U.S. patent application number 10/983924 was filed with the patent office on 2005-03-31 for optical alignment apparatus.
This patent application is currently assigned to VISUAL PATHWAYS, INC.. Invention is credited to Cornsweet, Tom N..
Application Number | 20050070772 10/983924 |
Document ID | / |
Family ID | 23261358 |
Filed Date | 2005-03-31 |
United States Patent
Application |
20050070772 |
Kind Code |
A1 |
Cornsweet, Tom N. |
March 31, 2005 |
Optical alignment apparatus
Abstract
The glucose concentration in the bloodstream is directly
correlated to the concentration of glucose in the aqueous humor.
Furthermore, variation in the glucose concentration in the aqueous
humor will cause like variations in its index of refraction. Thus,
by measuring the refractive index of the aqueous humor, the glucose
concentration in the blood can be determined. The refractive index
of the aqueous humor can be measured by interferometry. In various
embodiments of the invention that employ interferometry, two beams
may be directed onto the eye and caused to interfere, thereby
producing a fringe pattern. The fringe pattern may be analyzed to
determine the index of refraction of the aqueous humor in the eye
and the glucose concentration therein. The glucose level in the
blood can be ascertained from this information.
Inventors: |
Cornsweet, Tom N.;
(Prescott, AZ) |
Correspondence
Address: |
C. Robert von Hellens
Cahill, von Hellens & Glazer P.L.C.
155 Park One
2141 E. Highland Avenue
Phoenix
AZ
85016
US
|
Assignee: |
VISUAL PATHWAYS, INC.
|
Family ID: |
23261358 |
Appl. No.: |
10/983924 |
Filed: |
November 8, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10983924 |
Nov 8, 2004 |
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10247753 |
Sep 19, 2002 |
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6836337 |
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60323939 |
Sep 20, 2001 |
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Current U.S.
Class: |
600/319 ;
356/517 |
Current CPC
Class: |
A61B 5/1455 20130101;
A61B 5/14532 20130101; A61B 3/152 20130101 |
Class at
Publication: |
600/319 ;
356/517 |
International
Class: |
A61B 005/00; G01N
021/43 |
Claims
1-18. (Cancelled)
19. An alignment apparatus for lateral aligning an eye with respect
to said apparatus comprising: a) a central light source; b) a
partially reflecting concave mirror having an optical axis passing
therethrough, said central light source centrally disposed along
said optical axis such that at least a portion of said light from
said central light source propagates through said partially
reflecting concave mirror along said optical axis; and c) first and
second offset light sources disposed in a plane passing through
said optical axis, said first and second offset light sources on
opposite sides of said optical axis, said first and second offset
light sources emitting light at an oblique angle toward said
optical axis.
20. The alignment apparatus of claim 19, wherein said central light
source comprises a light emitting diode.
21. The alignment apparatus of claim 19, wherein said partially
reflecting concave mirror comprises a metalized mirror.
22. The alignment apparatus of claim 19, wherein said first and
second offset light sources comprise light emitting diodes.
23. The alignment apparatus of claim 19, wherein said first and
second offset light sources are spaced apart from said optical axis
by equal distances.
24. The alignment apparatus of claim 19, wherein said first and
second offset light source have respective positions and
orientations such that said light emitted from said light sources
is substantially directed toward a common point on said optical
axis.
25. A method of aligning a device with respect to a cornea, said
cornea having a substantially spherical curvature defined by a
center of curvature, said method comprising: a) propagating light
toward said cornea, said light having substantially spherical
wavefronts defined by a center of curvature that is substantially
coincident with said center of curvature of said cornea; b)
retroreflecting a portion of said light from said cornea; c)
collecting said retroreflected light; and d) focusing said
collected light on an optical detector having a photosensitive area
such that when said center of curvature of said wavefronts is
substantially coincident with said center of curvature of said eye,
said light focused on said photosensitive area has a different
intensity than when said respective centers of curvature are
non-coincident.
26. The method of claim 25, further comprising covering at least a
portion of said optical detector such that when said center of
curvature of said wavefronts is non-coincident with said center of
curvature of said eye, said light incident on said photosensitive
area is reduced.
Description
RELATED APPLICATION
[0001] This application claims priority under 35 U.S.C. .sctn.
119(e) from U.S. Provisional Patent Application No. 60/323,939,
filed Sep. 20, 2001, entitled "Non-Invasive Blood Glucose
Monitoring by Interferometry", which is hereby incorporated herein
by reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention is directed to glucose monitoring, and
more specifically, to apparatus and methods for monitoring glucose
using interferometry.
[0004] 2. Description of the Related Art
[0005] Diabetics are advised to closely monitor the concentration
of glucose in their bloodstream. If the concentration is outside of
a normal healthy range, the patient needs to adjust his or her
insulin dosage or sugar intake to counter the risk of diabetic
complications. Current monitoring methods involve drawing blood
from the patient several times a day, which is costly, painful, and
poses the risk of infection. As a result, many diabetics test their
blood glucose less frequently than would be desirable, increasing
the possibility of diabetic related health problems. Thus, what is
needed is a painless, non-invasive approach for determining the
glucose level within the bloodstream.
SUMMARY OF THE INVENTION
[0006] One aspect of the invention comprises a method of measuring
glucose levels in blood of a living being having an eye. The eye
comprises a cornea and a lens, which together form an anterior
chamber. The eye further comprises an iris and aqueous humor in the
anterior chamber of the eye. The aqueous humor has an index of
refraction that is correlated to the glucose level in the blood. To
measure the glucose levels in the blood, two substantially coherent
beams of light are propagated through the cornea to illuminate a
region of the iris. The two substantially coherent beams of light
propagate through the aqueous humor to reach the iris. The two
beams are overlapped on the region of the iris. These two beams are
sufficiently coherent so as to produce an interference pattern in
this region of the iris where they overlap. The interference
pattern comprises a plurality of fringes having a spatial
arrangement that depends on the index of refraction of the aqueous
humor. The interference pattern is imaged onto a light sensitive
optical detector, and the glucose level in the blood is determined
from the spatial arrangement of the fringes in the interference
pattern.
[0007] Another aspect of the invention comprises an apparatus for
monitoring glucose fluctuations by measuring optical properties of
an eye. The apparatus comprises a light source which emits a beam
of light, an optical element, an optical detector and imaging
optics. The optical element is situated to receive this beam of
light from the light source and to split the beam of light into
first and second probe beams that propagate along respective first
and second optical paths. The apparatus further includes at least
one optical element in one of the optical paths to alter the
optical path such that first and second probe beams intersect at a
target plane. The optical detector and imaging optics are arranged
to image the target plane onto the optical detector.
[0008] Another aspect of the invention comprises a method of
monitoring glucose levels in blood of a living being having an eye.
