Multidimensional sample separation with pressure adjustment

Patent metadata

Field	Value
Publication number	US-11933769-B2
Application number	US-201917051701-A
Country	US
Kind code	B2
Filing date	Apr 30, 2019
Priority date	Apr 30, 2018
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

A multidimensional sample separation apparatus includes a first separation dimension for separating a fluidic sample, a second separation dimension for further separating the fluidic sample, a switching mechanism, and a control unit. The first separation dimension includes a first fluid drive unit and a first sample separation unit. The second separation dimension includes a second fluid drive unit for driving the separated fluidic sample, and second and third sample separation units each configured for further separating the separated fluidic sample. The switching mechanism is configured for selectively switching an outlet of the first separation dimension in fluid communication with a selected one of the second sample separation unit and/or the third sample separation unit. The control unit is configured for controlling a pressure at inlets of the second sample separation unit and the third sample separation unit to be substantially the same at least at the time of the switching.

First claim

The invention claimed is:

1. A multidimensional sample separation apparatus for separating a fluidic sample, the sample separation apparatus comprising:
a first separation dimension for separating the fluidic sample and comprising a first fluid drive unit configured to drive the fluidic sample and a first sample separation unit configured to separate the fluidic sample;
a second separation dimension for further separating the fluidic sample separated by the first separation dimension, wherein the second separation dimension comprises a second fluid drive unit configured to drive the separated fluidic sample and a second sample separation unit and a third sample separation unit each configured to further separate the separated fluidic sample;
a switching mechanism configured to selectively switch an outlet of the first separation dimension in fluid communication with at least one selected one of the second sample separation unit and the third sample separation unit; and
a control unit configured to control a pressure at inlets of the second sample separation unit and the third sample separation unit to be substantially the same at least at the time of the switching.

2. The sample separation apparatus according to claim 1 , configured as a two-dimensional liquid chromatography sample separation apparatus.

3. The sample separation apparatus according to claim 1 , wherein the control unit is configured for controlling pressure values at the inlets of the second sample separation unit and of the third sample separation unit to differ at least at the time of the switching by less than 10%.

4. The sample separation apparatus according to claim 1 , wherein the control unit is configured to control a difference between pressure values at the inlets of the second sample separation unit and of the third sample separation unit to be, at least at the time of the switching, less than 100 bar.

5. The sample separation apparatus according to claim 1 , wherein the control unit is configured to control pressure values at the inlet of the second sample separation unit and at the inlet of the third sample separation unit, at least at the time of the switching, to be at least 1000 bar.

6. The sample separation apparatus according to claim 1 , wherein the control unit is configured to control pressure values at the inlet of the second sample separation unit and at the inlet of the third sample separation unit to be substantially the same over an entire operation of the sample separation apparatus.

7. The sample separation apparatus according to claim 1 , wherein the control unit is configured to control pressure values at the inlet of the second sample separation unit and at the inlet of the third sample separation unit to be substantially at a predefined pressure value at least at the time of switching.

8. The sample separation apparatus according to claim 1 , wherein the switching mechanism is configured to alternatingly couple the outlet of the first separation dimension to the second sample separation unit and the third sample separation unit, respectively.

9. The sample separation apparatus according to claim 1 , wherein the switching mechanism comprises at least one fluidic valve being switchable under control of the control unit.

10. The sample separation apparatus according to claim 1 , wherein the switching mechanism comprises at least one fluidic restriction being adjustable under control of the control unit.

11. The sample separation apparatus according to claim 1 , comprising a first dimension detector coupled to an outlet of the first sample separation unit.

12. The sample separation apparatus according to claim 1 , comprising a second dimension detector arranged downstream of the second sample separation unit and being configured for detecting the further separated fluidic sample.

13. The sample separation apparatus according to claim 1 , comprising at least one fluidic restriction downstream of the third sample separation unit and configured to at least partially equilibrate a pressure at the second sample separation unit and a pressure at the third sample separation unit, wherein the at least one fluidic restriction comprises a feature selected from the group consisting of: a fluidic restriction switchable between outlets of the second sample separation unit and of the third sample separation unit; and two adjustable fluidic restrictions.

14. The sample separation apparatus according to claim 1 , wherein the second fluid drive unit is configured to provide a flow rate being larger than another flow rate provided by the first fluid drive unit.

15. The sample separation apparatus according to claim 1 , comprising a third fluid drive unit fluidically connected between an outlet of the first sample separation unit and an inlet of at least one of the second sample separation unit and the third sample separation unit.

16. The sample separation apparatus according to claim 15 , wherein the third fluid drive unit is configured to dilute the pre-separated fluidic sample prior to the further separation.

17. The sample separation apparatus according to claim 15 , wherein the control unit is configured to control the sample separation apparatus so that a sum of a flow rate of the first fluid drive unit and a flow rate of the third fluid drive unit is substantially the same as a flow rate of the second fluid drive unit.

18. The sample separation apparatus according to claim 15 , wherein the first fluid drive unit, the second fluid drive unit and the third fluid drive unit are fluidically interconnectable or switchable via the switching mechanism.

19. The sample separation apparatus according to claim 1 , wherein the switching mechanism is configured to place the second sample separation unit and the third sample separation unit in fluid communication with each other at least at the time of the switching.

20. A method of operating a multidimensional sample separation apparatus for separating a fluidic sample, the method comprising:
separating the fluidic sample by a first separation dimension comprising a first fluid drive unit for driving the fluidic sample and a first sample separation unit for separating the fluidic sample;
after separating the fluidic sample by the first separation dimension, supplying the separated fluidic sample to a second separation dimension for further separating the fluidic sample, wherein the second separation dimension comprises a second fluid drive unit for driving the separated fluidic sample and comprises a second sample separation unit and a third sample separation unit each of which being configured for further separating the separated fluidic sample; and
for further separating the fluidic sample by the second separation dimension, switching an outlet of the first separation dimension in fluid communication with at least one selected one of the second sample separation unit and the third sample separation unit so that an inlet pressure of the second sample separation unit and of the third sample separation unit is substantially the same at least at the point of time of switching.

Assignees

• Agilent Technologies Inc

Inventors

• Stoll Dwight Robert
• Witt Klaus
• Shoykhet Konstantin

Classifications

• G01N30/32 Primary

  of pressure or speed (G01N30/36 takes precedence) · CPC title

• G01N30/463 Primary

  for multidimensional chromatography · CPC title

• G01N30/466

  with separation columns in parallel · CPC title

• G01N30/468

  involving switching between different column configurations · CPC title