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 avarious 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
 surface 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
 surface 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.