Cross-reactive sensors

• US 7,250,267 B2
• Filed: 03/14/2001
• Issued: 07/31/2007
• Est. Priority Date: 03/14/2000
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Walt, David R., Steemers, Frank J., Schauer, Caroline L.
• Primary Examiner(s): TATE, CHRISTOPHER ROBIN
• Application Number:
  US10/221,815
• Publication Number:
  US 20070122861A1
• Time in Patent Office: 2,330 Days
• Field of Search: 435/7.9, 435/18, 435/19, 435/23, 435/24, 435/25, 436/172, 436/164, 436/165
• US Class Current: 435/15
• CPC Class Codes: C12Q 1/37 involving peptidase or proteinase
• CPC Class Codes: C12Q 1/44 involving esterase

Abstract

The present invention provides a novel cross-reactive sensor system utilizing cross-reactive recognition elements. In the inventive system, each of said one or more cross-reactive recognition elements is capable of interacting with more than one species of liquid analyte of interest, whereby each of said one or more cross-reactive recognition elements reacts in a different manner with each of said one or more species of liquid analytes of interest to produce a detectable agent of each analyte of interest, whereby said detectable agent is analyzed and the information is processed for data acquisition and interpretation. In certain preferred embodiments, the detectable agent and/or change is detected directly, while in certain other preferred embodiments, the detectable agent and/or change is detected with the help of a transducing agent capable of relaying information about each detectable agent generated for each of said species of liquid analyte of interest, whereby said information is processed for data acquisition and interpretation. The present invention also provides method for the analysis of analytes comprising contacting one or more analytes with the inventive system described above.

Claims

1. A method for the analysis of analytes comprising steps of:

contacting one or more analytes with a sensor system, wherein said sensor system comprises;

one or more cross-reactive recognition elements, wherein each of said cross-reactive recognition elements is an enzyme or a protein receptor and wherein each of said cross-reactive recognition elements interacts directly with more than one species of liquid analyte of interest, whereby each of said cross-reactive recognition elements interacts in a different manner with each of said more than one species of liquid analyte of interest to produce a detectable event for each analyte of interest, wherein said detectable event is a detectable agent, a detectable change or both; and

analyzing the detectable event produced for each analyte of interest to obtain information about said detectable event, process the information for data acquisition, and provide interpretation of data.

5. The method of any one of claims 1 to 4, wherein said sensor system includes a transducer.

6. The method of claim 5, wherein said transducer is selected from the group consisting of electrochemical transducer, optical transducer, thermal transducer, and acoustic transducer.

7. The method of claim 6, wherein said transducer is an optical transducer involving an energy transduction mode selected from the group consisting of absorbance, chemiluminescence, electrogenerated chemiluminescence, fluorescence, fluorescence lifetime, fiber optic waveguides, near-field microscopy, near-field spectroscopy, near-infrared, planar waveguides, surface enhanced raman, and surface plasmon resonance.

8. The method of claim 7, wherein said optical transducer comprises a pH sensitive dye.

9. The method of claim 8, wherein said pH sensitive dye is selected from the group consisting of fluorescein, carboxyfluorescein, SNAFL, SNARF, LysoSensor Green DND-189, Oregon Green NERF, LysoSensor Yellow/Blue DND-160, HPTS (pyranine), BCECF, BCPCF, and Bodipy.

10. The method of claim 7, wherein said optical transducer comprises an oxygen sensitive dye.

11. The method of claim 10, wherein said oxygen sensitive dye comprises Ru(4,7-diphenyl-1,10-phen)₃(Cl)₂, or Ru(bipy)₃Cl₂.

12. The method of any one of claims 1 to 4, wherein the step of analyzing comprises utilizing a processing unit to provide interpretation of data.

13. The method of claim 12 further comprising processing interpreted data using chemoinformatics.

14. The method of claim 13, wherein said step of processing using chemoinformatics comprises interpreting data using computational analysis.

15. The method of any one of claims 1 to 4, wherein said cross-reactive recognition elements are provided in array format having a plurality of addresses, wherein each address in the array contains one cross-reactive recognition element.

16. The method of claim 15, wherein the array comprises a plurality of addresses, wherein two or more of the addresses contain the same type of cross-reactive recognition element.

17. The method of claim 15, wherein the array comprises a plurality of addresses, wherein each address contains the same cross-reactive recognition element.