In this method, light is propagated through a portion of the eye
comprising aqueous humor having an index of refraction that varies
with glucose concentration. Phase information associated with the
light is obtained through optical interference. The phase
information depends at least in part on the index of refraction of
the aqueous humor. The phase information is used to determine the
glucose levels in the blood.
[0009] Yet another aspect of the invention comprises an alignment
apparatus for lateral aligning an eye with respect to the
apparatus. The apparatus comprises a central light source, a
partially reflecting concave mirror, and first and second offset
light sources. The partially reflecting concave mirror has an
optical axis passing therethrough. The central light source is
centrally disposed along this optical axis such that at least a
portion of the light from the central light source propagates
through the partially reflecting concave mirror along the optical
axis. The first and second offset light sources are disposed in a
plane passing through the optical axis. The first and second offset
light sources are on opposite sides of the optical axis and emit
light at an oblique angle toward the optical axis.
[0010] Still another aspect of the invention comprises an method of
aligning a device with respect to a cornea wherein the cornea has a
substantially spherical curvature defined by a center of curvature.
In this method light is propagated toward the cornea. This light
has substantially spherical wavefronts defined by a center of
curvature that is substantially coincident with the center of
curvature of the cornea. A portion of the light from the cornea is
retrorefect, collected, and focusing onto an optical detector
having a photosensitive area. When the center of curvature of the
wavefronts is substantially coincident with the center of curvature
of the eye, the light focused on the photosensitive area has a
different intensity than when the respective centers of curvature
are non-coincident.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a schematic illustration of the anatomy of the eye
including the cornea, iris, lens, and anterior chamber containing
aqueous humor.
[0012] FIG. 2 schematically illustrates a device for measuring the
concentration of glucose in the bloodstream of a subject by
measuring optical properties of the aqueous humor within the
eye.
[0013] FIGS. 3A and 3B schematically illustrates the interference
of two cylindrical wavefronts produced by Young's double slit
configuration.
[0014] FIG. 3C is an exemplary interference pattern comprising a
plurality of fringes resulting from the interference of the two
cylindrical wavefronts produced in the configuration schematically
illustrated in FIGS. 3A and 3B.
[0015] FIG. 4 shows profiles of the fringe patterns obtained using
the device schematically illustrated in FIG. 2 for four different
aqueous glucose concentrations.
[0016] FIG. 5 illustrates how the peak locations change with
refractive index over a range of glucose concentrations from zero
to about 600 milligrams per deciliter (mg/dl) or about six times
the typical level found in healthy human beings.
[0017] FIG. 6 schematically illustrates a subsystem used for
lateral alignment of the probe beams with respect to the eye in two
orthogonal directons (x, y) that are normal to the visual axis.
[0018] FIG. 7 schematically illustrates a side view of subsystem
used for longitudinal alignment along an axis through the center of
curvature of the cornea, such that the distance separating the
optical system and the eye is appropriate for accurate measurement
of the glucose concentration.
[0019] FIG. 8 schematically illustrates a system for measuring the
concentration of glucose in the bloodstream of a subject together
with the aligning subsystems shown in FIGS. 6 and 7.
[0020] FIG. 9 is an artistic rendering of a compact instrument for
measuring the concentration of glucose in the bloodstream of a
subject.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0021] These and other embodiments of the present invention will
also become readily apparent to those skilled in the art from the
following detailed description of the preferred embodiments having
reference to the attached figures, the invention not being limited
to any particular embodiment(s) disclosed. Accordingly, the scope
of the present invention is intended to be defined only by
reference to the appended claims.
[0022] As is well known and illustrated in FIG. 1, an eye 10
includes a lens 20 for imaging onto a retina 30 located at the back
of the eyeball. Dense relatively opaque tissue, the sclera 40,
together with a curved transparent window, the cornea 60, forms a
chamber inside of which is the ocular lens 20. This lens 20 is held
in place by the ciliary body 50 and fibrous muscle included
therewith. An iris 80 comprising opaque diffusely reflecting tissue
that includes a central opening, i.e., the pupil 75, lies on an
anterior surface of the lens 20. The refractive powers of the lens
20 and the cornea 60 combine to focus light on the retina 30. A
tiny region approximately at the center of the retina 30 known as
the fovea 85, comprises densely packed photoreceptor, which
provides vision for fine detail. When the eye 10 peers at a distant
object, such as for example a star, the eye 10 rotates until an
image of the distant object falls on the fovea 85. A straight line
drawn through the center of the pupil 75 and the fovea 85 is known
as the visual axis 90, sometimes referred to as the line of sight.
The cornea 60 and the lens 20 together form a cavity 70 called the
anterior chamber 70. The anterior chamber 70 is filled with a
transparent liquid known as aqueous humor.
[0023] Advantageously, the glucose concentration in the aqueous
humor closely tracks the glucose concentration in the bloodstream
to within a delay of only minutes. Increases in the glucose level
of the blood are mimicked by proportional rises in the glucose
level in the aqueous humor. Accordingly, by monitoring the glucose
concentration of the aqueous humor, changes in the glucose
concentration in the blood can be sensed.
[0024] Fluctuations in the glucose concentration of the aqueous
humor have also been shown to produce a corresponding shift, in the
index of refractive of the aqueous humor. Therefore, devices and
methods for measurements of the refractive index of the aqueous
humor can be used to quantify variations in the concentration of
glucose in the aqueous humor. By measuring this aqueous glucose
concentration in this manner, patients can determine the
concentration of glucose in the blood and adjust their insulin and
sugar intake accordingly.
[0025] Interferometry can be employed to measure the index of
refraction of the aqueous humor. Other optical methods can be used
that monitor optical properties that are dependant on the
refractive index of this fluid in the eye 10. Identifying and
quantifying fluctuations in the index of refraction of the aqueous
humor using light is preferred as it is clean, non-invasive, and
relatively precise. Interferometers offer one approach for
optically determining the refractive index of the aqueous humor,
however, other well known techniques as well as those yet devised
are possible alternatives.
[0026] An optical instrument 100 for measuring the refractive index
of the aqueous humor is schematically illustrated in FIG. 2. This
optical instrument 100 comprises a light source 110, an
interferometer 120, and a detection system 130. The light source
110 preferably comprises a coherent source 115 such as a laser.
This light source 110 preferably outputs invisible radiation such
as infrared but is not limited to any particular wavelength range.
The wavelength of the light may, for example, be between about 500
to 950 nanometers (nm). Other types of light sources may also be
used.
[0027] The light source 110 may further include beam shaping optics
117 for producing a beam 130 possessing suitable properties such as
intensity and diameter. In one preferred embodiment, the beam
shaping optics 117 includes a beam expander. An exemplary beam
expander comprises an afocal system similar to a telescope in which
a substantially collimated input beam entering the beam expander
exits with substantially the same degree of collimation, but with a
diameter different from that of the input beam. The beam expander
may increase or decrease the diameter of the beam 130 depending on
the desired spatial extent and the beam size of the coherent source
115. The beam shaping optics 117 may further include a neutral
density filter as well as possibly polarizers and apertures to
suite the particular application. Other optics may be included in
the beam shaping optics 117 and elsewhere in the instrument
100.
