Circuits for in vivo detection of biomolecule concentrations using fluorescent tags

• US 7,378,056 B2
• Filed: 11/07/2001
• Issued: 05/27/2008
• Est. Priority Date: 11/09/2000
• Status: Active Grant

• Current Assignee: SNC Holdings Corp.
• Original Assignee: Sicel Technologies, Inc.
• Inventors: Black, Robert D.
• Primary Examiner(s): Le; Long V.
• Assistant Examiner(s): Counts; Gary W.
• Application Number:
  US10/005,889
• Publication Number:
  US 20020102212A1
• Time in Patent Office: 2,393 Days
• Field of Search: 422/50, 422/55, 422/68.1, 422 8205- 8208, 422/99, 435/7.1, 435/808, 435/288.7, 436/63, 436/164, 436/172, 356/73.1, 356/319, 600/486, 600/407
• US Class Current: 422/82.05
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61K 49/0058 Antibodies

Abstract

Methods are disclosed wherein labeled antibodies can be provided in vivo to tissue having antigens that specifically bind the labeled antibody. A first optical radiation is emitted into the tissue in vivo to excite the labeled antibody bound to the antigen in vivo. A second optical radiation that is emitted by the excited labeled antibody, in response to the excitation thereof, can be detected in vivo. Related telemetric circuits and compositions of matter are also disclosed.

Claims

1. A circuit for detecting biomolecules in vivo, the circuit comprising

an optical radiation source configured for in vivo use that emits first optical radiation;

an optical radiation detector configured for in vivo use that detects second optical radiation emitted by excited labeled binding molecules; and

a processor circuit, coupled to the optical radiation source and the optical radiation detector,

wherein the processor circuit is configured to release fluorescently labeled antibodies selected to bind with predetermined Tumor Specific Antigens (TSAs),

the processor circuit is further configured to activate the in vivo optical radiation source after a predetermined first time interval after release of the fluorescently labeled antibodies, the predetermined first time interval selected to allow a first portion of the fluorescently labeled antibodies to bind with local available TSAs and a second portion of the fluorescently labeled antibodies to become remote from the circuit so that the first optical radiation excites the first portion of the fluorescently labeled antibodies bound with the local available TSAs and does not excite the second portion of the fluorescently labeled antibodies that become remote,

the processor circuit is further configured to sense a voltage generated by the in vivo optical radiation detector after a second predetermined time interval, the second predetermined time interval being after emission of the first optical radiation has ceased.

2. A circuit according to claim 1, wherein the optical radiation source comprises a laser.

3. A circuit according to claim 1, wherein the optical radiation detector is selected from a group consisting of a phototransistor, a photodiode, and a photomultiplier.

4. A circuit according to claim 1, wherein the first optical radiation has a first frequency and the second optical radiation has a second frequency.

5. A circuit according to claim 4, wherein the first frequency is greater than the second frequency.

6. A circuit according to claim 1 further comprising:

an emission filter coupled to the optical radiation source; and

an absorption filter coupled to the optical radiation detector.

7. A circuit according to claim 1, further comprising:

an inductor coupled to the processor, wherein the inductor provides power to the circuit in response to a power signal received from the ex vivo system.

8. A circuit according to claim 1, wherein the circuit is on a platform having a diameter of about 2 mm.

9. A circuit according to claim 1, wherein the signal is digitally encoded.

10. A circuit according to claim 1, wherein the circuit is on a platform coated with a biocompatible optical translucent layer.

11. A circuit according to claim 1 wherein the first and second optical radiation comprises first and second optical radiation at respective first and second wavelengths selected to promote transmission of the first and second optical radiation through a bio-fouling tissue on the optical radiation source and the optical radiation detector.

12. A circuit according to claim 1 wherein the circuit comprises an implantable circuit configured for in vivo implantation for at least six months.

13. A circuit according to claim 1 wherein the processor circuit is further configured to provide the signal for wireless transmission to the ex vivo system.

14. A circuit according to claim 1 further comprising:

a piezoelectric circuit responsive to the processor circuit, wherein the piezoelectric circuit is configured to vibrate under control of the processor circuit to release the labeled binding molecules.

15. A circuit according to claim 1, wherein the processor circuit is further configured to control release of unlabled binding antibodies separate from the fluorescently labeled antibodies.

16. A circuit according to claim 15 wherein the processor circuit is further configured to release the unlabled binding antibodies during a first time interval and to release the fluorescently labeled antibodies during a second time interval.