Precision controlled thermostat for capillary electrophoresis

• US 20040173457A1
• Filed: 12/19/2003
• Published: 09/09/2004
• Est. Priority Date: 12/20/2002
• Status: Abandoned Application

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation), Northeastern University
• Original Assignee: Northeastern University
• Inventors: Fallon, Joseph M., Karger, Barry L., Miller, Arthur W., Deka, Chiranjit
• Application Number:
  US10/740,906
• Publication Number:
  US 20040173457A1
• Time in Patent Office: Days
• US Class Current: 204/451
• CPC Class Codes: G01N 27/44708 Cooling
• CPC Class Codes: G01N 27/44782 of a plurality of samples
• CPC Class Codes: G05D 23/1931 to control the temperature of one space
• CPC Class Codes: G05D 23/24 the sensing element having a resistance varying with temperature, e.g. a thermistor

Abstract

A thermostat control system, that can be configured to include an array of two or more capillary columns or two or more channels in a microfabricated device, is disclosed. A thermally conductive material is in contact with each column or channel in the array. One or more independently controlled heating or cooling elements is positioned adjacent to or within the thermally conductive material, each heating or cooling element being connected to a source of heating or cooling. One or more independently controlled temperature sensing elements and one or more independently controlled temperature probes are also positioned adjacent to or within the thermally conductive material. Each temperature sensing element is connected to a temperature controller, and each temperature probe is connected to a thermometer. When the system is in use, each source of heating or cooling is automatically regulated by the temperature controller in response to feedback from one or more of the temperature sensing elements so as to control temperature stability to within a specified range, and the temperature controller is automatically regulated in response to feedback from one or more of the temperature probes to the thermometer so as to maintain the reference temperature of the thermally conductive material within a specified range of a pre-set target temperature.

Claims

1. A thermostat control system comprising:

one or more capillary columns or one or more channels in a microfabricated device;

a thermally conductive material in contact with said capillary columns or channels;

one or more independently controlled heating or cooling elements positioned adjacent to or within said thermally conductive material, wherein each heating or cooling element is connected to a source of heating or cooling;

one or more independently controlled temperature sensing elements positioned adjacent to or within said thermally conductive material, wherein each temperature sensing element is connected to a temperature controller; and

one or more independently controlled temperature probes positioned adjacent to or within said thermally conductive material, wherein each temperature probe is connected to a thermometer and

wherein, when said system is in use, each said source of heating or cooling is automatically regulated by said temperature controller in response to feedback from one or more of said temperature sensing elements so as to control temperature stability to within a specified range, and said temperature controller is automatically regulated in response to feedback from one or more of said temperature probes to said thermometer so as to maintain the reference temperature of said thermally conductive material within a specified range of a pre-set target temperature.

2. The control system of claim 1, said system comprising multiple independent said capillary columns or multiple independent said channels in a microfabricated device, or multiple independent clusters of said capillary columns or said channels, wherein said columns or channels are distributed among different instruments.

3. A thermostat control system comprising:

one or more capillary columns;

a capillary body support surrounding each said capillary column;

two or more discs of a first thermally conductive material supporting said capillary body support or supports;

a second thermally conductive material surrounding said capillary body support or supports adjacent to said discs of said first thermally conductive material, wherein the melt temperature of said first thermally conductive material is higher than the melt temperature of said second thermally conductive material;

one or more independently controlled heating or cooling elements positioned adjacent to or within said first and second thermally conductive materials, wherein each heating or cooling element is connected to a source of heating or cooling; and

one or more independently controlled temperature sensing elements positioned adjacent to or within said first and second thermally conductive materials, wherein each temperature sensing element is connected to a temperature controller.

4. The control system of claim 3, further comprising:

one or more independently controlled temperature probes positioned adjacent to or within said first and second thermally conductive materials, wherein each temperature probe is connected to a thermometer and

wherein, when said system is in use, each said source of heating or cooling is automatically regulated by said temperature controller in response to feedback from one or more of said temperature sensing elements so as to control temperature stability to within a specified range and said temperature controller is automatically regulated in response to feedback from one or more of said temperature probes to said said thermometer so as to maintain the reference temperature of said first and second thermally conductive materials within a specified range of a pre-set target temperature.

5. The control system of claim 4, said system comprising multiple independent said capillary columns, or multiple independent clusters of said capillary columns, wherein said columns or channels are distributed among different instruments.

6. A thermostat array control system comprising:

two or more capillary columns or two or more channels in a microfabricated device, wherein said two or more columns or said two or more channels are associated in an array;

a thermally conductive material in contact with said capillary columns or channels;

one or more independently controlled heating or cooling elements positioned adjacent to or within said thermally conductive material, wherein each heating or cooling element is connected to a source of heating or cooling;

one or more independently controlled temperature sensing elements positioned adjacent to or within said thermally conductive material, wherein each temperature sensing element is connected to a temperature controller; and

one or more independently controlled temperature probes positioned adjacent to or within said thermally conductive material, wherein each temperature probe is connected to a thermometer and

wherein, when said system is in use, each said source of heating or cooling is automatically regulated by said temperature controller in response to feedback from one or more of said temperature sensing elements so as to control temperature stability to within a specified range, and said temperature controller is automatically regulated by feedback from one or more of said temperature probes to said said thermometer so as to maintain the reference temperature of said thermally conductive material within a specified range of a pre-set target temperature.

9. The control system of claim 6, wherein said one or more heating or cooling elements are positioned adjacent to individual said columns or channels and wherein each individual said column or channel is thermally insulated from every other said column or channel.

