Diffuse reflectance monitoring apparatus

An improved method and apparatus for diffuse reflectance spectroscopy. A specular control device is provided that can discriminate between diffusely reflected light that is reflected from selected depths or layers within the tissue. The specular control device permits a spectroscopic analyzer to receive the diffusely reflected light that is reflected from, for example, a first layer or depth within the tissue, while preventing the remaining diffusely reflected light from reaching the spectroscopic analyzer. Furthermore, the specular control device may prevent the specularly reflected light (e.g. surface reflected light) from reaching the spectroscopic analyzer.

TECHNICAL FIELD 
The present invention relates generally to diffuse reflectance 
spectroscopy; and more particularly, to an improved method and apparatus 
for the spectroscopic measurement or analysis of an analyte concentration 
in human tissue; and still more particularly, to an improved method and 
apparatus including a specular reflectance control device for use in such 
a measurement system. 
BACKGROUND OF THE INVENTION 
The need and demand for an accurate, non-invasive method for determining 
analyte concentrations in human tissue is well documented. Barnes et al. 
(U.S. Pat. No. 5,379,764), for example, disclose the necessity for 
diabetics to frequently monitor glucose levels in their blood. It is 
further recognized that the more frequent the analysis and subsequent 
medication, the less likely there will be large swings in glucose levels. 
These large swings are associated with symptoms and complications of the 
disease, whose long term effects can include heart disease, 
arteriosclerosis, blindness, stroke, hypertension, kidney failure, and 
premature death. As described below, systems have been proposed for the 
non-invasive measurement of glucose in blood. However, despite these 
efforts, a lancet cut into the finger is still necessary for all presently 
commercially available forms of home glucose monitoring. This is believed 
so compromising to the diabetic patient that the most effective use of any 
form of diabetic management is rarely achieved. 
The various proposed non-invasive methods for determining blood glucose 
level, discussed individually below, generally utilize quantitative 
infrared spectroscopy as a theoretical basis for analysis. Infrared 
spectroscopy measures the electromagnetic radiation (0.7-25 .mu.m) a 
substance absorbs at various wavelengths. Atoms do not maintain fixed 
positions with respect to each other, but vibrate back and forth about an 
average distance. Absorption of light at the appropriate energy causes the 
atoms to become excited to a higher vibration level. The excitation of the 
atoms to an excited state occurs only at certain discrete energy levels, 
which are characteristic for that particular molecule. The most primary 
vibrational states occur in the mid-infrared frequency region (i.e., 
2.5-25 .mu.m). However, non-invasive analyte determination in blood in 
this region is problematic, if not impossible, due to the absorption of 
the light by water. The problem is overcome through the use of shorter 
wavelengths of light which are not as attenuated by water. Overtones of 
the primary vibrational states exist at shorter wavelengths and enable 
quantitative determinations at these wavelengths. 
It is known that glucose absorbs at multiple frequencies in both the mid- 
and near-infrared range. There are, however, other infrared active 
analytes in the blood which also absorb at similar frequencies. Due to the 
overlapping nature of these absorption bands, no single or specific 
frequency can be used for reliable non-invasive glucose measurement. 
Analysis of spectral data for glucose measurement thus requires evaluation 
of many spectral intensities over a wide spectral range to achieve the 
sensitivity, precision, accuracy, and reliability necessary for 
quantitative determination. In addition to overlapping absorption bands, 
measurement of glucose is further complicated by the fact that glucose is 
a minor component by weight in blood, and that the resulting spectral data 
may exhibit a non-linear response due to both the properties of the 
substance being examined and/or inherent non-linearities in optical 
instrumentation. 
Robinson et al. (U.S. Pat. No. 4,975,581) disclose a method and apparatus 
for measuring a characteristic of unknown value in a biological sample 
using infrared spectroscopy in conjunction with a multivariate model that 
is empirically derived from a set of spectra of biological samples of 
known characteristic values. The above-mentioned characteristic is 
generally the concentration of an analyte, such as glucose, but also may 
be any chemical or physical property of the sample. 
The method of Robinson et al. involves a two-step process that includes 
both calibration and prediction steps. In the calibration step, the 
infrared light is coupled to calibration samples of known characteristic 
values so that there is differential attenuation of at least several 
wavelengths of the infrared radiation as a function of the various 
components and analyte comprising the sample with known characteristic 
value. The infrared light is coupled to the sample by passing the light 
through the sample or by reflecting the light from the sample. Absorption 
of the infrared light by the sample causes intensity variations of the 
light that are a function of the wavelength of the light. The resulting 
intensity variations at the at least several wavelengths are measured for 
the set of calibration samples of known characteristic values. Original or 
transformed intensity variations are then empirically related to the known 
characteristic of the calibration samples using a multivariate algorithm 
to obtain a multivariate calibration model. 
In the prediction step, the infrared light is coupled to a sample of 
unknown characteristic value, and the calibration model is applied to the 
original or transformed intensity variations of the appropriate 
wavelengths of light measured from this unknown sample. The result of the 
prediction step is the estimated value of the characteristic in the 
unknown sample. The disclosure of Robinson et al. is incorporated herein 
by reference. 
Dahne et al. (U.S. Pat. No. 4,655,225) further disclose a method utilizing 
near infrared spectroscopy for non-invasively transmitting optical energy 
in the near infrared spectrum through a finger or earlobe of a subject. 
