Integrated temperature control/alignment system for high performance capillary electrophoretic apparatus

• US 4,898,658 A
• Filed: 11/25/1987
• Issued: 02/06/1990
• Est. Priority Date: 11/25/1987
• Status: Expired due to Term

• Current Assignee: Northeastern University
• Original Assignee: Northeastern University
• Inventors: Paulus, Aran, Nelson, Robert J., Karger, Barry L., Cohen, Aharon S.
• Primary Examiner(s): Niebling, John F.
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US07/125,539
• Time in Patent Office: 804 Days
• Field of Search: 204/299 R, 204/180.1, 204/183.3
• US Class Current: 204/603
• CPC Class Codes: F25B 21/04 reversible
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44708 Cooling

Abstract

An integrated temperature control/alignment system for use with a high performance capillary electrophoretic apparatus is disclosed. In one exemplary embodiment the integrated temperature control/alignment system comprises a pair of capillary column mounting plates for mounting a capillary column as a constituent of the electrophoretic apparatus, a pair of secondary support plates, a pair of thermoelectric plates and external heat sink plates. Detection openings are formed in each of the plates as required so that a continuous detection path exists through the integrated temperature control/alignment system. The capillary column is seated and locked in grooves formed in the capillary column mounting plates so that the detection windows of the capillary column are coordinated with the aligned detection openings formed in the applicable plates of the integrated temperature control/alignment system. The temperature of substantially the entire capillary column, including the detection zone, is controlled or regulated by the temperatures of the thermoelectric plates which comprise one or more thermoelectric circuits utilizing the Peltier effect. Regulation of current flow in the thermoelectric plates controls the temperature effect exerted by the thermoelectric plates, thereby controlling both the direction and rate of heat transfer with the capillary column.

Claims

1. An integrated temperature control/alignment system disposed in an ambient environment for use with a high performance electrophoretic apparatus including a capillary column and an externally prepositioned on-column detection device, comprising:

means for thermoelectrically regulating heat transfer between the capillary column and the ambient environment to maintain the capillary column at a predetermined electrophoretic operating temperature, said thermoelectric regulating means including

means for mounting the capillary column as part of the electrophoretic apparatus, said mounting means being formed from an electrical insulating material having a coefficient of thermal conductivity to provide efficient heat transfer between the capillary column and said mounting means sufficient to maintain the capillary column at said predetermined electrophoretic operating temperature, said mounting means including

means for aligning the capillary column in a predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system as part of the electrophoretic apparatus for on-column detection, and

means for physically engaging the capillary column to lock the capillary column in said predetermined position within said integrated temperature control/alignment system.

2. The integrated temperature control/alignment system of claim 1 wherein said capillary column mounting means comprises at least one thermoelectric member having an interior facing surface and an exterior facing surface, said at least one thermoelectric member having aligned detection openings formed therethrough from said interior facing surface to said exterior facing surface for aligning the capillary column in said predetermined position to the externally prepositioned on-column detection device for on-column detection, said aligned detection openings comprising said capillary column alignment means, and wherein said interior facing surface of said at least one thermoelectric member comprises said means for physically engaging the capillary column to lock the capillary column within said integrated temperature control/alignment system in said predetermined position, and wherein said at least one thermoelectric member comprises at least one thermopile thermoelectrically regulating said heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

3. An integrated temperature control/alignment system disposed in an ambient environment for use with a high performance electrophoretic apparatus including a capillary column and an externally prepositioned on-column detection device, comprising:

means for mounting the capillary column as part of the electrophoretic apparatus, said mounting means being formed from an electrical insulating material having a coefficient of thermal conductivity to efficient provide heat transfer between the capillary column and said mounting means sufficient to maintain the capillary column at a predetermined electrophoretic operating temperature, said mounting means further comprising

means for aligning the capillary column in a predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system as part of the electrophoretic apparatus, and

means for physically engaging the capillary column to lock the capillary column in said predetermined position within said integrated temperature control/alignment system; and

means for thermoelectrically regulating heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

4. The integrated temperature control/alignment system of claim 3 wherein said thermoelectric regulating means provides thermoelectric cooling for the capillary column to transfer Joule heat from the capillary column to the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

5. The integrated temperature control/alignment system of claim 3 wherein said thermoelectric regulating means provides thermoelectric heating for the capillary column to transfer heat to the capillary column to maintain the capillary column at said predetermined electrophoretic operating temperature.

