Temperature gradient calorimeter

• US 5,255,976 A
• Filed: 07/10/1992
• Issued: 10/26/1993
• Est. Priority Date: 07/10/1992
• Status: Expired due to Fees

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Connelly, Patrick R.
• Primary Examiner(s): Cuchlinski, Jr., William A.
• Assistant Examiner(s): Bennett, G. Bradley
• Application Number:
  US07/911,592
• Time in Patent Office: 473 Days
• Field of Search: 422/51, 422/68.1, 422/99, 374/31, 374/33, 374/36, 374/37, 374/43, 374/44, 374/112, 374/10, 374/11, 374/30, 250/361 C
• US Class Current: 374/31
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: B01L 7/54 using spatial temperature gradients
• CPC Class Codes: G01N 25/4846 for a motionless, e.g. solid sample

Abstract

A temperature gradient calorimeter and method of calculating heats of reactions is disclosed. The calorimeter has a two dimensional array of reaction chambers located in a thermally conductive substrate. A first heat transfer medium is in thermal contact with the thermal conductive substrate and is located at one region of the array of reaction chambers. A second heat transfer medium is in thermal contact with the thermal conductive substrate and is located on the opposite side of the array from the first heat transfer medium. The first and second heat transfer mediums are at two different temperatures. That temperature difference produces a temperature gradient across the array of reaction chambers.

The fluorescence intensities are measured for reactant samples located in the array of reaction chambers. By inserting the fluorescence intensity data into thermodynamic equations expressing the degree of advancement and the heat of reaction, the heat of reaction for the reaction process of the sample can be determined.

Claims

1. Apparatus for monitoring reactions comprising:

(a) a two dimensional array of reaction chambers formed in a heat conductive substrate;

(b) a first heat transfer medium at a temperature T₁ in thermal contact with a first region of said substrate;

(c) a second heat transfer medium at a constant temperature T₂ in thermal contact with a second region of said substrate;

whereby a thermal gradient is established across said array and between said first and second regions which is proportional to the difference in temperature, T₁ -T₂, between the two mediums.

2. The apparatus of claim 1 including a sensor for sensing radiation intensity emitted from each chamber as a reaction occurs.

3. The apparatus of claim 2 where the intensity of radiation emitted from each chamber is measured with a sensor belonging to the group comprising a sensor for measuring the intensity of fluorescence resulting, a sensor for measuring radioactive labelled materials, a sensor for measuring the absorption of ultraviolet radiation and a sensor for measuring the absorption of visible radiation.

4. The apparatus of claim 1 further comprising a dialysate chamber which is separated from the reaction chambers by a semi-permeable membrane.

5. The apparatus of claim 1 further comprising a transparent window covering the array of reaction chambers.

6. The apparatus of claim 1 where the heat conductive substrate is substantially enclosed within an insulating material.

7. The apparatus of claim 1 including a filling system for filling the array of reaction chambers comprising a series of canals connecting a plurality of reaction chambers.

8. The apparatus of claim 1 where the first and second heat transfer mediums comprise temperature controlled water baths.

9. The apparatus of claim 1 where the reaction chambers are coated with a chemically inert and optically reflective material having good thermal conductive properties.

10. The apparatus of claim 1 where the heat conductive substrate is made from a metallic material from the group comprising saphire, silicon, copper, aluminum or stainless steel.

11. The apparatus of claim 1 in which the reaction involve temperature changes.

12. The apparatus of claim 1 in which the reactions are chemical reactions.

13. The apparatus of claim 1 in which the thermal gradient is a fixed temperature gradient.

19. The method of monitoring reactions of claim 13 where the radiation intensity measured emitted from the reactant solution in each reaction chamber is fluorescence intensity.

20. The method of monitoring reactions of claim 13 where the step of determining the heat of reaction for the reactant solution includes correlating fluorescence intensity data with thermodynamic expressions of heat of reaction and degree of advancement of reaction.

14. A temperature gradient calorimeter comprising:

a) a two dimensional array of reaction chambers arranged in a substrate and wherein a constant thermal gradient is established across the array;

b) a sensor for measuring the intensity of radiation emitted by reactions occurring in the reaction chambers in which intensity varies in proportion to the thermal gradient.

15. The temperature gradient calorimeter of claim 14 where the sensor measures fluorescence intensity emitted by reactions occurring in the reaction chambers.

16. A method of monitoring reactions comprising:

creating a constant temperature gradient across a two dimensional array of reaction chambers disposed in a heat conductive substrate;

measuring the intensity of radiation emitted from the reactant solution in each reaction chamber across the array of reaction chambers;

determining the heat of reaction for each reaction from the measured intensities of the reaction in each chamber.

17. The method of monitoring reactions of claim 16 including the step of connecting the reaction chambers in each row with a canal and filling each canal with reactant solution, each canal carrying reactant solution to a row of reaction chambers, thereby filling each reaction chamber.

18. The method of monitoring reactions of claim 16 where the step of creating a temperature gradient across the array of reaction chambers comprises placing a first heat transfer medium at a temperature T₁ in thermal contact with a first region of the heat conductive substrate;

and by placing a second heat transfer medium at a temperature T₂ in thermal contact with a second region of the heat conductive substrate.

21. The method of monitoring reactions of claim 17 where the step of determining the heat of reaction for the reactant solution further includes using a computer for computing the heat of reaction and the degree of advancement of reaction.

22. The method of monitoring reactions of claim 16 in which the reactions involve temperature changes.

23. The method of monitoring reactions of claim 16 in which the reactions are chemical reactions.

24. A temperature gradient calorimeter comprising:

a) a two dimensional array of reaction chambers formed in a heat conductive substrate, said reaction chambers in the two dimensional array being arranged in horizontal rows on the x-axis and vertical columns on the y-axis;

b) a first heat flow medium at a temperature T₁ in thermal contact with a first region of said substrate;

c) a second heat flow medium at a constant temperature T₂ in thermal contact with a second region of said substrate;

whereby a thermal gradient is established between said first and second regions which is proportional to the difference in temperature, T₁ -T₂, between the two mediums;

d) a sensor for measuring the fluorescence intensity emitted by reactions occurring in the reaction chambers in which intensity varies in proportion to the thermal gradient.