Sheathless interface for capillary electrophoresis/electrospray ionization-mass spectrometry
Inventors
Lunte, Craig E. • Johnson, Ryan Tyler • To, Nhan • Lunte, Susan M. • Osbourn, Damon
Assignees
University of Kansas • National Institutes of Health NIH
Publication Number
US-10121645-B2
Publication Date
2018-11-06
Expiration Date
2037-12-05
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Abstract
Provided herein are capillaries for use in an electrophoretic separations. The capillaries can comprise an elongated tubular wall defining a path for fluid flow from an inlet to a tapered outlet; and a decoupler junction positioned within the elongated tubular wall upstream of the tapered outlet. The decoupler junction can comprise a plurality of microchannels penetrating through the elongated tubular wall and an ion-permeable polymer coating the plurality of microchannels. Also provided are sheathless interfaces for coupling capillary electrophoresis (CE) with mass spectrometry that employ these capillaries.
Core Innovation
Provided herein are capillaries for use in electrophoretic separations. These capillaries comprise an elongated tubular wall defining a path for fluid flow from an inlet to a tapered outlet and a decoupler junction positioned within the wall upstream of the tapered outlet. The decoupler junction includes a plurality of microchannels penetrating through the wall, coated with an ion-permeable polymer.
The invention addresses challenges present in interfacing capillary electrophoresis (CE) with electrospray ionization mass spectrometry (ESI-MS). While sheath-flow interfaces offer robustness and ease of use, they cause analyte dilution and reduced sensitivity. Existing sheathless interfaces enhance sensitivity but suffer from issues such as short capillary lifetimes, dead volume, irreproducible fabrication, fragility, or hazardous fabrication processes requiring hydrofluoric acid.
The invention overcomes these shortcomings by providing capillaries with a decoupler junction comprising multiple microchannels coated with an ion-permeable polymer to enable efficient, durable, and reliable sheathless interfaces for CE-ESI-MS. The design preserves mechanical stability, allows electrical connection without analyte dilution, and enables modulation of pH post-separation to improve ionization efficiency.
Claims Coverage
The patent contains three independent claims covering a capillary for electrophoretic separation, a sheathless interface for coupling CE with mass spectrometry, and methods of characterizing samples and forming capillaries.
Capillary with a decoupler junction comprising multiple microchannels coated with an ion-permeable polymer
The capillary includes an elongated tubular wall with a tapered outlet and a decoupler junction upstream of the tapered outlet. The decoupler junction consists of multiple microchannels penetrating through the wall and coated with an ion-permeable polymer.
Sheathless interface for coupling capillary electrophoresis with mass spectrometry using the capillary
The interface comprises the above capillary, a buffer reservoir in liquid contact with the decoupler junction filled with a reservoir liquid, and an electrode contacting the reservoir liquid to establish electrical connection.
Method of characterizing a sample via sheathless CE-MS interface
The method involves providing the sheathless interface comprising the capillary, buffer reservoir, electrode, mass spectrometer, and power supply; injecting a sample into the capillary; electrophoretically separating the sample; and directing the separated sample into the mass spectrometer for analysis.
Method of forming a capillary with tapered outlet, laser-ablated microchannels, and ion-permeable polymer coating
The method includes providing an electrophoretic capillary, modifying the outlet to form a tapered outlet (e.g., by sharpening), laser ablating multiple microchannels through the tubular wall, and coating the microchannels with an ion-permeable polymer.
The claims cover the structural features of the capillary with microchannel-based decoupler coated with ion-permeable polymer, the configuration of a sheathless interface integrating the capillary and electrical contacts, methods for analyzing samples using this interface, and methods to fabricate such capillaries providing improved reliability and sensitivity in CE-ESI-MS systems.
Stated Advantages
The interface does not compromise sensitivity and avoids sample dilution typical of sheath-flow interfaces.
Reproducible and operationally robust fabrication method employing laser ablation and polymer casting allows high-throughput production and avoids hazardous chemicals like hydrofluoric acid.
Mechanical stability is preserved due to axial alignment and spacing of microchannels and protective polymer coating.
The design allows positioning close to the mass spectrometer inlet without arcing or bubble formation.
The semi-permeable polymer coating enables modulation of pH post-separation to enhance ionization efficiency without dilution.
Stable electrospray operation with lifetimes similar to unmodified fused silica capillaries and minimal dead volume.
Documented Applications
Coupling capillary electrophoresis with electrospray ionization mass spectrometry (CE-ESI-MS) for analysis of biological matrices.
Characterizing samples comprising one or more analytes by electrophoretic separation and mass spectrometry detection using the sheathless interface.
Use with different electrophoretic separation modes including capillary zone electrophoresis (CZE), capillary isotachophoresis (CITP), capillary isoelectric focusing (CIEF), or capillary electrochromatography.
Integration with a microfluidic device as a sample inlet to the capillary for separation prior to mass spectrometry analysis.
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