6. The integrated temperature control/alignment system of claim 3 wherein said capillary column mounting means comprises

at least one capillary column mounting member having interior and exterior facing surfaces, said at least one capillary column mounting member having aligned detection openings formed therethrough from said interior facing surface to said exterior facing surface for aligning the capillary column in said predetermined position for on-column detection, said aligned detection openings comprising said capillary column alignment means, and wherein said interior facing surface of said at least one capillary column mounting member comprises said means for physically engaging the capillary column to lock the capillary column within said integrated temperature control/alignment system in said predetermined position to the externally prepositioned on-column detection device, and wherein

said thermoelectric regulating means acts upon said exterior facing surface of said at least one capillary column mounting member to regulate thermoelectrically said heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

7. The integrated temperature control/alignment system of claim 6 wherein said thermoelectric regulating means comprises

at least one thermoelectric member having interior and exterior facing surfaces and detection passageways formed therethrough in alignment with said aligned detection openings of said at least one capillary column mounting member to align the capillary column in said predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system for on-column detection, and wherein said interior facing surface of said at least one thermoelectric member is disposed adjacent said exterior facing surface of said at least one capillary column mounting member to regulate thermoelectrically said heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

8. The integrated temperature control/alignment system of claim 7 wherein said at least one capillary column mounting member comprises

first and second capillary column mounting plates having a groove formed in said interior facing surface of each said first and second capillary column mounting plates, said grooves comprising said means for physically engaging the capillary column to lock the capillary column within said integrated temperature control/alignment system in said predetermined position to the externally prepositioned on-column detection device for on-column detection, and wherein

said aligned detection openings are formed through said first and second capillary column mounting plates from said interior facing surfaces to said exterior facing surfaces substantially centered about said grooves for alignment of the capillary column in said predetermined position to the externally prepositioned on-column detection device for on-column detection, and wherein said aligned detection opening of said first capillary column mounting plate is a detection slit and said aligned detection opening of said second capillary column mounting plate is a detection hole, and wherein

said at least one thermoelectric member comprises first and second thermoelectric plates having said interior facing surfaces disposed adjacent respective exterior facing surfaces of said first and second capillary column mounting plates and said exterior facing surfaces exposed to the ambient environment, and wherein

said detection passageways are formed through said first and second thermoelectric plates from said interior facing surfaces to said exterior facing surfaces in alignment with said aligned detection openings of said first and second capillary column mounting plates with said first and second thermoelectric members disposed adjacent said first and second capillary column mounting plates, respectively, and wherein said first and second thermoelectric plates thermoelectrically regulate said heat transfer between the capillary column locked in said grooves of said first and second capillary column mounting plates and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

9. The integrated temperature control/alignment system of claim 7 wherein said at least one thermoelectric member comprises

at least one thermopile having a first plurality of dissimilar junctions and a second plurality of dissimilar junctions disposed adjacent said interior and exterior facing surfaces, respectively, to regulate thermoelectrically said heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature, and

current generator means for regulating current flow direction and magnitude in said at least one thermopile wherein current flow in a first direction maintains said first plurality of dissimilar junctions at a first temperature and said second plurality of junctions at a second temperature to provide thermoelectric cooling of the capillary column and wherein current flow in a second direction maintains said first plurality of dissimilar junctions at a third temperature and said second plurality of junctions at a fourth temperature to provide thermoelectric heating of the capillary column.

10. The integrated temperature control/alignment system of claim 7 further comprising at least one secondary support member having interior and exterior facing surfaces and detection slots formed therethrough in alignment with said aligned detection openings of said at least one capillary column mounting member and said detection passageways of said at least one thermoelectric member with said at least one secondary support member disposed intermediate said at least one capillary column mounting member and said at least one thermoelectric member to align the capillary column in said predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system for on-column detection, and wherein said thermoelectric regulating means coacts with said at least one secondary support member to regulate thermoelectrically said heat transfer between the capillary column and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

11. The integrated temperature control/alignment system of claim 10 further comprising

at least one heat sink member having interior and exterior facing surfaces and detection apertures formed therethrough, and wherein said detection apertures are aligned with said detection passageways of said at least one thermoelectric member with said at least one heat sink member disposed adjacent said exterior facing surface of said at least one thermoelectric member to align the capillary column in said predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system for on-column detection, and wherein said at least one heat sink member coacts with said at least one thermoelectric member to transfer thermal energy between said at least one thermoelectric member and the ambient environment.

12. The integrated temperature control/alignment system of claim 11 further comprising

means for forcing a fluid over said exterior facing surface of said at least one heat sink member for convective cooling thereof to facilitate transfer of said thermal energy between said at least one heat sink member and the ambient environment.

13. The integrated temperature control system of claim 11 wherein said at least one heat sink member further includes means for circulating a cooling fluid proximal said exterior facing surface of said at least one heat sink member for conductive cooling thereof to facilitate transfer of said thermal energy between said at least one heat sink member and the ambient environment.

