Microfluidic ESI Voltage Feedback for Intact Protein MS
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Solution Overview
Problem
Current methods for interfacing protein sample preparation techniques with mass spectrometers, such as liquid chromatography and electrospray ionization, face limitations due to the need for peptide fragment analysis and linear flow paths, which restrict the utility and provide limited characterization of intact proteins, and struggle with maintaining constant voltage at the electrospray ionization tip.
Innovation Solution
The method involves maintaining a constant voltage at the electrospray ionization tip by applying voltages to a separation channel and an auxiliary fluid channel, using a feedback loop to adjust for changes in resistance and voltage, allowing for more accurate characterization of analyte peaks and improved correlation between chemical separation and mass spectrometry data.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If liquid chromatography is used to prepare protein samples, then sample fractions can be collected for mass spectrometry, but the proteins must be digested into peptide fragments which increases the number of fractions and data complexity
Solution Approach 1:
The invention extracts the essential function of sample separation while eliminating the digestion step. By using electrospray ionization directly on intact proteins, the method takes out the peptide fragmentation step that creates complexity, allowing direct analysis of whole proteins without generating numerous peptide fractions that require complex data reconstruction.
Solution Approach 2:
The invention segments the analysis process by separating the ionization function from the chromatography function. The microfluidic device performs separation and the electrospray tip performs ionization independently, allowing intact proteins to be analyzed without requiring digestion into peptides, thus reducing the number of fractions while maintaining separation quality.
2Ease of operation
If capillaries are used for electrospray ionization, then a convenient droplet volume can be provided, but the linear flow path does not allow for multi-step sample processing
Solution Approach 1:
The invention segments the sample processing function from the electrospray ionization function. The microfluidic device handles multi-step sample processing in separate chambers while the electrospray tip maintains its simple capillary structure for convenient droplet generation. This segmentation allows complex sample preparation without compromising the ease of electrospray operation.
Solution Approach 2:
The invention introduces a microfluidic device as an intermediary between sample preparation and electrospray ionization. This intermediary component enables multi-step processing while maintaining compatibility with the simple capillary electrospray design, bridging the gap between complex sample needs and simple ionization requirements.
3Power
If voltage is applied to the electrospray tip for ionization, then gas phase ions can be produced, but internal fluid resistances can change over time altering the voltage at the ESI tip
Solution Approach 1:
The invention implements a feedback control system that continuously monitors the voltage at the electrospray tip and adjusts the applied voltage to compensate for changes in internal fluid resistance. This feedback mechanism maintains stable ionization conditions despite variations in fluid properties over time, ensuring consistent voltage at the ESI tip.
Solution Approach 2:
The invention dynamically adjusts the voltage parameter in response to changing fluid resistance conditions. By monitoring and modifying the applied voltage in real-time, the system compensates for resistance changes and maintains stable electrospray performance throughout the analysis.
4Ease of operation
If microfluidic devices are used for sample preparation, then additional control and complexity can be provided, but limited characterization of separated analyte fractions is available prior to mass spectrometry introduction
Solution Approach 1:
The invention uses the microfluidic device itself as an intermediary that enables both precise fluid control and analytical characterization. The device incorporates features that allow monitoring and characterization of analyte fractions during the transfer process, providing information before mass spectrometry analysis without compromising fluid manipulation capabilities.
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 enables more precise characterization of analyte peaks and improved data quality in mass spectrometry, facilitating better analysis of complex mixtures and biologic drug characterization by maintaining stable electrospray performance and accurate voltage control.
Implementation Method 1
electrospray ionization (ESI). In ESI, small droplets of sample and solution are emitted from a distal end of a capillary or microfluidic device comprising an electrospray feature, such as an emitter tip or orifice, by the application of an electric field between the capillary tip or emitter tip and the mass spectrometer source plate
Implementation Method 2
Separation of analyte components from a more complex analyte mixture on the basis of an inherent quality of the analytes
Data Source
AI summary
Methods, devices, and systems for improving the quality of electrospray ionization mass spectrometer (ESI-MS) data are described, as are methods, devices, and systems for achieving improved correlation between chemical separation data and mass spectrometry data.