Microcolumnar analytical apparatus with microcolumnar flow gating interface and method of using the apparatus

• US 5,646,048 A
• Filed: 07/24/1995
• Issued: 07/08/1997
• Est. Priority Date: 07/24/1995
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Hewlett-Packard Company (HP Inc.)
• Inventors: Templin, Catherine Keely, McManigill, Douglass
• Primary Examiner(s): Drodge, Joseph W.
• Application Number:
  US08/505,941
• Time in Patent Office: 715 Days
• Field of Search: 210/95, 210/198.2, 210/656, 210/659, 204/601, 96/104, 96/106, 422/69, 422/70, 422/103, 422/104, 436/161, 436/180, 285/177, 285/911, 285/382, 285/382.1, 285/382.2, 285/382.7
• US Class Current: 436/180
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44773 Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/461 with serial coupling of separation columns
• CPC Class Codes: G01N 30/6039 in series
• CPC Class Codes: G01N 30/6047 with supporting means; Holders
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10S 285/911 Glass
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A microcolumnar analytical apparatus having a flow gating interface system for interfacing a first microcolumn and a second microcolumn is provided. The apparatus includes a flow gating interface, a first fluid conduit (e.g. a liquid chromatograph microcolumn) of a fluid sample, a flush liquid supplier, and a second fluid conduit (e.g. a capillary electrophoresis microcolumn) for analysis of the effluent fluid sample from the first fluid conduit. The flow gating interface includes a first microcolumnar section, a second microcolumnar section, and a channel. The channel, having an inwardly facing wall, encloses at least a portion each of the first microcolumnar section and the second microcolumnar section for conducting a flush fluid flow past the outlet end of the first microcolumnar section and the inlet end of the second microcolumnar section. The inwardly facing wall of the channel nonfixedly constrains and aligns said end portions of the first and second microcolumnar section due to the relative curvature and elasticity of the microcolumnar sections and the channel. The first fluid conduct is connected to and in fluid communication with the first microcolumnar section of the flow gating interface. The second fluid conducting means has a microcolumn. This microcolumn is connected to and in fluid communication with the second microcolumnar section of the flow gating interface. The flush liquid supplier is connected to and in fluid communication with the channel.

Claims

1. A microcolumnar analytical apparatus, comprising:

a flow gating interface comprising;

(A) a first microcolumnar section having a center line, an outlet end portion having an outlet end, and a lumen for conducting a fluid flow;

(B) a second microcolumnar section having a center line, an inlet end portion having an inlet end, and a lumen for conducting a fluid flow; and

(C) a channel having a center line and inwardly facing wall, the channel enclosing at least a portion of the first microcolumnar section and at least a portion of the second microcolumnar section for conducting a flush fluid flow past said ends of the microcolumnar sections, the inwardly facing wall of the channel nonfixedly constraining and aligning said end portions of the first and second microcolumnar sections due to the relative curvature and elasticity of the microcolumnar sections and the channel;

a first fluid conducting means for transferring a fluid sample, the first fluid conducting means being operatively connected to and in fluid communication with the first microcolumnar section;

a flush liquid supply means operatively connected to and in fluid communication with the channel for flowing the flush fluid through the channel; and

a second fluid conducting means for analysis of an effluent fluid sample exiting the first microcolumnar section, the second fluid conducting means having a microcolumn and being operatively connected to and in fluid communication with the second microcolumnar section.

2. The analytical apparatus according to claim 1 wherein the outlet end of the first microcolumnar section is proximate the inlet end of the second microcolumnar section and oriented such that the center lines of the outlet end portion and the inlet end portion are generally parallel to facilitate the transfer of fluid from the outlet end of the first microcolumnar section to the inlet end of the second microcolumnar section when desired.

3. The analytical apparatus according to claim 1 wherein the channel and said end portions of the microcolumnar sections are arranged such that said center lines at a location proximate said ends of said end portions lie on a plane.