14. The integrated temperature control/alignment system of claim 8 further comprising

first and second secondary support plates having interior and exterior facing surfaces and detection slots formed through said first and second secondary support plates between said interior and exterior facing surfaces thereof, and wherein said first and second secondary support plates are disposed intermediate said first and second capillary column mounting plates and said first and second thermoelectric plates, respectively, with said detection slots aligned with said detection slit and said detection hole of said first and second capillary column mounting plates, respectively, and said detection passageways of said first and second thermoelectric plates to align the capillary column in said predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system for on-column detection, and wherein said first and second thermoelectric plates coact with said first and second secondary support plates, respectively, to regulate thermoelectrically said heat transfer between the capillary column locked in said grooves of said first and second capillary column mounting plates and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

15. The integrated temperature control system of claim 14 further comprising

at least one heat sink plate having an interior facing surface, an exterior facing surface and a detection apertures formed therethrough between said interior facing surface and said exterior facing surface, and wherein said detection aperture is aligned with said detection passageway of one of said first and second thermoelectric plates with said at least one heat sink plate disposed adjacent said exterior facing surface of said one of said first and second thermoelectric plates to align the capillary column in said predetermined position to the externally prepositioned on-column detection device within said integrated temperature control/alignment system for on-column detection, and wherein said one of said first and second thermoelectric plates coacts with said at least one heat sink plate to regulate thermoelectrically said heat transfer between the capillary column and the ambient environment by transferring thermal energy between said at least one heat sink plate and the ambient environment to maintain the capillary column at said predetermined electrophoretic operating temperature.

16. An integrated temperature control/alignment system for use with a high performance electrophoretic apparatus situated in an ambient environment, the electrophoretic apparatus including a capillary column having opposed detection windows and an externally prepositioned on-column detection means for measuring an analyte electrophoretically migrating through the capillary column, comprising:

at least one capillary column mounting member for mounting the capillary column in a predetermined position with respect to the externally prepositioned on-column detection means for measuring the analyte electrophoretically migrating through the capillary column, said at least one capillary column mounting member being formed from an electrical insulating material having a coefficient of thermal conductivity to provide efficient heat transfer between the capillary column and said at least one capillary column mounting member sufficient to maintain the capillary column at a predetermined electrophoretic operating temperature, said at least one capillary column mounting member having interior and exterior facing surfaces and aligned detection openings formed therethrough from said interior facing surface to said exterior facing surface in alignment with the opposed detection windows of the capillary column, said interior facing surface further including means for physically engaging the capillary column to lock the capillary column within said integrated temperature control/alignment system in said predetermined position with respect to the externally prepositioned on-column detection device;

at least one secondary support member having interior and exterior facing surfaces, said interior facing surface disposed in contact with said exterior facing surface of said at least one capillary column mounting member, said at least one secondary support member including detection slots formed therethrough from said interior facing surface to said exterior facing surface in alignment with the opposed detection windows of the capillary column;

at least one thermoelectric member having interior and exterior facing surfaces, said interior facing surface disposed in contact with said exterior facing surface of said at least one secondary support member, said at least one thermoelectric member including detection passageways formed therethrough from said interior facing surface to said exterior facing surface in alignment with said detection slots of said at least one secondary support member; and

current generator means for regulating current flow magnitude and direction through said at least one thermoelectric member;

wherein regulation of said current flow magnitude and direction through said at least one thermoelectric member thermoelectrically regulates heat transfer between the capillary column and the ambient environment via said at least one capillary column mounting member, said at least one secondary support member and said at least one thermoelectric member to maintain the capillary column at said predetermined electrophoretic operating temperature.

17. The integrated temperature control system of claim 16 further comprising

at least one heat sink member having interior and exterior facing surfaces, said interior facing surface of said at least one heat sink member disposed in contact with said exterior facing surface of said at least one thermoelectric member, said at least one heat sink member including detection apertures formed therethrough from said interior facing surface to said exterior facing surface in alignment with said detection passageways of said at least one thermoelectric member, and wherein said at least one heat sink member coacts with said at least one thermoelectric member to transfer thermal energy between said at least one thermoelectric member and the ambient environment.

18. The integrated temperature control system of claim 17 wherein said at least one thermoelectric member thermoelectrically regulates heat transfer between the capillary column and the ambient environment to provide thermoelectric cooling of the capillary column to said predetermined electrophoretic operating temperature.

19. The integrated temperature control system of claim 16 wherein said at least one thermoelectric member thermoelectrically regulates heat transfer between the capillary column and said at least one thermoelectric member to provide thermoelectric heating of the capillary column to said predetermined electrophoretic operating temperature.