U.S. patent application number 14/943990 was filed with the patent office on 2016-06-02 for multiplexed pathlength resolved noninvasive analyzer apparatus with dynamic optical paths and method of use thereof.
The applicant listed for this patent is Alan Abul-Haj, Kevin Hazen, Timothy Ruchti. Invention is credited to Alan Abul-Haj, Kevin Hazen, Timothy Ruchti.
Application Number | 20160151002 14/943990 |
Document ID | / |
Family ID | 52133267 |
Filed Date | 2016-06-02 |
United States Patent
Application |
20160151002 |
Kind Code |
A1 |
Ruchti; Timothy ; et
al. |
June 2, 2016 |
MULTIPLEXED PATHLENGTH RESOLVED NONINVASIVE ANALYZER APPARATUS WITH
DYNAMIC OPTICAL PATHS AND METHOD OF USE THEREOF
Abstract
A noninvasive analyzer apparatus and method of use thereof is
described comprising a near-infrared source, a detector, and a
photon transport system configured to direct photons from the
source to the detector via an analyzer-sample optical interface.
The photon transport system includes a dynamically position light
directing unit used to, within a measurement time period for a
single analyte concentration determination, change any of: radius,
energy, intensity, position, incident angle, solid angle, and/or
depth of penetration of a beam of photons entering skin of a
subject.
Inventors: |
Ruchti; Timothy; (Gurnee,
IL) ; Abul-Haj; Alan; (Mesa, AZ) ; Hazen;
Kevin; (Gilbert, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Ruchti; Timothy
Abul-Haj; Alan
Hazen; Kevin |
Gurnee
Mesa
Gilbert |
IL
AZ
AZ |
US
US
US |
|
|
Family ID: |
52133267 |
Appl. No.: |
14/943990 |
Filed: |
November 17, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14493283 |
Sep 22, 2014 |
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14943990 |
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13963925 |
Aug 9, 2013 |
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14493283 |
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13963933 |
Aug 9, 2013 |
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13963925 |
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13941411 |
Jul 12, 2013 |
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13963933 |
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13941389 |
Jul 12, 2013 |
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13941411 |
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13941369 |
Jul 12, 2013 |
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13941389 |
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61672195 |
Jul 16, 2012 |
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61700291 |
Sep 12, 2012 |
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61700294 |
Sep 12, 2012 |
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61885365 |
Oct 1, 2013 |
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Current U.S.
Class: |
600/310 |
Current CPC
Class: |
A61B 2562/04 20130101;
A61B 5/1455 20130101; A61B 2562/046 20130101; A61B 5/6801 20130101;
A61B 5/14532 20130101 |
International
Class: |
A61B 5/1455 20060101
A61B005/1455; A61B 5/145 20060101 A61B005/145 |
Claims
1. A method for noninvasively determining an analyte concentration
of a person, comprising the steps of: providing a near-infrared
analyzer, comprising: at least one near-infrared source; a
detector; and a photon transport system configured to direct
photons from said source, via a sample illumination zone, to said
detector via both a detection zone and a face of an analyzer-sample
optical interface; dynamically changing, within a time window of
data collection for a single analyte concentration determination, a
mean radial illumination position of incident light from said
near-infrared source relative to a center of the detection zone of
said analyzer-sample optical interface, said step of dynamically
changing further comprising: directing the photons, during a first
time period of the time window, to a first arc of illumination
optics at a first range of radial distances from the detection
zone; and directing the photons, during a second time period of the
time window, to a second arc of illumination optics at a second
range of radial distances from the detection zone, wherein at said
analyzer-sample optical interface none of said first range of
radial distances overlap any of said second range of radial
distances.
2. The method of claim 1, said step of dynamically changing a mean
radial illumination position further comprising the steps of: at a
first time, directing light from said source to a first optic; and
at a second time, directing light from said source to a second
optic, said second optic in a distinct optical path not using said
first optic.
3. The method of claim 2, further comprising the step of: within
the time window for collection of data for determination of the
single analyte concentration determination, changing an effective
depth of penetration of the incident light into skin of the person
by at least twenty percent.
4. The method of claim 3, further comprising the steps of: at a
first time, directing photons from said near-infrared source to a
first subset of fiber optics in a fiber optic bundle; and at a
second time, directing photons from said near-infrared source to a
second subset of fiber optics in said fiber optic bundle.
