In-Emitter Elution Electrospray for Low-Quantity Biomolecule Analysis

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Solution Overview

Problem

Current label-free technologies for biomolecular interactions cannot effectively identify or characterize the structural details of interacting partners, requiring complex coupling with mass spectrometry due to low sample quantity limitations on sensing probe tips.

Innovation Solution

The microprobe-capture in-emitter elution-electrospray ionization (MPIE-ESI) method captures analytes on a probe, elutes them within an electrospray emitter, and nebulizes them for high-resolution mass spectrometry analysis, directly coupling label-free analysis with MS for precise identification and characterization of biomolecular interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If label-free technologies are used to capture biomolecules on sensing probe tips, then real-time measurement of biomolecular interactions is achieved, but the sample quantity is limited making structural analysis difficult

Engineering Contradiction:
Improvereal-time measurement capabilityVSAvoidsample quantity on probe tips
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent combines label-free sensing probe technology with mass spectrometry analysis into an integrated system. The sensing probe captures biomolecules and directly interfaces with the mass spectrometer, merging two previously separate techniques to simultaneously achieve real-time measurement and structural analysis with sufficient sample quantity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent introduces an intermediary elution step where captured biomolecules are released from the sensing probe into a collection vessel before mass spectrometry analysis. This intermediary step allows accumulation of sufficient sample quantity while maintaining the real-time capture capability of the original label-free technology.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If separate elution and injection steps are used to couple label-free analysis with mass spectrometry, then structural analysis is enabled, but the experiment process becomes very complicated

Engineering Contradiction:
Improvestructural analysis capabilityVSAvoidexperiment process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the elution and mass spectrometry injection steps into a single integrated operation. The sensing probe is directly coupled to the mass spectrometer interface, allowing eluted biomolecules to be immediately introduced for analysis without requiring separate manual handling steps, thereby enabling structural analysis while simplifying the overall experiment process.

Inventive Principle:
Principle #5Merging (Combining)

3Quantity of substance

If conventional biomolecule fishing tools are used, then biomolecules can be captured, but background noise in mass spectrometry analysis increases

Engineering Contradiction:
Improvebiomolecule capture capabilityVSAvoidbackground noise in MS analysis
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the biomolecule capture function from conventional fishing tools and implements it directly on the mass spectrometry interface. By using a sensing probe that elutes captured molecules directly into the MS system, non-specific binding materials and background contaminants are excluded, achieving effective biomolecule capture while minimizing background noise in the mass spectrometry analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

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 simplifies the experiment, enhances sensitivity, and reduces background noise, allowing for real-time monitoring and precise identification of biomolecules, including proteins and nucleic acids, with optimized surface chemistry for capturing large biomolecules from complex matrices.

Implementation Method 1

capturing an analyte on a probe that comprises a binding agent

Methodology Applied
Scientific EffectBinding interaction: Adsorption

Implementation Method 2

releasing the analyte from the probe while it is in the emitter using an elution liquid

Methodology Applied
Scientific EffectElution: Desorption

Implementation Method 3

nebulizing the analyte by electrospray

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Data Source

PatentUS20230305019A1Microprobe-capture in-emitter elution-electrospray ionization
Publication Date: 2023.09.28 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US20230305019A1 patent drawing
  • US20230305019A1 patent drawing
  • US20230305019A1 patent drawing

AI summary

Provided herein is a method for analyzing a molecular interaction. In some embodiments the method may comprise: capturing an analyte on a probe that comprises a binding agent, inserting the probe into the interior capillary of an electrospray emitter, releasing the analyte from the probe while it is in the emitter using an elution liquid, nebulizing the analyte by electrospray; and analyzing the nebulized analyte by mass spectrometry.