Sensor and method for detecting predetermined chemical species in solution

• US 5,705,399 A
• Filed: 05/20/1994
• Issued: 01/06/1998
• Est. Priority Date: 05/20/1994
• Status: Expired due to Fees

• Current Assignee: The Cooper Union for the Advancement of Science and Art
• Original Assignee: The Cooper Union For The Advancement of Science and Art Incorporated
• Inventors: Larue, Rebecca A.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/247,041
• Time in Patent Office: 1,327 Days
• Field of Search: 73/61.75, 73/64.53, 73/579, 73/580, 73/584, 73/DIG. 4, 310/311, 310/312, 310/313 R, 310/313 A, 310/340, 310/361, 310/365, 310/367, 310/369, 422/50, 422/68.1, 422/82.01, 435/7.1, 435/287, 435/291, 435/287.1, 435/287.2, 436/500, 436/501, 436/518, 436/524, 436/525, 436/527, 436/531, 436/532, 436/149-151, 436/806, 436/807, 436/817
• US Class Current: 436/501
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A chemical sensor for measuring a change in the sensor mass relating to the interaction of a surface of the sensor with a solution comprises a crystal detector oscillator capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator. The crystal detector oscillator has a first crystal side for directly contacting the solution, and a second crystal side isolated from contacting the solution. A first electrode is integral to the first crystal side, with the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode. A second electrode is integral to the second crystal side. The sensor may be employed to detect the concentration of predetermined species in solution by adsorbing a predetermined species-specific complementary material such as an antibody onto the active crystal sites of the first crystal side, and thereafter contacting the first crystal side with the species-containing solution. The sensor may also be used to measure the change in sensor mass relating to the degradation of a coating applied to the first crystal side thereof.

Claims

1. A quartz crystal microbalance chemical sensor comprising:

(a) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the detector oscillator, the crystal detector oscillator having a first crystal side for directly contacting a solution, and a second crystal side isolated from contacting the solution;

(b) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(c) a second electrode integral to the second crystal side.

2. The sensor of claim 1, wherein the sensor measures the concentration of predetermined chemical species in solution with the first crystal side having a coating applied thereto, and a change in sensor mass relating to degradation of the coating in response to the presence of the chemical species is measured.

3. The sensor of claim 2, wherein the coated first crystal side is contacted with a solution containing the predetermined chemical species.

4. The sensor of claim 1, wherein the crystal detector oscillator is a quartz crystal.

5. The sensor of claim 4, wherein the crystal detector oscillator is an AT-cut quartz crystal.

6. The sensor of claim 1, wherein the first electrode is gold, silver, nickel, chromium or tantalum, and the second electrode is gold, silver, nickel, chromium or tantalum.

7. The sensor of claim 1, wherein the first and second electrodes are vacuum deposited on the first and second crystal sides, respectively.

8. The sensor of claim 1, wherein the sensor additionally comprises means operatively coupled to the crystal detector oscillator for conveying the measurement signal for signal processing.

9. The sensor of claim 1, wherein the first electrode is ring-shaped.

10. The sensor of claim 1, wherein the first crystal side is contacted with a solution containing a predetermined chemical species-specific complementary material prior to contacting the first crystal side with a predetermined chemical species-containing solution.

11. The sensor of claim 10, wherein the complementary material is an antibody.

12. The sensor of claim 11, wherein the predetermined chemical species is thyroxine and the antibody is anti-thyroxine.

13. The sensor of claim 11, wherein the predetermined chemical species is calcitonin and the antibody is anti-calcitonin.