Dahne also disclose measuring reflected light energy to determine analyte 
concentration. The reflected light energy is further stated as comprised 
of light reflected from the surface of the sample and light reflected from 
deep within the tissue. It is the near infrared energy diffusely reflected 
from deep within the tissues that Dahne disclose as containing analyte 
information, while surface reflected light energy gives no analyte 
information and interferes with interpreting or measuring light reflected 
from deep in the tissue. The present invention is directed to an apparatus 
for improved measurement of diffusely reflected light, while eliminating 
the effects of surface reflected light and other light not reflected from 
deep within the tissue. 
Reflectance spectroscopy is known in other non-medical applications. In 
general, such spectroscopy is concerned with identification of the 
chemical structure of the sample through the use of reflected information. 
Diffuse reflectance spectroscopy is also generally known, and is widely 
used in the visible and near-infrared regions of the light spectrum to 
study materials such as grains and other food products. 
In broad terms, diffuse reflectance spectroscopy utilizes the fact that the 
sample materials will tend to scatter light in a more or less random 
fashion. A fraction of the light will eventually be scattered back from 
the sample and collected by a detector to provide a quantitative or 
qualitative representation of the sample. 
In infrared spectroscopy it is often desirable to use the mid-infrared 
region of the spectrum. The fundamental vibrational absorptions described 
earlier are strongest here, in the fundamental region. The goal of 
infrared spectroscopy sampling is often to prepare a sample so that it may 
be analyzed with this mid-infrared light. Reflectance spectroscopy is one 
very popular way of making a sample compatible with mid-infrared light. If 
a sample is too thick to get any light through in transmission, often a 
result can be obtained by reflectance. Reflectance spectroscopy is 
complicated however, by the fact that there is more than one optical 
phenomenon occurring in this mode. 
Reflectance of light from a sample can be largely divided into two 
categories, diffuse reflectance and specular reflectance. The specular 
reflectance of a sample is the light which does not propagate into the 
sample, but rather reflects "like a mirror" from the front surface of the 
sample. This component contains information about the sample at the 
surface. If the material is homogeneous, this surface reflection can be 
related to the bulk. While the specular component does not physically 
appear much like an absorbance spectrum, it can be related to the 
absorbance spectrum of the bulk material through a transformation called 
the Kramers-Kronig transformation. Still, most experts agree that the 
diffuse component is much more useful for sample qualification and 
quantification than is the specular component. There has been a lot of 
effort, by the applicants and by others, to enhance the diffuse component, 
and de-emphasize the specular component and to essentially cause the 
reflectance spectrum to be more transmission-like. 
Generally these efforts fall largely into three categories: optical 
discrimination against specular, mechanical discrimination, and secondary 
methods of sample preparation designed to minimize specular. A fourth, 
non-independent approach is to move away from the mid-infrared region in 
order to relax the sample preparation requirements. By moving to the 
near-infrared or visible region of the spectrum, the vibrational 
spectroscopy becomes more blunt and imprecise, but often this can be made 
up for by the improvements observed in the quality and signal-to-noise 
ratio of the data obtained because of improved sampling ability, more 
appropriate path length, and better discrimination against specular 
reflectance. This approach is especially useful when quantitative 
information is desired. 
Most experts would agree that the diffuse component is desirable, and even 
essential, if the sample material is layered or non-homogeneous. The 
specular component will largely contain information about the surface of 
the sample and not about the bulk. Nevertheless, U.S. Pat. No. 5,015,100, 
issued May 14, 1991 to Walter M. Doyle, describes an example of the 
specular approach. The specular component of the light is significantly 
wavelength dependent, and contains information about the complex 
refractive index of the material under test. This complex refractive index 
contains an imaginary term which relates to the absorption coefficient of 
the material. 
Doyle indicates that the potential utility of specular reflectance 
spectroscopy is well-known to those of skill in the art and points out 
that mathematical expressions, namely the Kramers-Kronig relation, can be 
used to convert measured reflectance spectra into absorbance spectra. 
These calculated spectra are then useful for identifying samples by 
comparison with existing libraries of absorbance spectra. However, the 
work of the prior art has not been used for quantitative measurements such 
as the composition analysis of tissue fluids. In fact, it would perform 
poorly for this purpose, since there is little tissue fluid information at 
the surface of the skin. The diffuse component must be used. 
Paper No. 424, presented at the 16th Annual FACSS Conference in October, 
1989, by Doyle and McIntosh, concluded that the Kramers-Kronig relations 
could not be used to obtain accurate absorbance spectra from reflectance 
data unless the equations used were modified to take into consideration 
polarization and angle of incidence, or unless the experimental apparatus 
provided radiation which approximated the conditions at normal incidence. 
The Doyle patent reference describes the use of apparatus in a specular 
reflectance system in which the analytical radiation reflected by the 
sample approximates the conditions existing at normal incidence, and 
proposed a solution by ensuring essentially equal contributions from rays 
polarized parallel to the plane of incidence and from rays polarized 
perpendicular to the plane of incidence. Doyle teaches that a 
semi-transparent beamsplitter used in such an apparatus would achieve the 
desired polarization balance, but would sacrifice radiation efficiency 
because of losses in pre-sample transmission, post-sample reflection, and 
absorbance loss in the beamsplitter. The Doyle reference then described a 
system of improved radiation efficiency utilizing a split field 
beamsplitter having a surface area divided into an uneven plurality of 
reflecting blades and open transmitting areas. 
