System and method for detecting and identifying molecular events in a test sample using a resonant test structure

• US 6,586,946 B2
• Filed: 02/01/2001
• Issued: 07/01/2003
• Est. Priority Date: 11/13/2000
• Status: Expired due to Fees

• Current Assignee: Mds Sciex
• Original Assignee: Signature BioScience, Inc.
• Inventors: Peng, Hong, Hefti, John
• Primary Examiner(s): Le, N.
• Assistant Examiner(s): Teresinski, John
• Application Number:
  US09/775,710
• Publication Number:
  US 20020149377A1
• Time in Patent Office: 880 Days
• Field of Search: 324/667, 324/668, 324/675, 324/674, 324/676, 324/682, 324/708, 324/707, 324/710, 324/425, 324/436, 324/442, 324/315, 324/633, 324/653, 324/652, 324/636
• US Class Current: 324/636
• CPC Class Codes: G01N 22/00 Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more G01N3/00 - G01N17/00, G01N24/00 take precedence
• CPC Class Codes: G01N 33/487 of liquid biological material

Abstract

A system and method for detecting a molecular event in a test sample using a resonant test structure is presented. The method includes providing a resonant test structure having a resonant response associated therewith. Next, a first resonant response of the resonant test structure is obtained when the resonant test structure is electromagnetically coupled to a reference sample, the reference sample having a known composition. A second resonant response is also obtained when the resonant test structure is electromagnetically coupled to the test sample, the test sample having an unknown composition. Subsequently, one or more first electrical parameters, such as the q-factor of the resonator, are derived from the first resonant response. One or more second electrical parameters are similarly derived from the second resonant response. The similarity or difference between the first and second electrical parameters are analyzed to determine the presence or absence of the molecular event in the test sample.

Claims

1. A method for detecting a molecular event in a test sample, the method comprising:

providing a test structure having a measureable signal response when a test signal is input and an output signal is recovered, wherein the measureable signal response is a resonant response;

obtaining a first resonant response of the test structure when the test structure is electromagnetically coupled to a reference sample;

obtaining a second resonant response of the test structure when the test structure is electromagnetically coupled to the test sample;

deriving one or more electrical parameters from the first resonant response;

deriving one or more electrical parameters from the second resonant response;

detecting similarity or difference between the electrical parameters derived from the first and second resonant responses as an indication of the molecular event in the test sample;

determining the difference between the electrical parameters derived from the first and second resonant response; and

indicating that, if the reference sample contains the molecular event and if the difference between the one or more electrical parameters derived from the first and second resonant responses does not exceed a predefined value, the test sample includes the molecular event.

2. The method of claim 1 wherein the one or more electrical parameters comprise s-parameter measurements, Q-factor measurements, or resonant frequency measurements.

3. The method of claim 1, wherein detecting similarity or difference between the one or more electrical parameters derived from the first and second resonant responses, wherein the electrical parameters are Q-factor measurements, comprises:

computing difference quantity Δ

Q as the difference between a second Q-factor derived from the second resonant response and a first Q-factor derived from the first resonant response; and

indicating that, if the reference sample contains the molecular event and if the difference quantity Δ

Q does not exceed a predefined value, the test sample includes the molecular event.

4. The method of claim 1, wherein providing a resonant test structure comprises providing a resonant coaxial probe.

5. The method of claim 1, wherein obtaining a first resonant response and deriving one or more electrical parameters are performed prior to the act of measuring a second resonant response, the method further comprising storing the one or more electrical parameters derived from the first resonant response in a database.

6. The method of claim 1, wherein obtaining first and second resonant responses comprises obtaining first and second input s-parameter responses at one or more frequencies in the range of 10 MHz and 1000 GHz.

7. The method of claim 1, wherein detecting similarity or difference between the one or more electrical parameters derived from the first and second resonant responses, wherein the electrical parameters are Q-factor measurements, comprises:

computing difference quantity Δ

Q as the difference between a second Q-factor derived from the second resonant response and a first Q-factor derived from the first resonant response; and

indicating that, if the reference sample does not contain the molecular event and if the difference quantity Δ

Q does not exceed a predefined value, the test sample excludes the molecular event.

8. The method of claim 5, further comprising retrieving the one or more electrical parameter derived from the first resonant response from the database.

9. The method of claim 1, wherein detecting similarity or difference between the one or more electrical parameters derived from the first and second resonant responses, wherein the electrical parameters are resonant frequency measurements, comprises:

computing a difference quantity Δ

f_res as the difference between a second resonant frequency derived from the second resonant response and a first resonant frequency derived from the first resonant response; and

indicating that, if the reference sample contains the molecular event and if the difference quantity Δ

f_res does not exceed a predefined value, the test sample includes the molecular event.

