Functionalized IM-MS Calibrants for Wider CCS and m/z Coverage
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Solution Overview
Problem
Current ion mobility-mass spectrometry (IM-MS) calibrants exhibit a limited range for both collisional cross-section (CCS) and mass-to-charge ratio (m/z) dimensions, with narrow peak widths and limited diversity in compactness, which restricts their analytical capabilities.
Innovation Solution
Development of calibrant compounds with alcohol or amine functionalized cores and peripheral functionalities, including multifunctional cores and dendrimers, which are synthesized through esterification and amidation reactions to provide a wider range of CCS and m/z values, doubling the existing range and ensuring compatibility with both positive and negative ion modes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional calibrants are used, then the calibration process is simple, but the range of CCS and m/z values is limited
Solution Approach 1:
The calibrant molecules are segmented into modular components: a core structure (alcohol or amine functionalized) and peripheral functionalities. This segmentation allows systematic variation of molecular weight and collisional cross-section by changing the number and type of peripheral groups, thereby expanding the calibration range while maintaining structural control
Solution Approach 2:
The calibrants are designed with universal core structures that can accommodate multiple types of peripheral functionalities. This multi-functionality enables a single core structure to generate multiple calibrant variants with different m/z and CCS values, expanding the calibration range without proportionally increasing overall system complexity
2Quantity of substance
If calibrants with wider CCS range are used, then the analytical capability is improved, but the peak width dispersity increases
Solution Approach 1:
The calibrant design applies local quality by maintaining a consistent core structure (providing uniform local properties) while varying peripheral functionalities. This ensures that all calibrants share similar structural characteristics that produce narrow, well-defined peaks, while the peripheral variations expand the overall CCS range
Solution Approach 2:
The calibrants are composite molecules combining a rigid core structure with controlled peripheral groups. This composite structure provides both the structural integrity needed for sharp peaks and the molecular diversity required for wide CCS range coverage
3Measurement precision
If diverse calibrant structures are used, then the characterization precision is improved, but the synthesis complexity increases
Solution Approach 1:
The core structures are pre-synthesized with standardized alcohol or amine functional groups before adding peripheral functionalities. This preliminary action creates a uniform starting platform that simplifies subsequent functionalization steps, enabling diverse calibrant structures to be manufactured through systematic, repeatable processes
Solution Approach 2:
The synthesis approach uses parameter changes by systematically varying the type and number of peripheral functionalities attached to the core. This allows precise control over molecular weight and CCS while following similar synthetic pathways, maintaining ease of manufacture despite structural diversity
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
The new calibrants offer expanded CCS and m/z ranges, enabling more precise characterization of molecules and improving the analytical capabilities of IM-MS systems, while maintaining stability and ease of use.
Implementation Method 1
ionizing the at least one calibrant compound to provide at least one charged ion
Implementation Method 2
Ion mobility spectrometry (IMS) is capable of separating molecules that may have the same mass to charge ratio (m/z) but different conformational arrangements
Implementation Method 3
synthesized through esterification and amidation reactions
Implementation Method 4
synthesized through esterification and amidation reactions
Data Source
AI summary
Calibrants and methods of making the same include using mixtures of multifunctional core compounds or multifunctional dendrimers that are functionalized to yield a set of discrete compounds which cover a range of collisional cross sections (CCSs) for calibrating ion mobility and variation in molecular weight to calibrate the mass to charge (m/z) measurements of mass spectrometry, as well as for calibrating tandem instruments that measure both dimensions. Methods of using the calibrants are also disclosed, such as in mass spectrometry.