Microwave apparatus and methods of performing chemical reactions

• US 20020175163A1
• Filed: 05/20/2002
• Published: 11/28/2002
• Est. Priority Date: 12/17/1998
• Status: Active Grant

• Current Assignee: Personal Chemistry I Uppsala AB
• Original Assignee: Personal Chemistry I Uppsala AB
• Inventors: Fagrell, Magnus
• Granted Patent: US 6,720,540 B2
• Time in Patent Office: Days
• US Class Current: 219/709
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/12 employing electromagnetic waves
• CPC Class Codes: B01J 19/126 Microwaves
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/1209 Features relating to the reactor or vessel
• CPC Class Codes: B01J 2219/1215 Single reactor
• CPC Class Codes: B01J 2219/1218 Multiple reactors
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: H05B 6/68 for monitoring or control
• CPC Class Codes: H05B 6/806 for laboratory use
• CPC Class Codes: Y02B 40/00 Technologies aiming at improving the efficiency of home appliances, e.g. induction cooking or efficient technologies for refrigerators, freezers or dish washers

Abstract

The present invention relates to an apparatus and methods for performing chemical reactions. In particular, the present invention relates to an apparatus for heating chemical reaction mixtures. The apparatus applies one or more semiconductor based microwave generators making the apparatus suitable for parallel processing of chemical reaction mixtures. The invention further relates to methods for performing chemical reactions, e.g. methods for heating a plurality of samples simultaneously or sequentially, methods for monitoring a microwave heated chemical reaction, and methods where the optimum conditions with respect to parameters, such frequency and applied power can be determined for the system consisting of apparatus plus sample.

Claims

1. An apparatus for providing electromagnetic radiation to a first applicator, said apparatus comprising:

a) a first generating means for generating electromagnetic radiation,

b) a first amplifying means for amplifying the generated electromagnetic radiation,

c) means for guiding the amplified electromagnetic radiation to the first applicator, and

d) means for controlling the first generating means and the first amplifying means,

wherein the generated electromagnetic radiation comprises a plurality of frequencies, and wherein the first generating means and the first amplifying means are essentially constituted by semiconductor components.

2. An apparatus according to claim 1 further comprising a second applicator.

3. An apparatus according to claim 2, wherein the guiding means further comprises means for guiding at least part of the amplified electromagnetic radiation to the second applicator.

4. An apparatus according to any of claims 1-3 further comprising a second generating means for generating electromagnetic radiation at a plurality of frequencies and a second amplifying means for amplifying the electromagnetic radiation generated by the second generating means.

5. An apparatus according to claim 4, wherein the second generating means and the second amplifying means are essentially constituted by semiconductor components

6. An apparatus according to claim 5 further comprising guiding means for guiding the electromagnetic radiation amplified by the second amplifying means to the second applicator.

7. An apparatus according to claim 6, wherein the guiding means further comprises means for guiding at least part of the electromagnetic radiation amplified by the second amplifying means to the first applicator,

and second applicator, and wherein the guiding means comprises means for switching the electromagnetic radiation amplified by the second amplifying means between the first and second applicator.

9. An apparatus according to any of the preceding claims, wherein the first and second applicators are selected from the group consisting of near field, surface field, single mode and multi mode applicators.

10. An apparatus according to any of the preceding claims, wherein the semiconductor components constituting the first and second amplifying means comprise silicon-carbide power transistors.

11. An apparatus according to any of claims 4-10, wherein the frequency of the electromagnetic radiation generated by the first and second generating means varies according to a first and second control signal, respectively, said first end second control signal being provided by the control means.

12. An apparatus according to any of claims 4-11, wherein the amplification of the first and second amplifying means varies according to a first and second control signal, respectively, said first and second control signal being provided by the control means.

13. An apparatus according to claim 11, wherein the frequency of the electromagnetic radiation generated by the first and second generating means is within the range 300 MHz-300 GHz, such as within the range 0.5-3 GHz or within the range 50-100 GHz.

14. An apparatus according to any of the preceding claims, wherein the control means comprises a general purpose computer.

16. A method according to claim 15, wherein the electromagnetic radiation is provided specifically and independently to each of the samples.

17. A method according to claim 15 or 16, wherein the applied electromagnetic radiation comprises one or more pulses.

20. A method according to any of claims 15-19, wherein the electromagnetic radiation is provided by an apparatus according to any of claims 1-14.

27. A method according to any of claims 21-26, wherein the reaction is conducted in an apparatus according to any of claims 1-14.

30. A method according to claim 28 or 29, wherein the reaction is conducted in an apparatus according to any of claims 1-14.

31. The use of an apparatus according to any of claims 1-14 for temperature cycling a PCR mixture.

32. The use according to claim 31 for performing a chemical reaction in a sample, wherein the frequency of the electromagnetic radiation applied to the sample in the applicator, the level of irradiated power and the period of applying the electromagnetic radiation is determined by pre-set values for the chemical reaction in question, such pre-set values being stored in a storage means associated with the control means.

33. The use according to claim 31 or 32, wherein corresponding data of frequency and reflection factor are stored in a memory for further processing.

34. The use according to claims 33, wherein further processing is performed in a neural network.

36. A kit for chemically reacting chemical species with a reagent according to claim 35, said kit further comprising instructions regarding addition of the chemical species to the sample holder.