4. The analytical apparatus according to claim 1 wherein the channel has one or more arcuate portions such that the curvature of the one or more arcuate portions and the elasticity of the first and second microcolumnar sections cause the wall of the one or more arcuate portions to press on the microcolumnar sections to align the microcolumnar sections so that the center lines of said end portions and the channel are generally parallel.

5. The analytical apparatus according to claim 4 wherein the channel has three or more arcuate portions such that each of the microcolumnar sections is pressed by two adjacent but generally oppositely directing arcuate portions on the wall of each of the microcolumnar sections so that said ends of the first and second microcolumnar sections are proximate and the center lines of the sections at said ends are collinear.

6. The analytical apparatus according to claim 1 wherein the channel has an arcuate portion such that the curvature of the arcuate portion and the elasticity of the first and second microcolumnar sections cause said ends of the microcolumnar sections to rest against the wall of the channel such that the center lines of the microcolumnar sections at said ends are substantially collinear with each other but are offset from the center line of the channel.

7. The analytical apparatus according to claim 1 wherein said ends divide the flush fluid flow into an upstream portion and a downstream portion and the gating interface is adapted such that the outlet end of the first microcolumnar section is separated from the inlet end of the second microcolumnar section with a sufficient distance to form a gap such that when transfer of fluid from the first microcolumnar section to the second microcolumnar section is not desired the flush fluid flushes the fluid exiting the first microcolumnar section from the gap downstream to prevent said exiting fluid from entering the second microcolumnar section.

8. The analytical apparatus according to claim 7 wherein the microcolumnar sections have similar outside diameters and said gap between said ends of the microcolumnar sections is from 0.2 to 1 times the outside diameter of the microcolumnar sections for flushing.

9. The analytical apparatus according to claim 7 further comprising a control means for stopping the flush fluid flow in the channel when transfer of fluid from the first microcolumnar section to the second microcolumnar section is desired.

10. The analytical apparatus according to claim 7 further comprising a means for operatively moving at least one of the microcolumnar sections to decrease the distance between said ends of the microcolumnar sections to facilitate transfer of fluid from the first microcolumnar section to the second microcolumnar section when such transfer is desired and to increase the distance between said ends of the microcolumnar sections to prevent transfer of fluid form the first microcolumnar section to the second microcolumnar section when such transfer is not desired.

11. The analytical apparatus according to claim 10 wherein at least one of the outlet end of the first microcolumnar section and the inlet end of the second microcolumnar section moves in a path substantially parallel to the center line of the first microcolumnar section at said ends.

12. The analytical apparatus according to claim 10 wherein at least one of the outlet end of the first microcolumnar section and the inlet end of the second microcolumnar section moves in a path that is nonparallel to the center line of the channel at said ends of the microcolumnar sections.

13. The analytical apparatus according to claim 10 further comprising solenoid means for moving the at least one of the microcolumnar sections.

14. The analytical apparatus according to claim 1 wherein said first and second microcolumnar sections are slidably constrained by the channel.

15. The analytical apparatus according to claim 1 wherein the channel includes a section sufficiently transparent such that the positions of said ends can be observed therethrough.

16. The analytical apparatus according to claim 1 wherein the first fluid conducting means comprises an analytical microcolumn.

17. The analytical apparatus according to claim 16 wherein the first fluid conducting means has a chromatographic microcolumn and the second fluid conducting means has a capillary electrophoresis capillary.

18. A microcolumnar analytical apparatus having a flow gating interface system for interfacing a first microcolumn and a second microcolumn, comprising:

a flow gating interface comprising;

(A) a first microcolumnar section having a center line, an outlet end portion having an outlet end, and a lumen for conducting a fluid flow;

