DNA Origami Site-Specific Immobilization via ssDNA Capture Strands

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Solution Overview

Problem

Current methods for immobilizing DNA origami structures on solid substrates lack site-specificity and are inefficient, relying on costly and time-consuming processes, with insufficient lateral resolution and inability to pattern multiple different proteins or peptides effectively.

Innovation Solution

A method involving pre-patterned optically transparent solid substrates functionalized with ssDNA capture strands that bind to ssDNA strands protruding from DNA origami structures via Watson-Crick pairing, allowing for controlled, site-specific immobilization of DNA origami structures on selected areas, using a buffer with sodium dodecylsulphate to maintain structural integrity and enable precise binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If conventional top-down patterning techniques (photolithography, electron-beam lithography) are used to immobilize DNA origami structures, then large-area spatially ordered arrays can be produced, but the lateral resolution is insufficient and multiple different proteins cannot be patterned effectively

Engineering Contradiction:
Improvearray coverage areaVSAvoidlateral resolution
Core Design Contradiction:
Area of stationary objectVSManufacturing precision

Solution Approach 1:

The substrate is divided into multiple distinct regions, each functionalized with different ssNA capture strands specific to different DNA origami types. This segmentation enables simultaneous patterning of multiple different proteins and peptides with high lateral resolution while maintaining large-area coverage

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

ssNA capture strands are introduced as intermediary molecules that mediate the specific binding between DNA origami structures and the substrate. These capture strands provide sequence-specific recognition, enabling precise spatial control and multi-type patterning with high lateral resolution

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If electrostatic interactions are used for origami immobilization on nanopatterned surfaces, then deposition is feasible, but site-selectivity cannot be realized

Engineering Contradiction:
Improveimmobilization feasibilityVSAvoidsite-selectivity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

Different regions of the substrate are functionalized with different types of ssNA capture strands, creating local quality variations that enable site-selective binding. Each region has specific binding properties tailored to attract particular DNA origami structures, achieving both ease of manufacture and high site-selectivity

Inventive Principle:
Principle #3Local quality

3Manufacturing precision

If direct writing of multiple different cell specific peptide and protein ligands by dip-pen nanolithography is attempted, then protein feature sizes >50 nm can be achieved, but the technique is generally not feasible due to individual buffer composition requirements for different polypeptides

Engineering Contradiction:
Improveprotein feature sizeVSAvoidbuffer composition complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The substrate functionalization approach is made universal by using ssNA capture strands that can be incorporated into a single common buffer system. This multi-functional platform enables patterning of multiple different proteins and peptides simultaneously without requiring individual buffer optimization for each polypeptide, maintaining high feature size precision while reducing overall system complexity

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

4Area of stationary object

If nanoparticle-decorated origami structures are deposited on nanopatterned surfaces prepared by electron-beam lithography and etching processes, then large-area spatially ordered arrays can be generated, but the production is very cost and time consuming

Engineering Contradiction:
Improvearray areaVSAvoidproduction time
Core Design Contradiction:
Area of stationary objectVSLoss of time

Solution Approach 1:

The substrate is pre-functionalized with ssNA capture strands in advance, creating a ready-to-use platform that enables direct, rapid immobilization of DNA origami structures. This preliminary preparation eliminates time-consuming deposition processes while maintaining large-area array generation capability

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

Enables full control over the spatial location of DNA origami structures on substrates, achieving site-specific immobilization while maintaining the integrity of DNA origami structures and substrates, allowing for precise arrangement of objects-of-interest like proteins and peptides with high binding efficiency.

Implementation Method 1

the ssNA capture strands are capable of binding to the ssNA strands protruding from the DNA origami structure by Watson-Crick pairing

Methodology Applied
Scientific EffectWatson-Crick pairing: Chemical Bonding

Implementation Method 2

step (c) is carried out in the presence of a buffer comprising sodium dodecylsulphate (SDS) and under conditions that (i) do not compromise the structure and integrity of the DNA origami structures, the ssNA strands, and the solid substrate

Methodology Applied
Scientific EffectSDS buffer stabilization: Surfactant

Data Source

PatentEP3009520B1Site-specific immobilization of DNA origami structures on solid substrates
Publication Date: 2018.12.12 KARLSRUHER INST FUR TECH
  • EP3009520B1 patent drawingFigure 1a~1
  • EP3009520B1 patent drawingFigure 2
  • EP3009520B1 patent drawingFigure 3A

AI summary

The present invention relates to methods for the site-specific immobilization of DNA origami structures on solid substrates, as well as to respective assemblies comprising DNA origami structures immobilized on a solid substrate and uses thereof.