Ultrasound based antigen binding detection

• US 9,370,321 B2
• Filed: 06/25/2012
• Issued: 06/21/2016
• Est. Priority Date: 06/25/2012
• Status: Expired due to Fees

• Current Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Original Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Inventors: Ozdil, Deniz, Manion, Michael Keoni, Peppou, George Charles
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): HOFFMAN, JOANNE M
• Application Number:
  US13/993,908
• Publication Number:
  US 20130345527A1
• Time in Patent Office: 1,457 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 10/00 Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis vaccination prophylaxis, vaccination therapy A61B17/20; Sex determination; Ovulation-period determination menstruation tables G06C3/00; Throat striking implements
• CPC Class Codes: A61B 10/0283 with vacuum aspiration, e.g. caused by retractable plunger or by connected syringe A61B10/025, A61B10/0266 take precedence
• CPC Class Codes: A61B 2562/066 in a matrix array
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 8/12 in body cavities or body tracts, e.g. by using catheters catheters per se A61M25/00
• CPC Class Codes: A61B 8/52 Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves image processing per se G06T
• CPC Class Codes: A61B 8/5223 for extracting a diagnostic or physiological parameter from medical diagnostic data for algorithms to analyse biomedical images G06T7/0012
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Embodiments provided here generally relate to combinations of ultrasound aspects and antibodies. In some embodiments, antibodies are immobilized on a surface and binding of the antibodies to antigens can be detected by detecting changes in the vibrational properties of the surface.

Claims

1. An endoscopic ultrasound probe comprising:

a piezoelectric wafer;

at least one antibody immobilized on the piezoelectric wafer;

an electrode transducer on a needle, the piezoelectric wafer being stacked on the electrode transducer;

the endoscopic ultrasound probe being configured to apply an ultrasound energy to the piezoelectric wafer to create a vibration in the piezoelectric wafer; and

the electrode transducer being configured to detect an electrical signal generated by the piezoelectric wafer in response to the vibration in the piezoelectric wafer and transmit the detected electric signal to a recording device for the detection of a change in the vibration in the piezoelectric wafer due to binding of an antigen to the antibody immobilized on the piezoelectric wafer.

2. The endoscopic ultrasound probe of claim 1, wherein the piezoelectric wafer is crystalline.

3. The endoscopic ultrasound probe of claim 1, wherein the change in the vibration in the piezoelectric wafer due to binding of an antigen to the antibody immobilized on the piezoelectric wafer is a change in frequency of the vibration in the piezoelectric wafer.

4. The endoscopic ultrasound probe of claim 1, further comprising a processor, wherein the electrode is in data communication with the processor.

5. The endoscopic ultrasound probe of claim 1, wherein the at least one antibody-immobilized on the piezoelectric wafer comprises:

at least a first antibody immobilized on a first area of the piezoelectric wafer; and

at least a second antibody immobilized on a second area of the piezoelectric wafer.

6. The endoscopic ultrasound probe of claim 5, wherein the at least the first antibody specifically binds to a first antigen, and wherein the at least the second antibody specifically binds to a second antigen.

7. The endoscopic ultrasound probe of claim 6, wherein the first antigen comprises a first tissue-specific marker, and wherein the second antigen comprises a second tissue-specific marker.

8. The endoscopic ultrasound probe of claim 5, wherein the first area and second area are arranged in a systematic pattern on the piezoelectric wafer.

9. A method of detecting the presence of an antigen, the method comprising:

providing an endoscopic ultrasound probe comprising;

a piezoelectric wafer;

a needle;

an electrode transducer on the needle, the piezoelectric wafer being stacked on the electrode transducer; and

at least one antibody immobilized on the piezoelectric wafer;

stimulating the endoscopic ultrasound probe with at least one ultrasound wave to supply an ultrasound energy to the piezoelectric wafer to create a vibration in the piezoelectric wafer;

detecting an electrical signal generated by the piezoelectric wafer in response to the vibration in the piezoelectric wafer;

transmitting the detected electrical signal to a detecting device; and

detecting a change in vibration of the piezoelectric wafer upon binding of an antigen to the at least one antibody.

10. The method of claim 9, wherein detecting a change in vibration comprises:

determining a first vibration frequency of the piezoelectric wafer when no antigen is bound to the at least one antibody; and

determining a second vibration frequency of the piezoelectric wafer when an antigen is bound to the at least one antibody.

11. The method of claim 9, wherein detecting a change in vibration comprises monitoring data in real time.

12. The method of claim 9, wherein the at least one antibody is configured to bind specifically to the tissue-specific antigen, the method further comprising binding the at least one antibody to a tissue-specific antigen.

13. The method of claim 9, wherein the at least one antibody immobilized on the piezoelectric wafer comprises:

at least a first antibody immobilized on a first area of the piezoelectric wafer; and

at least a second antibody immobilized on a second area of the piezoelectric wafer.

14. The method of claim 13, wherein the first antibody specifically binds to a tissue-specific antigen, and wherein the second antibody does not bind to the tissue-specific antigen, the method further comprising:

binding the first antibody to a tissue-specific antigen;

detecting a vibration frequency of the first area when the first antibody is bound to the tissue-specific antigen; and

detecting a vibration frequency of the second area.

15. The method of claim 14, wherein detecting a vibration frequency of the second area occurs when the first antibody is bound to the tissue-specific antigen at the first area.

16. The method of claim 9, wherein the at least one antibody binds to an albumin, an albumin fragment, or lactose dehydrogenase (LDH).

17. An aspiration needle comprising:

an electrode transducer on the aspiration needle;

a piezoelectric wafer on the electrode transducer, the piezoelectric wafer being configured to vibrate in response to ultrasound energy; and

at least one antibody on the piezoelectric wafer;

wherein the aspiration needle is configured to fit on an endoscopic ultrasound probe; and

wherein the electrode transducer is configured to detect an electrical signal generated by the piezoelectric wafer in response to the vibration in the piezoelectric wafer.

18. The aspiration needle of claim 17, wherein the at least one antibody binds specifically to an extracellular marker.

19. The aspiration needle of claim 17, wherein the at least one antibody comprises:

a first antibody that binds specifically to a first antigen, wherein the first antibody is immobilized on a first area of the piezoelectric wafer; and

a second antibody that binds specifically to a second antigen, wherein the second antibody is immobilized on a second area of the piezoelectric wafer.

20. The aspiration needle of claim 19, wherein the first area of the piezoelectric wafer and the second area of the piezoelectric wafer are positioned in a random pattern on a surface of the piezoelectric wafer.

21. The aspiration needle of claim 19, wherein the first area of the piezoelectric wafer and the second area of the piezoelectric wafer are positioned in an ordered array on a surface of the piezoelectric wafer.

22. The aspiration needle of claim 19, wherein the at least one antibody further comprises a third antibody configured to bind specifically to the first antigen, wherein the third antibody is immobilized on a third area of the piezoelectric wafer.

23. The aspiration needle of claim 19, further comprising an electrical lead in electrical communication with the electrode transducer.

24. A kit comprising:

at least one aspirator needle;

at least one ultrasound transducer configured to attach to a surface of the aspirator needle;

at least one piezoelectric wafer configured to attach to a surface of the ultrasound transducer and to vibrate in response to ultrasound energy;

at least one antibody;

wherein the at least one ultrasound transducer is configured to supply ultrasound energy to the at least one piezoelectric wafer, the ultrasound transducer being configured to detect an electrical signal generated by the piezoelectric wafer in response to the vibration in the piezoelectric wafer.

25. The kit of claim 24, wherein the at least one antibody is immobilized on the at least one piezoelectric wafer.