U.S. Pat. No. 4,852,955 also issued to Doyle, describes a system which 
obviates the problem of limited beamsplitter efficiency by using a 100% 
reflecting mirror intercepting half of the system aperture, and arranging 
for the illuminating and outgoing beams to use opposite halves of the 
aperture. However, the use of the split field beamsplitter of this 
reference involves a distribution of incident radiation which is 
asymmetrical with respect to an axis normal to the sample surface. As a 
result, there is no assurance that the p and s polarization states will be 
balanced when the suggested beamsplitter is in use. 
The limitations of Doyle's prior art are clear. Specular reflectance is 
only useful when the bulk material is adequately represented by surface 
composition. When this is not the case, such as when performing 
non-invasive blood analyte measurements, this methodology will give a 
spurious result. 
Optical means have also been used to separate diffuse and specular 
components. A recent example is described by Ralf Marbach in his PhD. 
thesis entitled "Messverfahren zur IR-spektroskopishen Blutglucose 
bestimmung" (English translation: "Measurement Techniques for IR 
Spectroscopic Blood Glucose Determination"), and published in Duesseldorf 
in 1993. Marbach employs an optical discrimination system quite similar in 
principle to that used by Harrick Scientific Corp. in the Praying Mantis 
diffuse reflectance instrument first introduced in 1980. The concept here 
is that the specular light reflects from a sample with an angle equal and 
opposite to the angle of incidence to the surface normal. Using this fact, 
it is a simple matter to collect light only outside the input collection 
angle. Marbach and Harrick then limit the input angle to a small range, so 
that a larger range of output angles may be used for collection. 
Note that there is a limited region of space over which light can be 
launched into and collected from a sample. In terms of solid angle, for a 
planar surface sample, this working volume can be stated to be 2.pi. 
steradians in solid angle. In the Harrick device, a small and equal solid 
angle is subtended by the input and the output optics. Less than 1/2.pi. 
steradians is subtended by either the input or the output optic. This 
leads to an efficiency of less than 50% of the available solid angle. 
Another critical factor in collecting diffusely reflected light is the 
directionality of the collected light. Many samples, including the tissue 
samples required for non-invasive measurements are quite forward 
scattering. That is to say that a scattered photon will change only a 
small angle in direction after a scattering event. The Harrick device 
requires a photon to deviate through a large angle before it can be 
collected by the output optics. This poor performance in the presence of 
sample anisotropy and the relatively low efficiency are severe problems 
with the Harrick device. 
The Marbach device improves on the Harrick device in a number of ways. 
First, the total volume available for input and collection of light 
approaches 2.pi. steradians which is the theoretical limit. This is 
accomplished by allowing 360.degree. azimuthal angular subtense for both 
the input and output light. Second, the forward directionality of scatter 
is taken into account. Rays which deviate only a few degrees in angle can 
be collected. The downfall of this approach is that the input and output 
optical systems are completely unmatched in terms of magnification. Any 
diffuse reflectance system must work in concert with the source and the 
detector of the system. 
Since detectors in the near-infrared region of the spectrum get noisier 
when they get bigger, it should be a goal to make the detector as small as 
possible. A bright compact source is also advantageous. In the Marbach 
system, the image of the source is very much magnified relative to the 
image of the detector in the sample plane. This means that the source 
energy density which can be imaged onto the detector is limited. In 
addition, the collected energy from the sample is demagnified as it 
travels to the detector. Again, energy efficiency is compromised. An ideal 
situation would leave the input and output magnifications equal. 
Another important limitation of the Marbach design relates to the choice of 
angles for input and output. Real optical systems are good at imaging with 
large f/numbers. Small f/number systems, especially with large field stop 
diameters, tend to image poorly. Marbach notes this fact in his thesis. In 
his design, the prime, large f/number, near-normal space is all reserved 
for input light, and the non-ideal near-grazing light is used for output. 
It is quite conceivable that the device would work better if used 
"backwards" from the mode employed by Marbach, where the source site and 
the detector site would be switched. The device described in this 
application provides an even better solution. 
Another method of eliminating specular contribution to a diffuse 
reflectance spectrum is to modify the sample itself to reduce its 
propensity to reflect specularly. One way to accomplish this is to dilute 
a powdered sample in a non-absorbing matrix material with a low refractive 
index. The low index matrix will have a low amount of specular component 
and will mitigate the specular problem. Unfortunately, the goal of 
non-invasive analysis does not allow for modification of the sample, and 
so in the field of use described here, these dilution methods are not an 
option. 
Finally, an apparatus for mechanically discriminating against specular 
reflectance is shown in U.S. Pat. No. 4,661,706, issued Apr. 28, 1987, to 
Robert G. Messerschmidt and Donald W. Sting. Messerschmidt et al. 
demonstrate that the specular and the diffuse component of reflected light 
can be separated mechanically, taking advantage of the fact that the 
specular component emanates from the surface of the sample. A blade-like 
device, or blocker, "skims" the specular light before it can impinge on 
the detector. 
