Capillary electrophoresis

• US 5,384,024 A
• Filed: 03/13/1992
• Issued: 01/24/1995
• Est. Priority Date: 03/13/1992
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Kowallis, Reid B., Moring, Stephen E., Lee, Thomas E., Orpin, Timothy S., Nickel, John H., Woods, Janice C., Albin, Michael S., Oldham, Mark F., Reel, Richard T., Mead, Dennis E.
• Primary Examiner(s): Czaja, Donald E.
• Assistant Examiner(s): Cano, Milton I.
• Application Number:
  US07/850,764
• Time in Patent Office: 1,047 Days
• Field of Search: 204/299 R, 204/180.1, 204/300 R, 215/247, 215/355, 215/D3, 422/63-65
• US Class Current: 204/602
• CPC Class Codes: G01N 27/44782 of a plurality of samples

Abstract

An instrument for capillary electrophoresis has a vertically translatable carrier holding one end of the capillary and an electrode connected to a power supply, and a rotary carousel for presenting containers of sample and buffer solutions to a load position where the end of the capillary and the electrode may be inserted by operating the carrier. The other end of the capillary and a second electrode connected to the power supply are immersed in an outlet buffer reservoir. The instrument has a vacuum supply for providing a relative vacuum over the solution in the outlet buffer reservoir, so simple material may be injected into the capillary either by electromigration or by differential pressure. After injection, the first end of the capillary and the electrode may be immersed in buffer to accomplish electrophoresis. By manipulating the carousel and carrier, multiple samples may be electrophoresed in series. In a preferred embodiment the instrument includes a flexible duck-billed septum for closing containers while permitting easy access for the electrode and the capillary tube. Also in a preferred embodiment the instrument is controlled by a microprocessor-based controller.

Claims

1. A capillary electrophoresis instruments having an external enclosure, comprising:

a carrier within the enclosure configured for carrying a first end of an electrophoresis capillary and a first electrode positioned side-by-side relative to one another;

a carrier drive configured for translating the carrier vertically at a load position for inserting the first end of the capillary and the first electrode into a container for liquid, and for withdrawing therefrom;

an outlet station within the enclosure configured for holding a buffer reservoir and for positioning a second end of the capillary and a second electrode in the second buffer reservoir;

a rotary carousel having a circular array of support positions for liquid containers; and

a delivery apparatus configured for supporting and moving the rotary carousel from without the enclosure to within the enclosure and from within the enclosure to without the enclosure, and for rotating the carousel within the enclosure, presenting the support positions for liquid containers individually at the load position.

2. A capillary electrophoresis instrument as in claim 1 further comprising a detector positioned between the load position and the outlet station, the detector configured for monitoring separated sample bands passing along a capillary tubing.

3. A capillary electrophoresis instrument as in claim 1 further comprising a control system including a microcontroller for operating the delivery apparatus and controlling electrophoresis operations, and a user interface for entering commands and selecting operational sequences.

4. A capillary electrophoresis instrument as in claim 3 wherein the control system is configured for powering the first and second electrodes with the first electrode and the first end of the capillary immersed in a sample to perform electrokinetic injection of sample material into the first end of the capillary.

5. A capillary electrophoresis instrument as in claim 1 wherein the rotary carousel comprises a removable tray having the circular array of support positions for liquid containers, the removable tray removable and replaceable with the rotary carousel supported on the delivery apparatus outside the enclosure.

6. A capillary electrophoresis instrument as in claim 1 wherein the rotary carousel comprises plural concentrically-arranged circular arrays of support positions for liquid containers, and the delivery apparatus is configured to move the centerpoint of the rotary carousel within the enclosure, and to rotate the carousel, to present the support positions for liquid containers in each circular array at the load position.

7. A capillary electrophoresis instrument as in claim 6 wherein the rotary carousel comprises a removable tray having the plural concentrically-arranged circular arrays of support positions for liquid containers, the removable tray removable and replaceable with the rotary carousel supported on the delivery apparatus outside the enclosure.

8. A capillary electrophoresis instrument as in claim 1 wherein said rotary carousel comprises a temperature adjustment system for maintaining sample materials in liquid containers supported by the carousel at other than ambient temperature.

9. A capillary electrophoresis instrument as in claim 1 further comprising a temperature control system for maintaining a portion of the volume within the enclosure at other than ambient temperature.

10. A capillary electrophoresis instrument as in claim 1 wherein the carrier comprises adjustable holders configured to provide adjustment of the physical relationship of the first end of the capillary and the first electrode.

11. A capillary electrophoresis instrument as in claim 1 wherein the outlet station is configured for holding a sealed second buffer reservoir with the second end of the capillary and the second electrode immersed in a buffer solution held in the sealed second buffer reservoir, and the capillary electrophoresis instrument further comprises a vacuum system for creating a variable vacuum over a buffer solution held in the sealed buffer reservoir, providing a variable pressure differential across the first end and the second end of the capillary, promoting flow in the capillary toward the second end for providing controlled injection of sample material at the first end of the capillary.

