Nanospray Ionization Capillary Tip for Single-Cell Mass Spectrometry

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Solution Overview

Problem

Current methods for analyzing cellular components are limited by low sensitivity, requiring large quantities of cells, averaging data, and not allowing real-time detection of molecular dynamics in individual cells, which hinders the understanding of molecular mechanisms and disease marker discovery.

Innovation Solution

A method using nanospray ionization capillary tips to capture and ionize cellular components directly from individual cells, enabling real-time mass spectrometry analysis with high sensitivity and specificity, allowing for the detection of molecular changes at the single-cell level.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional molecular analysis methods are used, then analysis can be performed on cellular components, but the sensitivity is low and large quantities of cells are required

Engineering Contradiction:

Improveanalytical sensitivityVSAvoidquantity of cells required

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and analyzes molecular components from individual cells using micropipette aspiration to isolate cell fluid, then applies high-sensitivity detection methods to the extracted sample. This extraction approach enables analysis of single-cell contents without requiring large cell populations, directly resolving the contradiction between sensitivity and quantity required.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an intermediary aspiration medium through the micropipette that facilitates the transfer and concentration of cellular components into a detectable state. This intermediary system enables the bridge between single-cell extraction and high-sensitivity detection, overcoming the limitation of low analytical sensitivity in conventional methods.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If conventional analysis methods are used, then molecular components can be detected, but real-time detection of molecular dynamics in individual cells is not possible

Engineering Contradiction:

Improvedetection of molecular dynamicsVSAvoidtime for analysis

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary aspiration and extraction of cell fluid before analysis, preparing the sample in advance to enable rapid real-time detection. This preliminary action of isolating the cell fluid through micropipette aspiration allows subsequent high-speed molecular analysis without requiring time-consuming processing steps, achieving both precision and speed.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent establishes a continuous workflow from cell aspiration through fluid extraction to real-time molecular analysis, eliminating interruptions and time delays. This continuous process enables real-time detection of molecular dynamics in individual cells, resolving the contradiction between detection precision and analysis time.

Inventive Principle:

Principle #20Continuity of useful action

3Measurement precision

If data from multiple cells are averaged, then analysis can be performed, but individual cell variations and molecular mechanisms are obscured

Engineering Contradiction:

Improvedetection of individual cell characteristicsVSAvoidcomplexity of analysis method

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the analysis to focus on individual cells rather than averaging multiple cells. By using micropipette aspiration to isolate and analyze single-cell fluid contents, the method captures individual cell variations and molecular mechanisms without the complexity of coordinating and averaging multiple cell analyses, achieving precision through segmentation.

Inventive Principle:

Principle #1Segmentation

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 rapid, direct, and reliable analysis of cellular components, clarifying molecular mechanisms and identifying key molecules associated with cellular behavior and disease states, facilitating the discovery of new medicinal substances and diagnostic methods.

Implementation Method 1

introducing the ionization supporting solvent from the back-end of the nanospray ionization capillary tip; ionizing the cellular components by nanospray ionization

Methodology Applied

Scientific EffectNanospray ionization: Ionisation

Data Source

PatentUS9502227B2Capturing of cell fluid and analysis of its components under observation of cells and instruments for the cell fluid capturing and the analysis

Publication Date: 2016.11.22 HUMANIX

AI summary

A method captures cellular components from a single cell and performs mass spectrometry on the components. The method includes inserting a nanospray ionization capillary tip into a specific region of the cell under observation with a microscope. The nanospray ionization capillary tip can include a filament in the interior. The method further includes capturing the cellular components of the specific region of the cell into the opening of the nanospray ionization capillary tip and keeping the components at the nanospray ionization capillary tip, supplying an ionization supporting solvent from a back-end of the nanospray ionization capillary tip, applying an electric field between a sample inlet of a mass spectrometer and the nanospray ionization capillary tip, whereby nanospray ionization to the cellular components is implemented, and performing the mass spectrometry on the cellular components captured at the nanospray ionization capillary tip.