Homopolymer Encoded Nucleic Acid Memory for High Throughput Storage

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Solution Overview

Problem

Current DNA digital storage methods face limitations in speed, cost, and error tolerance due to reliance on high-fidelity sequencing techniques and toxic byproducts, which restrict the adoption and scalability of DNA digital storage technology.

Innovation Solution

The use of homopolymer tracts in nucleic acid memory strands allows for lower fidelity sequencing, enabling higher throughput and reduced costs through techniques like nanopore sequencing and enzymatic synthesis, while minimizing toxic waste production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high-fidelity sequencing techniques are used to accurately read data encoded in DNA, then measurement precision is improved, but productivity deteriorates due to slower sequencing speed and higher costs

Engineering Contradiction:
Improvesequencing fidelityVSAvoidsequencing throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent segments the DNA sequence into homopolymer tracts (repeated nucleotide sequences) where each tract represents a data unit. This segmentation allows lower-fidelity sequencing techniques to read the data by detecting tract transitions rather than individual bases, thereby improving productivity while maintaining acceptable measurement precision for data retrieval

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the sequencing parameter from single-base resolution to homopolymer tract resolution. By encoding data in terms of tract transitions rather than individual nucleotides, the system can use faster, lower-cost sequencing methods that tolerate higher error rates at the single-base level while maintaining data integrity through tract-level detection

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If conventional phosphoramidite synthesis techniques are used to produce nucleic acid strands, then manufacturing precision is maintained, but productivity deteriorates due to length limitations and toxic byproduct production

Engineering Contradiction:
Improvesynthesis fidelityVSAvoidsynthesis speed and scalability
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent extracts the problematic toxic byproducts from the synthesis process by using enzymatic synthesis methods (such as terminal deoxynucleotidyl transferase) that do not generate harmful waste products like conventional phosphoramidite chemistry. This allows for scalable production of long nucleic acid strands without the environmental and safety constraints of traditional methods

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the chemical phosphoramidite synthesis mechanism with an enzymatic mechanism. Using enzymes like TdT to catalyze nucleotide addition eliminates the need for complex chemical deprotection and coupling steps, reducing synthesis time, eliminating toxic byproducts, and enabling production of longer strands with maintained precision

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

3Manufacturing precision

If conventional synthesis techniques are used to produce nucleic acids greater than 200 base pairs, then manufacturing precision is maintained, but productivity deteriorates due to high breakage rates and side reactions

Engineering Contradiction:
Improvesynthesis accuracyVSAvoidyield and strand integrity
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent replaces conventional chemical synthesis with enzymatic synthesis using terminal deoxynucleotidyl transferase. This enzymatic approach provides superior strand integrity and reduces breakage rates compared to chemical methods, enabling production of long nucleic acid strands (>200 bp) with maintained accuracy and higher yield

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

Solution Approach 2:

The patent changes the synthesis parameters by using enzymatic catalysis instead of chemical reactions. This parameter change results in milder reaction conditions, reduced side reactions, and lower breakage rates, thereby improving both productivity (yield) and maintaining manufacturing precision for long strands

Inventive Principle:
Principle #35Parameter changes

4Productivity

If homopolymer tracts of 2-10 nucleotides are used to encode data, then productivity is improved through higher throughput sequencing, but measurement precision deteriorates due to reduced resolution

Engineering Contradiction:
Improvesequencing throughputVSAvoidbase resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments data encoding into homopolymer tract transitions rather than individual bases. Each tract (2-10 nucleotides) serves as a discrete encoding unit, allowing sequencing techniques to read data at tract-level resolution. This segmentation enables higher throughput while maintaining sufficient measurement precision for data retrieval, as the transition between tracts provides clear positional information

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses slightly longer homopolymer tracts (2-10 nucleotides) than the minimum single base, providing excessive action in terms of tract length. This ensures that even with lower base-resolution sequencing, the tracts are long enough to be reliably distinguished and counted, maintaining measurement precision while enabling higher throughput sequencing

Inventive Principle:
Principle #16Partial or excessive action

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 long nucleic acid strands with increased data storage density and reduced synthesis costs, tolerating errors in sequencing and allowing for efficient data encoding and retrieval.

Implementation Method 1

template-independent polynucleotide synthesis of using, for example, a nucleotidyl transferase are capable of synthesizing long strands at reduced costs and with lower waste production

Methodology Applied
Scientific EffectEnzymatic synthesis: Enzyme

Implementation Method 2

sequencing techniques such as nanopore sequencing, zero-mode waveguide (ZMW) single molecule sequencing, and mass spectrometry may be used to increase speed and reduce cost

Methodology Applied
Scientific EffectNanopore sequencing: Nanopore

Implementation Method 3

Representing each bit in the data sequence using a homopolymer tract of repeated bases (e.g., 2-10 nucleotides) allows for higher throughput and less expensive sequencing techniques to be used

Methodology Applied
Scientific EffectHomopolymer encoding:

Data Source

PatentUS11174512B2Homopolymer encoded nucleic acid memory
Publication Date: 2021.11.16 MOLECULAR ASSEMBLIES INC
  • US11174512B2 patent drawing
  • US11174512B2 patent drawing
  • US11174512B2 patent drawing

AI summary

Nucleic acid memory strands encoding digital data using a sequence of homopolymer tracts of repeated nucleotides provides a cheaper and faster alternative to conventional digital DNA storage techniques. The use of homopolymer tracts allows for lower fidelity, high throughput sequencing techniques such as nanopore sequencing to read data encoded in the memory strands. Specialized synthesis techniques allow for synthesis of long memory strands capable of encoding large volumes of data despite the reduced data density afforded by homopolymer tracts as compared to conventional single nucleotide sequences.