14. The sensor of claim 1, wherein the solution is human blood.

15. A method for detecting the concentration of predetermined chemical species in solution, the method consisting essentially of:

(a) providing a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the detector oscillator, the crystal detector oscillator having a first crystal side for contacting the species-containing solution, and a second crystal side isolated from contacting the species-containing solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode, and (iii) a second electrode integral to the second crystal side;

(b) contacting the first crystal side with a solution containing a predetermined species-specific complementary material to the predetermined chemical species, wherein the species-specific complementary material is adsorbed onto the first crystal side;

(c) measuring the resonant frequency of the crystal detector oscillator after contacting with the solution containing the complementary material;

(d) contacting the first crystal side with a solution containing the predetermined chemical species, thereby causing binding of the predetermined chemical species to the complementary material-adsorbed first crystal side;

(e) measuring the resonant frequency of the crystal detector oscillator after contacting the first crystal side with the species-containing solution; and

(f) comparing the difference in resonant frequencies measured in steps (c) and (e) to determine the concentration of the species in the species-containing solution.

16. The method of claim 15, further comprising the steps of providing a reference oscillator having a reference resonant frequency, comparing the difference between the resonant frequency measured in step (c) and the reference resonant frequency to obtain a first normalized resonant frequency, comparing the difference between the resonant frequency measured in step (e) and the reference resonant frequency to obtain a second normalized resonant frequency, and comparing the difference between the first and second normalized resonant frequencies to determine the concentration of the chemical species in the species-containing solution.

17. The method of claim 15, wherein the complementary material is an antibody.

18. The method of claim 17, wherein the predetermined chemical species is thyroxine and the antibody is anti-thyroxine.

19. The method of claim 17, wherein the predetermined chemical species is calcitonin and the antibody is anti-calcitonin.

20. The method of claim 15, wherein the species-containing solution is human blood.

21. The method of claim 15, further comprising after step (f) the step of contacting the first crystal side with a cleaning solution to remove the species and complementary material from the surface of the first crystal side and regenerate active sites on the surface of the first crystal side.

22. An apparatus comprising:

a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator, the crystal detector oscillator having a first crystal side for directly contacting a solution, and a second crystal side isolated from contacting the solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(iii) a second electrode integral to the second crystal side; and

sensor detecting means operatively coupled to the sensor for detecting the resonant frequency of the crystal detector oscillator and providing a detector output signal representative of the crystal detector oscillator resonant frequency.

23. The apparatus of claim 22, further comprising:

display means operatively coupled to the sensor detecting means for displaying the detector output signal.

24. The apparatus of claim 22, further comprising:

a reference oscillator having a resonant frequency;

reference detecting means operatively coupled to the reference oscillator for detecting the resonant frequency of the reference oscillator and providing a reference output signal representative of the reference oscillator resonant frequency; and

signal comparison means operatively coupled to the sensor detecting means and the reference detecting means for comparing the difference between the detector output signal and the reference output signal and providing a difference output signal.

25. The apparatus of claim 24, further comprising:

display means operatively coupled to the signal comparison means for displaying the difference output signal.

26. The apparatus of claim 22, wherein the sensor measures the concentration of predetermined chemical species in solution with the first crystal side having a coating applied thereto, and a change in sensor mass relating to degradation of the coating in response to the presence of the chemical species is measured.

27. The apparatus of claim 26, wherein the coated first crystal side is contacted with a solution containing the predetermined chemical species.

28. A method for detecting the concentration of predetermined chemical species in solution, the method consisting essentially of:

(a) providing an apparatus which comprises a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator, the crystal detector oscillator having a first crystal side for contacting the species-containing solution, and a second crystal side isolated from contacting the species-containing solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining, an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(iii) a second electrode integral to the second crystal side; and

sensor detecting means operatively coupled to the sensor for detecting the resonant frequency of the crystal detector oscillator and providing a detector output signal representative of the crystal detector oscillator resonant frequency;

(b) contacting the first crystal side with a solution containing a predetermined species-specific complementary material to the predetermined chemical species, wherein the species-specific complementary material is adsorbed onto the first crystal side;

(c) measuring the resonant frequency of the crystal detector oscillator after contacting with the solution containing the complementary material;

(d) contacting the first crystal side with a solution containing the predetermined chemical species, thereby causing binding of the predetermined chemical species to the complementary material-adsorbed first crystal side;

(e) measuring the resonant frequency of the crystal detector oscillator after contacting the first crystal side with the species-containing solution; and

(f) comparing the difference in resonant frequencies measured in steps (c) and (e) to determine the concentration of the species in the species-containing solution.