[0028] The interferometer 120 comprises two arms, a first and
second with corresponding first and second probe beams 140, 150
that are interfered. The interferometer 120 includes a beamsplitter
155 which splits the optical beam 130 from the light source 110
into the two probe beams 140, 150. Other methods and devices (such
as, other splitters comprising for example a prism) may also be
employed for creating the two probe beams 140, 150 from the
original beam 130. Since the first and second probe beams 140, 150
are interfered, the coherent light source 115 preferably has a
coherence length that is longer than the optical path length
difference between the two optical paths 140, 150. A relatively
long coherence length may advantageously increase the optical
contrast of the resultant interference pattern.
[0029] The inteferometer 120 further comprises optics, such as a
mirror or reflector 160 and a lens 170 to direct light in the
second probe beam 150 towards the eye 10 and to focus this beam.
The lens 170 causes the beam 150 to be converging when incident on
the eye 10, which in certain embodiments is beneficial; such a
configuration, however, is not required and may vary in other
designs. The use of the mirror 160 in FIG. 2 is illustrative of a
preferred embodiment for directing light and should not be
construed as limiting since other optical components and
configurations may be used. For example, a different number of
mirrors or reflectors may otherwise be employed.
[0030] The interferometer 120 is preferably adjusted such that the
first probe beam 140 and the second probe beam 150 are incident on
the eye 10 and, more particularly, overlap each other over a region
175 of the iris 80. A fringe pattern is formed where the two beams
140, 150 overlap.
[0031] The detection system 130 in the instrument 100 comprises an
optical sensor 190 and an imaging element 200 such as a lens. In
one preferred embodiment, the lens 200 has a power and is
positioned appropriately to produce an image of the iris 80 on the
optical detector 190.
[0032] Preferably, the principle plane of the imaging lens 200 is
oriented at an angle to satisfy the Scheimpflug condition. The
Scheimpflug condition is met when three lines through the plane of
the iris 80, the principle plane of the imaging lens 200, and the
plane of the sensor 190 all intersect at a common point. Under
these circumstances, in theory all the points in the plane of the
iris 80 may be simultaneously focused in the plane of the sensor
190 by the imaging lens 200.
[0033] In certain preferred embodiments, the optical sensor 190
comprises a one or two dimensional sensor array such as a charge
coupled device (CCD) or a complementary metal oxide semiconductor
(CMOS) detector array. Other types of optical detectors 190 may
also be used. In certain embodiments, the sensor 190 produces an
image signal that is received by a computer and/or other
electronics for processing the image signal.
[0034] In one preferred embodiment, an image is obtained of the
interference fringes formed in the region 175 in the iris 80 where
the first and second beams 140, 150 intersect. The interference
fringes formed on the iris 80 in the region 175 are produced due to
mutual coherence of the two intersecting probe beams 140, 150.
Phase differences resulting from the optical path difference
traveled by the first and second probe beam 140, 150 cause
constructive and destructive interference which varies with
position within the overlap region 175. Consequently, bright and
dark regions, i.e., a fringe pattern, are produced in the overlap
region 175 on the iris 80.
[0035] As stated previously, variations in the glucose
concentration of the aqueous humor alter the refractive index of
the aqueous humor 20. Since the probe beams 140, 150 both pass
through the aqueous humor, the interference fringes formed on the
iris 80 are affected by changes in the refractive index of the
aqueous humor. More particularly, the optical path length of the
first and second probe beams 140, 150 varies with the index of
refraction of the aqueous humor in the anterior chamber 70 of the
eye 10. The fringe pattern varies as well. Thus, variations in the
glucose concentration of the aqueous humor are directly correlated
to quantitative changes in the fringes formed on the iris 80 in the
overlap region 175.
[0036] The nature of the fringes formed on the iris 80 may be
generally understood by reference to FIGS. 3A-3C, which
schematically illustrate the formation of interference fringes
using Young's double slit configuration 300. In this optical
arrangement, a monochromatic light source 301 emits light that is
transmitted through a narrow vertically oriented elongated slit
305, which diffracts the light incident thereon. The result is an
optical beam having cylindrical wavefronts. These cylindrical
wavefronts illuminate two other vertically oriented elongated slits
310, 315 which are laterally (i.e., horizontally) separated from
each other by a distance a. Light is diffracted by the two slits
310, 315, the output of which is a pair of beams also characterized
by vertically oriented cylindrical wavefronts. The two beams
illuminate a diffuse screen 320 where they interfere constructively
and destructively producing vertical fringes such as the ones
schematically illustrated in FIG. 3C.
[0037] The cause of the elongated bright and dark regions in FIG.
3C has been well characterized and may be understood as follows.
Constructive or destructive interference results when the two beams
are overlapped. The interference at a given location on the diffuse
screen 320 is determined by the respective optical path distance
from the two slits 310, 315 to that specific location on the
diffuse screen. For example, a ray 325 shown in FIG. 3B that is
transmitted through the first slit 310, travels a distance r.sub.1,
and illuminates the diffuse screen 320 at a point 330, which is
located a distance x.sub.0 from a centerline 332. The centerline
332 through the system is defined as a line normal to the diffuse
screen 320 that bisects the two slits 310; 315. The distance from
the diffuse screen 320 to the plane containing the two slits 310,
315 is defined as D. A second ray 335 is transmitted through the
second slit 315, travels a distance r.sub.2, and illuminates the
diffuse screen 320 at the same point 330. The distances through
which the two rays travel may differ, as indicated in FIG. 3B, by
the distance .DELTA.r=r.sub.1-r.sub.2. If the original slit 305 is
sufficiently narrow, the light emerging from it (in the x-z plane)
is substantially coherent and the waves associated with rays
produced by the light source 301 oscillate in phase with one
another. The phase of the two rays 325, 335 at the point 330 on the
screen 320 is determined in part by the respective path lengths
r.sub.1 and r.sub.2. More particularly, the relative phase between
the two rays 325, 335 is proportional to the difference in the two
path lengths, i.e., .DELTA.r. If the two rays 325, 335 have the
same intensity I.sub.1=I.sub.2=I.sub.o, then the intensity at the
point 330 is given by the well known relation,
I=I.sub.o(1+I.sub.o cos(.delta.)) (1)
[0038] where I.sub.o is the intensities of rays 325, 335 and
.delta. the relative phase between the rays 325, 335 given by the
relation (.delta.=2.pi..DELTA.r/.lambda.), where .lambda. is the
wavelength of the source 301. In this case, the light emitted from
the slits 310, 315 propagates though air or vacuum to the diffusely
reflecting screen 320.
