Method and apparatus for non-invasive phase sensitive measurement of blood glucose concentration

Claims

I claim:

1. An apparatus for non-invasive precision phase-sensitive measurement of blood glucose concentration comprising:

a source which produces an infrared laser beam;

a polarizing frequency shifter having an optical input receiving said laser beam, a piezoelectric transducer imparting phase modulation to said laser beam, and an optical output which produces a polarized-modulated infrared laser beam;

a piezoelectric controller operatively connected to said piezoelectric transducer to operate the piezoelectric transducer at a selected modulation frequency;

an optical transducer which has a glucose measuring head and an optical input receiving said polarized-modulated infrared laser beam from said output of said polarizing frequency shifter and an output providing a reference electric signal, said glucose measuring head having a space for receiving a blood sample and generating a probe electric signal corresponding polarized component of the polarized-modulated laser beam passing through the blood sample and a thickness measurement signal corresponding to a thickness of said blood sample; and

an electronic signal processing unit which has an input which is electrically connected to said optical transducer for receiving said reference electric signal and inputs which are electrically connected to said glucose measuring head for receiving said probe electric signal and thickness measurement signal, said electronic signal processing unit having a feedback loop to said piezoelectric controller for controlling the piezoelectric transducer and means for measuring a glucose concentration of said blood sample based on said probe and reference electric signals.

2. The apparatus of claim 1 wherein said polarizing frequency shifter comprises:

a polarizing beam splitter cube having a center, a beam input side and a beam output side which is perpendicular to said input side;

a first quarter-wave plate which is located on a side of said polarizing beam splitter cube which is opposite to said beam input side;

a second quarter-wave plate located on a side of said polarizing beam splitter cube which is opposite to said beam output side;

a third quarter-wave plate located on said beam output side of said polarizing beam splitter cube;

a first mirror which is located on an outer side of said first quarter-wave plate and a second mirror which is located on an outer side of said second quarter-wave plate, wherein said piezoelectrical transducer is attached to one of the first and second mirrors;

wherein the beam splitter cube input side, first quarter wave plate and first mirror are on a first optical axis and the beam splitter cube output side, second quarter wave plate and second mirror are on a second optical axis and the difference between distances of said first and said second mirrors and said center of said polarizing beam splitter cube is smaller than a coherent length of said infrared laser beam.

3. The apparatus of claim 1 wherein said electronic signal processing unit comprises a phase-sensitive homodyne receiver which receives said reference electrical signal and said probe electrical signal, a microcontroller connected to said phase-sensitive homodyne receiver, and a memory connected to said microcontroller.

4. The apparatus of claim 3 further comprising:

an audio transmitter connected to said microcontroller;

an analog-to-digital converter connected to said microcontroller; and

a display unit connected to said analog-to-digital converter.

5. The apparatus of claim 1 wherein the blood sample is a blood carrying body part and said glucose measuring head comprises:

a housing having said space for receiving said blood-carrying body part;

an optical measurement signal input located on one side of said space for receiving said probe optical signal; and

a photoreceiver located on a side of said space opposite to said one side, the photoreceiver having an output signal that is said probe electrical signal.

6. The apparatus of claim 5 wherein the glucose measuring head further comprises:

fixation means for fixing said blood-carrying body part in position relative to said space; and

compression means for compressing said blood-carrying body part.

7. The apparatus of claim 1 wherein said optical transducer further comprises an optical attenuator, a reference calibration cartridge with at least two cells containing glucose solutions of different concentrations, a reference polarizer, and a reference sensor, wherein said optical attenuator, reference calibration cartridge, reference polarizer and reference sensor are spatially arranged sequentially on a common optical axis aligned with said reference optical output side.

8. The apparatus of claim 1 wherein said optical transducer comprises:

a beam splitter cube having an optical input side for receiving said polarized-modulated infrared laser beam which is split into a reference optical signal and a probe optical signal, a reference optical output side, and a measurement optical output side; and

a measurement sensor in the form of a balanced receiver which produces at its output said probe electrical signal,

wherein the glucose measuring head is disposed between the measurement sensor and said measurement optical output side.

9. The apparatus of claim 8 wherein said balanced receiver is a photoreceiver.

10. The apparatus of claim 9 wherein said polarizing frequency shifter comprises:

a polarizing beam splitter cube having a center, a beam input side and a beam output side which is perpendicular to said input side;

a first quarter-wave plate which is located on a side of said polarizing beam splitter cube which is opposite to said beam input side;

a second quarter-wave plate located on a side of said polarizing beam splitter cube which is opposite to said beam output side;

a first mirror which is located on an outer side of said first quarter-wave plate and a second mirror which is located on an outer side of said second quarter-wave plate wherein said piezoelectric transducer is attached to one of the first and second mirrors;

wherein the beam Splitter cube input side, first quarter-wave plate and first mirror are on a first optical axis and the beam splitter cube output side, second quarter-wave plate and second mirror are on a second optical axis and the difference between distances of said first and said second mirrors and said center of said polarizing beam splitter cube is smaller than a coherent length of said infrared laser beam.

