Large volume sample injection for liquid chromatography

Patent metadata

Field	Value
Publication number	US-2021302396-A1
Application number	US-202117210924-A
Country	US
Kind code	A1
Filing date	Mar 24, 2021
Priority date	Mar 31, 2020
Publication date	Sep 30, 2021
Grant date	—

Abstract

Described are methods and fluidic networks for injecting a sample into a liquid chromatography system. The method may be applied for separations in which increased sensitivity is desired and a large sample volume in a strong solvent is to be injected. The method may include merging a flow of a solvent having a sample dissolved therein with a flow of a diluent. The merging occurs in a fluidic path to an injection valve. The full amount of sample previously contained in a smaller volume of solvent is maintained in a larger volume of a diluted sample that includes the strong solvent and the diluent. The entire volume of the diluted sample is loaded into a sample loop coupled to the injection valve and subsequently injected into the system flow of the chromatography system.

First claim

What is claimed is:

1 . A method for injecting a sample into a liquid chromatography system, the method comprising:
providing a first diluent flow in a fluid path coupled to an injection valve having a plurality of ports and a sample loop coupled between two of the ports, the injection valve being in a first valve state to conduct a chromatography system flow through the sample loop, the fluid path having an end coupled to one of the ports, merging a sample flow with the first diluent flow to create a flow of a diluted sample in the fluid path, the sample flow comprising a sample dissolved in a solvent and the diluted sample having a diluted sample volume; terminating the sample flow and the first diluent flow so that the fluid path contains a first volume of diluent followed by the diluted sample; switching the injection valve to a second valve state in which the fluid path is coupled to the sample loop; providing a second diluent flow to the fluid path to push an entirety of the diluted sample from the fluid path into the sample loop, wherein at least a portion of the diluent in the first diluent flow and a portion of the diluent in the second diluent flow are in the sample loop; and switching the injection valve to the first valve state, wherein the sample loop is inserted into the system flow to thereby inject the entirety of the diluted sample volume into the system flow.

2 . The method of claim 1 further comprising drawing the sample from a sample source prior to merging the sample flow with the portion of the first flow of the diluent.

3 . The method of claim 1 wherein the sample volume is at least 1 microliter.

4 . The method of claim 1 wherein the first diluent flow and the second diluent flow are flows of a same diluent.

5 . The method of claim 1 wherein the sample flow and the first diluent flow are terminated at a same time.

6 . The method of claim 1 wherein the sample flow is terminated before the first diluent flow so that the fluid path contains a first volume of diluent followed by the diluted sample volume followed by a second volume of diluent.

7 . The method of claim 1 wherein the diluted sample has a diluted sample volume that is equal to the sum of the merged volumes of sample and diluent.

8 . The method of claim 1 further comprising providing a flow of a wash solvent through the fluid path coupled to the injection valve.

9 . A fluidic network for injecting a diluted sample into a liquid chromatography system, comprising:
an injection valve having a plurality of ports wherein one of the ports is configured to receive a system flow of a liquid chromatography system and another one of the ports is configured to provide the system flow, the injection valve being configurable in at least two valve states and comprising a sample loop coupled at each end to one of the ports; a sample needle; an injection block; a sample syringe configured to aspirate and to dispense a sample; a sample syringe valve operable in at least two valve states, wherein, when the sample syringe valve is in a first valve state, the sample syringe is coupled to the sample needle; a diluent syringe configured to aspirate and to dispense a diluent; a diluent syringe valve operable in at least two valve states, wherein, when the diluent syringe valve is in a first valve state, the diluent syringe is coupled through the injection block and a fluid path to a port of the injection valve and wherein, when the diluent syringe valve is in a second valve state, the diluent syringe is coupled to a source of diluent; and a processor in communication with the injection valve, the sample syringe and the diluent syringe, the processor controlling the valve state of the injection valve, a flow rate of a sample flow from the sample syringe and a flow rate of a diluent flow from the diluent syringe.

10 . The fluidic network of claim 9 and wherein, when the sample syringe valve is in a second valve state, the sample syringe is coupled to a source of wash solvent.

11 . The fluidic network of claim 9 , wherein the sample needle is movable to enable coupling of the sample syringe valve to the injection block and to a source of sample.

12 . The fluidic network of claim 9 , wherein the sample loop has a volume of at least 10 microliters.

13 . The fluidic network of claim 9 , wherein the sample loop has a volume that does not exceed one milliliter.

14 . The fluidic network of claim 9 further comprising a wash tower coupled to the injection block and configured to receive the sample needle.

15 . A fluidic network for injecting a diluted sample into a liquid chromatography system, comprising:
an injection valve having a plurality of ports wherein one of the ports is configured to receive a system flow of a liquid chromatography system and another one of the ports is configured to provide the system flow, the injection valve being configurable in at least two valve states and comprising a sample loop coupled at each end to one of the ports; a sample needle; a sample syringe in communication with the sample needle and configured to aspirate a sample through the sample needle and to dispense a sample into a fluid path to the injection valve; a diluent syringe configured to aspirate a diluent from a source of diluent and to dispense the diluent into the fluid path to the injection valve; and a processor in communication with the injection valve, the sample syringe and the diluent syringe, the processor controlling the valve state of the injection valve, a flow rate of a sample flow from the sample syringe and a flow rate of a diluent flow from the diluent syringe, wherein a diluted sample is created by a merging of the sample flow and the diluent flow in the fluid path to the injection valve.

16 . The fluidic network of claim 15 , wherein the sample loop has a volume of at least 100 microliters.

17 . The fluidic network of claim 15 , wherein the sample needle is movable to enable coupling of the sample syringe valve to the fluid path to the injection valve and to a source of sample.

Assignees

• Waters Technologies Corp

Inventors

• Cormier Sylvain Gilles
• Hill Jason F

Classifications

• G01N2030/201

  multiport valves, i.e. having more than two ports · CPC title

• G01N2030/202

  rotary valves · CPC title

• G01N30/26

  Conditioning of the fluid carrier; Flow patterns · CPC title

• G01N30/20 Primary

  using a sampling valve · CPC title

• G01N2030/207

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