# US 10,373,816 B2 · Method for enhancing electrospray

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- Number: US 10,373,816 B2
- Document ID: US10373816B2
- Status: Granted
- Kind: B2
- Application number: 15/461,337
- Filed: 2017-03-16
- Published: 2017-11-16
- Granted: 2019-08-06
- Earliest claimed: 2016-05-13
- Assignees: Agilent Technologies, Inc.
- Applicants: Agilent Technologies, Inc.; Memorial Sloan Kettering Cancer Center
- Inventors: Steven M. Fischer; Justin R. Cross
- Web page: https://patentgrep.com/patent/US10373816B2

## CPC

- H01J 49/165: {Electrospray ionisation}
- H01J 49/0027: {Methods for using particle spectrometers}
- H01J 49/0431: {for liquid samples (interfaces to liquid chromatographs G01N30/7233)}
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

Provided herein, among other things, is a method of ionizing a first stream of liquid by an electrospray ion source having a nebulizer, wherein the first stream of liquid may comprise an analyte. In some embodiments, the method may comprise: a) providing the first stream of liquid to the nebulizer; b) adding a second stream of liquid to the first stream of liquid, wherein the second stream of liquid comprises a co-solvent that has a relatively high boiling point and an enhancement solvent that a relatively high boiling; and c) nebulizing and ionizing the resulting liquid.

## Claims

### Claim 1

A method of ionizing a first stream of liquid by an electrospray ion source having a nebulizer, wherein the first stream of liquid may comprise an analyte, the method comprising:
a) providing the first stream of liquid to the nebulizer;
b) adding a second stream of liquid to the first stream of liquid in the nebulizer, at an input end of the nebulizer, or upstream of the nebulizer; and wherein the second stream of liquid comprises a mixture of a co-solvent and an enhancement solvent, the co-solvent having a boiling point between 4° C. and 110° C., and the enhancement solvent having a boiling point between 150° C. and 300° C.; and
c) nebulizing and ionizing the resulting liquid,
wherein, if the enhancement solvent is DMSO, then the electrospray ion source is run in negative ion mode.

### Claim 2 (depends on 1)

The method of claim 1, wherein the electrospray ion source is operated in negative ion mode.

### Claim 3 (depends on 1)

The method of claim 1, wherein the electrospray ion source is operated in positive ion mode and the enhancement solvent is not DMSO.

### Claim 4 (depends on 1)

The method of claim 1, wherein the boiling point of the co-solvent is between 4° C. and 70° C.

### Claim 5 (depends on 1)

The method of claim 1, wherein the co-solvent is selected from the group consisting of acetone, acetonitrile, ethanol, isopropanol and THF.

### Claim 6 (depends on 1)

The method of claim 1, wherein the co-solvent is acetone.

### Claim 7 (depends on 1)

The method of claim 1, wherein the boiling point of the enhancement solvent is between 150° C. and 200° C.

### Claim 8 (depends on 1)

The method of claim 1, wherein the enhancement solvent is selected from the group consisting of DMSO, 2-(2-methoxyethoxy)ethanol and propylene glycol.

### Claim 9 (depends on 1)

The method of claim 1, wherein the enhancement solvent is DMSO.

### Claim 10 (depends on 1)

The method of claim 1, wherein the relative concentration (v/v) of the enhancement solvent to the co-solvent in the second stream of liquid is in the range of 1% to 25% (enhancement solvent):75% to 99% (co-solvent).

### Claim 11 (depends on 1)

The method of claim 1, wherein the relative concentration (v/v) of the enhancement solvent to the co-solvent in the second stream of liquid is in the range of 5% to 15% (enhancement solvent):80% to 95% (co-solvent).

### Claim 12 (depends on 1)

The method of claim 1, wherein the combined concentration of the enhancement solvent and co-solvent in the resulting liquid of (c) is in the range of 1% to 90%.

### Claim 13 (depends on 1)

The method of claim 1, wherein the combined final concentration of the enhancement solvent and co-solvent in the resulting liquid of (c) is in the range of 40% to 60%.

### Claim 14 (depends on 1)

The method of claim 1, wherein the resulting liquid is nebulized at a rate in the range of 50 μl/min to 400 μl/min.

### Claim 15 (depends on 1)

The method of claim 1, wherein the nebulizing is gas-assisted.

### Claim 16 (depends on 1)

The method of claim 1, further comprising separating a sample to produce the first stream of liquid.

### Claim 17 (depends on 16)

The method of claim 16, wherein the separating is done by liquid chromatography, supercritical fluid chromatography or capillary electrophoresis.

### Claim 18 (depends on 1)

The method of claim 1, wherein the first stream of liquid comprises a sample in which analytes have not been separated.

### Claim 19 (depends on 1)

The method of claim 1, further comprising analyzing the ionized sample by mass spectrometry.

### Claim 20 (depends on 19)

The method of claim 19, wherein addition of the second stream of liquid to the first stream of liquid results in an increase in sensitivity of detection of the ionized analyte.