Messerschmidt et al. teach that a "thin" blocker is essential to maximizing 
the efficiency of the system, and minimizing the distortion of the output 
spectrum. More particularly, Messerschmidt et al. state that to obtain the 
maximum efficiency and the closest approximation to the Kubelka-Munk 
relationship, a thin blocker device should be used having an edge that is 
a fraction of the optical depth of the sample. A thicker blocker, 
Messerschmidt et al. explain, will remove energy that penetrates only a 
short distance into the sample before reflecting, and thus may have a 
catastrophic effect on the efficiency when used with a sample having a 
shallow optical depth. 
Messerschmidt et al. also state that a thick blocker may introduce spectral 
distortions caused by energy that is once reflected by the sample to the 
lower surface of the blocker and again reflected from the blocker to the 
sample before energy escapes from the far side of the blocker. This is 
problematic, according to Messerschmidt et al., because the energy 
reflected from the lower surface of the blocker will acquire the 
reflectance spectral features of the blocker itself and thus distort the 
output spectrum. 
Applicants have discovered that the "thin" blocker approach of 
Messerschmidt et al. suffers from a number of limitations, some of which 
are discussed below. First, the "thin" blocker approach does not provide 
any discrimination between the diffusely reflected energy that is 
reflected from various depths within the sample. This limitation is of 
particular importance when the sample is layered or otherwise 
non-homogeneous, and only a selected set of the layers contain the desired 
information. Second, the "thin" blocker of Messerschmidt et al. may not 
perfectly conform to a rough surface of a sample. This can cause locations 
where the light effectively leaks or pipes under the blocker without 
interacting with the sample, thereby distorting the resulting output 
spectrum. 
SUMMARY OF THE INVENTION 
The present invention overcomes many of the disadvantages of the prior art 
by providing a method and apparatus for improved measurement of diffusely 
reflected light for analyte concentration determination within human 
tissue. The present invention incorporates a specular control device that 
can discriminate between diffusely reflected light that is reflected from 
selected depths or layers within the tissue. The specular control device 
permits a spectroscopic analyzer to receive the diffusely reflected light 
that is reflected from, for example, a first layer or depth within the 
tissue, while preventing the remaining diffusely reflected light from 
reaching the spectroscopic analyzer. Furthermore, the specular control 
device may prevent the specularly reflected light (e.g. surface reflected 
light) from reaching the spectroscopic analyzer. 
The specular control device may include an immersion lens that has a flat 
bottom surface and a semi-circular shaped top surface. The flat bottom 
surface is positioned on the surface of the tissue sample. A blocker blade 
is positioned within the immersion lens, and extends substantially 
perpendicular to the surface of the tissue sample. In a preferred 
embodiment, the blocker blade divides the immersion lens into 
approximately two equal halves, and extends downward to the flat bottom 
surface of the immersion lens. The blocker blade is constructed to either 
reflect or absorb light having a wavelength in the range of the expected 
specularly and diffusely reflected light. 
The incident light is directed to one of the two equal halves of the 
immersion lens. The blocker blade substantially prevents the incident 
light from traveling to the other half of the immersion lens. The 
immersion lens directs the incident light to the tissue sample, and in 
some embodiments, focuses the light on an illuminated spot on the surface 
of the tissue sample. A first portion of the incident light may be 
specularly reflected from the surface of the sample. A second portion of 
the light may enter the sample, and be diffusely reflected by the material 
within the sample. The diffusely reflected light is typically reflected at 
various depths within the sample. 
The blocker blade may have two opposing surfaces including a front surface 
and a back surface, with a thickness defined therebetween. The thickness 
may be defined such that the blocker blade discriminates between light 
rays that are diffusely reflected from a first depth within the tissue 
from those light rays that are diffusely reflected from a second depth. 
The thickness of the blocker blade is dependent, at least in part, on the 
angle of incidence and the spot size of the incident light rays on the 
tissue. The thickness of the blocker blade is made sufficiently thick to 
substantially prevent those light rays that are diffusely reflected from a 
selected depth or layer within the sample from reaching the spectroscopic 
analyzer. 
The present invention is particularly useful for obtaining a diffuse 
reflectance spectra from human tissue for the non-invasive measurement of 
blood analytes such as glucose. It is known that human skin typically 
includes an outer epidermis layer and an inner dermis layer. The epidermis 
layer contains very little or no blood, and thus the corresponding 
diffusely reflected light reflected from the epidermis layer typically 
contains little or no glucose information. Thus, the diffusely reflected 
light from the epidermis layer tends to contaminate the desired spectrum 
of the diffusely reflected light from the information rich dermis layer. 
By preventing the diffusely reflected light from the epidermis layer from 
reaching the spectroscopic analyzer, a information rich spectrum from the 
dermis layer can be obtained and analyzed. Thus, Applicants have 
discovered that it is desirable to exclude the diffusely reflected light 
rays that are reflected from the epidermis layer. 
To achieve discrimination, the back surface of the blocker blade may be 
laterally spaced a distance from the illuminated portion of the tissue 
sample such that the light rays that are diffusely reflected from the 
epidermis layer are substantially prevented from reaching the 
spectroscopic analyzer. The front surface of the blocker blade may be 
positioned directly adjacent the illuminated portion of the tissue sample, 
within the illuminated portion, or laterally spaced toward the back surf 
ace relative to the illuminated portion. 