10. The control system of claim 6, said system further comprising multiple said columns or channels, wherein two or more of said multiple columns or channels are heated or cooled by a single heating or cooling element and multiple clusters of such columns or channels heated or cooled by a single heating or cooling element are associated in said thermostat array control system and wherein said columns or channels heated or cooled by a single heating or cooling element within a cluster of said columns or channels can be maintained at the same temperature and different clusters within said array are independently controllable.

13. The control system of claim 6 or claim 7, wherein said one or more heating or cooling elements are also used as said temperature sensing elements.

14. The control system of claim 6, wherein said capillary columns or channels are suitable for use in a separation method calling for an electric field and said columns or channels are electrically isolated from said heating or cooling elements.

16. The control system of claim 6, wherein said heating or cooling elements surround said capillary columns or channels.

18. The control system of claim 6, comprising two or more independently controlled heating or cooling elements associated with an individual said column or channel, wherein said two or more heating or cooling elements are positioned along said associated column or channel so as to be capable of inducing a thermal gradient along the length of said column or channel.

20. The control system of claim 6, wherein said independently controlled heating or cooling elements associated with an individual said column or channel are configured for temperature programming.

22. The control system of claim 6 or claim 7, wherein said heating or cooling elements are solid-state.

23. The control system of claim 6 or claim 7, wherein said heating or cooling elements are a fluid.

24. The control system of claim 23, wherein said fluid heating or cooling element is a liquid.

25. The control system of claim 23, wherein said fluid heating or cooling element is a gas.

26. A method of finding the optimum temperature for an analysis procedure for a particular sample, said method comprising the steps of:

providing the thermostat array control system of claim 6;

determining the number of different temperature values to be examined;

including within the thermostat array a number of columns or channels equal to the number of different temperature values to be examined;

configuring each said column or channel for carrying out said analysis procedure for said sample;

adjusting said temperature controller associated with said thermostat array so as to maintain the temperature at each individual said column or channel at one of said different temperature values to be examined;

carrying out said analysis procedure on different aliquots of said sample simultaneously in each of said columns or channels, each of said individual columns or channels being maintained at a different one of said temperature values to be examined; and

comparing the results of said analysis procedure carried out in said individual columns or channels to determine the optimum temperature for said analysis procedure for said sample.

27. The method of claim 26, wherein said analysis procedure is constant denaturant capillary electrophoresis.

28. The method of claim 26, wherein said analysis procedure is a single strand conformational polymorphism analysis.

29. A method of carrying out an analysis procedure simultaneously for multiple samples, each said sample having a different temperature optimum for said procedure, said method comprising the steps of:

providing the thermostat array control system of claim 6;

determining the number of different samples to be examined;

including within the thermostat array a number of columns or channels, or clusters of columns or channels, equal to the number of different samples to be examined;

configuring each said column or channel for carrying out said analysis procedure for one of said multiple samples;

adjusting said temperature controller associated with said thermostat array so as to maintain the temperature at each individual said column or channel at the optimum temperature for carrying out said analysis procedure for an individual said sample;

carrying out said analysis procedure on said different samples simultaneously in each of said columns or channels, each of said individual columns or channels being maintained at the optimum analysis temperature for the individual said sample associated with said individual column; and

obtaining the results of said analysis procedure for each of said samples.

30. The method of claim 29, wherein said analysis procedure is constant denaturant capillary electrophoresis.

31. The method of claim 29, wherein said analysis procedure is a single strand conformational polymorphism analysis.

7. A thermostat array control system comprising:

two or more capillary columns, wherein said two or more columns are associated in an array;

a capillary body support surrounding each said capillary column;

two or more discs of a first thermally conductive material supporting said capillary body supports;

a second thermally conductive material surrounding said capillary body supports adjacent to said discs of said first thermally conductive material;

one or more independently controlled heating or cooling elements positioned adjacent to or within said first and second thermally conductive materials, wherein each heating or cooling element is connected to a source of heating or cooling; and

one or more independently controlled temperature sensing elements positioned adjacent to or within said first and second thermally conductive materials, wherein each temperature sensing element is connected to a temperature controller.

8. The control system of claim 7, further comprising:

one or more independently controlled temperature probes positioned adjacent to or within said first and second thermally conductive materials, wherein each temperature probe is connected to a thermometer and

wherein, when said system is in use, each said source of heating or cooling is automatically regulated by said temperature controller in response to feedback from one or more of said temperature sensing elements so as to control temperature stability to within a specified range and said temperature controller is automatically regulated in response to feedback from one or more of said temperature probes to said said thermometer so as to maintain the reference temperature of said first and second thermally conductive materials within a specified range of a pre-set target temperature.

11. The control system of claim 7, wherein said one or more heating or cooling elements are positioned adjacent to individual said columns and wherein each individual said column is thermally insulated from every other said column.

12. The control system of claim 7, said system further comprising multiple said columns, wherein two or more of said multiple columns are heated or cooled by a single heating or cooling element and multiple clusters of such columns heated or cooled by a single heating or cooling element are associated in said thermostat array control system and wherein said columns heated or cooled by a single heating or cooling element within a cluster of said columns can be maintained at the same temperature and different clusters within said array are independently controllable.

15. The control system of claim 7, wherein said capillary columns are suitable for use in a separation method calling for an electric field and said columns are electrically isolated from said heating or cooling elements.

17. The control system of claim 7, wherein said heating or cooling elements surround said capillary columns or channels.

19. The control system of claim 7, comprising two or more independently controlled heating or cooling elements associated with an individual said column, wherein said two or more heating or cooling elements are positioned along said associated column so as to be capable of inducing a thermal gradient along the length of said column.

21. The control system of claim 7, wherein said independently controlled heating or cooling elements associated with an individual said column are configured for temperature programming.