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
Engineering 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
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.
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.
2Reliability
If mask sets are designed to minimize Border Length, then synthesis errors are reduced, but the device complexity increases
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.
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.
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
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.
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.
Data Source
Figure 1A~1B
Figure 2
Figure 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.