Biological Sample Labels Using Hybridized Click-Chemistry Attachment
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Solution Overview
Problem
Existing labels and markers for biological samples, such as those used in fluorescent microscopy, are complex to produce due to individual assembly of their components, leading to inefficiencies and losses during reaction and purification.
Innovation Solution
A label comprising labelling oligonucleotides with integrated reaction moieties that facilitate easy assembly through hybridization and subsequent covalent bonding, utilizing click chemistry or catalysts for robust attachment to affinity reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If individual parts of the label are generated and assembled using specific chemistries and linkers, then the label can be produced with functional components, but the production becomes complex and results in losses due to limited reaction efficiency and purification losses
Solution Approach 1:
The patent merges the labelling oligonucleotide and the attachment oligonucleotide into a single integrated molecule. This unified structure eliminates the need for separate assembly steps using chemistries and linkers, directly resolving the contradiction by simplifying production while maintaining functional integrity.
Solution Approach 2:
The integrated oligonucleotide performs multiple functions simultaneously: it provides the labelling sequence, contains the attachment sequence, and enables covalent bonding through reaction moieties. This multi-functionality consolidates what would otherwise require separate components and assembly steps.
2Productivity
If individual parts of the label are assembled using specific chemistries and linkers, then the label can be constructed with functional components, but reaction efficiency is limited and purification losses occur
Solution Approach 1:
By combining the labelling and attachment functions into one oligonucleotide, the patent eliminates intermediate purification steps required when assembling separate parts. This directly improves productivity and prevents substance loss by avoiding repeated purification operations.
Solution Approach 2:
The reaction moieties are pre-integrated into the oligonucleotide structure during synthesis. This preliminary incorporation of functional groups eliminates the need for subsequent chemical assembly steps and associated purification losses.
3Ease of manufacture
If reaction moieties are integrated into the oligonucleotide to enable easy assembly, then the label becomes easier to produce, but the label requires covalent bonding steps that need catalysts or specific conditions
Solution Approach 1:
The patent uses complementary base pairing between the labelling and attachment sequences as an intermediary mechanism. This natural hybridization process brings the reaction moieties into proximity and correct orientation, facilitating the covalent bonding step while minimizing the need for complex reaction conditions.
Solution Approach 2:
The oligonucleotide structure itself provides the mechanism for assembly through complementary base pairing. The sequence complementarity automatically guides the reaction moieties into the correct configuration for covalent bonding, making the system self-organizing and reducing external intervention requirements.
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 efficient, stable, and versatile labels and markers that are easier to produce, with improved robustness under extreme conditions and extended shelf-life.
Implementation Method 1
The first and second reaction moieties may in particular react based on a click chemistry. Such a chemistry may be, for example, copper-catalyzed azide-alkyne cycloaddition (CuCAAC), metal-free click reactions based on thiolene radical additions, Diels-Alder reactions, or Michael additions
Implementation Method 2
The reaction moieties are configured to react with each other, in particular, in the presence of a catalyst. Such a catalyst may be an element, for example copper, or a physical input such as radiation at a particular wavelength, or a temperature change
Implementation Method 3
the attachment nucleic acid with at least one first attachment sequence to which the at least one first labelling oligonucleotide is at least partially complementary
Data Source
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AI summary
In a first aspect a label (100, 200) for analysing a biological sample is provided. The label (100, 200) comprises at least one first labelling oligonucleotide (102, 202) and a labelling moiety (104) attached to the at least one first labelling oligonucleotide (102, 202). The at least one first labelling oligonucleotide (102, 202) comprises a first reaction moiety (116). Further, either the at least one first labelling oligonucleotide (102, 202) comprises a second reaction moiety (118), or the label (100, 200) further comprises an attachment nucleic acid (206) with at least one first attachment sequence to which the at least one first labelling oligonucleotide (102, 202) is at least partially complementary and the attachment nucleic acid (206) comprises a second reaction moiety (118). Further, the first reaction moiety (116) and the second reaction moiety (118) are configured to react with each other. In further aspects, a marker and a reagent kit for analysing a biological sample are provided. Further a method for generating the label is provided.