5. The method of claim 4, further comprising the step of: using a
rotatable and selectable opaque perimeter aperture to change a
cross-sectional diameter of a light beam from said near-infrared
source by at least twenty-five percent within the time window.
6. (canceled)
7. (canceled)
8. The method of claim 1, said step of dynamically changing, within
the time window of data collection for the single analyte
concentration determination, the mean radial illumination position
of incident light, further comprising the steps of: at a first
point in time, radially directing and positioning the incident
light at a first radial distance from the center of the
analyzer-subject interface yielding a median maximum depth of
penetration in an epidermis layer of skin of the subject; and at a
second point in time, radially directing and positioning the
incident light at a second radial distance from the center of the
analyzer-subject interface yielding a mean maximum depth of
penetration in a dermis layer of skin of the subject.
9. The method of claim 1, further comprising the steps of, during
the time window of data collection for the single analyte
concentration determination: generating a subject specific tissue
map; and subsequently performing said step of dynamically changing
a mean radial illumination position of the incident light using
information from the subject-specific tissue map.
10. The method of claim 1, said step of dynamically changing a mean
radial illumination position of the incident light further
comprising the steps of: delivering the incident light proximate at
least one of: an edge of a detector array; and a corner of a
detector array.
11. The method of claim 1, said step of dynamically changing a mean
radial illumination position of the incident light further
comprising the step of: delivering the incident light sequentially
to at least four optical fibers proximate at least one of: an edge
of a detector array; and a corner of a detector array.
12. The method of claim 1, further comprising the step of:
dynamically changing, within the time window of data collection for
the single analyte concentration determination, a solid angle of
incident light striking the analyzer-tissue interface by greater
than ten percent.
13. The method of claim 12, said step of dynamically changing a
solid angle further comprising the step of: within the time window,
irradiating the subject with two solid angles of incident light
overlapping by less than twenty percent.
14. An apparatus for noninvasively determining an analyte
concentration of a person, comprising: a near-infrared analyzer,
comprising: at least one near-infrared source; a detector; and a
photon transport system configured to direct photons from said
source, via a sample illumination zone, to said detector via both a
detection zone and a face of an analyzer-sample optical interface,
said photon transport system further comprising: means for
dynamically changing, within a time period of data collection for a
single analyte concentration determination, a radial illumination
position of incident light from said near-infrared source relative
to a center of the detection zone of said analyzer-sample optical
interface, said means for dynamically changing the radial
illumination position comprising a dynamically positioned optic
system; a first arc of illumination optics configured to direct the
photons, during a first time period of the time window, to a first
range of radial distances from the detection zone; and a second arc
of illumination optics configured to direct the photons, during a
second time period of the time window, to a second range of radial
distances from the detection zone, wherein at said analyzer-sample
optical interface none of said first range of radial distances
overlap than any of said second range of radial distances.
15. (canceled)
16. The apparatus of claim 14, said means for dynamically changing
the radial position of the incident light, comprising: an
electromechanically directed mask wheel.
17. The apparatus of claim 16, said detector further comprising: a
two-dimensional detector array comprising at least six,
electrically connected in series, detector elements along an arc of
at least forty-five degrees.
18. The apparatus of claim 14, said means for dynamically changing
the radial position of the incident light comprising an array of
light emitting diodes at least eighty percent circumferentially
surrounded by said detector at the analyzer-sample optical
interface, said detector comprising at least one detector
array.
19. The apparatus of claim 14, said photon transport system further
comprising: at least one fiber optic terminating at said
analyzer-sample interface at a third radial distance from the
detection zone of said analyzer-sample optical interface, said
third radial distance both larger than said first radial distance
and smaller than said second radial distance.
20. The method of claim 1, further comprising the step of:
directing the photons to a third range of radial distances from the
detection zone at said analyzer-sample optical interface, during a
third time period of the time window, using a third arc of
illumination optics, said third range of radial distances
overlapping at least some of said first range of radial distances.
Description
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 14/493,283 filed Sep. 22, 2014, which: [0002]
is a continuation-in-part of U.S. patent application Ser. No.
13/963,925 filed Aug. 9, 2013; [0003] is a continuation-in-part of
U.S. patent application Ser. No. 13/963,933 filed Aug. 9, 2013,
which is a continuation-in-part of U.S. patent application Ser. No.
