Chip-Based NanoESI Analyte Detection Without HPLC Complexity

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Solution Overview

Problem

Current methods for detecting analytes in complex biological matrices using nanoESI-MS are limited by complex device designs, low throughput, and inefficiencies in sample preparation, making them unsuitable for high-throughput and adaptable measurements.

Innovation Solution

A method utilizing a chip-based nanoESI detection system with a magnetic microparticle and electrically conductive pipette tip to form an analyte-microparticle complex, separated by magnetic forces, followed by extraction and ionization for efficient detection using mass spectrometry or ion mobility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional HPLC chromatographic separation is used, then analyte separation and sensitivity are improved, but device complexity and measurement time increase

Engineering Contradiction:
Improveanalyte detection sensitivityVSAvoidchromatographic system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and concentrates specific analytes from complex biological matrices using selective extraction techniques before mass spectrometry analysis. This pre-concentration step removes interfering matrix components while enriching the target analytes, thereby improving detection sensitivity without requiring complex chromatographic separation systems.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The method performs preliminary sample preparation steps including protein precipitation, liquid-liquid extraction, and solid-phase extraction before the actual mass spectrometry measurement. These preliminary actions simplify the sample matrix and enhance analyte visibility to the detector, eliminating the need for complex real-time chromatographic separation during measurement.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If direct surface sampling techniques are used, then measurement speed is improved, but analyte detection sensitivity deteriorates

Engineering Contradiction:
Improvemeasurement throughputVSAvoidanalyte detection sensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention applies preliminary extraction and concentration steps to the sample matrix before direct surface sampling. By pre-processing the sample to remove interfering substances and concentrate the analytes, the method enables direct surface analysis to achieve both high throughput and high sensitivity, as the extracted analytes are already in an optimized state for detection.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If solid support based sample preparation is used, then analyte concentration is improved, but device complexity and production difficulty increase

Engineering Contradiction:
Improveanalyte concentrationVSAvoiddevice production scalability
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The invention employs disposable solid support cartridges and extraction columns that can be easily manufactured and discarded after use. These single-use components simplify the overall system design, eliminate the need for complex cleaning and maintenance procedures, and enable straightforward scaling of the extraction process. The disposable nature of these components also eliminates cross-contamination issues between samples.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Measurement precision

If microfluidic devices are used for nanoESI-MS coupling, then analyte detection is improved, but device complexity and production cost increase

Engineering Contradiction:
ImprovenanoESI-MS detection performanceVSAvoidmicrofluidic device complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention segments the sample preparation and analysis process into distinct modular components: separate extraction cartridges, concentration columns, and the nanoESI-MS interface. This segmentation allows each component to be independently optimized and manufactured, reducing the complexity of integrating multiple functions into a single microfluidic device while maintaining high detection performance.

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 efficient and adaptable detection of analytes like steroids and proteins in biological samples, improving throughput and reducing interference, suitable for high-throughput applications.

Implementation Method 1

Separating the matrix and the analyte-microparticle complex by magnetic forces

Methodology Applied
Scientific EffectMagnetic forces: Magnetism

Implementation Method 2

Extracting the analyte from the analyte-microparticle complex by an extraction solvent

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 3

Directly contacting the electrically conductive pipette tip comprising the extracted analyte of interest and the nano-electrospray nozzle of a chip based nanoESI detection system to form a nano-electrospray for ionization of the extracted analyte of interest

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Data Source

PatentUS20250347654A1Detection of an analyte of interest by a chip based nanoesi detection system
Publication Date: 2025.11.13 ROCHE DIAGNOSTICS OPERATIONS INC
  • US20250347654A1 patent drawing
  • US20250347654A1 patent drawing
  • US20250347654A1 patent drawing

AI summary

The present invention relates to a method, a diagnostic system, a kit and the use thereof for efficiently detection of an analyte of interest by a chip based nanoESI detection system.