Software for microfluidic systems interfacing with mass spectrometry

Abstract

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.

1 .- 17 . (canceled) 
     
     
         18 . A method comprising:
 a) providing a sample comprising a mixture of two or more analytes;   b) performing a separation within a fluid channel containing the sample to resolve individual analyte peaks from the mixture of two or more analytes;   c) calculating a velocity of an analyte peak upon mobilization of the fluid channel's contents towards a fluid channel exit; and   d) using the velocity of the analyte peak to determine a time at which the analyte peak reaches the fluid channel exit.   
     
     
         19 . The method of  claim 18 , wherein the fluid channel is a lumen of a capillary. 
     
     
         20 . The method of  claim 18 , wherein the fluid channel is part of a microfluidic device. 
     
     
         21 . The method of  claim 18 , wherein the separation is based on isoelectric focusing (IEF), capillary zone electrophoresis (CZE), capillary gel electrophoresis (CGE), capillary isotachophoresis (CITP), or micellar electrokinetic chromatography (MEKC). 
     
     
         22 . The method of  claim 18 , wherein the velocity of the analyte peak is calculated from a time interval required for the analyte peak to move from a first position to a second position. 
     
     
         23 . The method of  claim 22 , wherein the first position, second position, and time interval are determined from a series of two or more images of the fluid channel. 
     
     
         24 . The method of  claim 23 , wherein the series of two or more images comprise ultraviolet light absorbance images, visible light absorbance images, or fluorescence images. 
     
     
         25 . The method of  claim 18 , wherein the fluid channel exit comprises an electrospray interface with a mass spectrometer. 
     
     
         26 . The method of  claim 18 , wherein the time at which the analyte peak reaches the fluid channel exit is used to correlate mass spectrometer data with the analyte peak. 
     
     
         27 . The method of  claim 18 , wherein the mobilization of the fluid channel's contents comprises the use of an electroosmotic mobilization technique, a chemical mobilization technique, a hydrodynamic mobilization technique, or any combination thereof. 
     
     
         28 . The method of  claim 18 , wherein the two or more analytes comprise proteins, protein-drug conjugates, peptides, nucleic acid molecules, carbohydrate molecules, lipid molecules, metabolite molecules, small organic compounds, or any combination thereof. 
     
     
         29 . The method of  claim 26 , wherein a comparison of mass spectrometer data collected for samples of a biologic drug candidate and a reference drug is used to make a determination of biosimilarity. 
     
     
         30 . The method of  claim 18 , wherein the velocity of the analyte peak is used in a feedback loop to adjust a control parameter for the separation or mobilization of the analyte peaks. 
     
     
         31 . The method of  claim 30 , wherein the control parameter is a voltage. 
     
     
         32 . The method of  claim 30 , wherein the feedback loop operates at a frequency of at least 0.1 Hz. 
     
     
         33 .- 62 . (canceled) 
     
     
         63 . A computer-implemented method comprising:
 a) receiving, using a processor, image data comprising two or more images acquired using a detector configured to image all or a portion of a separation channel in a capillary or a microfluidic device;   b) processing the image data using the same or a different processor to determine a position of an analyte peak within the separation channel in the two or more images;   c) calculating, using the same or a different processor, a velocity of the analyte peak based on the position of the analyte peak in the two or more images and a known time interval between acquisition of the two or more images; and   d) determining, using the same or a different processor, a time at which the analyte peak will reach a separation channel outlet.   
     
     
         64 . The computer-implemented method of  claim 63 , wherein a separation reaction performed within the separation channel comprises isoelectric focusing (IEF), capillary zone electrophoresis (CZE), capillary gel electrophoresis (CGE), capillary isotachophoresis (CITP), or micellar electrokinetic chromatography (MEKC). 
     
     
         65 . The computer-implemented method of  claim 63 , wherein the two or more images comprise ultraviolet light absorbance images, visible light absorbance images, or fluorescence images. 
     
     
         66 . The computer-implemented method of  claim 63 , wherein the separation channel outlet is in fluid communication with or comprises an electrospray interface with a mass spectrometer. 
     
     
         67 . The computer-implemented method of  claim 63 , wherein the time at which the analyte peak reaches the separation channel outlet is used to correlate mass spectrometer data with the analyte peak. 
     
     
         68 . The computer-implemented method of  claim 63 , wherein the analyte is separated from a mixture and comprises a protein, a protein-drug conjugate, a peptide, a nucleic acid molecule, a carbohydrate molecule, a lipid molecule, a metabolite molecule, or a small organic compound. 
     
     
         69 . The computer-implemented method of  claim 63 , wherein a comparison of mass spectrometer data collected for samples of a biologic drug candidate and a reference drug is used to make a determination of biosimilarity. 
     
     
         70 . The computer-implemented method of  claim 63 , wherein the velocity of the analyte peak is used in a feedback loop to adjust a control parameter for a separation reaction performed in the separation channel. 
     
     
         71 . The computer-implemented method of  claim 70 , wherein the control parameter is a voltage. 
     
     
         72 . The computer-implemented method of  claim 70 , wherein the feedback loop operates at a frequency of at least 0.1 Hz.