Optical-based sensing devices

• US 8,233,953 B2
• Filed: 10/26/2007
• Issued: 07/31/2012
• Est. Priority Date: 08/26/1998
• Status: Expired due to Fees

• Current Assignee: Senseonics, Incorporated (Senseonics Holdings, Inc.)
• Original Assignee: Sensors For Medicine and Science Incorporated
• Inventors: Colvin, Arthur E. Jr.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US11/925,272
• Publication Number:
  US 20080108885A1
• Time in Patent Office: 1,740 Days
• Field of Search: 600/310, 600/316, 600/317, 600/322, 600/342, 128/903
• US Class Current: 600/316
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6861 Capsules, e.g. for swallowing or implanting
• CPC Class Codes: G01N 2021/7773 Reflection
• CPC Class Codes: G01N 2021/7783 Transmission, loss
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 128/903 Radio telemetry

Abstract

An optical-based sensor for detecting the presence or amount of an analyte using both indicator and reference channels. The sensor has a sensor body with a source of radiation embedded therein. Radiation emitted by the source interacts with indicator membrane indicator molecules proximate the surface of the body. At least one optical characteristic of these indicator molecules varies with analyte concentration. For example, the level of fluorescence of fluorescent indicator molecules or the amount of light absorbed by light-absorbing indicator molecules can vary as a function of analyte concentration. In addition, radiation emitted by the source also interacts with reference membrane indicator molecules proximate the surface of the body. Radiation (e.g., light) emitted or reflected by these indicator molecules enters and is internally reflected in the sensor body. Photosensitive elements within the sensor body generate both indicator channel and reference channel signals to provide an accurate indication of the concentration of the analyte. Preferred embodiments are totally self-contained and are sized and shaped for use in vivo in a human being. Such embodiments preferably include a power source, e.g. an inductor, which powers the source of radiation using external means, as well as a transmitter, e.g. an inductor, to transmit to external pickup means the signal representing the level of analyte.

Claims

1. An implantable electro-optical sensing device for detecting the presence of an analyte in a medium, said sensing device comprising:

a. a radiation source that emits radiation;

b. a first and a second photosensitive elements configured to receive radiation and output an electrical signal in response thereto;

c. a first and a second indicator elements positioned to receive radiation from the radiation source and to transmit radiation to said first and second photosensitive elements, said first and second indicator elements each containing indicator molecules with an optical characteristic responsive to the presence of an analyte; and

wherein said first indicator element is exposed to an exterior of the device and is responsive to a presence of an analyte in a medium external to the device, and wherein said second indicator element is exposed to the exterior of the device and is configured such that an optical response thereof is insensitive to the presence of the analyte in the medium external to the device, and wherein said sensing device is configured to be implantable in an animal.

2. The sensing device of claim 1, wherein said sensing device is formed in a smooth, oblong or rounded shape.

3. The sensing device of claim 1, wherein said sensing device is configured to be implantable in a human without interfering with essential bodily functions or causing excess pain or discomfort.

4. The sensing device of claim 1, wherein the sensing device has a length less than or equal to 0.5 inches.

5. The sensing device of claim 4, wherein the length of the sensing device has a length greater than or equal to 500 microns.

6. The sensing device of claim 1, wherein the sensing device has a diameter less than or equal to 0.3 inches.

7. The sensing device of claim 6, wherein diameter of the sensing device is greater than or equal to 300 microns.

8. The sensing device of claim 1, further comprising a sensor/tissue interface layer.

9. The sensing device of claim 8, wherein the sensor/tissue interface layer is prepared from a material that causes little or acceptable levels of fibrotic encapsulation to form.

10. The sensor device of claim 8, wherein the sensor/tissue interface layer comprises:

a tissue ingrowth sublayer that promotes tissue in growth; and

a sublayer that is a biocompatible layer with a pore size that is significantly smaller than the pore size of the tissue ingrowth sublayer.

11. The sensor device of claim 10, wherein the sensor/tissue interface layer further comprises a molecular weight cut-off layer that provides a molecular cut-off function.

12. The sensing device of claim 1, wherein said indicator molecules have an optical characteristic responsive to the presence of oxygen.

13. The sensing device of claim 12, wherein said indicator molecules are tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) perchlorate.

14. The sensing device of claim 1, wherein said first indicator element and said first photosensitive element comprise a signal channel, and wherein said second indicator element and said second photosensitive element comprise a reference channel.

15. The sensing device of claim 14, wherein said signal channel and said reference channel are incorporated into a chip-like structure with leads extending therefrom.

16. The sensing device of claim 1, wherein said radiation source is a light emitting diode.

17. The sensing device of claim 1, wherein power to the sensing device is provided from an internal power source.

18. The sensing device of claim 17, wherein said internal power source is a battery.

19. The sensing device of claim 1, wherein power to the sensing device is provided from an external source through an induction circuit formed in the sensing device.

20. The sensing device of claim 1, wherein said indicator molecules have an optical characteristic responsive to the presence of glucose.

21. The sensing device of claim 1, wherein said second indicator element is at least partially covered.

22. The sensing device of claim 1, wherein said indicator molecules are fluorescent indicator molecules.

23. A method for detecting an analyte of interest in a medium located within a living animal, said method comprising:

a. providing an electro-optical sensing device containing a first and a second indicator elements each containing indicator molecules having an optical characteristic responsive to the presence of an analyte and positioned to receive excitation radiation from a radiation source and to transmit resultant radiation to a pair of photosensitive elements, and wherein said second indicator element is configured such that an optical response thereof is insensitive to the presence of the analyte in a medium external to the device;

b. implanting the sensing device within the living animal such that the medium located within the living animal contacts said first and second indicator elements;

c. activating said radiation source to emit radiation to said first and second indicator elements,

d. optically detecting an optical response of said first and second indicator elements; and

e. evaluating said response to determine the presence or concentration of at least one analyte of interest in the sample, wherein said response detected from said second indicator element is used as a reference to cancel variables that affect both said first and second indicator elements.

24. The method of claim 23, wherein said indicator molecules are fluorescent indicator molecules.

25. The method of claim 24, wherein said living animal is a living human.