10. The method of claim 1, wherein detecting similarity or difference between the one or more electrical parameters derived from the first and second resonant responses, wherein the electrical parameters are resonant frequency measurements, comprises:

computing a difference quantity Δ

f_res as the difference between a second resonant frequency derived from the second resonant response and a first resonant frequency derived from the first resonant response; and

indicating that, if the reference sample does not contain the molecular event and if the difference quantity Δ

f_res does not exceed a predefined value, the test sample excludes the molecular event.

11. The method of claim 9, wherein obtaining a first resonant response and deriving a first resonant frequency are performed prior to obtaining a second resonant response, the method further comprising storing the first resonant frequency in a database.

12. The method of claim 11, further comprising retrieving the first resonant frequency from the database.

13. A system configured to detect a molecular event in a test sample, the system comprising:

a test structure having a measureable signal response when a test signal is input and an output signal is recovered, wherein the measureable signal response is a resonant response;

means for obtaining a first resonant response of the test structure when the test structure is electromagnetically coupled to a reference sample;

means for obtaining a second resonant response of the test structure when the test structure is electromagnetically coupled to the test sample;

means for deriving one or more electrical parameters from the first resonant response;

means for deriving one or more electrical parameters from the second resonant response; and

means for detecting similarity or difference between the one or more electrical parameters derived from the first and second resonant responses as an indication of the molecular event in the test sample.

14. The system of claim 13 wherein the resonant test structure comprises a resonant coaxial probe.

15. The system of claim 13, wherein the means for obtaining the first and second resonant responses each comprise a vector network analyzer.

16. The system of claim 13, wherein the means for obtaining the first and second resonant responses each comprise a scalar network analyzer.

17. The system of claim 13, wherein the means for deriving a first resonant frequency from the first resonant response and a second resonant frequency from the second resonant response comprises an automated network analyzer.

18. The system of claim 13, wherein the means for detecting a difference between the first and second electrical parameters comprises a computer.

19. The system of claim 13 wherein the one or more electrical parameters comprise s-parameter measurements, Q-factor measurements, or resonant frequency measurements.

20. A computer program product stored on a computer-readable medium and operable to control a test system to detect a molecular event in a test sample, the computer program product comprising:

code that directs the test system to obtain a first resonant response of a test structure when the test structure is electromagnetically coupled to a reference sample;

code that directs the test system to obtain a second resonant response of the test structure when the test structure is electromagnetically coupled to the test sample;

code that directs the test system to derive one or more electrical parameters from the first resonant response;

code that directs the test system to derive one or more electrical parameters from the second resonant response; and

code that directs the test system to detect similarity or difference between the one or more electrical parameters derived from the first and second resonant responses as an indication of the molecular event in the test sample.

21. The computer program product of claim 20, wherein code that directs the test system to obtain first and second resonant responses comprises code that directs the test system to obtain first and second input s-parameters of the test structure when electromagnetically coupled to the reference and test samples, respectively.

22. The computer program product of claim 21, wherein code that directs the test system to derive one or more electrical parameters from the first and second resonant responses, respectively, comprises code that directs the test system to derive first and second resonant frequencies from the first and second resonant responses, respectively.

23. The computer program product of claim 21, wherein code that directs the test system to derive one or more electrical parameters from the first and second resonant responses, respectively, comprises code that directs the test system to derive first and second Q-factors from the first and second resonant responses, respectively.

24. The computer program product of claim 23, wherein code that directs the test system to detect similarity or difference between the first and second Q-factors comprises code that directs the test system to detect a difference between the first and second Q-factors.

25. The computer program product of claim 23, further comprising:

code that directs the test system to derive a first resonant frequency from the first resonant response; and

code that directs the test system to derive a second resonant frequency from the second resonant response.

26. The computer program product of claim 25, further comprising code that directs the test system to detect a difference between the first and second resonant frequencies.

27. A computer readable database stored in a computer readable medium for storing data indicating a molecular event within a reference sample, the computer readable database including one or more data structures operable to store data comprising first data representing the Q-factor of a test structure when the test structure is electromagnetically coupled to the reference sample.

28. The computer readable database of claim 27, further comprising second data representing the resonant frequency of the test structure when the test structure is electromagnetically coupled to the reference sample.

29. The computer readable database of claim 27, further comprising third data representing the temperature of the reference sample when the test structure is electromagnetically coupled to the reference sample.

30. The computer readable database of claim 27, further comprising fourth data representing the composition of the reference sample when the test structure is electromagnetically coupled to the reference sample.

31. The computer readable database of claim 27, further comprising fifth data representing the pH of the reference sample when the test structure is electromagnetically coupled to the reference sample.