(B) a second microcolumnar section having a center line, an inlet end portion having an inlet end, and a lumen for conducting a fluid flow;

end

(C) a channel having a center line and enclosing at least a portion of the first microcolumnar section and at least a portion of the second microcolumnar section for conducting a flush fluid flow past said ends of the microcolumnar sections, the inwardly facing wall of the channel slidably constraining said end portions of the first and second microcolumnar sections, due to the relative curvature and elasticity of the microcolumnar sections and the channel, such that the outlet end of the first microcolumnar section is proximate the inlet end of the second microcolumnar section and such that the center lines of the outlet end portion and the inlet end portion are generally parallel to facilitate the transfer of fluid from the outlet end of first microcolumnar section to the inlet end of the second microcolumnar section when desired;

a means for reciprocatively, operatively moving at least one of the microcolumnar sections to alternatively decrease and increase the distance between said ends of the microcolumnar sections;

a first microcolumnar means for analysis of a fluid sample, the first microcolumnar means having a microcolumn operatively connected to and in fluid communication with the first microcolumnar section;

a flush liquid supply means operatively connected to and in fluid communication with the channel for flowing the flush fluid through the channel; and

a second microcolumnar means for analysis of an effluent fluid sample from the first microcolumnar section, the second microcolumnar means having a microcolumn operatively connected to and in fluid communication with the second microcolumnar section.

19. A microcolumnar analytical apparatus having a flow gating interface system for interfacing a first microcolumn and a second microcolumn, comprising:

a flow gating interface comprising;

(A) a first microcolumnar section having a center line, an outlet end portion having an outlet end, and an tureen for conducting a fluid flow;

(B) a second microcolumnar section having a center line, an inlet end portion having an inlet end, and a lumen for conducting a fluid flow; and

(C) a bent channel having a center line and enclosing at least a portion of the first microcolumnar section and at least a portion of the second microcolumnar section for conducting a flush fluid flow past said ends of the microcolumnar sections, the inwardly facing wall of the bent channel nonfixedly constraining said end portions of the first and second microcolumnar sections, due to the relative curvature and elasticity of the microcolumnar sections and the channel, such that the outlet end of the first microcolumnar section is proximate the inlet end of the second microcolumnar section and such that the center lines of the outlet end portion and the inlet end portion are generally parallel to facilitate the transfer of fluid from the outlet end of first microcolumnar section to the inlet end of the second microcolumnar section when desired;

a first microcolumnar means for analysis of a fluid sample, the first microcolumnar means having a microcolumn with an inlet end and an outlet end, the outlet end being operatively connected to and in fluid communication with the first microcolumnar section;

a flush liquid supply means operatively connected to and in fluid communication with the channel for flowing the flush fluid through the channel; and

a second microcolumnar means for analysis of an effluent fluid sample from the first microcolumnar section, the second microcolumnar having a microcolumn with an inlet end and an outlet end, the inlet end being operatively connected to and in fluid communication with the second microcolumnar section.

20. A method for analyzing a liquid sample, comprising:

(a) transferring the liquid sample through a first microcolumnar device which includes a first microcolumn;

(b) coupling the first microcolumn to a second microcolumn which is part of a second microcolumn device to control fluid flow from the first microcolumn to the second microcolumn, comprising;

(A) using the inwardly facing wall of a channel to nonfixedly constrain an outlet end portion of a first microcolumnar section operatively connected to and in fluid communication with the first microcolumn and to constrain an inlet end portion of a second microcolumnar section operatively connected to and in fluid communication with the second microcolumn, by the relative curvature and elasticity of the microcolumnar sections and the channel, such that an outlet end of said outlet end portion is proximate an inlet end of said inlet end portion and such that center lines of said outlet end portion are inlet end portion are substantially parallel to facilitate the transfer of fluid from said outlet end of the first microcolumnar section to said inlet end of the second microcolumnar section when desired, the channel being adapted to conduct a flush fluid flow;

(B) substantially preventing transfer of fluid from the first microcolumnar section to the second microcolumnar section by flushing the flush fluid in the channel through a gap between the outlet end of the first microcolumnar section and the inlet end of the second microcolumnar section to substantially carry away fluid exiting said outlet end; and

(C) transferring fluid from the first microcolumnar section to the second microcolumnar section by reducing the amount of fluid exiting said outlet end from being carried away by the flush fluid; and

(c) analyzing the fluid transferred from the first microcolumnar device to the second microcolumnar device.