29. The method of claim 28, further comprising:

providing a reference oscillator;

providing reference detecting means operatively coupled to the reference oscillator for detecting the resonant frequency of the reference oscillator and providing a reference output signal representative of the reference oscillator resonant frequency;

providing signal comparison means operatively coupled to the sensor detecting means and the reference detecting means for comparing the difference between the detector output signal and the reference output signal and providing a difference output signal;

comparing the difference between the resonant frequency measured in step (c) and the reference resonant frequency to obtain a first normalized resonant frequency, comparing the difference between the resonant frequency measured in step (e) and the reference resonant frequency to obtain a second normalized resonant frequency; and

comparing the difference between the first and second normalized resonant frequencies to determine the concentration of the chemical species in the species-containing solution.

30. A quartz crystal microbalance chemical sensor for measuring the concentration of predetermined chemical species in solution by measuring a change in sensor mass relating to interaction of a surface of the sensor with a solution, the sensor comprising:

(a) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the detector oscillator, the crystal detector oscillator having a first crystal side for contacting the solution, and a second crystal side isolated from contacting the solution;

(b) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(c) a second electrode integral to the second crystal side, wherein the first crystal side has a coating applied thereto and a change in sensor mass relating to interaction of the coating with the predetermined chemical species is measured.

31. The sensor of claim 30, wherein the coated first crystal side is contacted with a solution containing the predetermined chemical species.

32. The sensor of claim 30, wherein the crystal detector oscillator is a quartz crystal.

33. The sensor of claim 30, wherein the crystal detector oscillator is an AT-cut quartz crystal.

34. The sensor of claim 30, wherein the first electrode is gold, silver, nickel, chromium or tantalum, and the second electrode is gold, silver, nickel, chromium or tantalum.

35. The sensor of claim 30, wherein the first and second electrodes are vacuum deposited on the first and second crystal sides, respectively.

36. The sensor of claim 30, wherein the sensor additionally comprises means operatively coupled to the crystal detector oscillator for conveying the measurement signal for signal processing.

37. The sensor of claim 30, wherein the first electrode is ring-shaped.

38. The sensor of claim 30, wherein the first crystal side is coated by contacting the first crystal side with a solution containing a predetermined species-specific complementary material prior to contacting the first crystal side with the species-containing solution.

39. The sensor of claim 38, wherein the complementary material is an antibody.

40. The sensor of claim 39, wherein the predetermined chemical species is thyroxine and the antibody is anti-thyroxine.

41. The sensor of claim 38, wherein the predetermined chemical species is calcitonin and the antibody is anti-calcitonin.

42. The sensor of claim 30, wherein the species-containing solution is human blood.

43. A method for detecting the concentration of predetermined chemical species in solution by measuring a change in sensor mass relating to interaction of a surface of the sensor with a solution, the method consisting essentially Of:

(a) providing a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the detector oscillator, the crystal detector oscillator having a first crystal side for contacting the species-containing solution, and a second crystal side isolated from contacting the species-containing solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode, and (iii) a second electrode integral to the second crystal side;

(b) applying a coating to the first crystal side by contacting the first crystal side with a solution containing a predetermined species-specific complementary material to the predetermined chemical species;

(c) measuring the resonant frequency of the crystal detector oscillator after contacting with the solution containing the complementary material;

(d) contacting the first crystal side with a solution containing the predetermined chemical species;

(e) measuring the resonant frequency of the crystal detector oscillator after contacting the first crystal side with the species-containing solution; and

(f) comparing the difference in resonant frequencies measured in steps (c) and (e) to determine the concentration of the species in the species-containing solution.

44. The method of claim 43, further comprising the steps of providing a reference oscillator having a reference resonant frequency, comparing the difference between the resonant frequency measured in step (c) and the reference resonant frequency to obtain a first normalized resonant frequency, comparing the difference between the resonant frequency measured in step (e) and the reference resonant frequency to obtain a second normalized resonant frequency, and comparing the difference between the first and second normalized resonant frequencies to determine the concentration of the chemical species in the species-containing solution.

