DESI-MS Tissue Analysis for Intraoperative Biomarker Detection

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Solution Overview

Problem

Current methods for tumor diagnostics, such as light microscopy and immunohistochemistry, are time-consuming and provide delayed results, limiting immediate intraoperative surgical decision-making, as they often require days to yield results, whereas immediate feedback is crucial for surgical interventions.

Innovation Solution

The implementation of mass spectrometry systems, specifically desorption electrospray ionization-mass spectrometry (DESI-MS), for rapid analysis of tissue samples, enabling the detection of biomarkers like 2-Hydroxyglutarate (2-HG) directly from tissues with minimal preparation, providing real-time diagnostic information in the operating room.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If light microscopy and immunohistochemistry are used for tumor diagnostics, then diagnostic accuracy is improved, but analysis time increases significantly

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical/optical microscopy and immunohistochemistry methods with mass spectrometry technology. The DESI-MS system directly analyzes tissue metabolites by ionizing molecules in ambient conditions and measuring their mass-to-charge ratios, providing rapid metabolic profiling without requiring lengthy staining or sectioning procedures, thus reducing analysis time while maintaining diagnostic accuracy

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent shifts the diagnostic parameter from morphological features (visualized by microscopy) to metabolic parameters (detected by mass spectrometry). By monitoring metabolite profiles such as 2-hydroxyglutarate levels, the system provides real-time diagnostic information that reflects tumor biochemistry, enabling rapid classification and grading of gliomas within minutes rather than hours or days

Inventive Principle:
Principle #35Parameter changes

2Loss of information

If traditional histological methods are used, then detailed tissue characterization is achieved, but immediate intraoperative feedback is lost

Engineering Contradiction:
Improvetissue characterization informationVSAvoidfeedback time
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The patent replaces slow histological processing with rapid mass spectrometry analysis. The DESI-MS system performs direct tissue analysis by spraying ionizable solvent onto tissue sections and analyzing the resulting ion current, providing real-time metabolic information that enables immediate intraoperative decision-making while preserving comprehensive tissue characterization capabilities

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent performs preliminary metabolic analysis directly on fresh frozen tissue sections before formalin fixation. By analyzing metabolites in their native state using DESI-MS, the system provides immediate diagnostic information that guides surgical resection boundaries, allowing surgeons to maximize tumor removal while preserving healthy tissue without waiting for traditional pathological processing

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 allows for rapid tumor classification, prognostic information, and real-time discrimination between cancerous and normal tissues, facilitating immediate surgical decisions and optimizing tumor resection while minimizing healthy tissue loss.

Implementation Method 1

a system is provided that uses desorption electrospray ionization-mass spectrometry (DESI-MS) in ambient conditions with minimal pretreatment of the samples

Methodology Applied
Scientific EffectDesorption electrospray ionization:

Implementation Method 2

analyze the tissue sample using a mass spectrometry process to generate mass spectrometry data

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS9568477B2System and method for analysis of bio-metabolites for-use in image-guided surgery
Publication Date: 2017.02.14 THE BRIGHAM & WOMEN S HOSPITAL INC
  • US9568477B2 patent drawing
  • US9568477B2 patent drawing
  • US9568477B2 patent drawing

AI summary

A system for identifying a bio-marker using mass spectroscopy is provided that includes a sample receptacle configured to receive a tissue sample, a mass spectrometry apparatus configured to receive the tissue sample and analyze the tissue sample using a mass spectrometry process to generate mass spectrometry data, and a computer system that includes a computer processor having access to a non-transitory, computer-readable storage medium having stored thereon instructions. The instructions cause the computer processor to: receive the mass spectrometry data from the mass spectrometry apparatus; analyze the mass spectrometry data to determine a presence of 2-Hydroxyglutarate (2-HG) in the tissue sample; and generate a report indicating a health of the tissue sample based on the presence of 2-HG in the tissue sample.