Fluorescence sensor, needle-type fluorescence sensor, and method for measuring analyte

• US 8,649,836 B2
• Filed: 10/12/2011
• Issued: 02/11/2014
• Est. Priority Date: 04/13/2009
• Status: Active Grant

• Current Assignee: Terumo Kabushiki Kaisha
• Original Assignee: Terumo Kabushiki Kaisha
• Inventors: Matsumoto, Kazuya, Matsumoto, Atsushi, Shimizu, Etsuro, Ota, Ryo
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/271,732
• Publication Number:
  US 20120029328A1
• Time in Patent Office: 853 Days
• Field of Search: 600309-344
• US Class Current: 600/316
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2021/7753 Reagent layer on photoelectrical transducer
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator

Abstract

A needle-type fluorescence sensor that measures glucose based on fluorescence produced by excitation light is provided. The needle-type fluorescence sensor includes a needle body section including a sensor portion disposed in a needle distal end portion and metal lines disposed from the sensor portion to a needle proximal end portion, and a connector which is integrated with the needle body section and in which the metal lines extend. The sensor portion includes a silicon substrate having first and second principal surfaces, a PD device that converts fluorescence into an electric signal, an LED device that transmits fluorescence and emits excitation light, and an indicator layer that interacts with an analyte under the excitation light to produce fluorescence. The PD device, the LED device, and the indicator layer overlap with each other above the first principal surface of the silicon substrate.

Claims

1. A fluorescence sensor comprising:

a base member having first and second principal surfaces, the base member comprising silicon;

a photoelectric conversion device formed on the first principal surface of the base member and converts fluorescence into an electrical signal;

a light emitting diode device that emits excitation light, the light emitting diode device disposed above the photoelectric conversion device; and

an indicator layer that interacts with an analyte in a living body under the excitation light to produce fluorescence, the indicator layer disposed above the light emitting diode device;

wherein the photoelectric conversion device, the light emitting diode device, and the indicator layer overlap with each other above the first principal surface of the base member, and the fluorescence produced in the indicator layer passes through the light emitting diode device and impinges on the photoelectric conversion device.

2. The fluorescence sensor according to claim 1,

further comprising a filter between the photoelectric conversion device and the light emitting diode device,

wherein the filter reflects and/or absorbs the excitation light having a wavelength shorter than that of the fluorescence and transmits the fluorescence.

3. The fluorescence sensor according to claim 2,

wherein the filter is a light absorptive monolayer made of any one of silicon, silicon carbide, and gallium phosphide.

4. The fluorescence sensor according to claim 2,

wherein the filter is a multiple interference filter formed of a silicon layer and either a silicon oxide layer or a silicon nitride layer.

5. The fluorescence sensor according to claim 2,

wherein the analyte is a saccharide in blood or a body fluid.

6. The fluorescence sensor according to claim 5,

wherein the light emitting diode device is made of a gallium nitride-based compound semiconductor and formed on a sapphire substrate, and

the photoelectric conversion device is formed of a photodiode or a phototransistor.

7. The fluorescence sensor according to claim 6,

further comprising a light collecting section between the light emitting diode device and the indicator layer and/or between the filter and the photoelectric conversion device.

8. The fluorescence sensor according to claim 2,

wherein the filter is in contact with the light emitting diode device.

9. The fluorescence sensor according to claim 1,

wherein the photoelectric conversion device includes a first light receiving portion and a second light receiving portion to which the same bias voltage as applied to the first light receiving portion is applied, the second light receiving portion formed at a deeper level than the level where the first light receiving portion is formed, and

an electric signal of the incident excitation light is electrically cut off by detecting a current flowing through the second light receiving portion.

10. The fluorescence sensor according to claim 1,

further comprising a light blocking layer above the indicator layer.