13/941,411 filed Jul. 12, 2013, which is a continuation-in-part of
U.S. patent application Ser. No. 13/941,389 filed Jul. 12, 2013,
which is a continuation-in-part of U.S. patent application Ser. No.
13/941,369 filed Jul. 12, 2013, which claims the benefit of: [0004]
U.S. provisional patent application No. 61/672,195 filed Jul. 16,
2012; [0005] U.S. provisional patent application No. 61/700,291
filed Sep. 12, 2012; and [0006] U.S. provisional patent application
No. 61/700,294 filed Sep. 12, 2012; and [0007] claims the benefit
of U.S. provisional patent application No. 61/885,365 filed Oct. 1,
2013, [0008] all of which are incorporated herein in their entirety
by this reference thereto.
TECHNICAL FIELD OF THE INVENTION
[0009] The present invention relates to a near-infrared noninvasive
analyzer using a two-dimensional detector array.
DESCRIPTION OF THE RELATED ART
[0010] Patents and literature related to the current invention are
summarized herein.
[0011] Diabetes
[0012] Diabetes mellitus or diabetes is a chronic disease resulting
in the improper production and/or use of insulin, a hormone that
facilitates glucose uptake into cells. Diabetes is broadly
categorized into four forms grouped by glucose concentration state:
hyperinsulinemia (hypoglycemia), normal physiology, impaired
glucose tolerance, and hypoinsulinemia (hyperglycemia).
[0013] Diabetics have increased risk in three broad categories:
cardiovascular heart disease, retinopathy, and/or neuropathy.
Complications of diabetes include: heart disease, stroke, high
blood pressure, kidney disease, nerve disease and related
amputations, retinopathy, diabetic ketoacidosis, skin conditions,
gum disease, impotence, and/or fetal complications.
[0014] Diabetes is a common and increasingly prevalent disease.
Currently, diabetes is a leading cause of death and disability
worldwide. The World Health Organization estimates that the number
of people with diabetes will grow to three hundred million by the
year 2025.
[0015] Long term clinical studies show that the onset of diabetes
related complications is significantly reduced through proper
control of blood glucose concentrations, The Diabetes Control and
Complications Trial Research Group, "The Effect of Intensive
Treatment of Diabetes on the Development and Progression of
Long-Term Complications in Insulin-Dependent Diabetes Mellitus", N.
Eng. J. of Med., 1993, vol. 329, pp. 977-986.
[0016] Skin
[0017] The structure of skin varies widely among individuals as
well as between different skin sites on a single individual. The
skin has layers, including: (1) a stratum corneum of flat,
dehydrated, biologically inactive cell about 10 to 20 micrometers
thick; (2) a stratified epidermis, of about 10 to 150 micrometers
thickness, formed and continuously replenished by slow upward
migration of keratinocyte cells from the germinative basal layer of
the epidermis; (3) an underlying dermis of connective fibrous
protein, such as collagen, and a blood supply, which form a layer
of 0.5 to 4.0 millimeters in thickness with an average thickness of
about 1.2 millimeters; and (4) a underlying fatty subcutaneous
layer or adipose tissue.
[0018] Fiber Optic Sample Bundle
[0019] Garside, J., et. al., "Fiber Optic Illumination and
Detection Patterns, Shapes, and Locations for use in Spectroscopic
Analysis", U.S. Pat. No. 6,411,373 (Jun. 25, 2002) describe
software and algorithms to design fiber optic excitation and/or
collection patterns in a sample probe.
[0020] Maruo, K., et. al., "Device for Non-Invasive Determination
of Glucose Concentration in Blood", European patent application no.
EP 0843986 B1 (Mar. 24, 2004) describe the use of light projecting
fiber optics in the range of 0.1 to 2 millimeters from light
receiving fiber optics at the contacted fiber optic bundle/sample
interface.
[0021] Skin Thickness
[0022] Rennert, J., et. al., "Non-Invasive Method of Determining
Skin Thickness and Characterizing Layers of Skin Tissue In Vivo",
U.S. Pat. No. 6,456,870 B1 (Sep. 24, 2002) describe the use of
near-infrared absorbance spectra to determine overall thickness of
skin tissue and layer-by-layer thickness of skin tissue.
[0023] Ruchti, T. L., et. al., "Classification System for Sex
Determination and Tissue Characterization", U.S. Pat. No. 6,493,566
B1 (Dec. 10, 2002) describe the near-infrared tissue measurements
to yield predictions consisting of gender and one or more of
thickness of a dermis, collagen content, and amount of subcutaneous
fat.