11. The apparatus of claim 10 wherein said photoreceiver comprises a photodetector having an electrical output and producing an output signal, a filter unit including a high pass and a low pass filter connected in parallel, where the filter unit is connected in series with the photodetector electrical output, and a division amplifier having an input receiving the filtered photodetector output signal, said photodetector output signal corresponding to said probe optical signal from said glucose measuring head, said division amplifier having an output.

12. The apparatus of claim 11 wherein said electronic signal processing unit comprises a phase-sensitive homodyne receiver which receives said reference electrical signal and said probe electrical signal, a microcontroller connected to said phase-sensitive homodyne receiver, and a memory connected to said microcontroller.

13. The apparatus of claim 12 wherein the blood sample is a blood carrying body part and said glucose measuring head comprises:

a housing having said space for receiving said blood-carrying body part;

an optical measurement signal input located on one side of said space for receiving said probe optical signal, said photoreceiver being located on a side of said space opposite to said one side;

fixation means for fixing said blood-carrying body part in position relative to said space; and

compression means for compressing said blood-carrying body part.

14. The apparatus of claim 13 wherein said housing space further comprises a shape for receiving a finger.

15. The apparatus of claim 8 wherein said optical transducer further comprises an optical attenuator, a reference calibration cartridge with at least two cells containing glucose solutions of different concentrations, a reference polarizer, and a reference sensor, wherein said optical attenuator, reference calibration cartridge, reference polarizer and reference sensor are spatially arranged sequentially on a common optical axis aligned with said reference optical output side.

16. The apparatus of claim 8 wherein said measurement sensor comprises:

a beam splitter plate which receives said probe optical signal from said glucose measuring head and splits said probe optical signal into a first component and a second component;

a polarizer and first photodetector, said first component being passed to said first photodetector through said polarizer, said first photodetector having an output corresponding to the polarized component;

a second photodetector which receives said second component from said beam splitter plate having an output corresponding to a depolarized component of the probe optical signal passed through the blood sample;

a difference amplifier having a first input and a second input and an output, said first input of said difference amplifier being connected to said first photodetector output and said second input of said difference amplifier being connected to said second photodetector output;

a division amplifier having a first input, a second input, and an output; and

a low-pass filter electrically connected between said second photodetector and said second input of said division amplifier, said output of said difference amplifier being connected to said first input of said division amplifier.

17. The apparatus of claim 8 wherein the blood sample is a blood-carrying body part and said glucose measuring head comprises:

a housing having said space for receiving said blood-carrying body part;

an optical measurement signal input located on one side of said space for receiving said probe optical signal, said balanced receiver being located on a side of said space opposite to said one side; and

a sensor operatively connected to said housing for measuring said thickness of said blood-carrying body part for producing said thickness measurement signal.

18. The apparatus of claim 17 wherein said glucose measuring head further comprises:

fixation means for fixing said blood-carrying body part in position relative to said space; and

compression means for compressing said blood-carrying body part.

19. The apparatus of claim 17 wherein said housing space further comprises a shape for receiving a finger.

20. The apparatus of claim 17 wherein said optical transducer further comprises a polarization preserving fiber optic link connecting said glucose measuring head optical measurement signal input to said measurement optical output side of said beam splitter cube.

21. The apparatus of claim 17, wherein said optical transducer further comprises a polarization preserving fiber optic link connecting said glucose measuring head optical measurement signal input to said measurement optical output side of said beam splitter cube, a head appliance which can be attached to the subject's head and wherein said glucose measuring head is made in the form of a resilient U-shape clip for inserting into said U-shaped clip an ear lobule of another ear of said subject, said U-shaped clip having a first leg and a second leg, said first leg supporting said polarization preserving fiber-optic link and said second leg supporting said balanced receiver and said thickness measurement sensor, so that during operation of said apparatus said phase-modulated infrared laser beam is transmitted to said balanced receiver through said ear lobule.

22. The apparatus of claim 17 wherein said balanced receiver is a photoreceiver.

23. The apparatus of claim 22 wherein said polarizing frequency shifter comprises:

a polarizing beam splitter cube having a center, a beam input side and a beam output side which is perpendicular to said input side;

a first quarter-wave plate which is located on a side of said polarizing beam splitter cube which is opposite to said beam input side;

a second quarter-wave plate located on a side of said polarizing beam splitter cube which is opposite to said beam output side;

a first mirror which is located on an outer side of said first quarter-wave plate and a second mirror which is located on an outer side of said second quarter-wave plate wherein said piezoelectric transducer is attached to one of the first and second mirrors;

wherein the beam splitter cube input side, first quarter-wave plate and first mirror are on a first optical axis and the beam splitter cube output side, second quarter-wave plate and second mirror are on a second optical axis and the difference between distances of said first and said second mirrors and said center of said polarizing beam splitter cube is smaller than a coherent length of said infrared laser beam.

