Device for carrying out chemical or biological reactions
View Patent ↗The invention relates to a device for carrying out of chemical or biological reactions with a reaction vessel receiving element for receiving a microtiter plate with several reaction vessels, wherein the reaction vessel receiving element has several recesses arranged in a regular pattern to receive the respective reaction vessels, a heating device for heating the reaction vessel receiving element, and a cooling device for cooling the reaction vessel. The invention is characterized by the fact that the reaction vessel receiving element is divided into several segments. The individual segments are thermally decoupled from one another, and each segment is assigned a heating device which may be actuated independently of the others. By means of the segmentation of the reaction vessel receiving element, it is possible for zones to be set and held at different temperatures. Because the reaction vessel receiving element is suitable for receiving standard microtiter plates, the device according to the invention may be integrated in existing process sequences.
1. A method for processing biological or chemical samples comprising:
denaturing samples in a first portion of a microtiter plate received in a sample block at a temperature T d1 by heating a first zone of the sample block, wherein a first thermo electric cooling device (TEC) provides heating and cooling;
denaturing samples in a second portion of the microtiter plate at a temperature T d2 by heating a second zone of the sample block, wherein a second thermo electric cooling device (TEC) provides heating and cooling,
providing at least one control unit electrically connected to the first thermo electric cooling device (TEC) and the second thermo electric cooling device (TEC), wherein the at least one control unit (a) stores temperatures T d1 and T d2 , and (b) controls the first thermo electric cooling device (TEC) and the second thermo electric cooling device (TEC) to maintain the first portion of the microtiter plate at temperature T d1 and maintain the second portion of the microtiter plate at temperature T d2 ; and
further wherein the first zone and the second zone are thermally decoupled from one another and each of the first TEC and the second TEC are independently actuatable from the other.
2. The method of claim 1 , wherein the first thermo electric cooling device provides coarse heating of the first zone to a temperature near T d1 and a first heating element provides fine heating of the first zone to about T d1 .
3. The method of claim 1 , wherein the second thermo electric cooling device provides coarse heating of the second zone to a temperature near T d2 and a second heating element provides fine heating of the second zone to about T d2 .
4. The method of claim 1 , further comprising denaturing samples in a third portion of the microtiter plate at a third temperature T d3 by heating a third zone of the sample block, wherein the third zone is thermally decoupled from the first zone and the second zone, T d2 ≠T d3 and T d1 >T d2 , wherein a third thermo electric cooling device (TEC) provides heating and cooling, and wherein the at least one control unit (a) stores temperatures T d3 , and (b) controls the third thermo electric cooling device (TEC) to maintain the third portion of the microtiter plate at temperature T d3 .
5. The method of claim 1 , further comprising denaturing samples in a third portion of the microtiter plate at a third temperature T d3 by heating a third zone of the sample block, wherein the third zone is thermally decoupled from the first zone and the second zone, T d1 ≠T d2 and T d1 <T d2 , wherein a third thermo electric cooling device (TEC) provides heating and cooling, and wherein the at least one control unit (a) stores temperatures T d3 , and (b) controls the third thermo electric cooling device (TEC) to maintain the third portion of the microtiter plate at temperature T d3 .
6. The method of claim 1 , further comprising:
annealing samples in the first portion of the microtiter plate at a temperature T a1 by cooling the first zone of the sample block; and
annealing samples in the second portion of the microtiter plate at a temperature T a2 by cooling the second zone of the sample block, wherein T a2 is not equal to T a1 .
7. The method of claim 6 , further comprising:
elongating samples in the first portion of the microtiter plate at a temperature T e1 by heating the first zone of the sample block; and
elongating samples in the second portion of the microtiter plate at a temperature T e2 by heating the second zone of the sample block, wherein T e2 is not equal to T e1 .
8. The method of claim 1 , further comprising:
repeating for a first number of cycles at least one of the steps of denaturing, annealing, and elongating samples in the first portion of the microtiter plate; and
repeating for a second number of cycles at least one of the steps of denaturing, annealing, and elongating samples in the second portion of the microtiter plate, wherein the first number of cycles is not equal to the second number of cycles.
9. The method of claim 6 , wherein a rate of cooling the first zone to anneal samples in the first portion of the microtiter plate is not equal to the rate of cooling the second zone to anneal samples in the second portion of the microtiter plate.
10. The method of claim 1 , wherein a ramp rate to T d1 is not equal to a ramp rate to T d2 .
11. The method of claim 1 , wherein a volume of the samples in the first portion of a microtiter plate is different than a volume of the samples in the second portion of the microtiter plate.
12. The method of claim 6 , wherein a residence time for annealing samples in the first portion of the microtiter plate is different than a residence time for annealing samples in the second portion of the microtiter plate.
13. The method of claim 7 , wherein a residence time for elongating samples in the first portion of the microtiter plate is different than a residence time for elongating samples in the second portion of the microtiter plate.
14. The method of claim 1 , further comprising denaturing samples in a third portion of the microtiter plate, wherein the samples in the first, second, and third portions of the microtiter plate undergo different thermal and chemistry protocols.
15. The method of claim 1 , further comprising independently amplifying three or more types of targets simultaneously using different thermal and chemistry protocols for each type of target.
16. The method of claim 15 , wherein the microtiter plate comprises six portions and the six portions are used for independent zonal amplification.
17. The method of claim 1 , wherein the first zone of the sample block comprises a first set of reaction vessel receiving elements, and wherein the second zone of the sample block comprises a second set of reaction vessel receiving elements.
18. The method of claim 1 , wherein the sample block comprises a first sample block segment corresponding to the first zone, and wherein the sample block comprises a second sample block segment corresponding to the second zone, the first sample block segment and the second sample block segment being separate from each other.
19. The method of claim 18 , wherein the first sample block segment comprises a first set of reaction vessel receiving elements, and wherein the second sample block segment comprises a second set of reaction vessel receiving elements.
20. The method of claim 1 , wherein a temperature difference between T d1 and T d2 ranges from 5° C. to 15° C.
21. The method of claim 1 , wherein a temperature difference between T a1 and T a2 ranges from 5° C. to 15° C.
22. The method of claim 1 , further comprising maintaining the temperature of the first zone at a first temperature while maintaining the temperature of the second zone at a second temperature that is different than the first temperature by from 5° C. to 15° C.
23. The method of claim 1 , wherein the first zone and the second zone are separated from one another by a gap.
24. The method of claim 1 , wherein the first zone and the second zone are separated from one another by a non heat-conducting material.