[0024] Mattu, M., et. al., "Classification and Screening of Test
Subjects According to Optical Thickness of Skin", U.S. Pat. No.
6,738,652 B2 (May 18, 2004) describe the use of near-infrared
reflectance measurements of skin to determine the optical thickness
of skin through analysis of water, fat, and protein marker
bands.
[0025] Sample Probe/Tissue Contact
[0026] Abul-Haj, A., et. al., "Method and Apparatus for Noninvasive
Targeting", U.S. patent application no. US 2006/0217602 A1 (Sep.
28, 2006) describe a sample probe interface method and apparatus
for targeting a tissue depth and/or pathlength that is used in
conjunction with a noninvasive analyzer to control spectral
variation.
[0027] Welch, J. M., et. al., "Method and Apparatus for Noninvasive
Probe/Skin Tissue Contact Sensing", WIPO international publication
no. WO 2008/058014 A2 (May 15, 2008) describe a method and
apparatus for determining proximity and/or contact of an optical
probe with skin tissue.
[0028] Problem Statement
[0029] What is needed is a noninvasive glucose concentration
analyzer having precision and accuracy suitable for treatment of
diabetes mellitus.
SUMMARY OF THE INVENTION
[0030] The invention comprises a noninvasive analyzer apparatus
comprising a dynamic optic system.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] A more complete understanding of the present invention is
derived by referring to the detailed description and claims when
considered in connection with the Figures, wherein like reference
numbers refer to similar items throughout the Figures.
[0032] FIG. 1 illustrates an analyzer;
[0033] FIG. 2 illustrates diffusely reflecting optical paths;
[0034] FIG. 3 illustrates probing tissue layers using a spatial
distribution method;
[0035] FIG. 4 illustrates varying illumination zones relative to a
detector;
[0036] FIG. 5 illustrates varying detection zones relative to an
illuminator;
[0037] FIG. 6A illustrates an end view of a detector array and FIG.
6B illustrates a side view of the detector array;
[0038] FIGS. 7(A-E) illustrate a coupled source detector array
system, FIG. 7A; a side illuminated/detector array system, FIG. 7B;
a corner illuminated/detector array system, FIG. 7C; a within array
illumination system, FIG. 7D; and an illuminated array/detector
array system, FIG. 7E;
[0039] FIG. 8A and FIG. 8B illustrate a first example of a multiple
two-dimensional detector array system and a second example of a
multiple two-dimensional detector array system, respectively;
[0040] FIG. 9A illustrates transmission spectra of longpass optical
filters and FIG. 9B relates longpass filters to water
absorbance;
[0041] FIG. 10 illustrates shortpass filter transmission
spectra;
[0042] FIG. 11A illustrates bandpass filters relative to
near-infrared spectral regions and FIG. 11B illustrates specialized
bandpass filters;
[0043] FIG. 12 illustrates elements of a bimodal optical
filter;
[0044] FIG. 13A and FIG. 13B illustrate a fat band filter and fat
band absorbance, respectively;
[0045] FIG. 14A and FIG. 14B illustrate a glucose filter and
glucose absorbance, respectively;
[0046] FIG. 15 illustrates a detector array with multiple filter
array layers;
[0047] FIG. 16 illustrates a source array proximate a combined
detector/filter array;
[0048] FIG. 17 illustrates a source relative to multiple
two-dimensional detector arrays;
[0049] FIG. 18A and FIG. 18B illustrate an illumination array
relative to multiple two-dimensional detector array types and
rotated two-dimensional detector arrays, respectively;
[0050] FIG. 19A and FIG. 19B illustrate a two-dimensional detector
array relative to an optic array in an expanded and assembled view,
respectively;
[0051] FIG. 20A and FIG. 20B illustrate a detector array, longpass
filter array, shortpass filter array, and optic array in an
exploded and assembled view, respectively;
[0052] FIG. 21A and FIG. 21B illustrate a detector array, longpass
filter array, shortpass filter array, and optic array in an
exploded and assembled view, respectively;
[0053] FIGS. 22(A-D) illustrate temporal resolution gating, FIG.
22A; probabilistic optical paths for a first elapsed time, FIG.
22B; probabilistic optical paths for a second elapsed time, FIG.