[0039] Accordingly, if for example the distance .DELTA.r
corresponds to an optical path difference over which light at the
wavelength .lambda. oscillates through precisely one-half of a
cycle (.pi. radians in phase), then the two rays 325, 335 will be
.pi. radians out of phase with each other at point 330 and the two
rays 325, 335 will cancel each other, resulting in a reflected
intensity of zero at point 330. If .DELTA.r is exactly an integer
number of cycles (i.e., an integer multiple of 2.pi. radians), the
two rays will be in phase at the point 330, and under ideal
conditions, the resulting reflected intensity will equal the sum of
the intensities of the two individual rays.
[0040] For points 330 on the screen 320 closer to the centerline
332 (i.e., for smaller values of x), .DELTA.r is reduced, reaching
a value of zero at a center point 340 where the centerline
intersects the screen. The optical path difference Ar increases
again for positions below the centerline (i.e., negative values on
the x-axis). The intensity on the screen 320 oscillates between
high and low on both sides of the centerline 332 as illustrated in
FIG. 3C. Specifically, the reflected intensity I fluctuates along
the diffusing surface 320 accordingly to the relation,
I=4A.sub.o cos.sup.2[a.pi.x/(D.lambda.)] (2)
[0041] where A.sub.o is the amplitude of the rays 325, 335 at the
diffuse screen 320, x is the distance along the x-axis across the
diffuse screen 320 as measured from the centerline 332 where x=0, a
is the lateral distance separating the two slits 310, 315, D is the
distance from the diffuse screen 320 to the plane containing the
two slits 310, 315, and .lambda. is the wavelength of the source
301. Since the difference in path lengths, .DELTA.r, is
substantially the same for the plurality of points on the screen
320 in the .+-.y-direction, the interference fringes produced by
the elongated slits 310, 315, which are oriented lengthwise
parallel to the y-axis, are linear and also oriented along the
y-direction.
[0042] The relations derived based on FIGS. 3A and 3B assume that
the region between the slits 310, 315 and the diffuse screen 320 is
filled with air or vacuum. Constructive or destructive
interference, however, does not depend solely on the distance
traveled by the light and, more specifically, the difference in the
distance between the two physical paths, .DELTA.r. Rather, the time
it takes the light to travel through that optical path difference
determines the result of the interference. The phase of the light
depends upon time, not distance. Accordingly, the index of
refraction of the medium through which the light propagates along
the optical paths will affect the resultant fringe pattern as the
refractive index determines the phase of the light.
[0043] If the region between the slits 310, 315 and the diffuse
screen 320 is filled, instead, with a liquid such as water, the
velocity of the light waves is reduced. The index of refraction of
water is 1.5. Accordingly, the speed of light in the region between
the slits 310, 315 and the diffuse screen 320 is approximately
three quarters of that in air. Under these conditions, the value of
.DELTA.r between two rays transmitted from slits 310, 315 will
produce a phase difference that is {fraction (4/3)} larger than
when the region between the slits 310, 315 and the diffuse screen
320 is filled with air. Likewise, there will be {fraction (4/3)} as
many fringes per unit distance formed on the diffuse screen 320
than when the region between the slits 310, 315 and the diffuse
screen 320 is filled with air. The number of fringes per unit
distance across the screen 320 is therefore directly proportional
to the speed of light in the medium. In certain embodiments, this
relationship between refractive index of a media and the spacing
between fringes may be used to determine the refractive index of
that media. Other effects on the fringe pattern can also be
measured and quantified to determine the index of refraction of the
medium.
[0044] Referring again to FIG. 2, light from light source 115 is
transmitted through the beam shaping optics 117 and is incident on
the beamsplitter 155. A fraction of the light is transmitted
through the beamsplitter 155 to produce the first probe beam 140.
This probe beam 140 is preferably substantially parallel to the
visual axis 90 of the eye 10. When light from the probe beam 140
illuminates the cornea 60, the light is refracted toward the pupil
75 and illuminates the iris 80.
[0045] Another fraction of the light, i.e., the remainder, is
reflected from the beamsplitter 155 forming the second probe beam
150. In certain embodiments, the fraction of the light that is
transmitted through the beamsplitter 155 to produce the first probe
beam 140 and the fraction of light is reflected by the beamsplitter
155 to produce the second probe beam 150 are selected so that they
have substantially equal intensity when they are interfered on the
front surface of the iris 80. Favorable contrast can thereby be
achieved.
[0046] This reflected beam 150 is directed by the mirror or
reflector 160 through the focusing lens 170 towards the eye 10. In
certain embodiments, the focal length of the lens 170 is
substantially equal to the distance from the focusing lens 170 to a
point 260 located at the center of curvature, C of the front
corneal surface of the cornea 60. The light transmitted through the
lens 170 converges toward the center point 260 however is incident
on the cornea 60 before reaching its center, C. As discussed above,
the focal length of the focusing lens 170 is preferably selected to
substantially correspond to the distance from the lens to the
radius of curvature of the cornea 60. When this condition is
satisfied and the lens 170 is positioned such that its focal point
and this center of curvature are coincident, then the rays
associated with the second beam 150 that are incident on the
corneal surface will be substantially perpendicular thereto. With
an angle of incidence of substantially zero, the converging rays
are not refracted by the cornea 60.
[0047] As discussed above, the converging rays associated with this
second probe beam 150 preferably illuminate a substantially similar
region 175 of the iris 80 as the first probe beam 140. The overlap
of the two beams 140, 150 produces interference fringes on the iris
80 as a consequence of constructive and destructive interference.
The interference process is generally similar to the optical
phenomena related to the Young's double slit configuration 300
discussed above with reference to FIGS. 3A-3C. The configuration in
FIGS. 3A and 3B, however, differs from the interferometer 120 shown
FIG. 2. The fringes formed in the Young's double slit configuration
300 were produced by two probe beams each having cylindrical
wavefronts defined by substantially equal radii of curvature. The
first and second probe beams 140, 150 in the inteferometer 120
depicted in FIG. 2 comprise wavefronts having different radii of
curvature. In various preferred embodiments, first probe beam 140
is has a radius of curvature of about 25 millimeter. The refractive
power of the cornea 60 will cause the probe beam 140 to be
convergent such that spherical wavefronts are incident on the iris
80. At the iris 80, the second probe beam 150 also comprises
substantially spherical wavefronts. These spherical wavefronts are
defined by a radius of curvature that is approximately equal to the
distance from the focusing lens 170 to the center of curvature 260
of the cornea 60. The result of interfering substantially planar
waves with substantially spherical wavefronts is a plurality of
annular shaped fringes. In various preferred embodiments, the
overlap region 175 corresponds to a portion of these annular shaped
fringes. Accordingly, the fringes may not be complete rings but
only portions of annuli. An intensity profile across a
cross-section of these fringes corresponding, for example, to the
x-z plane is shown in FIG. 4. These fringes in FIG. 4 are for a
variety of glucose concentrations and respective refractive index
values. As shown, these fringe patterns have a point of symmetry
and the frequency of the fringes increases to either side of the
point of symmetry with distance away from the point of
symmetry.