11. A needle-type fluorescence sensor that penetrates a living body, the needle-type fluorescence sensor comprising:

a needle body section including a sensor portion disposed in a needle distal end portion that indwells in the living body and a plurality of metal lines disposed from the sensor portion to a needle proximal end portion; and

a connector which is integrated with the needle body section and in which the plurality of metal lines extend,

the sensor portion including

a base member having first and second principal surfaces, the base member comprising silicon,

a photoelectric conversion device that is formed on the first principal surface of the base member and converts fluorescence into an electrical signal;

a light emitting diode device that emits excitation light disposed above the photoelectric conversion device, and

an indicator layer that interacts with an analyte in the living body under the excitation light to produce fluorescence, the indicator layer disposed above the light emitting diode device,

wherein the photoelectric conversion device, the light emitting diode device, and the indicator layer overlap with each other above the first principal surface of the base member, and the fluorescence produced in the indicator layer passes through the light emitting diode device and impinges on the photoelectric conversion device.

12. The needle-type fluorescence sensor according to claim 11,

further comprising a filter between the photoelectric conversion device and the light emitting diode device,

wherein the filter reflects and/or absorbs the excitation light having a wavelength shorter than that of the fluorescence and transmits the fluorescence.

13. The needle-type fluorescence sensor according to claim 12,

wherein the filter is a light absorptive monolayer made of any one of silicon, silicon carbide, and gallium phosphide.

14. The needle-type fluorescence sensor according to claim 12,

wherein the filter is a multiple interference filter formed of a silicon layer and either a silicon oxide layer or a silicon nitride layer.

15. The needle-type fluorescence sensor according to claim 12,

wherein the analyte is a saccharide in blood or a body fluid.

16. The needle-type fluorescence sensor according to claim 15,

wherein the light emitting diode device is made of a gallium nitride-based compound semiconductor and formed on a sapphire substrate, and

the photoelectric conversion device is formed of a photodiode or a phototransistor.

17. The needle-type fluorescence sensor according to claim 16,

wherein the connector detachably fits into a body unit that sends information measured by the sensor portion.

18. The needle-type fluorescence sensor according to claim 17,

wherein the sensor portion further includes a temperature sensor.

19. The needle-type fluorescence sensor according to claim 17,

further comprising a second sensor portion including a second photoelectric conversion device that outputs an electric signal that is not affected by the analyte.

20. The needle-type fluorescence sensor according to claim 17,

wherein the needle body section further includes a resin substrate or the silicon substrate, a protective layer made of a resin, and the plurality of metal lines.

21. The needle-type fluorescence sensor according to claim 20,

wherein the plurality of metal lines are stacked with an insulating layer therebetween to form a multilayer structure.

22. The needle-type fluorescence sensor according to claim 17,

further comprising a light collecting section between the light emitting diode device and the indicator layer and/or between the filter and the photoelectric conversion device.

23. The needle-type fluorescence sensor according to claim 12,

wherein the filter is in contact with the light emitting diode device.

24. The needle-type fluorescence sensor according to claim 11,

wherein the photoelectric conversion device includes a first light receiving portion and a second light receiving portion to which the same bias voltage as applied to the first light receiving portion is applied, the second light receiving portion formed at a deeper level than the level where the first light receiving portion is formed, and

an electric signal of the incident excitation light is electrically cut off by detecting a current flowing through the second light receiving portion.

25. The needle-type fluorescence sensor according to claim 11,

further comprising a light blocking layer above the indicator layer.

26. A method for measuring an analyte by using a fluorescence sensor, the method comprising:

an excitation light irradiation step in which excitation light emitted from a light emitting diode device is introduced into an indicator layer, the indicator layer disposed above the light emitting diode device, the light emitting diode device disposed above a first principal surface of a base member, the base member having a first principal surface and a second principal surface, the base member comprising silicon;

a fluorescence emission step in which the indicator layer interacts with the analyte under the excitation light to produce fluorescence; and

a photoelectric conversion step in which the fluorescence produced in the indicator layer passes through the light emitting diode device, impinges on a photoelectric conversion device that is formed on the first principal surface of the base member, and is converted into an electric signal.

27. The method for measuring an analyte according to claim 26,

wherein the analyte is a saccharide in blood or a body fluid.