18. The method of any one of claims 1 to 4, wherein said cross-reactive recognition elements are provided in array format having a plurality of addresses, wherein each address in the array contains more than one cross-reactive recognition element.

19. The method of any one of claims 1 to 4, wherein the cross-reactive recognition element is attached to a solid support.

20. The method of claim 19, wherein the solid support is a bead, or a resin.

21. The method of claim 20, wherein the solid support is a bead, each bead is attached to one type of cross-reactive recognition element, and wherein together the beads are provided in array format having a plurality of addresses, wherein each address in the array contains one bead.

22. The method of claim 21, wherein the array comprises a plurality of addresses, wherein two or more of the addresses contain beads having the same type of cross-reactive recognition element.

23. The method of claim 21, wherein the array comprises a plurality of addresses, wherein each address contains beads having the same cross-reactive recognition element.

24. The method of claim 20, wherein the solid support is a bead, each bead is attached to one type of cross-reactive recognition element, and wherein together the beads are provided in array format having a plurality of addresses, wherein each address in the array contains more than one bead.

25. The method of any one of claims 1 to 4, wherein each of said cross-reactive recognition elements is an enzyme selected from the group consisting of esterases, proteases, hydrolases, isomerases, lysases, transferases, oxido-reductases, and ligases.

26. The method of claim 25, wherein each of said cross-reactive recognition elements is an esterase selected from the group consisting of esterase from rabbit liver, esterase from porcine liver, acetylcholine esterase from electrophorous electricus, esterase from hog pancrease, esterase from hog liver, esterase from horse liver, esterase from mucor miehei, esterase from bacillus sp., and esterase from bacillus thermoglucosidasius.

27. The method of claim 25, wherein each of said cross-reactive recognition elements is a protease selected from the group consisting of proteinase K, chymotrypsin, papain, carboxypepsidase A, substilisin, protease (staphylococcus), and protease VII.

2. A method for the analysis of analytes comprising steps of:

contacting one or more analytes with a sensor system, wherein said sensor system comprises;

two or more cross-reactive recognition elements, wherein each of said cross-reactive recognition elements is an enzyme or a protein receptor and wherein each of said cross-reactive recognition elements interacts directly with more than one species of liquid analyte of interest, whereby each of said cross-reactive recognition elements interacts in a different manner with each of said more than one species of liquid analyte of interest to produce a detectable event for each analyte of interest, wherein said detectable event is a detectable agent, a detectable change or both; and

analyzing the detectable event produced for each analyte of interest to obtain information about said detectable event, process the information for data acquisition, and provide interpretation of data.

3. A method for the analysis of analytes comprising steps of:

contacting one or more analytes with a sensor system, wherein said sensor system comprises;

two to five cross-reactive recognition elements, wherein each of said cross-reactive recognition elements is an enzyme or a protein receptor and wherein each of said cross-reactive recognition elements interacts directly with more than one species of liquid analyte of interest, whereby each of said cross-reactive recognition elements interacts in a different manner with each of said more than one species of liquid analyte of interest to produce a detectable event for each analyte of interest, wherein said detectable event is a detectable agent, a detectable change or both; and

analyzing the detectable event produced for each analyte of interest to obtain information about said detectable event, process the information for data acquisition, and provide interpretation of data.

4. A method for the analysis of analytes comprising steps of:

contacting one or more analytes with a sensor system, wherein said sensor system comprises;

two to ten cross-reactive recognition elements, wherein each of said cross-reactive recognition elements is an enzyme or a protein receptor and wherein each of said cross-reactive recognition elements interacts directly with more than one species of liquid analyte of interest, whereby each of said cross-reactive recognition elements interacts in a different manner with each of said more than one species of liquid analyte of interest to produce a detectable event for each analyte of interest, wherein said detectable event is a detectable agent, a detectable change or both; and

analyzing the detectable event produced for each analyte of interest to obtain information about said detectable event, process the information for data acquisition, and provide interpretation of data.

28. A method for the analysis of analytes comprising steps of:

contacting one or more analytes with a sensor system, wherein said sensor system comprises;

one or more cross-reactive recognition elements, wherein each of said cross-reactive recognition elements is an enzyme or protein receptor attached to a solid support and wherein each of said cross-reactive recognition elements interacts directly with more than one species of liquid analyte of interest, whereby each of said cross-reactive recognition elements interacts in a different manner with each of said more than one species of liquid analyte of interest to produce a detectable event for each analyte of interest, wherein said detectable event is a detectable agent, a detectable change or both; and

analyzing the detectable event produced for each analyte of interest to obtain information about said detectable event, process the information for data acquisition, and provide interpretation of data.