21. The method according to claim 20 wherein the fluid is transferred from the first microcolumnar section to the second microcolumnar section by at least one of reversibly stopping the flush fluid flow in the channel and reversibly positioning said outlet end of the first microcolumnar section and said inlet end of the second microcolumnar section in a substantially abutting configuration by reversibly moving at least one of the microcolumnar sections to narrow the gap such that the amount of fluid exiting the outlet end being carried away by the flush fluid is reduced.

22. The method according to claim 20 wherein the step of using a channel to constrain comprises arranging the channel and said end portions of the microcolumnar sections such that said center lines at a location proximate said ends of said end portions lie on a plane.

23. The method according to claim 20 wherein the step of using a channel to constrain comprises using a bent tube having a circular cross section such that the bent tube aligns said end portions of the microcolumnar sections and such that the center line of the channel is generally parallel to that of said end portions.

24. The method according to claim 20 wherein the step of using a channel to constrain comprises using a channel with an arcuate portion and said end portions of the microcolumnar sections are arranged such that the curvature of the arcuate portion and the elasticity of the microcolumnar sections cause said ends of the microcolumnar sections to rest against the inwardly facing wall of the channel such that the center lines of the microcolumnar sections at said ends substantially collinear with each other but are offset from the center line of the channel.

25. The method according to claim 20 wherein the step of using a channel to constrain comprises using a bent channel having three or more arcuate portions and arranging said end portions of the microcolumnar sections such that each of the microcolumnar sections is pressed by two adjacent but generally oppositely directing arcuate portions on the wall of the each of the microcolumnar sections so that said ends of the first and second microcolumnar sections are proximate and the center lines of the microcolumnar sections at the ends are collinear.

26. The method according to claim 20 wherein the step of using a channel to constrain comprises using a channel having a section that is transparent and the method further comprising adjusting the position of said ends of the microcolumnar sections while visually evaluating the position of said ends through said transparent section prior to steps (B) and (C).

27. The method according to claim 20 wherein the step of using a channel to constrain comprises using a bent channel and the method further comprises moving one of the first and second microcolumnar sections by a solenoid moving means so that said moved section reciprocatively slides on the inwardly facing wall of the channel between a first position wherein said ends of the first and second microcolumnar sections are in substantially abutting configuration for transfer of fluid from the first microcolumnar section to the second microcolumnar section and a second position wherein a sufficient gap results between said ends for the flush fluid to pass therethrough to prevent the transfer of fluid from the first microcolumnar section to the second microcolumnar section.

28. A method of making an analytical apparatus for analyzing a liquid sample, comprising:

(a) providing a first fluid conducting means for transferring the fluid sample;

(b) providing a second fluid conducting means for analysis of the fluid sample, the second fluid conducting means having a microcolumn;

(c) coupling the first fluid conducting means to the microcolumn of the second fluid conducting means with a flow gating interface to control fluid flow from the first fluid conducting means to the microcolumn of the second fluid conducting means, the flow gating interface comprising;

(A) a first microcolumnar section having a center line, an outlet end portion having an outlet end, and lumen for conducting a fluid flow, the first microcolumnar section being operatively connected and in fluid communication with the first fluid conducting means;

(B) a second microcolumnar section having a center line, an inlet end portion having an inlet end, and a lumen for conducting a fluid flow, the second microcolumnar section being operatively connected and in fluid communication with the microcolumn of the second fluid conducting means; and

(C) a channel having a center line and inwardly facing wall and enclosing at least a portion of the first microcolumnar section and at least a portion of the second microcolumnar section for conducting a flush fluid flow past said ends of the microcolumnar sections, the inwardly facing wall of the channel nonfixedly constraining and aligning said end portions of the first and second microcolumnar sections, due to the relative curvature and elasticity of the microcolumnar sections and the channel, such that said outlet end of the first microcolumnar section is proximate said inlet end of the second microcolumnar section and such that the center lines of said outlet end portion and said inlet end portion are generally parallel to facilitate the transfer of fluid from said outlet end of first microcolumnar section to said inlet end of second microcolumnar section when desired; and

(d) connecting a flush liquid supply means operatively to and in fluid communication with the channel for flowing the flush fluid through the channel.