Device and method to directly control the temperature of microscope slides

• US 6,300,124 B1
• Filed: 11/02/1999
• Issued: 10/09/2001
• Est. Priority Date: 11/02/1999
• Status: Expired due to Fees

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Arik, Mehmet, Schiller, Peter, Bar-Cohen, Avram, Blumenfeld, Martin, Cibuzar, Gregory T.
• Primary Examiner(s): Whisenant, Ethan
• Assistant Examiner(s): LU, FRANK WEI MIN
• Application Number:
  US09/432,012
• Time in Patent Office: 707 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/183, 435/283.1, 435/286.1, 435/287.1, 435/287.2, 435/288.4, 436/94, 536/23.1, 536/24.3, 536/24.33
• US Class Current: 435/287.2
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046

Abstract

A thermal cycling device for use with self-heating microscope slides is provided.

Claims

1. An apparatus, comprising:

a slide having a first edge and a second edge opposite the first edge and at least a first pad and a second pad coupled therewith, the first pad disposed proximal to the first edge and the second pad disposed proximal to the second edge; and

at least one resistive heating element associated with a lower surface of the slide and disposed alone a longitudinal axis of the slide, the heating element electrically coupled between the first pad and the second pad.

2. The apparatus of claim 1 which comprises a microscope slide.

3. The apparatus of claim 1 wherein the heating element is a thin-film heater.

4. The apparatus of claim 1 wherein the heating element is associated with a first horizontal surface of slide.

5. The apparatus of claim 1 wherein the heating element is transparent.

6. The apparatus of claim 5 wherein the heating element is light transparent.

7. The apparatus of claim 1 wherein the slide further comprises a third pad and a fourth pad coupled thereto.

8. The apparatus of claim 7 further comprising at least one temperature-monitoring element that is coupled between the third pad and the fourth pad.

9. The apparatus of claim 8 wherein the temperature-monitoring element is associated with a upper surface of the slide.

10. The apparatus of claim 8 further comprising a biological sample which comprises nucleic acid disposed on the slide.

11. The apparatus of claim 8 wherein the temperature-monitoring element is a thin-film resistive sensing element.

12. The apparatus of claim 1 or 6 wherein the heating element is formed of indium tin oxide.

13. The apparatus of claim 12 wherein the indium tin oxide is less than about 5,000 angstroms in thickness.

14. The apparatus of claim 1 or 6 wherein the heating element is formed of platinum.

15. The apparatus of claim 14 wherein the platinum is less than about 400 angstroms in thickness.

16. The apparatus of claim 8 wherein the temperature-monitoring element is a platinum resistance thermal sensing element.

17. The apparatus of claim 1 comprising at least two heating elements.

18. The apparatus of claim 8 comprising at least two temperature-monitoring elements.

19. A thermal cycling device, comprising:

a housing;

a cooling device associated with the housing, wherein the cooling device disperses air;

at least four conductive clips associated with the housing; and

a controller, wherein the controller is operatively connected to each conductive clip and the cooling device.

20. The device of claim 19 further comprising a slide comprising at least one heating element and at least one temperature-monitoring element associated therewith.

21. The device of claim 20 wherein the slide is associated with the conductive clips.

22. The device of claim 20 further comprising a biological sample comprising nucleic acid, wherein the sample is disposed on the slide.

23. The device of claim 21 wherein two conductive clips are operatively connected to the heating element, and two other conductive clips are operatively connected to the temperature-monitoring element.