[0048] FIG. 4 shows profiles of the fringe patterns for four
different aqueous glucose concentrations. Short vertical lines are
included to mark the locations of the peaks and troughs in the
interference pattern. Differences in the refractive index between
the aqueous humor solutions shown in the different profiles produce
variation in the plot pattern. For example, the shape of the
profile in the region near the point of symmetry as well as the
rate of change of fringe spacing varies. In contrast, the location
of the point of symmetry is substantially fixed over a wide range
of refractive indices.
[0049] An analytical expression can be derived that characterizes
the fringe pattern. In one exemplary case, the radius of curvature
of the cornea 60 is approximately 8.0 millimeters (mm) and the
distance from the corneal vertex to the plane of the iris 80 is
approximately 4 mm. (As used herein, and consistent with
conventional usage, the corneal vertex corresponds to the foremost
point of the cornea 60, where the cornea intersects the visual
axis.) Under these circumstance, the signal strength, I, of the
light reflected by the iris 80 is given by, 1 I = sin 2 ( 1 180 (
580645 g tan 2 ( sin - 1 ( r 8 ) - sin - 1 ( r 8 g ) ) ( u ) 2 + (
u ) 2 - 580645 g ( 8 - ( r - u tan ( sin - 1 ( r 8 ) - sin - 1 ( r
8 g ) ) ) 2 + 16 ) ) ) where u = 8 1 - r 2 64 - 4 ,
[0050] g is glucose concentration, and r is the distance in the
plane of the iris 80 between the visual axis 90 of the eye 10 and
the point where the strength is evaluated. This expression
quantifies the variation in intensity of light across region 175 of
the iris 80 illuminated by the two overlapping probe beams 140,
150. More specifically, this expression characterizes the variation
in intensity corresponding to the fringe pattern that results from
the interference of these two beams 140, 150. Accordingly,
equations such as these could be used to determine the index of
refraction and the relative glucose concentration from a given
fringe pattern. These equations, however, are complex and other
techniques may be preferred for ascertaining the relative levels of
glucose concentration.
[0051] In FIG. 5, a series of plots illustrates how the peak
locations move with increase in glucose concentration. The
plurality of plots corresponds to a range of glucose concentrations
from zero to about 600 milligram per deciliter (mg/dl), the later
value of which is about six times the normal level found in healthy
human beings. No two of these patterns are alike. Accordingly,
analysis of the pattern yields a sensitive and substantially
unambiguous reading of the refractive index over the entire range.
Thus, in various preferred embodiments, the signal from the sensor
190 may be processed to determine the location of the peaks and
troughs. The set of locations of the various peaks and troughs is
like a fingerprint which can be used to determine the relative
index of refraction and glucose concentration. In certain preferred
embodiments, the pattern of peaks and troughs, i.e., their relative
location and spacing with respect to each other and to the center
of symmetry, can be compared to a database of similar patterns for
different glucose concentrations. By looking up the pattern in
electronic look-up tables, a value of the refractive index can be
obtained from which the relative glucose concentration can be
calculated after calibrating the instrument 100. The look-up tables
may include glucose concentrations in other embodiments.
[0052] For example, in some embodiments, the signal from the sensor
190 may be digitized and sent to a computer, microprocessor, or
other electronics, which determines the point of symmetry and
locates the peaks and troughs within a range of this point of
symmetry. For instance, peaks and troughs within about 0.5 mm of
the point of symmetry can be determined. This mapping of the peaks
and valleys can be compared with a set of patterns computed from
analytical expressions for a range of plausible glucose levels. One
or more of the computed patterns from the set that substantially
matches the fringe pattern produced by the measurement can be used
to arrive at the measured value of relative glucose concentration.
Averaging and/or other signal processing techniques may be employed
to reduce noise or otherwise improve accuracy and precision.
[0053] In other preferred embodiments, the intensity of the fringe
pattern imaged on the sensor 190 can be fit to a curve, e.g., using
a least squares fits or other fitting techniques. Based on the
curve to which the intensity pattern is fit, unknowns such as the
index of refraction or glucose concentration in the aqueous humor
can be determined.
[0054] Still other techniques for ascertaining the index of
refraction of the aqueous humor from the intensity pattern of the
overlapping probe beams 140, 150 may be utilized, both those well
known and well as those yet to be devised. Also, variations and
additional processes, such as for example digital signal
processing, filtering, and noise reduction techniques, may be used
to yield more accurate or precise results or to simplify or
accelerate the analysis.
[0055] Thus, in various embodiments, light from the two probe beams
140, 150 is diffusely reflected off the iris 80, some of that light
being collected by the imaging lens 200 and focused onto the sensor
190. An image of the fringe pattern resulting from interfering the
two beams 140, 150 is thereby formed on the sensor 190. The signal
output from the sensor 190 is analyzed, for example, as described
above, to determine the glucose concentration based on the
relationship established between refractive index and glucose
concentration by calibrating the instrument with independent
measurements.
[0056] The profiles in the FIGS. 4 and 5 were computed using a
model wherein the iris 80 was assumed to be a smooth, reflecting
surface. In certain cases, however, the iris 80 is more accurately
represented as a surface that is rough compared to the dimensions
of the wavelength of the light from the coherent light source 115.
The roughness of the iris 80 gives rise to several effects. First,
the distance from the cornea 60 to different locations on the iris
80 does not change smoothly, but includes an additional random
perturbation added to it. Second, when illuminated by coherent
light, the iris roughness generates speckle. Speckle, which is well
known in the art, is a random-appearing variation in the intensity
of the reflected light that is superimposed upon or multiplied by
to the underlying fringe pattern.
[0057] In certain cases, errors that may be introduced by these
effects can be reduced by employing various instrument
configurations and measurement techniques. For example, the optical
sensor 190 may comprise a two-dimensional detector array, which
detects a plurality of elongated fringes corresponding to the
fringe pattern. Instead of simply obtaining a single intensity
distribution across a cross-section of the fringe pattern, a
plurality of such cross-sections can taken at different locations
along the length of the fringes. In this manner, the variations
caused by the roughness of the iris 80 may be averaged out over the
length of the fringes. For example, if the fringes are oriented
substantially vertically (i.e., along the y-direction), a separate
estimate of the fringe location and spacing can be produced for
each horizontal scan line (i.e., along the x-direction) of the
array 190. The results of averaging over several horizontal scan
lines produces an average value of fringe spacing that may be more
accurate than the value produced by a single horizontal scan across
the array 190. The variations due to the iris 80 being a rough
surface, can thereby be reduced.