45. The method of claim 43, wherein the complementary material is an antibody.

46. The method of claim 45, wherein the predetermined chemical species is thyroxine and the antibody is anti-thyroxine.

47. The method of claim 45, wherein the predetermined chemical species is calcitonin and the antibody is anti-calcitonin.

48. The method of claim 43, wherein the species-containing solution is human blood.

49. The method of claim 43, further comprising after step (f) the step of contacting the first crystal side with a cleaning solution to remove the species and complementary material from the surface of the first crystal side and regenerate active sites on the surface of the first crystal side.

50. An apparatus for measuring the concentration of predetermined chemical species in solution comprising:

a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator, the crystal detector oscillator having a first crystal side for contacting a solution, and a second crystal side isolated from contacting the solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(iii) a second electrode integral to the second crystal side; and

sensor detecting means operatively coupled to the sensor for detecting the resonant frequency of the crystal detector oscillator and providing a detector output signal representative of the crystal detector oscillator resonant frequency,

wherein the first crystal side has a coating applied thereto, and a change in sensor mass relating to interaction of the coating with the predetermined chemical species is measured.

51. The apparatus of claim 50, wherein the coated first crystal side is contacted with a solution containing the predetermined chemical species.

52. The apparatus of claim 50, further comprising:

display means operatively coupled to the sensor detecting means for displaying the detector output signal.

53. The apparatus of claim 50, further comprising:

a reference oscillator;

reference detecting means operatively coupled to the reference oscillator for detecting the resonant frequency of the reference oscillator and providing a reference output signal representative of the reference oscillator resonant frequency; and

signal comparison means operatively coupled to the sensor detecting means and the reference detecting means for comparing the difference between the detector output signal and the reference output signal and providing a difference output signal.

54. The apparatus of claim 53, further comprising:

display means operatively coupled to the signal comparison means for displaying the difference output signal.

55. A method for detecting the concentration of predetermined chemical species in solution by measuring a change in sensor mass relating to interaction of a surface of the sensor with a solution, the method consisting essentially of:

(a) providing an apparatus which comprises a quartz crystal microbalance chemical sensor which comprises (i) a crystal detector oscillator having a resonant frequency and capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator, the crystal detector oscillator having a first crystal side for contacting the species-containing solution, and a second crystal side isolated from contacting the species-containing solution, (ii) a first electrode integral to the first crystal side, the first electrode having an inner and outer perimeter defining, an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode; and

(iii) a second electrode integral to the second crystal side; and

sensor detecting means operatively coupled to the sensor for detecting the resonant frequency of the crystal detector oscillator and providing a detector output signal representative of the crystal detector oscillator resonant frequency;

(b) applying a coating to the first crystal side by contacting the first crystal side with a solution containing a predetermined species-specific complementary material to the predetermined chemical species;

(c) measuring the resonant frequency of the crystal detector oscillator after contacting with the solution containing the complementary material;

(d) contacting the first crystal side with a solution containing the predetermined chemical species;

(e) measuring the resonant frequency of the crystal detector oscillator after contacting the first crystal side with the species-containing solution; and

(f) comparing the difference in resonant frequencies measured in steps (c) and (e) to determine the concentration of the species in the species-containing solution.

56. The method of claim 55, further comprising:

providing a reference oscillator;

providing reference detecting means operatively coupled to the reference oscillator for detecting the resonant frequency of the reference oscillator and providing a reference output signal representative of the reference oscillator resonant frequency;

providing signal comparison means operatively coupled to the sensor detecting means and the reference detecting means for comparing the difference between the detector output signal and the reference output signal and providing a difference output signal;

comparing the difference between the resonant frequency measured in step (c) and the reference resonant frequency to obtain a first normalized resonant frequency, comparing the difference between the resonant frequency measured in step (e) and the reference resonant frequency to obtain a second normalized resonant frequency; and

comparing the difference between the first and second normalized resonant frequencies to determine the concentration of the chemical species in the species-containing solution.