., alternating transparent and opaque regions) before the synthesis process. These masks are configured in advance to ensure that adjacent polymers differ by exactly one subunit, thereby minimizing Hamming distance and reducing synthesis errors before the actual polymerization occurs.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the geometric parameters of the masks (e.g., pattern arrangement, transparent/opaque region distribution) to control the spatial relationship between adjacent polymers. By adjusting these parameters, the method ensures that each polymer differs from its neighbors by exactly one subunit, optimizing both synthesis accuracy and error correction capabilities.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If mask sets are designed to minimize Border Length, then synthesis errors are reduced, but the device complexity increases

Engineering Contradiction:
Improvesynthesis error reductionVSAvoidmask set complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the mask design into standardized geometric patterns (e.g., alternating transparent and opaque regions in regular arrangements). This segmentation allows complex mask sets to be broken down into repeating modular units, making them easier to manufacture and align while maintaining the error-minimizing properties.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses composite mask designs that combine multiple geometric patterns into unified structures. These composite masks integrate error-correction functionality with standard manufacturing capabilities, reducing overall system complexity while maintaining high synthesis accuracy.

Inventive Principle:
Principle #40Composite materials

3Area of stationary object

If arrays with no spaces between features are required, then chip utilization is maximized, but the difficulty of detecting and measuring adjacent polymers increases

Engineering Contradiction:
Improvechip utilizationVSAvoidpolymer detection difficulty
Core Design Contradiction:
Area of stationary objectVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies local quality by ensuring that each polymer has a unique local composition (differing by one subunit from neighbors) while maintaining uniform spacing and size. This local differentiation enables detection systems to distinguish between closely packed polymers based on their unique sequences, even when physically adjacent with no spaces.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent incorporates feedback mechanisms where the known geometric pattern of masks and the controlled one-subunit difference between adjacent polymers provide reference information for detection systems. This feedback enables accurate measurement and identification of polymers even in densely packed arrays with no spaces between features.

Inventive Principle:
Principle #23Feedback

Data Source

PatentEP3130682B1Methods for generating polymer arrays
Publication Date: 2020.03.18 CENTRILLION TECHNOLOGY HOLDINGS CORP
  • EP3130682B1 patent drawingFigure 1A~1B
  • EP3130682B1 patent drawingFigure 2
  • EP3130682B1 patent drawingFigure 3A

AI summary

The present disclosure provides a polymer array comprising a plurality of polymers, each of which is immobilized at a distinct locations and differs from adjacent polymers by one and only one subunit. Also provided herein are methods for generating a set of masks which may define strings of synthetic steps for forming polymer arrays on a substrate.