Patterned Surface Functionalization for Inkjet DNA Synthesis

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Solution Overview

Problem

Existing high-throughput in situ synthesis methods for nucleic acids by 3D inkjet printing face challenges in stabilizing droplets on glass or silicon substrates, requiring complex photolithography and calibration, which increases costs and reduces yield and throughput.

Innovation Solution

A surface functionalizing method involving hydroxyl enrichment, addition of hydrophobic molecules, etching with a fluoride compound, and application of hydrophilic molecules to create distinct hydrophilic and hydrophobic areas on substrates, using a multi-channel piezoelectric inkjet head assembly for precise droplet placement and synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If hydrophobic silane is added to block hydroxyl groups on glass slide surface to improve hydrophobicity for droplet morphology, then droplet morphology is improved, but reactive sites are reduced leading to reduced DNA synthesis yield

Engineering Contradiction:
Improvedroplet morphologyVSAvoidDNA synthesis yield
Core Design Contradiction:
ShapeVSQuantity of substance

Solution Approach 1:

The invention applies different surface properties to different regions of the glass slide. Hydrophobic silane is applied to the entire surface first, then hydrophilic regions are created locally through photolithography exposure. This local differentiation allows droplets to maintain good morphology on hydrophobic areas while providing reactive hydroxyl groups in exposed regions for DNA synthesis, resolving the contradiction between droplet morphology and synthesis yield.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The hydrophobic silane coating is applied in advance to the entire glass slide surface before the actual DNA synthesis process. This preliminary action ensures that the surface is pre-conditioned with hydrophobic properties for good droplet morphology, while the photolithography step subsequently creates the necessary hydrophilic reactive sites without requiring re-application of the hydrophobic layer.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If photolithography technology is used to create specific reaction areas on silicon slice surface, then specific reaction areas are formed, but device complexity and cost increase due to integration of photolithography devices and calibration requirements

Engineering Contradiction:
Improvereaction area positioningVSAvoidphotolithography device integration
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention uses a maskless photolithography approach where the pattern is directly written onto the photoresist layer through selective light exposure without requiring physical photolithography masks or complex alignment devices. This copying method achieves precise reaction area positioning while significantly reducing device complexity and calibration requirements compared to traditional photolithography.

Inventive Principle:
Principle #26Copying

3Measurement precision

If complex photolithography and calibration procedures are implemented to achieve precise droplet placement, then positioning accuracy is improved, but operation complexity and time consumption increase

Engineering Contradiction:
Improvedroplet placement accuracyVSAvoidoperation complexity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The system employs automatic image recognition and coordinate transformation algorithms that enable the printing head to self-align and self-position based on visual feedback from the substrate. This self-service capability achieves precise droplet placement accuracy while eliminating the need for manual calibration procedures, significantly reducing operation complexity and time consumption.

Inventive Principle:
Principle #25Self-service

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 reduces costs by eliminating the need for expensive photolithography devices, enhances yield by increasing reactive sites, and improves throughput without complex calibration, enabling high-resolution synthesis of long-chain oligonucleotides.

Implementation Method 1

a multi-channel piezoelectric inkjet head assembly for simultaneous droplets in situ etching

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

how to stabilize droplets in specific positions by taking advantage of a difference in hydrophobicity and hydrophilicity between groups on the surface

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Data Source

PatentUS12529086B2Surface functionalizing method for use in high-throughput in situ synthesis of nucleic acids by 3D inkjet printing
Publication Date: 2026.01.20 SHANGHAI DYNASTYGENE CO
  • US12529086B2 patent drawing
  • US12529086B2 patent drawing
  • US12529086B2 patent drawing

AI summary

A surface functionalizing method for use in high-throughput in situ synthesis of nucleic acids by 3D inkjet printing. The method includes subjecting a surface of a substrate to hydroxyl enrichment treatment; adding hydrophobic molecules to the surface of the substrate, the hydrophobic molecules being not reactive with phosphoramidite monomers; spraying, by a multi-channel piezoelectric inkjet head assembly, an etching ink to a predetermined area on the surface of the substrate for micro-etching, the etching ink being prepared with a fluoride compound reactive with the hydrophobic molecules; and adding hydrophilic molecules to the surface of the substrate. By using the method, a functionalized surface with given areas being patterned can be formed on the surface of the substrate, and then a same multi-channel piezoelectric inkjet head assembly can be directly used for subsequent high-resolution printing of phosphoramidite monomers and synthesis of nucleic acids.