[0058] In certain embodiments, the device 100 additionally
comprises a lateral alignment subsystem 400 schematically
illustrated in FIG. 6 that is used to align the device 100 with
respect to the eye 10. The subsystem 400 is preferably used for
"lateral" alignment, i.e., positioning along two orthogonal axes
(e.g., x, y) normal to the visual axis 90. The lateral alignment
subsystem 400 comprises a central light source 410, a lens 420, and
a curved mirror 430 aligned along an optical axis 435. The lateral
alignment subsystem further includes two additional light sources
440, 450 offset from and on opposite sides of the optical axis 435.
Other configurations and designs, however, are possible.
[0059] In one preferred embodiment, the central light source 410
comprises a light emitting diode (LED) that produces light in the
green portion of the light spectrum. Green is preferred since it is
easily detected by the eye, although the choice herein does not
preclude the used of other colors or other types of light sources.
The lateral spatial extent of the light produced by light source
410 preferably has a diameter that is relatively small in relation
to other dimensions of the subsystem 400, namely the focal length
of the lens 420, and approaches the characteristics of an idealized
point source. A pin hole or other aperture may be included to
reduce the effective spatial extent of the source of light 410.
[0060] The off-centered light sources 440, 450 may also comprise
light emitting diodes LEDs but may comprise other types of light
sources in other embodiments. In various preferred embodiments, the
light sources 440, 450 are white light-emitting diodes that
diffusely illuminate of the eye 10. The lateral spatial extent of
the light produced by these two light sources 440, 450 also is
preferably small in relation to other dimensions of the subsystem
400 and may approach the characteristics of an idealized point
source. A pin hole or other aperture may be included to reduce the
effective spatial extent of these light sources 440, 450. The two
offset light sources 440, 450 are preferably arranged on opposite
sides of the optical axis 435. In one preferred embodiment, the two
offset light sources 440, 450 are disposed above and below the
optical axis 435, in a vertical plane (e.g., the y-z plane) through
the optical axis. More preferably, the two offset light sources
440, 450 are equally distant from the optical axis 435 and are also
equally distant from the eye 10. In such a configuration, the two
light sources 440, 450 are disposed symmetrically about the optical
axis 435. Accordingly, the angle from the eye 10 to the first
offset source 440, as measured with respect to the optical axis
435, is equal and opposite to the angle from the eye to the second
offset source 450. Other arrangements are possible, however, the
first and second offset light sources 440, 450 are preferably on
opposite sides of the central light source 410 as seen by the eye
10. Preferably, the offset lights sources 440, 450 are close to the
eye such that the images of these light sources move independently
of the image of the green light source which appears to the eye 10
to be at infinity. For instance, the offset light sources 440, 450
may be a distance of about one inch (i.e., about 25 mm) from the
cornea.
[0061] Preferably, the lens 420 comprises a collimating lens. More
specifically, the lens 420 has a focal length and is positioned a
distance from the central light source 410 so as to provide a
substantially collimated beam that is directed toward the eye 10.
In other embodiments, other types of optical elements may provide
collimation such as, for example, concave mirrors and diffractive
optic elements.
[0062] The curved mirror 430 is partly transparent, which may be
accomplished with a partially silvered mirror 430. Some of the
light from the central light source 410 therefore is transmitted
through the mirror, while some of the light from the offset light
sources 440, 450 is reflected as will be discussed below.
Preferably, the mirror 430 is concave from the perspective of the
eye 10 and of uniform thickness such that it possesses
substantially zero refractive power. The use of the collimating
lens 420 and the curved mirror 430 is illustrative and does not
preclude the use of other optical elements in other
configurations.
[0063] In certain embodiments, the subsystem 400 is used to
correctly position the eye 10 laterally relative to the device 100
in two directions. This task may involve for example aligning the
apparatus 100 with respect to the eye 10 vertically and
horizontally. Light from the light source 410 is substantially
collimated by the lens 420, is transmitted through the curved
mirror 430, and enters the eye 10 through the cornea 60. Using this
configuration, a patient observes a small green spot of light that
is substantially centered on the optical axis 435 defined by the
source 410, the lens 420.
[0064] The additional offset light sources 440, 450, which are
preferably white light sources, diffusely illuminate the front of
the eye 10. Some of the light from the offset light sources 440,
450 is reflected from the surface of the eye 10 to the curved
mirror 430, which is approximately located at its focal distance
from the eye, or more specifically from the ocular lens. This
provides the patient with a view of the eye 10 that appears at
optical infinity. The view includes the iris 80, pupil 75, and
lids, etc. Moreover, light that is specularly reflected from the
steeply convex surface of the cornea 60 forms two tiny virtual
images of the offset light sources 440, 450, which appear to the
patient as bright white points approximately in the plane of the
iris 80. Similarly, the light from the central source 410 that is
reflected from the cornea 60 appears as a tiny green point. During
alignment, the patient moves laterally, e.g., horizontally and
vertically, with respect to the instrument 100 that includes the
alignment subsystem 400. The patient adjusts his or her lateral
position until the green dot image produced by the central light
source 410 is centered between the two images of the offset white
light sources 440, 450. The instrument 100 is considered to be
aligned in two orthogonal directions, e.g., the vertical and
horizontal axes, when the images of the two light sources 440, 450
are collinear with and bisected by the green dot image produced by
the central light source 410, and the green point reflected from
the cornea 60 is centered on the green source 410 seen directly
through the partially transparent mirror 430.
[0065] The above alignment procedure is based on an assumption that
the patient's vision is approximately emmetropic, that is that the
patient's eye is focused on a target at infinity and that he or she
is neither nearsighted nor farsighted. If the patient were, for
example, nearsighted, the image of the patient's eye 10 in the
above procedure would appear defocused, as would small green spot
image produced by the central light source 410. In certain
embodiments, such non-emmetropic conditions may be corrected by
adjusting the longitudinal position of the central light source 410
towards or away from the collimating lens 420 until the small green
spot image produced by the light source 410 appears sharp to the
patient. Correction may also be provided by positioning the curved
mirror 430 towards or away from the patient until the image of the
patient's eye appears sharp. To adjust the positioning, the
subsystem 400 may further comprise, for example, micrometers or
other translation devices mechanically coupled to the source 410,
collimating lens 420, and/or the curved mirror 430. In this
configuration, the patient adjusts the position of the source 410,
collimating lens 420, and/or the curved mirror 430 by adjusting the
translation devices. In other embodiments, after appropriate
adjustment has been reached, e.g., once the proper non-emmetropic
corrections have been made, the position is locked in place. In
still other embodiments, the amount of correction can be recorded
and made available so that several patients requiring different
non-emmetropic correction settings may easily use the same
instrument. Manual or electronic positioning and translation
components can be used. In the case where positioning is by
electronic apparatus, the one or more correction setting can be
stored in memory and adjustment can be automatic.
[0066] In addition to providing correct lateral, e.g., horizontal
and vertical, alignment, the instrument 100 is preferably located
an appropriate distance away from the eye 10. Most preferably, the
instrument 100 is positioned such that the focal point of the
focusing lens 170 in the second arm of the interferometer 150
corresponds to the center of curvature 260 of the cornea 80.