24. The device of claim 19 wherein the cooling device is a fan.

25. A device for thermal cycling, comprising:

a means for supporting at least one apparatus, wherein the apparatus comprises;

i) a microscope slide having at least four pads coupled therewith, ii) at least one heating element associated with the slide, the heating element coupled between the first pad and the second pad, and iii) at least one temperature-monitoring element associated with the slide, the temperature-monitoring element coupled between the third and the fourth pads;

a means for cooling a surface of the microscope slide wherein the means for cooling comprises an air movement device; and

a means for controlling a temperature of the microscope slide, wherein the means for controlling is operatively connected to the means for cooling, the heating element and the temperature-monitoring element such that the temperature of the slide can be rapidly and controllably increased and decreased by the controller in response to the temperature sensed by the temperature-monitoring element such that the apparatus can be subjected to rapid thermal cycling over a temperature range of at least 30°

C.

26. The device of claim 25 wherein the means for cooling comprises a fan.

27. A device for subjecting a plurality of biological samples disposed on at least one flat substrate to thermal cycling, comprising:

a thermal sensing means placed on the surface of one flat substrate and at least one flat substrate lacking the thermal sensing means and comprising at least one biological sample;

a means for holding the plurality of flat substrates, wherein the means for holding comprises a silicon sample plate, and wherein the flat substrates are disposed on the surface of the holding means;

a means for heating the lower surface of the means for holding, wherein the means for heating is positioned in close proximity to the means for holding;

a means for cooling the surface of the means for heating, wherein the means for cooling comprises a rotating means for dispersing air; and

a means for controlling, wherein the controlling means is operatively connected to the means for thermal sensing, the means for heating and the means for cooling such that the temperature of the substrates can be rapidly and controllably increased and decreased by the control means in response to the temperature sensed by the means for sensing such that the biological sample can be subjected to rapid thermal cycling over a temperature range of at least 40°

C.

29. The device of claim 27 or 28 wherein the means for sensing comprises a thermocouple.

30. The device of claim 27 or 28 wherein the means for sensing comprises a means other than a thermocouple.

31. The device of claim 27 or 28 wherein the flat substrate is a glass microscope slide.

32. The device of claim 27 or 28 wherein the heating means is an etched foil heater.

33. The device of claim 27 or 28 further comprising a housing containing the means for holding, the means for cooling, the means for heating, and the means for sensing.

28. A device for maintaining the temperature of a plurality of biological samples which are disposed on at least one flat substrate, comprising:

a thermal sensing means placed on the surface of one flat substrate and at least one flat substrate lacking the thermal sensing means and comprising at least one biological sample;

a means for holding the plurality of flat substrates, wherein the means for holding comprises a silicon sample plate, and wherein the flat substrates are disposed on the surface of the holding means;

a means for heating the surface of the means for holding, wherein the means for heating is positioned in close proximity to the means for holding;

a means for cooling the surface of the means for heating, wherein the means for cooling comprises a rotating means for dispersing air; and

a means for controlling, wherein the controlling means is operatively connected to the means for thermal sensing, the means for heating and the means for cooling such that the temperature of the substrates can be maintained at a particular temperature by the control means in response to the temperature sensed by the means for sensing such that the biological sample can be maintained at a particular temperature over a temperature range of at least 30°

C.

34. A device for subjecting a biological sample to thermal cycling comprising:

a housing;

a flat substrate having a thermal sensor coupled to the flat substrate, the flat substrate having a biological sample disposed thereon;

a holder for the flat substrate, the holder attached to the housing,

wherein the holder comprises a silicon sample plate, and wherein flat substrate is disposed on the surface of the silicon sample plate;

a cooler for the flat substrate, the cooler attached to the housing; and

a heater thermally coupled to the holder.

35. The device of claim 34 wherein the holder holds a plurality of flat substrates.

36. The device of claim 34 the cooler is a fan.

37. The device of claim 34 wherein the heater is positioned in close proximity to the holder.

38. The device of claim 34 further comprising:

a controller operatively connected to the thermal sensor, the heater and the cooler such that the temperature of the flat substrate can be controllably increased and decreased by the controller in response to the temperature sensed by the means for thermal sensor.

39. The device of claim 34 wherein the biological sample can be subjected to rapid thermal cycling over a temperature range of at least 40°

C.