Mass Spectrometer Fluorescence Imaging for Un-Mixed Molecular Spectra
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Solution Overview
Problem
Mass spectrometers primarily report molecules based on mass/charge ratio, lacking information on molecular identity, chemical composition, and activity, while optical spectroscopy provides rich information but is limited in separating signals from mixed molecular species.
Innovation Solution
Combining mass spectrometry with time-resolved hyperspectral imaging spectroscopy, using a Continuously Ultrafast Time-resolving Imaging Detector (CUTID) to perform optical fluorescence spectroscopy on mass-selected molecules, separating and analyzing them by mass and wavelength without time-gating, enabling detailed optical-spectroscopic information on individual molecular species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry is used to separate molecules by mass/charge ratio, then molecular separation and quantification are achieved, but information on molecular identity, chemical composition, and activity is lost
Solution Approach 1:
The patent combines mass spectrometry with optical fluorescence spectroscopy into a single integrated system. The mass spectrometer separates molecules by mass/charge ratio while the fluorescence spectroscopy component simultaneously provides optical spectra containing molecular identity and chemical composition information. This merging of two analytical techniques allows both precise molecular separation and retention of rich molecular characterization data without requiring separate measurement systems.
2Loss of information
If optical spectroscopy is used to obtain rich molecular information, then molecular identity and chemical composition are identified, but the ability to separate signals from mixed molecular species is limited
Solution Approach 1:
The patent applies segmentation by first using the mass spectrometer to separate molecular species according to their mass/charge ratios before optical detection. This pre-separation segments the mixed molecular sample into distinct mass-based groups, which then undergo fluorescence spectroscopy measurement. By segmenting the sample beforehand, the optical spectroscopy signals from different molecular species are already partially separated, making it easier to resolve and analyze individual species' optical spectra even when they coexist in complex mixtures.
3Measurement precision
If time-gating or modulating light sensitivity is used in fluorescence measurements, then signal resolution is improved, but measurement complexity and potential signal loss increase
Solution Approach 1:
The patent employs a continuously operating imaging sensor that maintains constant light sensitivity throughout the fluorescence measurement process. Instead of using pulsed illumination with synchronized time-gated detection, the system uses continuous excitation light and continuous detection. This continuous measurement approach simplifies the instrument design by eliminating the need for complex timing synchronization circuits and modulated light sources, while still achieving high-resolution fluorescence decay measurements through the sensor's inherent time-resolution capability.
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
Provides un-mixed optical spectra for each molecular species, enhancing the ability to identify and characterize molecules with sensitivity to individual photons, resolving fluorescence decay times and wavelengths, and correlating signals for improved statistical accuracy.
Implementation Method 1
performing Fluorescence-Lifetime-Spectroscopy (FLS) measurements with a time-resolving imaging sensor continuously
Implementation Method 2
manipulating them through electromagnetic—mostly electrostatic—interactions. Thus, the particles, which may be nanoparticles, molecules, or molecular fragments, are discriminated by their mass-to-charge ratio
Implementation Method 3
optical spectroscopy normally is concerned with a measurement of fluorescent light intensity over the wavelength spectrum of the excitation or emitted light or both
Data Source
AI summary
A method includes performing Fluorescence-Lifetime-Spectroscopy (FLS) measurements with a time-resolving imaging sensor continuously without time-gating or modulating a light sensitivity of the imaging sensor.