[0067] In certain embodiments, for example, the instrument 100
further comprises an alignment subsystem 500, such as schematically
illustrated in FIG. 7, that facilitates longitudinal positioning of
the instrument 100 with respect to the eye 10 as well as fine
adjustment of the lateral alignment. This subsystem 500 is for
establishing the appropriate distance between the optical device
100 and the eye 10. More specifically, the separation of the
instrument 100 from the eye 10 as measured along an axis through
the center of curvature, C, of the cornea 60 (i.e., along the
z'-axis shown in FIG. 7), is preferably such that accurate
measurement of the glucose concentration can be obtained. This
z'-axis is preferably offset from the visual axis 90 by a small
angle.
[0068] The fine longitudinal and lateral alignment subsystem 500
comprises a beamsplitter 510 which introduces two (i.e., third and
fourth) additional optical paths 515, 525 into the instrument 100
and two optical detectors 530, 540, one in each of these optical
paths. Two lenses 550, 560 are associated with the two detectors
530, 540 in the third and fourth optical paths 515, 525. The fine
lateral/longitudinal alignment subsystem 500 further includes an
optical filter 570 in the fourth path 525 for filtering light
directed to the detector 540. The detectors 530, 540 respectively
produce alignment and reference signals 580, 585, which together
enable substantially precise longitudinal as well as lateral
alignment.
[0069] The beamsplitter 510 may comprise a beamsplitter cube or a
plate with a partially reflective coating formed thereon. Other
types of beam separators may also be used. In certain embodiments,
the detectors 530, 540 may comprise photodiodes, which preferably
have a small light sensitive area. The detector 530 may further
include a pinhole that is used to decrease the effective
photosensitive area of the detector 530. In one preferred
embodiment, the pinhole aperture is less than about 0.2 millimeters
in diameter. In other embodiments, the detectors 530, 540 may
comprise two dimensional sensor arrays such as CCD or CMOS detector
arrays. The lenses 550, 560 focus light to a small spot on the
detectors 530, 540. Other types of detectors and optical elements
may be employed as well. The filter 570 may comprise a neutral
density filter or other type of filter or attenuator.
[0070] The subsystem 500 for fine longitudinal/lateral alignment is
inserted in the second arm of the instrument 100 such that the
second probe beam 150 from the coherent light source 115
propagating towards the focusing lens 170 is received by the
beamsplitter 510. A portion of the light in the second probe beam
150 is reflected by the beamsplitter 510 and is focused on a small
area of the detector 540 by the associated collecting lens 560. The
portion of the light in the beam 150 that is not reflected by the
beamsplitter 510 is transmitted and received by the focusing lens
170 which directs the light into the eye 10. Of the light incident
on the eye 10, about 3% will be specularly reflected by the outer
corneal surface for a typical human eye. When the focusing lens 170
is properly aligned, the light reflected by the corneal surface
propagates back toward the beamsplitter 510 along the same path by
which it arrived at the cornea 30. The retroreflected light
traverses substantially the same path on return because, when
properly aligned, the center of curvature 260 of the cornea 30 is
in the focal plane of the lens 170. Under these conditions
substantially all the rays in the beam 150 are normal to the
corneal surface and, therefore, propagate back along the same
path.
[0071] Thus, when the instrument 100 is properly aligned, some of
the light reflected by the cornea 60 is additionally directed by
the beamsplitter 510 toward the detector 530. This light is focused
by the lens 550 onto a small area of the detector 530 for
measurement. The magnitude of the alignment signal 580 is directly
related to the intensity of the spot falling on the detector 530.
Preferably, proper alignment produces the highest relative
intensity of the alignment signal 580 output by the detector 560. A
normalized signal 590 is produced by dividing the alignment signal
580 by the reference signal 585. This reference signal 585
corresponds to a fraction of the output emitted by the coherent
light source 115 that is transferred to the second probe beam 150
of the inteferometer 120. Accordingly, normalization adjusts for
fluctuations in the power output of the coherent light source
110.
[0072] If the instrument 100 is not correctly aligned so that the
focal point of the focusing lens 170 is not coincident with the
center of curvature, C, of the cornea 60, the rays in the second
probe beam 150 that are reflected off the corneal surface will have
non-normal reflection angles. These retroreflected rays will
therefore not follow the same path back to the lens 170 and the
beamsplitter 510. The deviations will result in a spot on the
detector 530 that is dimmer or one that partially or totally misses
the effective photosensitive region of the detector. Under
non-ideal conditions, when the longitudinal or lateral alignment is
off, the normalized alignment signal 590 is correspondingly smaller
than the aligned case where the alignment in all three orthogonal
directions is substantially correct.
[0073] Thus, in one preferred embodiment, when the instrument 100
is properly aligned, the alignment subsystem 500 preferably
produces the maximum normalized alignment signal 590. A small audio
speaker may be included to emit an audio verification when the
normalized signal 590 reaches its aligned value. The detector
electronics can be designed to automatically capture an image of
the fringes produced at the iris 80 at this time when suitable
alignment is achieved.
[0074] Under preferred alignment conditions, the light in the
second probe beam 150 that is reflected by the beamsplitter 510 and
directed onto the reference detector 540 is more intense than the
light reflected from the cornea 60. In certain embodiments, the
filter 570 is used to attenuate the intensity of the light focused
onto this detector 540. This filter 570 may reduce the intensity so
that the reference signal 585 is approximately equal to the
alignment signal 580 and the normalized signal 590 is approximately
one when suitable alignment is achieved. Other methods of
compensating for the higher intensity light received by the
detector 540 are also possible. For example, the light incident on
the detector 540 may be defocused to produce a lower value of the
reference signal 585.
[0075] In certain embodiments, such as schematically illustrated in
FIG. 8, the device 100 for measuring the concentration of glucose
in the bloodstream preferably includes both the rough lateral
alignment subsystem 400 as well as the fine lateral/longitudinal
alignment system 500. The lateral alignment subsystem 400 is
particularly well suited for aligning the instrument 100 laterally
with respect to the eye 10, i.e., in the x and y direction. The
fine lateral/longitudinal alignment subsystem 500 may be utilized
to position the device 100 at the appropriately in all three
directions, i.e., x, y, and z. Although alignment systems 400, 500
such as those described with reference to FIGS. 6 and 7 are shown,
other types of systems for aligning the instrument 100 may be
employed as well. Alignment systems both well known as well as
those yet to be devised are considered possible.
[0076] In various preferred embodiments, however, substantially all
the optical components are included in a common structure and may
be contained within an enclosure to produce a compact instrument
750 such as illustrated in FIG. 9. In the embodiment shown in FIG.
9, the compact enclosed instrument 750 is about the size of a small
book or pair of binoculars or preferably smaller. The particular
design, however, should not be so restricted and may take other
shapes and forms.