24. The apparatus of claim 23 wherein said photoreceiver comprises a photodetector having an electrical output and producing an output signal, a filter unit including a high pass and a low pass filter connected in parallel, where the filter unit is connected in series with the photodetector electrical output, and a division amplifier having an input receiving the filtered photodetector output signal, said photodetector output signal corresponding to said probe optical signal from said glucose measuring head, said division amplifier having an output.

25. The apparatus of claim 17 wherein said electronic signal processing unit comprises a phase-sensitive homodyne receiver which receives said reference electrical signal and said probe electrical signal, a microcontroller connected to said phase-sensitive homodyne receiver, and a memory connected to said microcontroller.

26. The apparatus of claim 25 wherein said housing space further comprises a shape for receiving a finger.

27. The apparatus of claim 8 wherein said polarizing frequency shifter comprises:

a polarizing beam splitter cube having a center, a beam input side and a beam output side which is perpendicular to said input side;

a first quarter-wave plate which is located on a side of said polarizing beam splitter cube which is opposite to said beam input side;

a second quarter-wave plate located on a side of said polarizing beam splitter cube which is opposite to said beam output side;

a third quarter-wave plate located on said beam output'side of said polarizing beam splitter cube;

a first mirror which is located on an outer side of said first quarter-wave plate and a second mirror which is located on an outer side of said second quarter-wave plate wherein said piezoelectric transducer is attached to one of the first and second mirrors;

wherein the beam splitter cube input side, first quarter wave plate and first mirror are on a first optical axis and the beam splitter cube output side, second quarter wave plate and second mirror are on a second optical axis and the difference between distances of said first and said second mirrors and said center of said polarizing beam splitter cube is smaller than a coherent length of said infrared laser beam.

28. The apparatus of claim 27 wherein said measurement sensor comprises:

a beam splitter plate which receives said probe optical signal from said glucose measuring head and splits said probe optical signal into a first component and a second component;

a polarizer and first photodetector, said first component being passed to said first photodetector through said polarizer, said first photodetector having an output corresponding to the polarized component;

a second photodetector which receives said second component from said beam splitter plate having an output corresponding to a depolarized component of the probe optical signal passed through the blood sample;

a difference amplifier having a first input and a second input and an output, said first input of said difference amplifier being connected to said first photodetector output and said second input of said difference amplifier being connected to said second photodetector output;

a division amplifier having a first input, a second input, and an output; and

a low-pass filter electrically connected between said second photodetector and said second input of said division amplifier, said output of said difference amplifier being connected to said first input of said division amplifier.

29. The apparatus of claim 28 wherein said electronic signal processing unit comprises a phase-sensitive homodyne receiver which receives said reference electrical signal and said probe electrical signal, a microcontroller connected to said phase-sensitive homodyne receiver, and a memory connected to said microcontroller.

30. The apparatus of claim 29 further comprising: an audio transmitter connected to said microcontroller;

an analog-to-digital converter connected to said microcontroller; and

a display unit connected to said analog-to-digital converter.

31. The apparatus of claim 30 wherein the blood sample is a blood-carrying body part and said glucose measuring head comprises:

a housing having said space for receiving said blood-carrying body part;

an optical measurement signal input located on one side of said space for receiving said probe optical signal, said balanced receiver being located on a side of said space opposite to said one side;

a sensor operatively connected to said housing for measuring said thickness of said blood-carrying body part for producing said thickness measurement signal;

fixation means for fixing said blood-carrying body part in position relative to said space; and

compression means for compressing said blood-carrying body part.

32. The apparatus of claim 31 wherein said housing space further comprises a shape for receiving a finger.

33. The apparatus of claim 32 wherein said optical transducer further comprises a polarization preserving fiber optic link connecting said glucose measuring head optical measurement signal input to said measurement optical output of said beam splitter cube.

34. The apparatus of claim 31, wherein said optical transducer further comprises a polarization preserving fiber optic link connecting said glucose measuring head optical measurement signal input to said measurement optical output of said beam splitter cube, a head appliance which can be attached to the subject's head and supports a microphone connected to an audio transmitter and located near one ear of said subject when said head appliance is attached to the subject's head, and wherein said glucose measuring head is made in the form of a resilient U-shape clip for inserting into said U-shaped clip an ear lobule of another ear of said subject, said U-shaped clip having a first leg and a second leg, said first leg supporting said polarization preserving fiber-optic link and said second leg supporting said balanced receiver and said thickness measurement sensor, so that during operation of said apparatus said phase-modulated infrared laser beam is transmitted to said balanced receiver through said ear lobule.

35. A method for non-invasive precision phase-sensitive measurement of blood glucose concentration comprising:

producing an infrared laser beam;

passing said laser beam through a polarizing frequency shifter including a piezoelectric transducer, controlling the piezoelectric transducer to operate at a selected modulation frequency to impart phase modulation to said laser beam, thereby providing a polarized-modulated infrared laser beam;

separating the polarized-modulated infrared laser beam into a probe beam and a reference beam;

passing the probe beam through a blood sample, detecting the probe beam after passage through the blood sample, and generating a probe electric signal corresponding a the polarized component of the polarized-modulated laser beam