In addition to the above describe advantages, the thick blocker blade of 
the present invention may substantially prevent the specularly reflected 
component of light from reaching the spectroscopic analyzer, even when the 
surf ace of the sample is not perfectly flat. One such sample is human 
skin. It is known that the surface of human skin is relatively rough and 
moderately rigid. Because the present invention provides a thick blocker 
blade, the leakage of light between the surface of the skin and the 
blocker blade may be reduced. This may improve the quality of the 
resulting spectrum that is provided to the spectroscopic analyzer. 
Finally, a method for obtaining a diffuse reflectance spectra from human 
tissue for the non-invasive measurement of blood analytes is contemplated. 
The method comprising the steps of: (a) generating infrared energy; (b) 
directing the infrared energy to the tissue; and (c) collecting the 
infrared energy that is reflected from a first depth and rejecting the 
infrared energy that is reflected from a second depth.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present invention is directed to an improved apparatus for 
spectrographic analysis or measurement of an analyte concentration. In 
preferred embodiments, the apparatus is utilized for measuring analyte 
concentrations in tissue of human patients, more particularly, the 
invention is focused on analyzing glucose concentration in the tissue. The 
basis for measurement is diffusely reflected light returning from the 
tissue sample after being illuminated by a wide-band near-infrared energy 
source. 
Referring first to FIG. 1, a schematic representation of light energy 
incident on an analyte-containing tissue sample is depicted. As depicted 
in the simplified representation, a tissue sample 12 includes an upper 
layer or epidermis 16, a middle layer or dermis 18 and subcutaneous tissue 
19. Incident light 10 illuminates the tissue sample 12, wherein portions 
of the light energy may be transmitted through the tissue sample, 
resulting in transmitted light 26 exiting the opposing side of the tissue 
sample. Alternatively, a tissue sample may absorb a portion of the light 
energy, resulting in absorbed light energy 24 as heat. A third phenomena 
includes specular reflection 14 of a portion of the incident light 10. 
Finally, a portion of the light energy can be diffusely reflected 30. 
The diffusely reflected light 30 undergoes several refractions due to 
contact with the various components within the tissue sample. Eventually a 
portion of the diffusely reflected light energy 30 returns to the surface 
of the tissue sample 12 and exits back through the skin surface to the 
measuring device. Thus, both specular reflected light 14 and diffuse 
reflected light 30 combine and are directed back toward the instrument of 
the present invention. 
Of the reflected light, only the diffusely reflected light 30 contains 
analyte or glucose information. The light, which is specularly reflected, 
contains information on the avascular epidermis, but does not contain 
glucose information. Thus, the goal of the present invention is to utilize 
only the diffusely reflected light 30 for analysis by separating such 
light from the specularly reflected light 14. Specularly reflected light 
14 can be viewed as contamination light as it does not contain the 
necessary information for analysis. 
Applicants have found that the problems associated with diffuse reflectance 
sampling of tissue can be minimized by the distribution of the input and 
output optics based on center symmetry. In a center symmetry 
configuration, the light rays 10 are focused onto the tissue sample 12 by 
an optical system, incorporating lenses. It has been found with this 
embodiment, the light rays which are specularly reflected off the surface 
of the tissue 12 exit the optical system on the opposite side of the beam 
focus. Any light ray entering the system and undergoing specular 
reflectance exits the system on the opposite side of the center focus. 
Referring now to FIG. 2, a schematic diagram is presented which illustrates 
the concept and effect on light rays passing through the lens system, 
which focuses the beam. As depicted in FIG. 2, light rays A, B, and C are 
depicted as passing through a generally circular transparent plate divided 
into four quadrants about the center point. The quadrants include first 
quadrant 32, second quadrant 34, third quadrant 38 and fourth quadrant 36. 
As represented, input light energy A 42 is incident on and passes through 
the plate in the first quadrant. Due to center point symmetry, the output 
light energy A 48 due to specular reflectance returns through the plate in 
the third quadrant. Likewise, input light energy B 40 is also incident on 
the first quadrant 32. Output light energy B 46, which is the result of 
spectral reflectance exits the third quadrant 38. Similarly, input light 
energy C 44, which is incident on the second quadrant 34, has a component 
of specularly reflected light which exits from the fourth quadrant 36 as 
indicated as output light energy C 50. 
In contrast to the concept of center point symmetry, a typical single 
mirror optical configuration for reflectance sampling includes an optical 
beam divided into an input and an output side about a single center line. 
This configuration is depicted in FIG. 3. Again, a generally circular 
plate having an input side 52 and an output side 54 is depicted. The sides 
are divided by a center line passing through the diameter of the plate. 
Input rays A 42, B 40 and C 50, which pass through the plate, have 
specularly reflected components or output light energy A 48, B 46 and C 
44, which are actually sampled by the output optics and will be seen by 
any detector. 
Applicants have found that the problems associated with specular 
reflectance can be eliminated by designing a specular control device 
incorporating the concepts of center point symmetry as depicted in FIG. 1 
to overcome the problems with standard single mirror optical 
configurations for reflectance sampling. Now referring to FIG. 4, a 
generally circular plate divided into four quadrants is depicted. With the 
configuration of FIG. 4, the first quadrant 32 and third quadrant 38 are 
defined as input quadrants. The second quadrant 34 and fourth quadrant 36 
are defined as output quadrants. With this embodiment, the light energy 
source is incident on the circular plate. However, the input quadrants 
allow the light energy to pass through, while the output quadrants are 
opaque. Thus, only light incident on the input quadrants passes through 
the specular control device to contact the tissue sample. 
