Glucose concentration measuring method and apparatus with a coherent source and heterodyne interferometer

• US 5,969,815 A
• Filed: 08/24/1998
• Issued: 10/19/1999
• Est. Priority Date: 05/16/1996
• Status: Expired due to Term

• Current Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Original Assignee: Fuji Photo Film Co Limited (Fujifilm Holdings Corporation)
• Inventors: Miyagawa, Ichirou, Toida, Masahiro
• Primary Examiner(s): Turner, Samuel A.
• Application Number:
  US09/138,563
• Time in Patent Office: 421 Days
• Field of Search: 356/349, 356/351, 356/361, 356/357, 351/211, 600/316
• US Class Current: 356/484
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01B 9/02003 using beat frequencies
• CPC Class Codes: G01B 9/02004 using frequency scans
• CPC Class Codes: G01B 9/02007 Two or more frequencies or sources used for interferometric measurement using only beat G01B9/02003
• CPC Class Codes: G01B 9/02014 by using pulsed light
• CPC Class Codes: G01B 9/02057 by using common path configuration, i.e. reference and object path almost entirely overlapping
• CPC Class Codes: G01B 9/0209 Low-coherence interferometers

Abstract

A low coherence light beam is irradiated to the eyeball. A backward scattered light beam, which is reflected from each depth position in the eyeball, and a reference light beam, which is reflected from a mirror capable of moving, are caused to interfere with each other. A first backward scattered light beam, which comes from the interface between the cornea and the anterior aqueous chamber, and a second backward scattered light beam, which comes from the interface between the anterior aqueous chamber and the crystalline lens, are thus separated accurately from each other. An optical absorbance of the anterior aqueous chamber (the aqueous humor) is calculated from the intensities of the two backward scattered light beams. Each of a plurality of low coherence light beams having different wavelengths is irradiated to the eyeball, and the aforesaid operation is repeated. The concentration of glucose in the aqueous humor is measured by utilizing near-infrared spectroscopy. The measurement is thus achieved non-invasively and accurately.

Claims

1. A glucose concentration measuring method, comprising the steps of:

i) splitting a coherent light beam, which has been radiated out of a predetermined light source and the frequency of which is swept temporally in a sawtooth-like form, into a signal light beam and a reference light beam, each of which travels along one of two different optical paths,

ii) irradiating said signal light beam to the eyeball lying at a predetermined position,

iii) causing a first backward scattered light beam of said signal light beam, said first backward scattered light beam coming from an interface between the cornea and the anterior aqueous chamber of the eyeball, and said reference light beam to interfere with each other, said reference light beam being constituted of the coherent light beam, which has been radiated out of said light source with a difference in time in accordance with a difference between an optical path length of said signal light beam and said first backward scattered light beam and an optical path length of said reference light beam, and which has a difference in frequency with respect to said first backward scattered light beam, a first interference light beam being thereby obtained,

iv) measuring an intensity of said first interference light beam,

v) calculating an intensity of said first backward scattered light beam from the intensity of said first interference light beam,

vi) causing a second backward scattered light beam of said signal light beam, said second backward scattered light beam coming from an interface between the anterior aqueous chamber and the crystalline lens of the eyeball, and said reference light beam to interfere with each other, said reference light beam being constituted of the coherent light beam, which has been radiated out of said light source with a difference in time in accordance with a difference between an optical path length of said signal light beam and said second backward scattered light beam and an optical path length of said reference light beam, and which has a difference in frequency with respect to said second backward scattered light beam, a second interference light beam being thereby obtained,

vii) measuring an intensity of said second interference light beam,

viii) calculating an intensity of said second backward scattered light beam from the intensity of said second interference light beam,

ix) obtaining light absorption characteristics of constituents of the aqueous humor, which fills the anterior aqueous chamber, from the intensity of said first backward scattered light beam and the intensity of said second backward scattered light beam,

x) obtaining light absorption characteristics of the constituents of the aqueous humor with respect to each of a plurality of other coherent light beams, which have wavelengths different from the wavelength of said coherent light beam, in the same manner, and

xi) calculating a concentration of glucose in the constituents of the aqueous humor from the light absorption characteristics, which have been obtained with respect to the plurality of said coherent light beams.

