Homopolymer-Unique Primers for Random Access in Enzymatic Data Storage

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Solution Overview

Problem

Conventional data storage systems struggle to keep pace with the increasing data production rates, and polynucleotides like DNA or RNA offer a high data storage capacity but lack efficient methods for random access, especially as systems scale up.

Innovation Solution

Utilizing a combination of homopolymer and unique primers in PCR to selectively amplify specific polynucleotides, enabling random access by ensuring only desired polynucleotides are amplified and sequenced, thereby reducing the need to sequence the entire pool.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If selective amplification is used to enable random access to specific polynucleotides, then data retrieval efficiency is improved, but the complexity of the amplification process increases due to the need for specific primer design and selective amplification conditions

Engineering Contradiction:
Improvedata retrieval efficiencyVSAvoidamplification process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The primer is divided into two functional segments: a homopolymer region that provides universal binding capability and a unique sequence region that provides specificity. This segmentation allows the primer to simultaneously achieve selective amplification of target polynucleotides while maintaining a relatively simple amplification process using standard PCR conditions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the primer have different functional properties: the homopolymer region enables broad binding to complementary sequences, while the unique sequence region provides local specificity for selective amplification. This local differentiation of primer properties enables random access without requiring complex amplification protocols.

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If homopolymer primers are used for selective amplification, then the ability to perform random access is improved, but the specificity of amplification may be reduced due to the non-specific binding nature of homopolymer sequences

Engineering Contradiction:
Improverandom access capabilityVSAvoidamplification specificity
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The primer is segmented into a homopolymer region for universal binding and a unique sequence region for specific recognition. This segmentation resolves the contradiction by allowing the homopolymer portion to provide random access capability while the unique sequence portion ensures amplification specificity, preventing non-specific amplification of non-target polynucleotides.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The primer functions as a composite structure combining two different sequence types: a homopolymer segment and a unique sequence segment. This composite design integrates the advantages of both homopolymer primers (versatility for random access) and specific primers (amplification precision), thereby resolving the contradiction between adaptability and manufacturing precision.

Inventive Principle:
Principle #40Composite materials

3Reliability

If the entire pool of polynucleotides is sequenced to retrieve specific data, then data retrieval completeness is ensured, but the time and computational resources required increase significantly

Engineering Contradiction:
Improvedata retrieval completenessVSAvoidsequencing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The method extracts only the specific polynucleotides containing the desired data from the entire pool through selective amplification using the homopolymer primer with unique sequence. By taking out only the relevant polynucleotides for amplification and sequencing, the approach ensures data retrieval completeness while dramatically reducing the time and computational resources needed compared to sequencing the entire pool.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Selective amplification is performed as a preliminary action before sequencing. The homopolymer primer with unique sequence specifically amplifies only the target polynucleotides containing the desired data, preparing a concentrated sample that ensures retrieval completeness. This preliminary selective amplification step reduces the subsequent sequencing workload and time requirements.

Inventive Principle:
Principle #10Preliminary 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 allows for efficient retrieval of specific digital data by amplifying and sequencing only the relevant polynucleotides, improving data access efficiency and reducing the computational burden as storage systems grow in size.

Implementation Method 1

Enzymatic synthesis uses an enzyme, a template independent polymerase, rather than chemical reactions to synthesize polynucleotides

Methodology Applied
Scientific EffectEnzymatic synthesis: Enzyme

Implementation Method 2

polymerase chain reaction (PCR) can be used to amplify the polynucleotides that encode digital data

Methodology Applied
Scientific EffectThermal cycling: Heating

Implementation Method 3

A pair of primers is used to specify which polynucleotides are amplified. The primers hybridize to only those polynucleotides with complementary primer binding sites

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentEP4397772B1Homopolymer primers for amplification of polynucleotides created by enzymatic synthesis
Publication Date: 2025.08.13 MICROSOFT TECHNOLOGY LICENSING LLC
  • EP4397772B1 patent drawingFigure 1
  • EP4397772B1 patent drawingFigure 2
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AI summary

This disclosure describes a technique for performing random access in a pool of polynucleotides by using one unique primer and one homopolymer primer to selectively amplify some but not all of the polynucleotides in the pool. The polynucleotides are synthesized by a template independent polymerase such as terminal deoxynucleotide transferase (TdT) rather than by phosphoramidite synthesis. Enzymatic synthesis efficiently creates homopolymer sequences through unregulated synthesis. Use of one homopolymer primer instead of two unique primers decreases the complexity, time, and cost of synthesizing the polynucleotides. Use of a unique primer provides a sequence that can be varied to uniquely identify multiple different groups of polynucleotides. This enables random access by polymerase chain reaction (PCR) amplification while still benefitting from the efficiency of homopolymer synthesis. The polynucleotides may include payload regions that use a sequence of nucleotides to encode digital data.