15. A method for performing a plurality of chemical reactions simultaneously or sequentially, said method comprising the steps of:

a) providing a first sample into a first applicator,

b) providing a second sample into a second applicator, and

c) applying electromagnetic radiation to the first and second samples simultaneously or sequentially for a predetermined period of time, said electromagnetic radiation having a frequency in the range of 300 MHz-300 GHz.

18. A method according to any of claims 15-17, wherein each sample is a PCR mixture.

19. A method according to any of claims 15-18, wherein the electromagnetic radiation is applied in cycles of at least two steps where the samples are cooled at least during a part of each cycle.

21. A method for performing a chemical reaction, said method comprising the steps of:

a) providing a sample in an applicator,

b) applying electromagnetic radiation to the sample for a first predetermined period of time at a first level of power and varying the frequency of the electromagnetic radiation between two predetermined values and with a predetermined resolution, and determining a reflection factor of electromagnetic radiation from the sample at at least some (two) of the frequencies covered by the range of the two predetermined values by determining the level of a feed-back signal, thereby obtaining a first set of reflection factors,

c) changing the physical and/or chemical properties of the sample,

d) applying electromagnetic radiation to the applicator at a second level of power and varying the frequency of the electromagnetic radiation between two predetermined values and with a predetermined resolution, the range defined by the predetermined values being included in the range defined by the predetermined values in step b), and determining a reflection factor of electromagnetic radiation from the sample at at least some (two) of the frequencies covered by the range of the two predetermined values by determining the level of the feed-back signal, thereby obtaining a second set of reflection factors, and

e) repeating step c) and d) until the difference in reflection factors calculated as the mathematical difference (subtraction) between the frequencies associated with the first and second set of reflection factors is within a predetermined range.

25. A method according to any of claims 21-24, wherein the starting frequency is in the range of 300 MHz-300 GHz.

26. A method according to any of claims 21-25, wherein the predetermined values between which the frequency of the electromagnetic field is varied are in the range of 300 MHz-300 GHz, such as within the range 0.5-3 GHz or within the range 50-100 GHz.

22. A method for performing a chemical reaction, said method comprising the steps of:

a) providing a sample in an applicator,

b) applying electromagnetic radiation to the sample, the electromagnetic radiation having a starting frequency,

c) varying the frequency of the applied electromagnetic radiation between two predetermined values and with a predetermined resolution,

d) determining a reflection factor of electromagnetic radiation from the sample by determining a level of a feed-back signal during at least part of the varying of the frequency of the electromagnetic radiation, and

e) determining, from the level of the feed-back signal, the frequency of the electromagnetic radiation where the reflection factor is within a predetermined range.

29. A method according to claim 28, wherein the mathematical operation for obtaining the first and second reflection spectra comprise Fourier Transformation.

23. A method for performing a chemical reaction, said method comprising the steps of:

a) providing a sample in an applicator,

b) applying electromagnetic radiation to the sample, the electromagnetic radiation having a starting frequency,

c) varying the frequency of the electromagnetic radiation incrementally around the starting frequency,

d) determining a reflection factor of electromagnetic radiation from the sample by determining a level of a feed-back signal at the starting frequency, at a frequency incrementally lower than the starting frequency and at a frequency incrementally higher than the starting frequency,

e) repeating step b) to d) until the reflection factor is minimum.

24. A method for performing a chemical reaction, said method comprising the steps of:

a) providing a sample in an applicator,

b) applying electromagnetic radiation to the sample, the electromagnetic radiation having a starting frequency,

c) varying the frequency of the electromagnetic radiation incrementally around the starting frequency,

d) determining a reflection factor of electromagnetic radiation from the sample by determining a level of a feed-back signal at the starting frequency, at a frequency incrementally lower than the starting frequency and a frequency incrementally higher than the starting frequency,

e) comparing the determined reflection factor with a predetermined reflection factor,

f) adjusting the starting frequency to a frequency so that the determined reflection factor is within a predetermined range around the predetermined reflection factor, and

g) repeating step c) to f) as often as desirable.

28. A method for performing a chemical reaction, said method comprising the steps of:

a) providing a sample in an applicator,

b) applying electromagnetic radiation to the sample in form of a first pulse with a predetermined shape and characterising a reflected pulse from the applicator by performing a mathematical operation so as to obtain a first reflected spectrum,

c) changing the physical and/or chemical properties of the sample,

d) applying electromagnetic radiation to the sample in form of a second pulse with a predetermined shape and characterising a reflected pulse from the applicator by performing a mathematical operation so as to obtain a second reflected spectrum,

e) repeating step c) and d) until the difference between the first and second reflected spectra calculated as the mathematical difference (subtraction) between the first and second spectra is within a predetermined range.

35. A kit for chemically reacting chemical species with a reagent optionally under the action of a catalyst, wherein the chemical reaction is performed in an apparatus according to any of claims 114, said kit comprising:

a) a sample holder comprising at least one of the reagent and the optional catalyst,

b) an electronic storage means comprising data concerning the chemical reaction between the chemical species and the reagent under the optional action of the catalyst, said electronic storage means and apparatus being adapted for retrieving the data from the storage means and processing said data so as to control the application of an electromagnetic radiation to said sample holder.