[0077] In certain embodiments of the device 750, the patient
activates the instrument using for example a switch. The light
sources 410, 440, 450, the detectors 190, 530, 540, and supporting
electronic are powered. The coherent light source 115 may be set at
a relatively low level. The patient then peers into an eyepiece
(e.g., a window) and sees his or her eye reflected from the curved
mirror 430. The patient proceeds to move the instrument 750
laterally in a plane normal to the visual axis 90, e.g., vertically
and horizontally, or in two other orthogonal directions depending
on the design. The patient endeavors to center the small green spot
of light produced by the central light source 410 between the two
images of the two offset light sources 440, 450. While maintaining
alignment in the plane normal to the visual axis 90, the patient
translates the instrument 750 toward or away from his or her eye 10
until an audio alignment signal is heard. The fringe pattern on the
iris 80 is captured and a reading appears on a display included in
the instrument 750.
[0078] As discussed above, an audio alignment signal may be
triggered when the normalized alignment signal 590 is maximized. In
certain embodiments, the instrument 750 may be configured such that
when this condition is satisfied, the coherent light source 115
momentarily brightens. Also, one video frame or field may be
captured by the detector 190. Subsequently, the coherent light
source 115 is turn off or otherwise powered down and the processing
or computations are performed. When the signal processing is
complete, the result can be displayed.
[0079] The fringes produced at the iris 80 are not an absolute
measure of glucose concentration. Fringe spacing, for example, has
a slight dependence on the shape of the particular patient's eye,
which, in turn, affects the various path lengths within the aqueous
humor. Therefore, in certain embodiments, the devices 100, 750 are
preferably calibrated to individual users. In various embodiments,
such as instruments 100, 750 used by a diabetic family, a single
instrument is calibrated separately for different users.
[0080] The calibration procedure may be as follows. For a period of
time, e.g. a few days, the user measures blood glucose one or more
times a day using one or more methods that provide an independent
accurate measure of glucose concentration. Methods well known in
the art such as the finger stick method may be suitable. The user
also performs a measurement of the index of refraction of the
aqueous humor with the instrument 100, 750 described above. The
user enters the results of both readings into the device 100, 750
possibly using an interface such as a keypad that plugs into the
instrument for such purposes. By storing measurements obtained over
a period of time, the instrument 100, 750 can be calibrated with
suitable accuracy. In various embodiments, the data are analyzed
automatically and the instrument 100, 750 indicates when sufficient
data have been obtained to generate a reliable calibration. The
appropriate constant or set of constants can be automatically
recorded by the instrument 100, 750. A display or other interface
can be used to indicate that the instrument 100, 750 is properly
calibrated and ready for regular use. In other embodiments, a
single measurement may be employed to calibrate the instrument 100,
750 although multiple measurements may improve accuracy.
[0081] Based on the independently measured glucose levels, the
values obtained by of the instrument 100 are preferably calibrated
so that the output produced by the instrument can be correlated
with the appropriate glucose level. As different eyes 10 are
physically different, the instrument 100 is preferably calibrated
separately for different patients.
[0082] Glucose, however, may not be the only substance dissolved in
the aqueous humor, and these other substances may affect the index
of refraction and the fringes produced on the iris 80. The effect
of such substances is expected to be sufficiently small so as not
to significantly alter the fringes produced on the iris 80 and
interfere with accurate measurements of glucose levels.
Nevertheless, the effect of such substances can be reduced or
substantially eliminated by employing various techniques. For
instance, the measurements can be performed at the appropriate
wavelengths to reduce the effect of other solutes on the measured
index of refraction. A given solute, such as for example glucose,
may cause a change in refractive index that varies with the
wavelength of the incident light. The variation in refractive index
with wavelength is called dispersion. Different solutes have
different dispersion characteristics. Therefore, in certain
embodiments, a suitable wavelength can be chosen such that
variations in glucose concentrations causes a significant change in
the refractive index, while any interfering substances do not. For
example, the concentration of sodium chloride in the aqueous humor
may fluctuate. However, such changes have a negligible effect on
the refractive index in the near infrared wavelengths where
variations in the glucose level do significantly affect the
refractive index.
[0083] In other embodiments, the measurement of the spacing and
locations of the fringes produced at the iris 80 can be performed
at two or more different wavelengths. Preferably, different
wavelengths are selected that manifest different variations in
refractive index with concentration of glucose and the interfering
material. Measurements of the fringe spacing or location at these
two wavelengths provides sufficient information to distinguish
between the effects of the two solutes. Two measurements are
performed, one at each wavelength and two values of refractive
index are obtained. The glucose concentration in the aqueous humor
can be determined from the two refractive index changes at the two
wavelengths. In general, if there are N solutes, the contribution
of one of the solutes, e.g., glucose, can be determined by
measuring the fringe pattern at N properly chosen wavelengths.
Other methods and variations, however, may be employed to ascertain
the level of glucose concentration.
[0084] In certain cases, the physical distance between the cornea
60 and the iris 80 varies. Such variations cause the fringe pattern
produced at the iris 80 to change, thus interfering with accurate
refractive index measurements. Such changes in this physical
distance, however, may be accounted for by various techniques.
[0085] In various embodiments, the effects of changes in the
physical length of the light paths can be separated out. These
optical path lengths govern in part the times required for light to
travel over the physical paths. To account for variations in
length, additional measurements can be obtained at different
wavelengths. In one preferred embodiment, for example, a second
coherent light source of different wavelength may be included in
the instrument 100, 750. Preferably, the refractive index of
glucose is different for the two wavelengths. Using the second
coherent light source, a second set of measurements of the
resulting fringe pattern can be obtained. This second set of
measurements will have the same pair of physical path lengths but a
different pair of optical path lengths as the index of refraction
is different for the two wavelengths. Thus, the difference between
the two fringe patterns is a measure of the difference in
refractive indices at the two wavelengths, which, in turn, can be
use to establish the physical path length. In this manner, the
measurement of glucose concentration can be calibrated for varying
thicknesses between the cornea 60 and the iris 80.
[0086] Other variations of the instrument design and configuration
are considered possible. For example, instead of using a video
camera, the image of the fringes could be swept across a vertical
slit or set of slits in front of one or more photodetectors, thus
converting the fringe spacing into temporal frequencies that could
be measured. The alignment might also be performed entirely
automatically, using, for example, a video image of the eye and
corneal reflection to drive motors that position the optical system
with respect to the eye. The instrument may also be interfaced to a
computer as well. Still other variations of the instrument and
techniques for measuring glucose concentration may be employed. The
methods and designs should not be limited only to those embodiments
disclosed herein.
[0087] Those skilled in the art will appreciate that the methods
and designs described above have additional applications and that
the relevant applications are not limited to those specifically
recited above. Also, the present invention may be embodied in other
specific forms without departing from the essential characteristics
as described herein. The embodiments described above are to be
considered in all respects as illustrative only and not restrictive
in any manner.
* * * * *