Expanded Radix Nucleic Acid Tags for High-Capacity Sequencing
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Solution Overview
Problem
Current methods for deciphering complex nucleic acid tags become increasingly complex and expensive as the number and length of tags increase, necessitating simplified detection and deciphering techniques.
Innovation Solution
The method involves providing nucleic acids with tag sequences that include nucleotides complementing different nucleotides, detecting them under conditions to distinguish signal intensities, and distinguishing tags based on these intensities, using a system that expands the numerical base of nucleic acid codes beyond the traditional radix of 4 by utilizing multiple states for each nucleotide and incorporating a punctuation nucleotide to separate code regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If the number and length of nucleic acid tags increase to expand code capacity, then the tagging capability and code space increase, but the complexity and cost of deciphering methods increase proportionally
Solution Approach 1:
The patent divides the nucleic acid tag sequence into multiple discrete code regions separated by punctuation nucleotides. Each code region can be independently detected and deciphered, breaking down the complex task of reading entire long sequences into simpler, manageable segments. This segmentation allows parallel processing of multiple regions simultaneously
Solution Approach 2:
The patent introduces punctuation nucleotides as intermediary elements that separate code regions and serve as detectable markers. These punctuation nucleotides act as mediators that facilitate the deciphering process by providing clear boundaries and reference points, enabling simpler detection methods to accurately identify and count nucleotides within each segmented region without being overwhelmed by the overall sequence complexity
2Adaptability or versatility
If more nucleotide types and states are used to expand radix beyond 4, then the code capacity increases exponentially, but the detection system complexity increases
Solution Approach 1:
The patent applies different detectable states to different nucleotide types within code regions. Each nucleotide type (A, C, G, T) can exist in multiple discrete states (e.g., different fluorescence intensities, colors, or emission wavelengths), allowing local differentiation of nucleotide identity and state. This local quality approach enables the system to encode more information per position without requiring a completely complex detection system
Solution Approach 2:
The patent uses periodic detection cycles where punctuation nucleotides serve as regular markers that define detection intervals. The detection system operates in periodic phases: detecting nucleotides within a code region, then detecting the punctuation nucleotide that marks the region boundary. This periodic action simplifies the detection of multiple nucleotide states by breaking it into discrete, repeatable measurement steps
3Device complexity
If traditional radix 4 nucleic acid codes are used, then the detection method is simple, but the code capacity is limited
Solution Approach 1:
The patent changes the parameters of nucleic acid codes by allowing each nucleotide position to have multiple discrete states rather than just four fixed states. By varying parameters such as fluorescence intensity levels, emission wavelengths, or other detectable properties across different nucleotide types and positions, the system expands from radix 4 to higher radices (e.g., radix 8, 16, or more), dramatically increasing code capacity while maintaining relatively simple detection methodologies
Data Source
AI summary
A method having steps of (a) providing nucleic acids having a tag sequence (N1)n(N2)n . . . (Nx)n, wherein N1, N2 and Nx are nucleotides that complement different nucleotides, respectively, wherein n is an integer that can differ for N1, N2 and Nx; (b) detecting the nucleic acids individually and under conditions to distinguish signal intensities for (N1)n sequences having different values for n, (N2)n sequences having different values for n and. (Nx)n sequences having different values for n; and (c) distinguishing the tags based on the signal intensities.