Thermo-stabilized nano- and micro- flow LC/ESI-MS interface and a method thereof

A liquid chromatography interface comprising:

• an integrated column/electrospray ionization (ESI) tip assembly including,
• a liquid chromatography separation column,
• an ESI tip for generating ions, and
• a temperature-controlled enclosure enclosing the liquid chromatography separation column;
• said enclosure having at least one opening and said ESI tip exposed outside the enclosure through said at least one opening;
• said enclosure having a heating or cooling device providing a substantially homogeneous distribution of temperature throughout an internal space of the enclosure where the liquid chromatography separation column is disposed;
• said enclosure holding liquid chromatography separation columns having different lengths,
• wherein the integrated column/ESI tip assembly, including the liquid chromatography separation columns having different lengths, resides within a thermo-stabilized volume of substantially the same temperature from an entrance of the liquid chromatography separation column to an end of the ESI tip.

A liquid chromatography interface comprising:

• a liquid chromatography separation column,
• a temperature-controlled enclosure enclosing the liquid chromatography separation column;
• said enclosure having a heating or cooling device providing a substantially homogeneous distribution of temperature throughout an internal space of the enclosure where the liquid chromatography separation column is disposed to provide a thermo-stabilized volume of substantially the same temperature from an entrance of the liquid chromatography separation column to an end of the liquid chromatography separation column,
• wherein the substantially homogeneous enclosure temperature distribution has a temperature differential from the entrance of the liquid chromatography separation column to the end of the liquid chromatography separation column of less than +/−2° C.

A system for analyte characterization, comprising:

• an integrated column/ESI tip assembly including,
• a liquid chromatography separation column,
• an ESI tip for generating ions, a temperature-controlled enclosure surrounding the liquid chromatography separation column, and
• a mechanism configured to characterize an analyte eluting from the liquid chromatography separation column;
• said enclosure having at least one opening and the ESI tip is exposed outside the enclosure through the opening;
• said enclosure having a heating or cooling device providing a substantially homogeneous distribution of temperature throughout an internal space of the enclosure where the liquid chromatography separation column is disposed;
• and
• said enclosure including at least one gas flow mixing element to permit heat exchange by directing a flow of gas toward the ESI tip,
• wherein the integrated column/ESI tip assembly resides within a thermo-stabilized volume of substantially the same temperature from an entrance of the liquid chromatography separation column to an end of the ESI tip.

A system for analyte characterization, comprising:

• an integrated column/ESI tip assembly including,
• a liquid chromatography separation column,
• an ESI tip for generating ions, a temperature-controlled enclosure surrounding the liquid chromatography separation column, and
• a mechanism configured to characterize an analyte eluting from the liquid chromatography separation column;
• said enclosure having at least one opening and the ESI tip is exposed outside the enclosure through the opening;
• said enclosure having a heating or cooling device providing a substantially homogeneous distribution of temperature throughout an internal space of the enclosure where the liquid chromatography separation column is disposed;
• and
• said enclosure holding liquid chromatography separation columns having different lengths,
• wherein the integrated column/ESI tip assembly resides within a thermo-stabilized volume of substantially the same temperature from an entrance of the liquid chromatography separation column to an end of the ESI tip.

A method for separation of analytes in elution time in a liquid chromatography separation column, comprising:

• providing a thermo-stabilized volume having a substantially same instantaneous temperature from an entrance of the liquid chromatography separation column to an outlet of an electrospray ionization (ESI) tip;
• introducing the analytes into the liquid chromatography separation column in the thermo-stabilized volume;
• temperature ramping the substantially same instantaneous temperature of the thermo-stabilized volume over a prescribed duration such that the instantaneous temperature is a controlled as a function of time, with no substantial variation of the instantaneous temperature along a column length;
• and
• eluting the analytes from the ESI tip over said prescribed duration.