Carrier Group Composition for Accurate DNA Synthesis

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Solution Overview

Problem

Current methods for synthesizing DNA strands, such as phosphoramidite solid phase synthesis and chip-based chemical DNA synthesis, are limited in their ability to accurately and efficiently attach nucleotides in a specific sequence, leading to potential errors that can impair DNA functionality.

Innovation Solution

A composition of matter that includes a payload group attached to a molecular chain via a carrier group, which can transition between loaded and empty states through selective cleavage, allowing for precise attachment and confirmation of nucleotides using a signaling group that emits a signature photon upon interrogation, enabling error correction and efficient assembly of DNA strands.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard phosphoramidite solid phase synthesis is used to attach nucleotides, then the synthesis process can proceed, but errors occur in nucleotide attachment that impair DNA functionality

Engineering Contradiction:
Improvenucleotide attachment accuracyVSAvoidnucleotide sequence accuracy
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent implements real-time monitoring of nucleotide attachment through signaling groups that generate detectable signals (fluorescence, electrochemical responses) when nucleotides are successfully attached. This feedback mechanism allows the system to verify each attachment event and trigger error correction protocols when failures are detected, thereby improving both reliability and manufacturing precision of DNA synthesis

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces traditional mechanical/chemical phosphoramidite coupling methods with enzyme-mediated nucleotide attachment using polymerases or terminal deoxynucleotidyl transferase (TdT). This substitution enables more accurate and controllable nucleotide incorporation, reducing errors while maintaining synthesis capability

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

2Reliability

If traditional DNA synthesis methods are used, then DNA strands can be synthesized, but error correction is not possible

Engineering Contradiction:
ImproveDNA functionalityVSAvoidsynthesis system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system continuously monitors nucleotide attachment through signaling groups and uses this feedback information to identify and correct errors in real-time, enabling error correction capability that was absent in traditional methods

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent integrates multiple functions into a single synthesis platform: nucleotide attachment, real-time monitoring via signaling groups, error detection, and error correction all occur within the same system. This multi-functionality adds complexity but enables comprehensive error correction that improves DNA functionality

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If rapid DNA synthesis is pursued, then productivity increases, but accuracy and error rates worsen

Engineering Contradiction:
ImproveDNA synthesis speedVSAvoidnucleotide attachment accuracy
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The real-time feedback from signaling groups allows the system to verify nucleotide attachment immediately, enabling rapid synthesis while maintaining accuracy through continuous monitoring and error correction

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs preliminary verification of nucleotide attachment through signaling groups before proceeding to the next nucleotide addition. This preliminary action ensures accuracy is maintained even as synthesis speed increases, preventing error accumulation

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 method allows for the rapid and reliable synthesis of DNA strands with thousands of nucleotides, ensuring high accuracy and functionality by confirming each nucleotide attachment and enabling the assembly of long DNA strands with minimal errors.

Implementation Method 1

The signaling group includes a fluorophore

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

a signaling group that emits a signature photon upon interrogation

Methodology Applied
Scientific EffectPhoton emission: Luminescence

Implementation Method 3

the carrier group transitions to the empty state via electrochemical cleavage of the first covalent bond

Methodology Applied
Scientific EffectElectrochemical cleavage: Electrolysis

Implementation Method 4

it does so as a result of a change in oxidation state of the carrier group

Methodology Applied
Scientific EffectOxidation-reduction: Redox Reactions

Implementation Method 5

it does so as a result of acceptance of an electron either by the carrier group or by the blocking group

Methodology Applied
Scientific EffectElectron transfer: Reduction

Data Source

PatentUS10975407B2Composition for use in molecular chain synthesis
Publication Date: 2021.04.13 THE CHARLES STARK DRAPER LABORATORY INC
  • US10975407B2 patent drawing
  • US10975407B2 patent drawing
  • US10975407B2 patent drawing

AI summary

A composition for use in extending a molecular chain includes a carrier group and a payload group. The carrier group comprising a signaling group and a blocking group. A first bond bonds the payload group to the carrier group and a second bond bonds the signaling group to the blocking group. The first and second bonds are selectively cleavable such that the first bond is cleavable without cleaving the second bond. The payload group is to be attached to the molecular chain, while the blocking group is to block further attachments to the molecular chain once the payload group has been attached. The signaling group comprises a photon emitter that emits a signature photon in response to interrogation by an interrogatory photon. The carrier group transitions from a loaded state to an empty state upon cleavage of the first covalent bond.