29. The method of claim 28, wherein said sensor system includes a transducer.

30. The method of claim 29, wherein said transducer is selected from the group consisting of electrochemical transducer, optical transducer, thermal transducer, and acoustic transducer.

31. The method of claim 30, wherein said transducer is an optical transducer involving an energy transduction mode selected from the group consisting of absorbance, chemiluminescence, electrogenerated chemiluminescence, fluorescence, fluorescence lifetime, fiber optic waveguides, near-field microscopy, near-field spectroscopy, near-infrared, planar waveguides, surface enhanced raman, and surface plasmon resonance.

32. The method of claim 31, wherein said optical transducer comprises a pH sensitive dye.

33. The method of claim 32, wherein said pH sensitive dye is selected from the group consisting of fluorescein, carboxyfluorescein, SNAFL, SNARF, LysoSensor Green DND-189, Oregon Green, NERF, LysoSensor Yellow/Blue DND-160, HPTS (pyranine), BCECF, BCPCF, and Bodipy.

34. The method of claim 31, wherein said optical transducer comprises an oxygen sensitive dye.

35. The method of claim 34, wherein the oxygen sensitive dye comprises Ru(4,7-diphenyl-1,10-phen)₃(Cl)₂, or Ru(bipy)₃Cl₂.

36. The method of claim 28 or 29, wherein the step of analyzing comprises utilizing a processing unit to provide interpretation of data.

37. The method of claim 36, further comprising processing interpreted data using chemoinformatics.

38. The method of claim 37, wherein said step of processing using chemoinformatics comprises interpreting data using computational analysis.

39. The method of claim 28 or 29, wherein the solid support is a bead, or resin.

40. The method of claim 39, wherein the solid support to which each of said cross-reactive recognition elements is attached is a bead and wherein together the beads are provided in array format having a plurality of addresses, whereby each address in the array contains one bead.

41. The method of claim 40, wherein the array comprises a plurality of addresses, wherein two or more of the addresses contain a bead containing the same type of cross-reactive recognition element.

42. The method of claim 40, wherein the array comprises a plurality of addresses, wherein each address contains a bead containing the same cross-reactive recognition element.

43. The method of claim 40, wherein the array comprises a plurality of addresses, wherein each address contains a bead containing a different cross-reactive recognition element.

44. The method of claim 40, wherein the array comprises a plurality of addresses, wherein two or more of the addresses contain a bead containing a different type of cross-reactive recognition element.

45. The method of claim 39, wherein the solid support to which each of said cross-reactive recognition elements is attached is a bead and wherein together the beads are provided in array format having a plurality of addresses, whereby each address in the array contains more than one bead.

46. The method of claim 28, wherein each of said cross-reactive recognition elements is an enzyme selected from the group consisting of esterases, proteases, hydrolases, isomerases, lysases, transferases, oxido-reductases, and ligases.

47. The method of claim 46, wherein each of said cross-reactive recognition elements is an esterase selected from the group consisting of esterase for rabbit liver, esterase from porcine liver, acetylcholine esterase from electrophorous electricus, cholesterol esterase from hog pancrease, esterase from hog liver, esterase from horse liver, esterase from mucor miehei, esterase from bacillus sp., and esterase from bacillus thermoglucosidasius.

48. The method of claim 46, wherein each of said cross-reactive recognition elements is a protease selected from the group consisting of proteinase K, chymotrypsin, papain, carboxypepsidase A, substilisin, protease (staphylococcus), and protease VII.

49. A method for the analysis of analytes in a liquid sample comprising steps of:

providing a liquid sample comprising two or more analytes;

providing a sensor system comprising two or more cross-reactive recognition elements, wherein;

each of said cross-reactive recognition elements is an enzyme or a protein receptor;

for each analyte, the sensor system includes at least first and second cross-reactive recognition elements, wherein at least one of first and second cross-reactive recognition elements interacts directly with said analyte in an analyte-recognition element interaction; and

each analyte-recognition element interaction produces a detectable event, wherein said detectable event is a detectable agent, a detectable change or both;

contacting the liquid sample with the sensor system so that interaction of any particular analyte with cross-reactive recognition elements generates a reproducible pattern of detectable events; and

analyzing the pattern of detectable events to obtain information about said detectable events.