Bubble based sample isolation in a transport liquid

Patent metadata

Field	Value
Publication number	US-12548747-B2
Application number	US-202218550016-A
Country	US
Kind code	B2
Filing date	Mar 22, 2022
Priority date	Mar 23, 2021
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

A method of evacuating a liquid sample from an open port interface (OPI) via a pressure drop includes applying the pressure drop to a transport liquid. This application generates a plurality of bubbles in the transport liquid during evacuation of the transport liquid from the OPI via a transfer conduit. The liquid sample is separated from a subsequent liquid sample by at least one of the generated bubbles.

First claim

What is claimed is:

1 . A method of separating samples received in an open port interface (OPI), the method comprising:
delivering a transport liquid to the OPI at a first flow rate, wherein the OPI is disposed in an atmosphere; aspirating the transport liquid from the OPI via a transfer conduit at a first pressure, so as to introduce a plurality of first bubbles into the transport fluid, wherein the plurality of first bubbles are introduced from the atmosphere and into the transfer conduit, wherein the plurality of first bubbles are generated at a first frequency; introducing a sample from a sample holder into the OPI, wherein the introduction of the sample terminates the generation of the plurality of first bubbles; and aspirating the sample and the transport liquid from the OPI via the transfer conduit at the first pressure, wherein the sample and at least a portion of the transport liquid are bounded on a leading end by one of the plurality of first bubbles and on a trailing end by one of a plurality of second bubbles.

2 . The method of claim 1 , further comprising, subsequent to aspirating the sample and the transport liquid from the OPI, aspirating the transport liquid from the OPI via the transfer conduit at the first pressure, so as to introduce the plurality of second bubbles into the transport fluid, wherein the plurality of second bubbles are introduced from the atmosphere and into the transfer conduit, wherein the plurality of second bubbles are generated at a second frequency.

3 . The method of claim 2 , wherein the second frequency is equal to the first frequency.

4 . The method of claim 1 , wherein the first flow rate comprises a range of about 10 uL/min to about 5 mL/min.

5 . The method of claim 1 , wherein the first pressure comprises a range of about 0.1 psi to about 14.7 psi.

6 . The method of claim 1 , wherein the first frequency comprises a range of about 0.1 Hz to about 10 kHz.

7 . The method of claim 1 , wherein delivering the transport liquid to the OPI at the first flow rate, aspirating the transport liquid from the OPI via the transfer conduit at the first pressure, and introducing the sample from the sample holder into the OPI are performed substantially simultaneously.

8 . The method of claim 1 , wherein delivering the transport liquid to the OPI at the first flow rate, introducing the sample from the sample holder into the OPI, and aspirating the sample and the transport liquid from the OPI via the transfer conduit at the first pressure are performed substantially simultaneously.

9 . The method of claim 1 , wherein the sample comprises a plurality of sub-samples.

10 . A method of evacuating a liquid sample from an open port interface (OPI) with a pressure drop, the method comprising applying the pressure drop to a transport liquid to generate a plurality of bubbles in the transport liquid during evacuation of the transport liquid from the OPI via a transfer conduit, wherein the liquid sample is separated from a subsequent liquid sample by at least one bubble.

11 . The method of claim 10 , further comprising generating the pressure drop by ejecting at least one of the transport liquid and the sample from an electrospray ionization (ESI) electrode disposed at an opposite end of the transfer conduit from the OPI.

12 . The method of claim 10 , further comprising delivering to the OPI the transport liquid during application of the pressure drop.

13 . The method of claim 10 , wherein applying the pressure drop to the transport liquid generates a flow rate of transport liquid through the transfer conduit corresponding to about 50% to about 90% of a flow rate based on the Hagen-Poiseuille equation.

14 . The method of claim 10 , wherein applying the pressure drop to the transport liquid generates a flow rate of transport liquid through the transfer conduit of no less than about 50% of a flow rate based on the Hagen-Poiseuille equation.

15 . The method of claim 10 , wherein applying the pressure drop to the transport liquid generates a flow rate of transport liquid through the transfer conduit of no greater than about 90% of a flow rate based on the Hagen-Poiseuille equation.

16 . The method of claim 11 , where the ESI electrode comprises a nebulizer-assisted ESI electrode, and the pressure drop is generated by a nebulizer gas expanding past an opposite end of the transfer conduit.

17 . The method of claim 11 , wherein the liquid sample comprises a first portion on a first side of a first bubble of the plurality of bubbles and a second portion on a second side of the plurality of bubbles.

18 . A method of separating samples received in an open port interface (OPI), the method comprising:
delivering a transport liquid to the OPI at a first flow rate, wherein the OPI is disposed in an atmosphere; aspirating the transport liquid from the OPI via a transfer conduit at a first pressure, so as to generate a plurality of bubbles in the transport fluid, wherein the plurality of bubbles are introduced from the atmosphere and into the transfer conduit, wherein the plurality of bubbles are generated at a first frequency; introducing a first sample from a sample holder into the OPI; and aspirating the first sample and the transport liquid from the OPI via the transfer conduit at the first pressure, wherein the first sample and at least a portion of the transport liquid form a first aliquot bounded on a leading end by a first one of the plurality of bubbles and on a trailing end by a second one of the plurality of bubbles.

19 . The method of claim 18 , further comprising:
introducing a second sample from the sample holder into the OPI; and aspirating the second sample and the transport liquid from the OPI via the transfer conduit at the first pressure, wherein the second sample and at least a portion of the transport liquid form a second aliquot bounded on a leading end by the second one of the plurality of bubbles and on a trailing end by a third one of the plurality of bubbles.

20 . The method of claim 18 , wherein each bubble of the plurality of bubbles are separated at a uniform frequency.

Assignees

• Dh Technologies Dev Pte Ltd

Inventors

• Kovarik Peter
• Schneider Bradley B
• Covey Thomas R

Classifications

• H01J49/165

  Electrospray ionisation · CPC title

• H01J49/0431

  for liquid samples (interfaces to liquid chromatographs G01N30/7233) · CPC title

• H01J49/0404 Primary

  Capillaries used for transferring samples or ions (electrospray nozzles H01J49/167) · CPC title