Bracketing fluidic sample using strong solvent

Patent metadata

Field	Value
Publication number	US-12510518-B2
Application number	US-202117913313-A
Country	US
Kind code	B2
Filing date	Mar 15, 2021
Priority date	Mar 24, 2020
Publication date	Dec 30, 2025
Grant date	Dec 30, 2025

Abstract

A sample separation device for separating a fluidic sample includes a fluid drive for driving a mobile phase and the fluidic sample when injected in the mobile phase, a sample separation unit for separating the fluidic sample in the mobile phase, and a control unit configured for bracketing the fluidic sample between two mobile phase portions of the mobile phase. At least one of the mobile phase portions is arranged directly next to the fluidic sample and has a higher solvent strength compared to a solvent of the fluidic sample.

First claim

The invention claimed is:

1 . A method of separating a fluidic sample, the method comprising:
providing a sample separation device comprising a fluid drive and a sample separation unit downstream from the fluid drive along a flow path; forming a fluid packet sequence comprising the fluidic sample bracketed between two mobile phase portions, wherein:
one of the two mobile phase portions follows the fluidic sample and the other of the two mobile phase portions leads the fluidic sample;
the fluidic sample has a first solvent strength; and
at least one of the two mobile phase portions is arranged directly next to the fluidic sample and has a second solvent strength higher than the first solvent strength;
driving a further mobile phase having a third solvent strength by the fluid drive along the flow path toward the sample separation unit, wherein the second solvent strength is higher than the third solvent strength; while driving the further mobile phase having the third solvent strength, injecting the fluid packet sequence into the flow path at a point between the fluid drive and the sample separation unit, wherein:
the further mobile phase having the third solvent strength comprises one further mobile phase portion following the one of the two mobile phase portions that follows the fluidic sample, and another further mobile phase portion leading the other of the two mobile phase portions that leads the fluidic sample; and
the fluid packet sequence is driven with the another further mobile phase having the third solvent strength toward the sample separation unit; and

separating the fluidic sample into different fractions by the sample separation unit.

2 . The method according to claim 1 , wherein the at least one of the two mobile phase portions with the second solvent strength comprises a mobile phase portion arranged in a flowing direction directly behind the fluidic sample.

3 . The method according to claim 2 , wherein the mobile phase portion arranged in the flowing direction directly behind the fluidic sample is driven through the sample separation unit.

4 . The method according to claim 1 , wherein the at least one of the two mobile phase portions with the second solvent strength comprises a mobile phase portion arranged in a flowing direction directly before the fluidic sample.

5 . The method according to claim 4 , wherein the mobile phase portion arranged in the flowing direction directly before the fluidic sample is prevented from flowing through the sample separation unit.

6 . The method according to claim 1 , wherein, of the two mobile phase portions bracketing the fluidic sample, one of the two mobile phase portions has the second solvent strength, and the other of the two mobile phase portions has a lower solvent strength compared to the first solvent strength of the fluidic sample.

7 . The method according to claim 1 , wherein the two mobile phase portions bracketing the fluidic sample each are arranged directly next to the fluidic sample and have the second solvent strength.

8 . The method according to claim 1 , wherein the third solvent strength of the further mobile phase is lower than the first solvent strength of the fluidic sample.

9 . The method according to claim 1 , comprising composing the further mobile phase to reduce a solvent strength profile between the fluidic sample and the at least one of the two mobile phase portions having the second solvent strength before the fluidic sample reaches the sample separation unit, by dilution with the further mobile phase having the third solvent strength.

10 . The method according to claim 1 , comprising composing the further mobile phase to selectively modify a dilution factor of the fluidic sample over time.

11 . The method according to claim 1 , wherein:
after the fluidic sample reaches the sample separation unit, at least part of the fluidic sample is adsorbed on the sample separation unit; and the method comprises releasing the at least part of the fluidic sample adsorbed on the sample separation unit by driving an eluent through the sample separation unit, wherein the eluent is driven through only part of conduits flown through by the fluidic sample before the fluidic sample reaches the sample separation unit.

12 . The method according to claim 1 , comprising injecting the fluidic sample into the flow path towards the sample separation unit by combining, at a fluidic coupling point, the fluidic sample with one or both of the two mobile phase portions bracketing the fluidic sample.

13 . The method according to claim 1 , comprising, after separating the fluidic sample in the mobile phase into different fractions by the sample separation unit, transferring one or more of the different fractions to a further sample separation unit to separate the transferred one or more of the different fractions.

14 . The method according to claim 1 , comprising injecting the fluidic sample into the flow path towards the sample separation unit by combining, at a fluidic coupling point, the fluid packet sequence with the further mobile phase.

15 . A method of separating a fluidic sample, the method comprising:
providing a sample separation device comprising a fluid drive and a sample separation unit downstream from the fluid drive along a flow path; forming a fluid packet sequence comprising the fluidic sample bracketed between two mobile phase portions, and at least one additional mobile phase portion, wherein:
one of the two mobile phase portions follows the fluidic sample and the other of the two mobile phase portions leads the fluidic sample;
the fluidic sample has a first solvent strength; and
at least one of the two mobile phase portions has a second solvent strength higher than the first solvent strength;
the at least one additional mobile phase portion is arranged directly next to the fluidic sample, and is interposed between the fluidic sample and the one of the two mobile phase portions that follows the fluidic sample;
driving a further mobile phase having a third solvent strength by the fluid drive along the flow path toward the sample separation unit, wherein the second solvent strength is higher than the third solvent strength; while driving the further mobile phase having the third solvent strength, injecting the fluid packet sequence into the flow path at a point between the fluid drive and the sample separation unit, wherein:
the further mobile phase having the third solvent strength comprises one further mobile phase portion following the one of the two mobile phase portions that follows the fluidic sample, and another further mobile phase portion leading the other of the two mobile phase portions that leads the fluidic sample;
the at least one additional mobile phase portion has a fourth solvent strength lower than the first solvent strength; and
the fluid packet sequence is driven with the another further mobile phase having the third solvent strength toward the sample separation unit; and
separating the fluidic sample into different fractions by the sample separation unit.

16 . The method according to claim 15 , wherein:
the at least one additional mobile phase portion directly next to the fluidic sample, and interposed between the fluidic sample and the one of the two mobile phase portions that follows the fluidic sample, is a first additional mobile phase portion; and the at least one additional mobile phase portion comprises a second additional mobile phase portion arranged directly next to the fluidic sample, interposed between the fluidic sample and the one

Assignees

• Agilent Technologies Inc

Inventors

• Stoll Dwight Robert
• Buckenmaier Stephan
• Lege Sascha
• Ortmann Thomas
• Shoykhet Konstantin

Classifications

• G01N30/463

  for multidimensional chromatography · CPC title

• G01N30/20 Primary

  using a sampling valve · CPC title

• B01D15/166 Primary

  Fluid composition conditioning, e.g. gradient · CPC title

• B01D15/14

  relating to the introduction of the feed to the apparatus · CPC title

• G01N30/34 Primary

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