22C; and a temporal distribution method, FIG. 22D;
[0054] FIGS. 23(A-C) illustrate a fiber optic bundle, FIG. 23A; a
first example sample interface end of the fiber optic bundle, FIG.
23B; and a second example sample interface end of the fiber optic
bundle, FIG. 23C;
[0055] FIG. 24A illustrates a third example sample interface end of
the fiber optic bundle and FIG. 24B illustrates a mask;
[0056] FIG. 25 illustrates a mask selection wheel;
[0057] FIG. 26A illustrates a position selection optic; FIG. 26B
illustrates the position selection optic selecting position; FIG.
26C illustrates solid angle selection using the position selection
optic; and FIG. 26D illustrates radial control of incident light
relative to a detection zone;
[0058] FIG. 27A and FIG. 27B illustrate a pathlength resolved
sample interface for a first subject and a second subject,
respectively;
[0059] FIG. 28 provides a method of use of a data processing
system; and
[0060] FIG. 29 provides a method of using a sample mapping phase
and a subsequent subject specific data collection phase.
[0061] Elements and steps in the figures are illustrated for
simplicity and clarity and have not necessarily been rendered
according to any particular sequence. For example, steps that are
performed concurrently or in a different order are illustrated in
the figures to help improve understanding of embodiments of the
present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0062] The invention comprises a noninvasive analyzer apparatus and
method of use thereof comprising a near-infrared source, a
detector, and a photon transport system configured to direct
photons from the source to the detector via an analyzer-sample
optical interface. The photon transport system includes a
dynamically position light directing unit optionally used to,
within a measurement time period for a single analyte concentration
determination, change any of: radius, energy, intensity, position,
incident angle, solid angle, and/or depth of penetration of photons
entering skin of a subject.
[0063] In another embodiment, two optically stacked arrays of
optical filters as a portion of a noninvasive analyzer apparatus
are used. The stacked arrays of optical filters are optionally
configured to pass multiple distinct and/or overlapping wavelength
ranges to an array of detectors, where the filter
combination--detector array distance resolves diffusely
reflected/partially absorbed optical pathlengths through skin.
[0064] In yet another embodiment, a noninvasive analyzer apparatus
and method of use thereof using a plurality of two-dimensional
near-infrared detector arrays is described.
[0065] In still yet another embodiment, subsets of signals from one
or more two-detector array are used to determine at least one of:
sampled pathlengths, internal consistency, precision enhancement,
skin type, photon path information, outlier analysis, and state of
the subject tested.
[0066] In a further embodiment, an apparatus and method of use
thereof is described using acquisition of noninvasive mapping
spectra of skin and subsequent optical/optical path reconfiguration
for subsequent subject specific data collection.
[0067] For example, a near-infrared noninvasive analyzer is
configured with a first optical configuration used to map an
individual and/or group of individuals through use of mapping
spectra. The mapping spectra are analyzed and used to reconfigure
the optical setup of the analyzer to a second optical configuration
suited to the individual and/or group of individuals. Subsequently,
collection of noninvasive spectra of the individual and/or group of
individuals is performed using the second optical configuration,
which is preferably optimized to yield additional information based
on the skin of the individual and/or group of individuals.
[0068] In yet another embodiment, a data processing system analyzes
data from an analyzer to estimate and/or determine an analyte
property, such as concentration using multiple types of data, such
as from an external sensor, from two or more radial positions,
and/or with two or more focusing depths.
[0069] In still another embodiment, an analyzer using light
interrogates the sample using one or more of: [0070] a spatially
resolved system; [0071] an incident light radial distance resolved
system; [0072] a controllable and variable incident light solid
angle system; and [0073] a controllable and variable incident light
angle system; [0074] a time resolved system, where the times are
greater than about 1, 10, 100, or 1000 microseconds; [0075] a
picosecond timeframe resolved system, where times are less than
about 1, 10, 100, or 1000 nanoseconds; [0076] collection of spectra
with varying radial distances between incident light entering skin
and detected light exiting the skin; [0077] an incident angle
resolved system; and [0078] a collection angle resolved system.
[0079] Data from the analyzer is analyzed using a data processing
system capable of using the information inherent in the resolved
system data.
[0080] In yet another embodiment, a data processing system uses
interrelationships of chemistry based a-priori spectral information
related to absorbance of a sample constituent and/or the effect of
the environment, such as temperature, on the spectral
information.
