Subtractive Contact Printing for Virus Array Patterning

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Solution Overview

Problem

Current self-assembly and directed assembly methods for viruses in biological libraries face a trade-off between specificity and generality, and often result in loss of antibody activity during sample preparation, limiting the feature size and pitch of the arrays formed.

Innovation Solution

The method employs subtractive contact printing to pattern an array of receptors on a substrate, using a deformable elastomer stamp to transfer receptor material and microorganisms, allowing for precise control of virus binding and reducing non-specific interactions, enabling the formation of densely packed nanoscale arrays with single virus occupancy per receptor site.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If self-assembly or directed assembly methods are used to form virus arrays, then the arrays can be formed with controlled organization, but there is a trade-off between specificity and generality of the approach

Engineering Contradiction:
Improvearray organization precisionVSAvoidmethod generality
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The method segments the array formation process into distinct steps: (1) forming a template with periodic structures, (2) applying receptor material to a stamp, (3) transferring receptors to the template via contact printing, and (4) allowing virus binding. This segmentation enables the same approach to be applied to different virus types and receptor materials while maintaining precise array organization through the template structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes physical parameters such as the periodicity and dimensions of the template structures, the concentration of receptor material, and the contact pressure during printing. These parameter adjustments allow the same subtractive contact printing method to be universally applied across different virus types and array configurations, resolving the trade-off between precision and generality.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If traditional screening methods are used with microtiter plates, then large libraries can be screened, but the process requires multiple screening rounds and is very difficult and time-consuming

Engineering Contradiction:
Improvelibrary screening capacityVSAvoidscreening time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The invention transitions from two-dimensional microtiter plate screening to three-dimensional structured arrays with periodic templates. This dimensional change enables parallel screening of numerous virus candidates simultaneously across the array surface, dramatically reducing the number of screening rounds needed while maintaining the capacity to handle large libraries.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The method performs preliminary organization of receptors into precise periodic arrays before virus screening. This pre-arrangement of receptors in defined spatial patterns allows for more efficient and faster screening compared to random distribution in microtiter plates, reducing the time required to identify specific virus interactions.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If soft lithographic methods are used to maintain antibody activity, then biomolecular activity is preserved, but feature size and pitch are limited by mechanical properties of elastomeric materials

Engineering Contradiction:
Improveantibody activity retentionVSAvoidfeature size and pitch control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

Instead of directly printing receptors onto the final substrate (which would be limited by elastomer mechanics), the invention uses subtractive contact printing: receptors are first applied to the elastomeric stamp, then the stamp is pressed against a rigid template with periodic structures. The template's mechanical properties, not the elastomer's, define the final feature size and pitch, overcoming the limitations of soft lithography while preserving antibody activity through the gentle contact printing process.

Inventive Principle:
Principle #13The other way round (Inversion)

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 screening of viruses from large libraries with high specificity and reproducibility, achieving single virus occupancy and high coverage on the array, while maintaining biomolecular activity and reducing mechanical limitations on feature size and pitch.

Implementation Method 1

applying a receptor material to a face of a second substrate; and contacting the face of the second substrate with the template to remove a portion of the receptor material from the second substrate

Methodology Applied
Scientific EffectElasticity: Elasticity

Implementation Method 2

contacting the face of the second substrate with the template to remove a portion of the receptor material

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 3

contacting the target substrate with a solution comprising the microorganisms to transfer a portion of the microorganisms to the array of receptors

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2329270B1Methods for screening and arraying microrganisms such as viruses using subtractive contact printing background
Publication Date: 2015.04.08 INTERNATIONAL BUSINESS MACHINE CORPORATION
  • EP2329270B1 patent drawingFigure 1~3
  • EP2329270B1 patent drawingFigure 4~5
  • EP2329270B1 patent drawingFigure 6

AI summary

Methods for screening and arranging microorganisms such as viruses in an array using subtractive contact printing are provided. In one embodiment, a method for forming an array of receptors for microorganisms comprises: patterning an array of structures on a first substrate to form a template on a surface of the first substrate; applying a receptor material to a face of a second substrate; and contacting the face of the second substrate with the template to remove a portion of the receptor material from the second substrate, thereby forming an array of receptors on the second substrate.