Light reflected from the tissue sample, including both specularly reflected 
light and diffusely reflected light is incident upon the opposite side of 
the specular control device. However, as explained for FIG. 1, all of the 
specularly reflected light returning from the tissue sample will be 
incident upon the first or third quadrants 32, 38 and will pass back 
through these openings. In contrast, a quantity of diffusely reflected 
light will be incident upon the second quadrant 34 and fourth quadrant 36 
without any interfering specular reflection. The diffusely reflected light 
can then be reflected from the surface of the second and fourth quadrants 
34, 36 and directed to the analyzer. In this way only the diffusely 
reflected light is analyzed. 
As shown in FIG. 5, the diffusely reflected portion of a light ray 56 would 
have to undergo a change in direction of at least 45 degrees before it 
could be collected by the output optics. It is recognized that the number 
of photons which would successfully complete this directional change 
without absorbance will be less than those that can successfully undergo a 
smaller directional change. Applicants have recognized that the efficiency 
of the optical system could be improved by further dividing the optical 
beam into numerous symmetrically based input and output sections. One such 
alternative embodiment is depicted in FIG. 6. In FIG. 6, the optical beam 
is divided into eight separate wedge shaped quadrants about the center 
point. In the eight quadrant configuration, a light ray located in the 
center of an input quadrant would have to undergo a directional change of 
only 22.5 degrees. Applicants recognize that the number of quadrants can 
be further increased. Alternatively, as depicted in FIG. 7, the optical 
beam can be divided into 16 generally square quadrants which are also 
symmetrical about the center point. 
FIG. 8A discloses a specular control device indicated generally at 110. The 
surface of specular control device 110 is divided into an even numbered 
plurality of sections, here shown as open sections 116 and 118, and 
reflective sections 112 and 114. Open sections 116 and 118 are intended to 
pass or transmit any beam of light which is incident to the surface of 
specular control device 110. 
In contrast, reflecting sections 112 and 114 are intended to block the 
incident beam and reflect portions of it to a predetermined site. 
In the embodiment of FIG. 8A, each of sections 112, 114, 116 and 118 are of 
equal size and thus the total surface area of the open sections 116 and 
118 is equal to the total surface area of reflecting sections 112 and 114. 
Further, each of reflecting sections 112 and 114 is situated between a 
pair of open sections 116 and 118; and, similarly, each of open sections 
116 and 118 is located between a pair of reflecting sections 112 and 114. 
Finally, each reflecting section such as 112 is opposite to another 
reflecting section such as 114; and, each open section such as 116 is 
opposite to another open section such as 118. 
Referring now to FIG. 8B, there is shown another embodiment of the 
apparatus of FIG. 8A. In FIG. 8B, specular control device 110 is again 
divided into a plurality of reflecting sections 112 and 114, and open 
sections 116 and 118. Each reflecting section such as 112 and 114 is 
situated between a pair of open sections 116 and 118, and similarly each 
of open sections 116 and 118 is situated between a pair of reflecting 
sections such as 112 and 114. Each reflecting section is opposite to 
another reflecting section, and each open section is opposite to another 
open section. 
In FIG. 8B, there is also shown a set of opaque spacers 113 and 111 located 
along the borders between each of sections 112, 116, 114 and 118. The 
effect of spacers 111 and 113 is to achieve a more precise definition 
between the analytical beam sent to illuminate a sample and the data beam 
reflected from the sample. The opaque spacing between the reflecting and 
open sections achieves this desired improvement by, for example, 
preventing cross talk in the various adjacent sections from transmitted 
and reflected light beams. 
When opaque spacers 111 and 113 are utilized along the diameters of a 
circular specular control device surface such as 110, they result in equal 
division of the remaining surface area between reflecting sections 112 and 
114 and open sections 116 and 118. As it may be desirable for the analysis 
of certain samples to have the reflecting sections surface area unequal to 
the open sections surface area, this is shown accomplished in FIG. 8B by 
the addition of opaque spacers 115 and 117. For purposes of description, 
opaque area 115 has been shown as added to opaque spacer 113 to decrease 
the surface area of open section 116; and, similarly, opaque area 117 has 
been added to opaque spacer 113 to decrease the surface area of open 
section 118. 
In the embodiment shown in FIG. 8B, in a system where the source analytical 
beam is transmitted through open areas 116 and 118, and the diffuse 
reflection from a sample is reflected by sections 112 and 114 to a 
detector, it will be apparent that though the addition of opaque sections 
115 and 117 will decrease the percentage of the source beam which 
illuminates the sample. 
Referring now to FIG. 9, there is shown a schematic of a diffuse 
reflectance spectroscopy system utilizing the apparatus of this invention. 
A specular control device 110 is shown having open area 118 and reflective 
area 114. It is recognized that specular control device 110 need not be of 
a circular configuration as shown in FIGS. 8A and 8B but could be, for 
example, elliptical or rectangular in shape. 
