CMOS Biochip Surface Functionalization via SPAAC Probe Immobilization

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Solution Overview

Problem

Current methods for surface functionalization of CMOS biosensor arrays require highly reactive chemical species and unfavorable reaction conditions such as high temperature or pH, and lack spatial control for immobilizing molecular probes.

Innovation Solution

The use of functionalized silanes and nucleic acid constructs with complementary chemical groups, such as azide-alkyne cycloaddition, for covalent immobilization on CMOS substrates, allowing for orthogonal reactions that are rapid, quantitative, and do not require extreme conditions, using methods like strain-promoted alkyne-azide cycloaddition (SPAAC) for bio-orthogonal reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If highly reactive chemical species are used for surface functionalization, then the reaction efficiency is improved, but the reaction conditions become unfavorable (high temperature or pH)

Engineering Contradiction:
Improvereaction efficiencyVSAvoidreaction temperature
Core Design Contradiction:
ProductivityVSTemperature

Solution Approach 1:

The patent changes the chemical parameters by using strained cycloalkyne groups (with inherent ring strain energy) instead of highly reactive species, enabling the reaction to proceed at neutral pH and room temperature while maintaining high reaction efficiency through the strain-promoted mechanism

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite approach by combining the strained cycloalkyne functional group with silane coupling agents, creating a dual-functional system that provides both covalent bonding capability and surface attachment functionality under mild conditions

Inventive Principle:
Principle #40Composite materials

2Productivity

If highly reactive chemical species are used for surface functionalization, then the reaction efficiency is improved, but extreme reaction conditions (high pH) are required

Engineering Contradiction:
Improvereaction efficiencyVSAvoidextreme pH conditions
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pH parameter from extreme conditions to neutral pH by utilizing the strain-promoted cycloaddition mechanism, which is sufficiently reactive to proceed efficiently without requiring alkaline or acidic environments, thereby eliminating the harmful effect of extreme pH on the CMOS substrate and biomolecules

Inventive Principle:
Principle #35Parameter changes

3Strength

If conventional surface functionalization methods are used, then covalent bonding is achieved, but spatial control is difficult

Engineering Contradiction:
Improvecovalent bondingVSAvoidspatial control
Core Design Contradiction:
StrengthVSManufacturing precision

Solution Approach 1:

The patent applies local quality by functionalizing only specific regions of the CMOS substrate surface with strained cycloalkyne groups, allowing spatially controlled covalent bonding of molecular probes to predetermined locations while maintaining covalent bond strength at each location

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs preliminary action by first immobilizing the strained cycloalkyne-functionalized silane to the substrate surface in a spatially controlled manner before introducing the molecular probes, thereby pre-establishing the bonding sites at specific locations prior to the actual probe attachment

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 approach enables efficient and controlled immobilization of nucleic acid constructs on CMOS substrates at neutral pH and room temperature, providing a stable and spatially controlled surface for molecular detection applications without the need for lengthy incubation times or extreme conditions.

Implementation Method 1

wherein the first chemical group reacts with the second chemical group via an azide-alkyne cycloaddition, thereby immobilizing the nucleic acid construct on the substrate

Methodology Applied
Scientific EffectAzide-alkyne cycloaddition: Chemical Bonding

Implementation Method 2

In some embodiments, the depositing comprises a vapor deposition

Methodology Applied
Scientific EffectVapor deposition: Physical Vapour Deposition

Implementation Method 3

In some embodiments, the depositing comprises a liquid deposition

Methodology Applied
Scientific EffectLiquid deposition: Deposition (physical)

Data Source

PatentUS11833503B2Methods and compositions for surface functionalization of optical semiconductor-integrated biochips
Publication Date: 2023.12.05 INSILIXA INC
  • US11833503B2 patent drawing
  • US11833503B2 patent drawing
  • US11833503B2 patent drawing

AI summary

The present disclosure provides methods and compositions for surface functionalization of solid substrates. The compositions include functionalized silanes and nucleic acid constructs which may react to immobilize the nucleic acid constructs on the surface on the solid substrate. The disclosure also provides methods for immobilization of silanes and nucleic acid constructs on the surface of the substrate.