12. A capillary electrophoresis instrument as in claim 11 further comprising a pressurizing system for creating a relative positive pressure in the sealed buffer reservoir, promoting flow in the capillary toward the first end for providing expulsion of separated sample bands from the capillary into individual ones of liquid containers supported on the rotary carousel.

13. A capillary electrophoresis instrument as in claim 1 comprising liquid containers for sample material supported on the carousel, individual ones of the liquid containers sealed with a duck-billed septum for allowing easy entry of the first end of the capillary and the first electrode while minimizing exposure of sample material in the liquid container, the duck-billed septum adapted for sealing to an opening of the liquid container and having a wedge-shaped opening comprising two opposing, inwardly-sloping surfaces extending toward the interior of the container, the inwardly-sloping surfaces ending in a slit for allowing penetration of the first end of the capillary and the first electrode side-by-side.

14. A capillary electrophoresis instrument comprising:

a carrier configured for carrying a first end of an electrophoresis capillary and the first electrode positioned side-by-side relative to one and;

a carrier drive configured for translating the carrier vertically at a load position for inserting a first end of the capillary and the first electrode into a container for liquid, and for withdrawing therefrom;

an outlet station configured for holding a buffer reservoir and for positioning a second end of the capillary and a second electrode in the buffer reservoir;

a delivery apparatus configured for supporting and moving liquid containers to and away from the load position; and

a control system configured for powering the first and second electrodes with the first electrode and the first end of the capillary immersed sample in a liquid container in a to perform electrokinetic injection of sample material into the first end of the capillary.

15. A capillary electrophoresis instrument as in claim 14 further comprising an external enclosure, and wherein the delivery apparatus comprises a rotary carousel having a circular array of support positions for liquid containers, and a carousel operator apparatus for supporting and translating the rotary carousel from without the enclosure to within the enclosure and from within the enclosure to without tile enclosure, and for rotating the carousel within the enclosure, presenting the support positions for liquid containers individually at the load position.

16. A capillary electrophoresis instrument as in claim 15 wherein the rotary carousel comprises a removable tray having the circular array of support positions for liquid containers, the removable tray removable and replaceable with the rotary carousel supported on the carousel operator apparatus outside the enclosure.

17. A capillary electrophoresis instrument as in claim 15 wherein the rotary carousel comprises plural concentrically-arranged circular arrays of support positions for liquid containers, and the carousel operator apparatus is configured to move the centerpoint of the rotary carousel within the enclosure, and to rotate the carousel, to present the support positions for liquid containers in each circular array at the load position.

18. A capillary electrophoresis instrument as in claim 17 wherein the rotary carousel comprises a removable tray having the plural concentrically-arranged circular arrays of support positions for liquid containers, the removable tray removable and replaceable with the rotary carousel supported on the carousel operator apparatus outside the enclosure.

19. A capillary electrophoresis instrument as in claim 15 wherein said rotary carousel comprises a temperature adjustment system for maintaining sample materials in liquid containers supported by the carousel at other than ambient temperature.

20. A capillary electrophoresis instrument as in claim 15 further comprising a temperature control system for maintaining a portion of a volume within the enclosure at other than ambient temperature.

21. A capillary electrophoresis instrument as in claim 14 further comprising a detector positioned between the load position and the outlet station, the detector configured for monitoring separated sample bands passing along a capillary tubing.

22. A capillary electrophoresis instrument as in claim 14 wherein the control system comprises a microcontroller for operating the delivery apparatus and controlling electrophoresis operations, and a user interface for entering commands and selecting operational sequences.

23. A capillary electrophoresis instrument as in claim 14 wherein the carrier comprises adjustable holders configured to provide adjustment the first end of the capillary and the first electrode.

24. A capillary electrophoresis instrument as in claim 14 wherein the outlet station is configured for holding a sealed second buffer reservoir with the second end of the capillary and the second electrode immersed in a buffer solution held in the sealed second buffer reservoir, and the capillary electrophoresis instrument further comprises a vacuum system for creating a variable vacuum over a buffer solution held in the sealed buffer reservoir, providing a variable pressure differential across the first end and the second end of the capillary, promoting flow in the capillary toward the second end for providing controlled injection of sample material at the first end of the capillary.

25. A capillary electrophoresis instrument as in claim 14 further comprising a pressurizing system for creating a relative positive pressure in the sealed buffer reservoir, promoting flow in the capillary toward the first end for providing expulsion of separated sample bands from the capillary into individual ones of liquid containers supported on the rotary carousel.

26. A capillary electrophoresis instrument as in claim 14 comprising liquid containers for sample material supported on the carousel, individual ones of the liquid containers sealed with a duck-billed septum for allowing easy entry of the first end of the capillary and the first electrode while minimizing exposure of sample material in the liquid container, the duck-billed septum adapted for sealing to an opening of the liquid container and having a wedge-shaped opening comprising two opposing, inwardly-sloping surfaces extending toward the interior of the container, the inwardly-sloping surfaces ending in a slit for allowing penetration of the first end of the capillary and the first electrode side-by-side.