Humidity-Stabilized Sample Preparation for Tissue Spectrometry

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Solution Overview

Problem

Current methods for maintaining stable relative humidity during sample preparation for spectrometric analysis, particularly for human and animal tissue sections, are challenging due to uncontrollable condensation and diffusion issues, which affect spatial resolution and image quality in imaging mass spectrometry.

Innovation Solution

Utilizing the physico-chemical phenomenon of deliquescence, where a temperature-controlled gas volume is maintained above a saturated salt solution or fed with a moist gas flow to achieve precise and stable humidity levels, allowing for enzymatic digestion and other chemical processes without excessive condensation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high humidity is used to enable enzymatic digestion and tissue swelling, then the enzyme can diffuse into the tissue section and act effectively, but uncontrolled condensation occurs which leads to lateral transport of molecules and reduces spatial resolution

Engineering Contradiction:
Improveenzymatic digestion effectivenessVSAvoidspatial resolution
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by precisely controlling the relative humidity to remain just below 100% (e.g., 95-98%) rather than allowing it to reach the dew point. This parameter optimization enables sufficient tissue swelling and enzyme diffusion while preventing condensation that would cause lateral molecule transport and loss of spatial resolution.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback control through continuous monitoring of relative humidity during the enzymatic digestion process. A humidity sensor detects the actual humidity level, and this information feeds back to a control system that adjusts the humidification to maintain humidity just below the dew point, thereby preventing condensation while ensuring adequate tissue swelling.

Inventive Principle:
Principle #23Feedback

2Productivity

If temperature is increased to accelerate enzymatic digestion, then digestion time is reduced, but the risk of condensation increases due to higher dew point

Engineering Contradiction:
Improvedigestion speedVSAvoidcondensation risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses feedback control to simultaneously manage temperature and humidity. Temperature sensors monitor the digestion temperature, and this information feeds back to the humidification control system, which adjusts the humidity level dynamically to remain just below the temperature-dependent dew point, thereby enabling high-temperature digestion while preventing condensation.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent applies parameter changes by dynamically adjusting the humidity parameter in response to temperature changes. As temperature increases to accelerate digestion, the system raises the humidity level to approach but remain below the elevated dew point, thereby maintaining high digestion speed while preventing condensation through coordinated parameter optimization.

Inventive Principle:
Principle #35Parameter changes

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 method ensures high humidity levels just below the dew point, maintaining optimal spatial resolution and image quality during sample preparation, while minimizing lateral transport of molecules and preventing uncontrolled condensation, thus enhancing the accuracy and reproducibility of spectrometric analysis.

Implementation Method 1

The invention exploits a physico-chemical phenomenon called 'deliquescence'. The deliquescence manifests itself through the fact that the relative humidity in a gas volume above a saturated solution of a suitable substance can be kept constant with a high degree of precision when a specified temperature is maintained.

Methodology Applied
Scientific EffectDeliquescence: Deliquescence

Data Source

PatentUS11781952B2Humidity stabilization during the preparation of biological samples for spectrometry
Publication Date: 2023.10.10 BRUKER DALTONIK GMBH & CO KG
  • US11781952B2 patent drawing
  • US11781952B2 patent drawing
  • US11781952B2 patent drawing

AI summary

The invention proposes preparing biological samples for spectrometry which contain cell structures and/or whole cells of human or animal origin (e.g. thin human and animal tissue sections) or prokaryotes (e.g. microorganisms), and which require constant relative humidity, in a temperature-controlled gas volume whose humidity is determined by a saturated substance solution, for example a suitable salt solution. The invention exploits a physico-chemical phenomenon called “deliquescence”, which manifests itself by keeping the relative humidity above the saturated substance solution constant with a high degree of precision when a specified temperature is maintained. Pure succinic acid exhibits deliquescence at approx. 99% relative humidity, for example. Since an enormous variety of deliquescent salts and other suitable substances are available, it is possible to find the suitable substance for almost any desired relative humidity, with adjustment of the temperature, where necessary.