A light or energy source 130 is shown for providing an analytical source 
beam indicated at 132, 134 and 136. Source beam 132, 134 and 136 impinges 
on a first surface of specular control device 110. That portion of the 
source beam indicated at 136 is incident to reflecting portion 114 of 
specular control device 110 and is reflected away as shown by the arrow. 
That portion of the source beam indicated at 132 and 134 passes through 
open area 118 of specular control device 110, and continues on to be 
reflected by an elliptical mirror 140 to a desired focus on sample 150. 
A diffuse reflectance beam 152 is reflected from sample 150 to mirror 140 
and thence to the reflective surface 114 as shown by the arrows. Diffusely 
reflected beam 152 is reflected onto an elliptical mirror 60 from which it 
is focused into a detector 170 where the beam is analyzed. 
In contrast to the diffusely reflected beam 152, a specularly reflected 
beam of light 154 is represented in FIG. 9. As is shown in FIG. 9, the 
specularly reflected beam 154 is reflected from the sample 150 to the 
mirror 140. This specularly reflected beam then passes through the open 
area 116 which is the open quadrant opposing the input quadrant 118 
through which that light beam entered. The specularly reflected light 154 
is thus not reflected to the analyzer 170 as described above for the 
diffusely reflected beam 152. 
In FIG. 9, specular control device 110 could be a single element of the 
type generally known and having the reflective and open sections as shown 
in FIGS. 8A and 8B. Or, should it be desirable for manufacturing purposes, 
specular control device 110 could be a unit of a desired thickness having 
a first and second surface, each of which surface is treated in the same 
manner shown in FIGS. 8A and 8B. The reflecting and open sections on a 
first surface would be directly opposite the reflecting and open surfaces 
on a second surface to achieve the desired results. 
FIG. 10 is a schematic drawing showing a "thin" blocker blade for 
mechanically discriminating against specular reflectance, in accordance 
with U.S. Pat. No. 4,661,706, issued Apr. 28, 1987, to Messerschmidt et 
al. Messerschmidt et al. demonstrate that the specular and the diffuse 
component of reflected light can be separated mechanically, taking 
advantage of the fact that the specular component emanates from the 
surface of the sample. A blade-like device, or blocker 202, "skims" the 
specular light before it can impinge on the detector. 
Messerschmidt et al. teach that a "thin" blocker 202 is essential to 
maximize the efficiency of the system, and minimizing the distortion of 
the output spectrum. More particularly, Messerschmidt et al. state that to 
obtain the maximum efficiency and the closest approximation to the 
Kubelka-Munk relationship, a thin blocker device 202 should be used having 
a thickness that is a fraction of the optical depth of the sample. A 
thicker blocker, Messerschmidt et al. explain, will remove energy that 
penetrates only a short distance into the sample before reflecting, and 
thus may have a catastrophic effect on the efficiency when used with a 
sample having a shallow optical depth. 
Messerschmidt et al. also state that a thick blocker may introduce spectral 
distortions caused by energy that is once reflected by the sample to the 
lower surface of the blocker and again reflected from the blocker to the 
sample before energy escapes from the far side of the blocker. This is 
problematic, according to Messerschmidt et al., because the energy 
reflected from the lower surface of the blocker will acquire the 
reflectance spectral features of the blocker itself and thus distort the 
output spectrum. 
Applicants have discovered that the "thin" blocker approach of 
Messerschmidt et al. suffers from a number of limitations, some of which 
are discussed below. First, the "thin" blocker blade 202 does not provide 
any discrimination between the diffusely reflected energy that is 
reflected from various depths within the sample. That is, the thin blocker 
202 does not provide any discrimination between the diffusely reflected 
light 220 reflected from a top layer and the diffusely reflected light 226 
reflected from a lower layer, as shown. 
This limitation is of particular importance when the tissue sample is 
layered or otherwise non-homogeneous, and only a selected set of the 
layers contain the desired information. This occurs in many applications 
including the non-invasive measurement of blood analytes, such as glucose, 
using the diffuse reflectance spectra reflected therefrom. For example, it 
is known that human skin has an outer epidermis layer 206 and a dermis 
layer 208. The epidermis layer 206 contains very little or no blood, and 
thus the corresponding diffusely reflected light 220 reflected from the 
epidermis layer 206 typically contains little or no glucose information. 
Applicants have discovered that the diffusely reflected light 220 from the 
epidermis layer 206 only contaminates the desired output spectrum 226 of 
the information rich dermis layer 208. 
In addition to the above, the "thin" blocker 202 of Messerschmidt et al. 
may not perfectly conform to the rough surface 210 of the tissue sample. 
This can cause locations where the light 212 effectively leaks or pipes 
under the blocker 202 without interacting with the sample, thereby further 
contaminating the resulting output spectrum. This is shown explicitly by 
light ray 216. 
FIG. 11A is a perspective view of in illustrative specular control device 
in accordance with the present invention. FIG. 11B is a cutaway view of 
the same. The specular control device includes an immersion lens 227 that 
has a flat bottom surface 229 and a semi-circular shaped top surface. The 
flat bottom surface 229 is positioned on the surface of the tissue sample 
(not shown). A blocker blade 228 is positioned within the immersion lens, 
and extends substantially perpendicular to the surface of the tissue 
sample. The blocker blade 228 may divide the immersion lens into 
approximately two equal halves 227a and 227b, and extends downward to the 
flat bottom surface 229 of the immersion lens 227. The blocker blade 228 
is constructed to either reflect or absorb light having a wavelength in 
the range of the expected specularly and diffusely reflected light. 