[0081] In yet still another embodiment, a data processing system
uses a first mapping phase to set instrument control parameters for
a particular subject, set of subjects, and/or class of subjects.
Subsequently, the control parameters are used in a second data
collection phase to collect spectra of the particular subject or
class of subjects.
[0082] In still yet another embodiment, a data processing system
uses information related to contact pressure on a tissue sample
site.
[0083] In another embodiment, a data processing system uses a
combination of any of: [0084] spatially resolved information;
[0085] temporally resolved information on a time scale of longer
than about one microsecond; [0086] temporally resolved information
on a sub one hundred picosecond timeframe; [0087] incident photon
angle information; [0088] photon collection angle information;
[0089] interrelationships of spectral absorbance and/or intensity
information; [0090] environmental information; [0091] temperature
information; and [0092] information related to contact pressure on
a tissue sample site.
[0093] In still yet another embodiment, a temporal resolution
gating noninvasive analyzer is used to determine an analyte
property of a biomedical sample, such as a glucose concentration of
a subject using light in the near-infrared region from 1000 to 2500
nanometers.
[0094] In yet still another embodiment, an apparatus and method of
use thereof is described using a plurality of time resolved sample
illumination zones coupled to at least one two-dimensional detector
array monitoring a plurality of detection zones linked to the
sample illumination zones.
[0095] Axes
[0096] Herein, axes systems are separately defined for an analyzer
and for an interface of the analyzer to a patient, where the
patient is alternatively referred to as a subject and/or a
person.
[0097] Herein, when referring to the analyzer, an x, y, z-axes
analyzer coordinate system is defined relative to the analyzer. The
x-axis is in the direction of the mean optical path. The y-axis
crosses the mean optical path perpendicular to the x-axis. When the
optical path is horizontal, the x-axis and y-axis define a x/y
horizontal plane. The z-axis is normal to the x/y plane. When the
optical path is moving horizontally, the z-axis is aligned with
gravity, which is normal to the x/y horizontal plane. Hence, the x,
y, z-analyzer coordinate system is defined separately for each
optical path element. If necessary, where the mean optical path is
not horizontal, the optical system is further defined to remove
ambiguity.
[0098] Herein, when referring to the patient, an x, y, z-axes
patient coordinate system is defined relative to a body part
interfaced to the analyzer. Hence, the x, y, z-axes body coordinate
system moves with movement of the body part. The x-axis is defined
along the length of the body part, the y-axis is defined across the
body part. As an illustrative example, if the analyzer interfaces
to the forearm of the patient, then the x-axis runs longitudinally
between the elbow and the wrist of the forearm and the y-axis runs
across the forearm. Together, the x,y plane tangentially touches
the skin surface at a central point of the interface of the
analyzer to the body part, which is referred to as the center of
the sample site, sample region, or sample site. The z-axis is
defined as orthogonal to the x,y plane. Rotation of an object is
further used to define the orientation of the object to the sample
site. For example, in some cases a sample probe of the analyzer is
rotatable relative to the sample site. Tilt refers to an off z-axis
alignment, such as an off z-axis alignment of a probe of the
analyzer relative to the sample site.
[0099] Analyzer
[0100] Referring now and throughout to FIG. 1, an analyzer 100 is
illustrated. The analyzer comprises at least: a light source system
110, a photon transport system 120, a detector system 130, and a
data processing system 140, where the data processing system is
optionally remotely located from the source/sample/detector system.
In use the analyzer 100 estimates and/or determines a physical
property, a sample state, a constituent property, and/or a
concentration of an analyte.
[0101] Patient/Reference
[0102] Still referring to FIG. 1, an example of the analyzer 100 is
presented. In this example, the analyzer 100 includes a sample
interface 150, which interfaces to a reference material 160 and/or
to a subject 170. Herein, for clarity of presentation a subject 170
in the examples is representative of a person, animal, a prepared
sample, and/or a patient. In practice, the analyzer 100 is used by
a user to analyze the user, referred to as the subject 170, and/or
is used by a medical professional to analyze a patient.