2. A method as defined in claim 1 wherein said coherent light beams are selectively radiated out of a single light source.

3. A method as defined in claim 1 wherein each of said coherent light beams is radiated out of one of a plurality of different light sources.

4. A glucose concentration measuring method, comprising the steps of:

with respect to concentrations of glucose in the constituents of the aqueous humor, which concentrations have been measured with a method as defined in claim 1, invasively measuring the corresponding concentrations of glucose in the blood, correlation between the concentrations of glucose in the constituents of the aqueous humor and the concentrations of glucose in the blood being thereby determined previously, and

thereafter non-invasively determining a concentration of glucose in the blood from a concentration of glucose in the constituents of the aqueous humor, which concentration is newly measured with a method as defined in claim 1, and said correlation.

5. A glucose concentration measuring apparatus, comprising:

i) a light source device for radiating out a plurality of coherent light beams, which have different wavelengths and the frequencies of which are swept temporally in a sawtooth-like form,

ii) an optical path splitting means for splitting each of said coherent light beams, which has been radiated out of said light source device and the frequency of which is swept, into a signal light beam irradiated to the eyeball and a reference light beam, each of which travels along one of two different optical paths,

iii) a wavefront matching means for;

matching a wave front of a first backward scattered light beam of said signal light beam, said first backward scattered light beam coming from an interface between the cornea and the anterior aqueous chamber of the eyeball, and a wave front of said reference light beam with each other, said reference light beam being constituted of the coherent light beam, which has been radiated out of said light source device with a difference in time in accordance with a difference between an optical path length of said signal light beam and said first backward scattered light beam and an optical path length of said reference light beam, and which has a difference in frequency with respect to said first backward scattered light beam, and

matching a wave front of a second backward scattered light beam of said signal light beam, said second backward scattered light beam coming from an interface between the anterior aqueous chamber and the crystalline lens of the eyeball, and a wave front of said reference light beam with each other, said reference light beam being constituted of the coherent light beam, which has been radiated out of said light source device with a difference in time in accordance with a difference between an optical path length of said signal light beam and said second backward scattered light beam and an optical path length of said reference light beam, and which has a difference in frequency with respect to said second backward scattered light beam,

iv) a photodetector for photoelectrically detecting an intensity of a first interference light beam, which is obtained from the matching of the wave front of said first backward scattered light beam and the wave front of said reference light beam, said reference light beam having the slight difference in frequency with respect to said first backward scattered light beam, with each other, and an intensity of a second interference light beam, which is obtained from the matching of the wave front of said second backward scattered light beam and the wave front of said reference light beam, said reference light beam having the slight difference in frequency with respect to said second backward scattered light beam, with each other,

v) a heterodyne operation means for calculating an intensity of said first backward scattered light beam from the intensity of said first interference light beam, and calculating an intensity of said second backward scattered light beam from the intensity of said second interference light beam,

vi) a light absorption characteristics analyzing means for obtaining light absorption characteristics of constituents of the aqueous humor, which fills the anterior aqueous chamber, from the intensity of said first backward scattered light beam and the intensity of said second backward scattered light beam, and

vii) a glucose concentration calculating means for calculating a concentration of glucose in the constituents of the aqueous humor from the light absorption characteristics, which have been obtained with respect to the plurality of said coherent light beams.

6. An apparatus as defined in claim 5 wherein said light source device comprises a single light source capable of selectively radiating out each of the plurality of said coherent light beams, and a control means for controlling said light source such that said light source may selectively radiate out one of the plurality of said coherent light beams.

7. An apparatus as defined in claim 5 wherein said light source device comprises a plurality of light sources, each of which radiates out one of said coherent light beams.

8. A glucose concentration measuring apparatus, comprising a table representing correlation between concentrations of glucose in the constituents of the aqueous humor, which concentrations have been measured with an apparatus as defined in claim 5, and concentrations of glucose in the blood, which have been measured previously,

wherein a concentration of glucose in the blood is non-invasively determined from a concentration of glucose in the constituents of the aqueous humor, which concentration is newly measured with an apparatus as defined in claim 5, and said table.