The incident light is directed to one of the two equal halves 227a,227b of 
the immersion lens 227. The blocker blade 228 substantially prevents the 
incident light from traveling to the other half of the immersion lens 227. 
The immersion lens 227 directs the incident light to the tissue sample, 
and in some embodiments, focuses the light on an illuminated spot (see 
FIG. 15) on the surface of the tissue sample. A first portion of the 
incident light will typically be specularly reflected from the surface of 
the sample. A second portion of the light will typically enter the sample, 
and be diffusely reflected by the material within the sample. The 
diffusely reflected light is typically reflected by material that is at 
various depths within the sample. 
FIG. 12 is a simplified schematic drawing detailing the "thick" blocker 
blade of the present invention. The immersion lens is positioned adjacent 
the top surface 238 of a tissue sample. In the illustrative diagram, the 
tissue sample is human skin having an outer epidermis layer 234 and an 
inner dermis layer 236. Because the top surface 238 of the tissue sample 
is rough, gaps will typically be present between at least parts of the 
immersion lens and the top surface 238 of the tissue sample as shown. 
In accordance with the present invention, a relatively thick blocker blade 
232 is provided. The blocker blade 232 has a back surface 240 and a front 
surface 241, with a thickness defined therebetween. The tissue sample may 
include a number of layers, including an epidermis layer 234 and a dermis 
layer 236. Applicants have discovered that it is desirable to exclude the 
diffusely reflected light rays that are reflected by the epidermis layer. 
To achieve discrimination, the back surface 240 of the blocker blade 232 is 
preferably laterally spaced a distance from the illuminated portion of the 
tissue sample such that the light rays 250 that are diffusely reflected 
from the epidermis layer 234 are substantially prevented from reaching the 
spectroscopic analyzer. As indicated above, the epidermis layer 234 may 
have little or no blood therein, and thus the diffusely reflected light 
from the epidermis layer 234 tends to contaminate the desired spectrum of 
the diffusely reflected light 254 from the information rich dermis layer 
236. By preventing the diffusely reflected light 250 of the epidermis 
layer 234 from reaching the spectroscopic analyzer, a contaminated 
spectrum from the dermis layer 236 can be obtained and analyzed. The front 
surface 241 of the blocker blade 232 may be positioned directly adjacent 
the illuminated portion of the tissue sample, within the illuminated 
portion, or laterally spaced toward the back surface 240 relative to the 
illuminated portion. 
The epidermis layer is typically about 40 micrometers to about 400 
micrometers in thickness at desired sample areas. Applicants have found a 
preferred blocker blade thickness for these applications is 100 
micrometers to 800 micrometers, with 400 micrometers most preferred. 
In addition to the above, the thick blocker blade 232 of the present 
invention may substantially prevent the specularly reflected component 243 
from reaching the spectroscopic analyzer, even when the surface of the 
sample is not perfectly flat as shown. Because the present invention 
provides a thick blocker blade 232, the leakage of light between the 
surface of the skin 238 and the blocker blade 232 may be reduced or 
eliminated. This may improve the quality of the resulting spectrum that is 
provided to the spectroscopic analyzer. 
As can readily be seen, a method for obtaining a diffuse reflectance 
spectra from human tissue for the non-invasive measurement of blood 
analytes is contemplated. The method comprising the steps of: (a) 
generating infrared energy; (b) directing the infrared energy to the 
tissue; and (c) collecting the infrared energy that is reflected from a 
first depth and rejecting the infrared energy that is reflected from a 
second depth. 
FIG. 13 is a simplified schematic drawing detailing the "thick" blocker 
blade of the present invention, made from a number of abutting thin 
blocker blades. Rather than forming the blocker blade 272 from a single 
homogeneous material, it is contemplated that a number of thin blocker 
blades, for example thin blocker blades 274, 276, may be used to form 
blocker blade 272. 
FIG. 14 is a simplified schematic drawing detailing an effectively "thick" 
blocker blade made from two spaced thin blocker blades 294 and 295. In 
this illustrative embodiment, the front blocker blade 295 is used to 
confine the incident light 296 to the left portion of the immersion lens. 
The back blocker blade 294 is used to prevent both specularly reflected 
light 300, and any diffusely reflected light 304 that is reflected from 
the epidermis layer, from reaching the spectroscopic analyzer. 
FIG. 15 is a simplified schematic drawing detailing an effectively "thick" 
blocker blade made from a single thin blocker blade that is laterally 
spaced from the illuminated spot of the incident light rays. As indicated 
above, the immersion lens may focus the incident light onto an illuminated 
spot 324. In this embodiment, no front blocker blade is needed to confine 
the incident light to the left portion of the immersion lens. Thus only 
one blocker blade is used, which is spaced a sufficient distance "D" 328 
from the illuminated spot 324 to prevent both specularly reflected light 
332 and any diffusely reflected light 336 provided by the epidermis layer, 
from reaching the spectroscopic analyzer. 
Having thus described the preferred embodiments of the present invention, 
those of skill in the art will readily appreciate the other useful 
embodiments within the scope of the claims hereto attached.