[0103] Controller
[0104] Still referring to FIG. 1 and referring now to FIGS. 4 and
5, the analyzer 100 optionally includes a system controller 180 or
controller. The system controller 180 is used to control one or
more of: the light source system 110 or a light source 112 thereof,
the photon transport system 120, the detector system 130 or a
detector 132 thereof, the sample interface 150, position of the
reference 160 relative to the sample interface 150, position of the
subject 170 relative to the sample interface 150, and/or
communication to an outside system 190, such as a personal
communication device 192, a smart phone, and/or a remote system 194
using a wireless communication system 196 and/or a hard wired
communication system 198. For example, the remote system includes a
data processing system, a data storage system, a data transfer
system, and/or a data organization system.
[0105] Still referring to FIG. 1, the optional system controller
180 operates in any of a predetermined manner or in communication
with the data processing system 140. In the case of operation in
communication with the data processing system 140, the controller
generates control statements using data and/or information about
the current state of the analyzer 100, current state of a
surrounding environment 162 outside of the analyzer 100,
information generated by the data processing system 140, and/or
input from a sensor, such as a sample interface sensor 152 or an
auxiliary system 10 or an auxiliary sensor 12 thereof. Herein, the
auxiliary system 10 is any system providing input to the analyzer
100.
[0106] Still referring to FIG. 1, the optional system controller
180 is used to control: photon intensity of photons from the source
using an intensity controller 122, wavelength distribution of
photons from the source 110 using a wavelength controller 124,
physical routing of photons from the source 110 using a position
controller 126. and/or timing of photon delivery.
[0107] Still referring to FIG. 1, for clarity of presentation the
optional outside system 190 is illustrated as using a personal
communication device 192, such as a smart phone. However, the
personal communication device 192 is optionally a cell phone, a
tablet computer, a phablet, a computer network, a personal
computer, and/or a remote data processing center. Similarly, the
smart phone also refers to a feature phone, a mobile phone, a
portable phone, and/or a cell phone. Generally, the personal
communication device 192 includes hardware, software, and/or
communication features carried by an individual that is optionally
used to offload requirements of the analyzer 100. For example, the
personal communication device 192 includes a user interface system,
a memory system, a communication system, and/or a global
positioning system. Further, the personal communication device 192
is optionally used to link to the remote system 194, such as a data
processing system, a medical system, and/or an emergency system. In
another example at least one calculation of the analyzer 100 in
noninvasively determining a glucose concentration of the subject
170 is performed using the personal communication device 192. In
yet another example, the analyzer gathers information from at least
one auxiliary sensor 12 and relays that information and/or a
processed form of that information to the personal communication
device 192, where the auxiliary sensor is not integrated into the
analyzer 100. Optionally data from the analyzer 100 is processed in
the cloud or a remote computing facility. Optionally, the personal
communication device 192 is used as a portal between the analyzer
100 and the cloud. Optionally, the remote system 194 is a data
processing center configured to receive signal from more than one
analyzer and to return a calculated analyte concentration and/or an
analyte property to the corresponding analyzer and/or to a
communication device of the user of the corresponding analyzer.
[0108] Source
[0109] Herein, the source system 110 generates photons in any of
the visible, infrared, near-infrared, mid-infrared, and/or
far-infrared spectral regions. In one case, the source system
generates photons in the near-infrared region from 1100 to 2500 nm
or any range therein, such as within the range of about 1200 to
1800 nm; at wavelength longer than any of 800, 900, 1000, and 1100
nm; and/or at wavelengths shorter than any of 2600, 2500, 2000, or
1900 nm.
[0110] Photon/Skin Interaction
[0111] Light interacts with skin through laws of physics to scatter
and transmit through skin voxels also referred to as volume pixels
or skin volumes.
[0112] Referring now to FIG. 2, for clarity of presentation and
without limitation, in several examples provided herein a
simplifying and non-limiting assumption is made, for some
wavelengths, for some temperatures, and for some optical
configurations, that a mean photon depth of penetration, with
subsequent detection at the incident surface of the subject,
increases with mean radial distance between a photon illumination
zone and a photon detection zone. For example, for photons
transmitting from a sample illumination zone, through the subject,
and through a photon detection zone, such as at a subject/analyzer
interface: [0113] at a first radial distance, photons penetrate
with a mean maximum depth of penetration into an epidermal layer of
a subject; [0114] at a second larger radial distance, photons
penetrate with a mean maximum depth of penetration into a dermal
layer of the subject; and [0115] at a third still larger radial
distance, photons penetrate with a mean maximum depth of
penetration into a subcutaneous fat layer of the subject.
