Phase-Separated Sample Ejection for Sensitive Mass Spectrometry
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Solution Overview
Problem
Current mass spectrometry systems face challenges in efficiently introducing samples, particularly for complex biological matrices, leading to ionization suppression and reduced assay sensitivity due to multi-drop scale sample loading and matrix interference.
Innovation Solution
A method involving the creation of a multi-phase liquid system where a target analyte is extracted from an aqueous phase into an organic phase, allowing for the selective introduction of analytes into a mass spectrometer using acoustic or controlled pressure pulses, reducing the need for additional sample preparation and minimizing ionization suppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If multi-drop scale sample loading is used in mass spectrometry, then sample introduction capacity is improved, but ionization suppression increases and assay sensitivity decreases
Solution Approach 1:
The sample introduction process is segmented into multiple phases (aqueous phase and organic phase) that are separated and introduced independently. The acoustic droplet ejection system divides the sample into discrete droplets that can be controlled individually, allowing high-throughput introduction without overwhelming the ionization source. This segmentation maintains sensitivity by preventing matrix overload while preserving productivity through automated multi-phase handling.
Solution Approach 2:
The target analyte is extracted from the complex aqueous biological matrix into a simpler organic phase. This extraction removes interfering matrix components that cause ionization suppression, thereby improving assay sensitivity. The organic phase containing the extracted analyte is then introduced into the mass spectrometer, maintaining high sample introduction capacity while reducing matrix effects.
2Measurement precision
If additional sample preparation steps are performed to reduce ionization suppression, then assay sensitivity is improved, but analytical throughput decreases
Solution Approach 1:
The sample preparation and sample introduction functions are merged into a single automated workflow. The acoustic droplet ejection system directly handles the multi-phase sample system from extraction through introduction without requiring separate manual preparation steps. This integration maintains high assay sensitivity through effective matrix separation while preserving analytical throughput by eliminating time-consuming intermediate steps.
Solution Approach 2:
The system uses the inherent phase separation properties of the extracted sample to perform its own preparation. The acoustic droplet ejection system automatically distinguishes and handles different phases based on their physical properties, eliminating the need for additional manual preparation steps. This self-service approach maintains sensitivity through effective matrix removal while keeping throughput high through automation.
3Loss of time
If complex biological matrices are introduced directly into the mass spectrometer, then sample preparation time is reduced, but ionization suppression increases
Solution Approach 1:
Phase separation and analyte extraction are performed as preliminary actions before mass spectrometry analysis. The multi-phase system is prepared in advance with the target analyte extracted into the organic phase, removing matrix interferents before introduction. This preliminary preparation minimizes ionization suppression while the automated acoustic droplet ejection system quickly introduces the prepared sample, keeping overall preparation time low.
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 enhances analytical throughput and sensitivity by reducing ionization suppression, allowing for high-throughput sample introduction and improved mass signal detection without additional sample preparation steps.
Implementation Method 1
an acoustic actuator can be employed to eject one or more droplets from an organic phase that contains at least a portion of the target analyte into the mass spectrometer
Implementation Method 2
one or more acoustic pulses can be applied to at least one of the phases (e.g., the aqueous or any of the organic phases) to cause one or more samples of that phase (e.g., in the form of a plurality of droplets) to be introduced into the mass spectrometer
Implementation Method 3
mixing the sample with a solvent in which a matrix of an aqueous phase of the sample is immiscible and in which at least a target analyte, when present in the sample, is miscible so as to extract at least a portion of the target analyte into said at least one solvent
Data Source
AI summary
In one aspect, a method of introducing a sample into an open port interface (OPI) of a mass spectrometer is disclosed, which includes mixing the sample with a solvent in which a matrix of an aqueous phase of the sample is immiscible and in which at least a target analyte, when present in the sample, is miscible so as to extract at least a portion of the target analyte into said at least one solvent, thereby generating a multi-phase liquid having said aqueous phase and one or more organic phases, wherein at least one of those organic phases contains at least a portion of the target analyte. In some embodiments, the method further calls for ejecting a plurality of droplets from at least one of the phases of the multi-phase liquid for introduction into the OPI of the mass spectrometer.