Mixer bypass sample injection for liquid chromatography

Patent metadata

Field	Value
Publication number	US-10209229-B2
Application number	US-201815910414-A
Country	US
Kind code	B2
Filing date	Mar 2, 2018
Priority date	Nov 30, 2012
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

Abstract

In a liquid chromatography system, a sample is injected into a column by flowing a solvent mixture from a mixer into the column along a solvent mixture flow path; and injecting a sample into the solvent mixture flow path downstream of the mixer. In another liquid chromatography system, a sample is injected into a column by loading an isolator fluid into a sample loop, loading a sample into the sample loop, and flowing the sample into the column as a plug in front of the isolator fluid.

First claim

What is claimed is:

1. A method for injecting a sample into a flow of a liquid chromatography system, the method comprising:
providing a flow of a mobile phase in a mobile phase flow path at a mobile phase pressure;
providing a fluidic junction in the mobile phase flow path, the fluidic junction communicating with a sample injection line and a chromatographic column;
pressurizing a sample injection flow path, containing a sample, to a pressure matching the mobile phase pressure;
connecting the sample injection flow path to the mobile phase flow path via the sample injection line and the fluidic junction;
combining a flow of the pressurized sample injection flow path with the flow of the mobile phase at the fluidic junction to control a degree of sample-band focusing.

2. The method of claim 1 , further comprising
injecting the sample from the sample injection flow path into the fluidic junction and thereby bypassing a solvent mixer.

3. The method of claim 1 , further comprising:
flowing a first solvent and a second solvent into a mixer to form a solvent mixture;
flowing the solvent mixture into the chromatographic column; and
while flowing the solvent mixture, injecting the sample into the column downstream from the mixer.

4. The method of claim 3 , wherein
the first solvent is selected from the group consisting of a weak solvent, water, an aqueous buffer fluid, and a supercritical or near supercritical fluid; and
the second solvent is selected from the group consisting of a strong solvent, an organic solvent, an alcohol, and a polar solvent.

5. The method of claim 1 , wherein combining comprises flowing the sample as a plug in front of an isolator fluid.

6. The method of claim 5 , wherein the isolator fluid is selected from the group consisting of a highly fluorinated fluid and a perfluorinated fluid.

7. The method of claim 1 , comprising loading an injection solvent into an injector valve and loading a sample into a sample loop communicating with the injection valve, wherein injecting comprises pushing the sample from the sample loop.

8. A method for injecting a sample into a solvent mixture path to a separation column of a liquid chromatography system, the method comprising:
establishing a solvent mixture flow into the column along a solvent mixture flow path at a solvent mixture flow path pressure;
providing a fluidic junction in the mobile phase flow path, the fluidic junction communicating with a sample injection line and a chromatographic column;
pressurizing a sample injection flow path, containing a sample, to a pressure matching the solvent mixture flow path pressure;
connecting the pressurized sample injection flow path to the solvent mixture flow path via the sample injection line and the fluidic junction; and
controlling a degree of sample-band focusing by controlling a pumping of the sample in the pressurized sample injection flow path into the solvent mixture flow path at the fluidic junction.

9. The method of claim 8 , further comprising
injecting the sample from the sample injection flow path into the fluidic junction and thereby bypassing a solvent mixer.

10. The method of claim 8 , wherein establishing a solvent mixture flow comprises:
flowing a first solvent and a second solvent into a mixer to form a solvent mixture;
flowing the solvent mixture into the chromatographic column; and
while flowing the solvent mixture, injecting the sample into the column downstream from the mixer.

11. A system for injecting a sample into a flow of a liquid chromatography system, the system comprising:
a chromatographic column;
a syringe configured to dispense a sample;
a first fluid channel configured to conduct a mobile phase;
a second fluid channel configured to receive the sample, and communicating with the syringe;
a junction comprising a first port communicating with the first fluid channel, a second port communicating with the second fluid channel, and a third port communicating with the chromatographic column; and
a controller configured to control pressurizing the second fluid channel and to control a degree of sample-band focusing by controlling a combining of the flow of the pressurized second fluid channel with a flow of the mobile phase in the first fluid channel, wherein the sample flows with the mobile phase into the chromatographic column.

12. The system of claim 11 , further comprising:
a first solvent source;
a second solvent source;
a mixer communicating with the first solvent source via a first solvent line, with the second solvent source via a second solvent line, and with the column via a solvent mixture line; and
an injection valve comprising a sample loop separate from the solvent mixture line and communicating with the junction and an injection solvent source, wherein the injection valve is adjustable to a sample injection position that defines a flow path for an injection solvent through the sample loop and to the junction, such that the injection solvent carries the sample in the sample loop into the solvent mixture line downstream from the mixer and therefore bypassing the mixer.

13. The system of claim 12 , further comprising a sample source communicating with the injection valve, wherein the injection valve is adjustable to a sample load position that defines a flow path for a sample to flow into the sample loop.

14. The system of claim 13 , further comprising an isolator fluid source communicating with the injection valve, wherein the injection valve is adjustable to an isolator fluid load position that defines a flow path for an isolator fluid to flow into the sample loop, and wherein at the sample injection position the isolator fluid pushes the injection solvent and the sample into the solvent mixture line.

15. The system of claim 11 , comprising:
an injection valve for injection of the sample into the second fluid channel; and
the syringe comprises a fluid moving device communicating with the injection valve, wherein the injection valve is adjustable to a pressurizing position at which the fluid moving device pressurizes the sample loop.

16. The LC system of claim 15 , comprising a configuration selected from the group consisting of:
a pressure transducer configured for measuring pressure in the sample loop, and a controller configured for controlling the fluid moving device based on pressure measurement signals received from the pressure transducer; and
a first pressure transducer configured for measuring pressure in the sample loop, a second pressure transducer configured for measuring pressure in the solvent mixture line, and a controller configured for controlling the fluid moving device based on comparing pressure measurement signals received from the first pressure transducer and the second pressure transducer.

17. The system of claim 11 , wherein the fluidic junction in the solvent mixture line is a first fluidic junction, and further comprising a flow restrictor in the second solvent line and a second fluidic junction between the second solvent source and the flow restrictor, and wherein:
the second solvent source comprises an injection solvent source; and
the flow path defined by the sample injection position runs from the second solvent source, through the sample loop and to the second fluidic junction, such that the second solvent carries the sample into the solvent mixture line.

18. The system of claim 11 , wherein the syringe comprises a fluid moving device communicating with the sample loop and configured for selectively pulling fluid into the sample loop a

Assignees

• Agilent Technologies Inc

Inventors

• Albrecht Jr Robert William

Classifications

• G01N2030/027

  Liquid chromatography · CPC title

• G01N30/20 Primary

  using a sampling valve · CPC title

• G01N2030/347

  mixers · CPC title

• G01N30/34

  of fluid composition, e.g. gradient (G01N30/36 takes precedence) · CPC title

• G01N2030/207

  with metering cavity, e.g. sample loop · CPC title