Mass Spectrometry Tag Fragmentation Multiplexing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional mass spectrometry tagging systems have limited multiplexing capacity, which restricts the number of samples that can be processed in a single stream and affects the precision and accuracy of quantitative measurements.
Innovation Solution
Development of mass spectrometry tags that fragment into multiple reporter ions under dissociation conditions, allowing for the use of distinguishable isotopomeric and isotopologous reporter regions, thereby increasing the multiplexing capacity beyond conventional systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional mass spectrometry tagging systems are used, then the system is simple to operate, but the multiplexing capacity is limited
Solution Approach 1:
The tag is divided into three distinct functional regions: a reporter region (R′) that generates detectable signals, a mass balance region (Q) that maintains isobaric mass, and a linker region (L) that connects to the analyte. This segmentation allows each region to be optimized independently, enabling complex multiplexing functionality while maintaining operational simplicity through standardized tag architecture.
Solution Approach 2:
The invention transitions from single-reporter ion tags to multi-reporter ion tags, adding a dimensional aspect to the detection capability. Each tag now produces multiple reporter ions with different mass-to-charge ratios, creating additional distinguishable dimensions for sample multiplexing beyond the conventional single ion detection approach.
2Productivity
If label-free approaches are used, then sample manipulation is minimized, but throughput is limited due to lack of parallelization
Solution Approach 1:
The mass spectrometry tag is designed with universal functionality that serves multiple purposes: it enables parallel processing of multiple samples through isobaric labeling, provides quantitative measurement capability through reporter ions, and maintains compatibility with standard mass spectrometry workflows. This multi-functionality allows a single tag system to address both throughput enhancement and quantitative analysis requirements.
3Adaptability or versatility
If heavy isotope-labeled samples are used, then simultaneous analysis in a single MS run is enabled, but multiplexing capacity is limited
Solution Approach 1:
The tag design implements local quality differentiation within the reporter region (R′), where specific isotopic compositions and chemical structures are assigned to generate distinct reporter ion patterns. This localized differentiation allows multiple samples to be distinguished through their unique reporter ion signatures while maintaining isobaric mass balance, thereby increasing multiplexing capacity without compromising quantitative precision.
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 enhanced multiplexing capacity enables the simultaneous analysis of multiple samples, improving the precision and accuracy of quantitative measurements in mass spectrometry-based proteomics.
Implementation Method 1
the tag is configured to fragment under dissociation conditions in a mass spectrometer to produce fragments comprising a primary reporter ion and a secondary reporter ion
Data Source
AI summary
In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.