[0116] Referring still to FIG. 2 and referring again to FIG. 5, a
photon transport system 200 through skin layers of the subject 170
is illustrated. The photon transport system optionally uses one or
more mirrors and/or lenses to direct light from a a source to a
detector via skin of a subject. In this example, the photon
transport system 120 guides light from a source 112 of the source
system 110 to the subject 170, optionally with an air gap 210
between a last optic of an illumination system and skin of the
subject 170. Further, in this example, the photon transport system
120 irradiates skin of the subject 170 over a narrow illumination
zone, such as having an area of less than about 9, 4, 1, 0.25, 0.1,
and/or 0.01 mm.sup.2. Optionally, the photons are delivered to the
skin of the subject 170 through an optic or set of optics
proximately contacting, but not actually contacting, the skin, such
as within about 0.5, 1.0, or 2.0 millimeters of the skin.
Optionally, the distance between the analyzer and the skin of the
subject 170 is maintained with a vibration and/or shake reduction
system, such as is used in a vibration reduction camera or lens.
For instance, shake of the sample site is monitored and the optical
system is dynamically adjusted to compensate for movement of the
sample site. For clarity of presentation, the photons are depicted
as entering the skin at a single point. A portion of the photons
traverse, or more particularly traverse through, the skin to a
detection zone. The detection zone is a region of the skin surface
where the detector system 130 gathers the traversing or diffusely
reflected photons. Various photons traversing or diffusely
scattering through the skin encounter a stratum corneum, an
epidermis 173 or epidermis layer, a dermis 174 or dermis layer, and
subcutaneous fat 176 or a subcutaneous fat layer. As depicted in
FIG. 2, the diffuse reflectance of the various photons through the
skin detected by the detection system 130 follow a variety of
optical paths through the tissue, such as shallow paths through the
epidermis 173, deeper paths through the epidermis 173 and dermis
174, and still deeper paths through the epidermis 173, dermis 174,
and subcutaneous fat 176. However, for a large number of photons,
there exists a mean photon path for photons from a point entering
the skin until exiting the skin and being detected by the detection
system 130. In the illustrations, optical pathlengths are
illustrated as straight lines and/or curved lines for clarity of
presentation; in practice light travels in straight lines between
multiple scattering events.
[0117] Pathlength
[0118] Herein, for clarity, without loss of generality and without
limitation, Beer's Law is used to describe photon interaction with
skin, though those skilled in the art understand deviation from
Beer's Law result from sample scattering, index of refraction
variation, inhomogeneity, turbidity, anisotropy, and/or absorbance
out of a linear range of the analyzer 100.
[0119] Beer's Law, equation 1, states that:
A a bC (eq. 1)
[0120] where A is absorbance, b is pathlength, and C is
concentration. Typically, spectral absorbance is used to determine
concentration. However, the absorbance is additionally related to
pathlength. Hence, determination of the optical pathlength traveled
by the photons is useful in reducing error in the determined
concentration. Two methods, described infra, are optionally used to
estimate pathlength: (1) spatial resolution of pathlength and (2)
temporal resolution of pathlength.
[0121] Algorithm
[0122] The data and/or derived information from each of the spatial
resolution method and temporal resolution method are each usable
with the data processing system 140. Examples provided, infra,
illustrate: (1) both cases of the spatial resolution method and (2)
the temporal resolution method. However, for clarity of
presentation and without limitation, the photons in most examples
are depicted as radially traversing from a range of input zones to
a range of detection zones. Similarly, photons are optionally
delivered, simultaneously and/or as a function of time, from an
input zone to a range of detection zones. Still further, photons
are optionally directed to a series of input zones, as a function
of time, and one or more detection zones are used to detect the
photons directed to the series of input zones, simultaneously
and/or as a function of time. Yet still further, sets of photons of
controlled wavelengths are delivered to corresponding incident
positions on the skin and filters and/or detectors are configured
at additional locations on the skin.
[0123] Spatial Resolution
[0124] The first method of spatial resolution contains two cases.
Herein, in a first case photons are depicted traversing from a
range of input points on the skin to a radially located detector to
derive photon interrogated sample path and/or depth information.
However, in a second case, similar systems optionally use a single
input zone of the photons to the skin and a plurality of radially
located detector zones to determine optically sampled photon paths
and/or depth information. Still further, a combination of the first
two cases, such as multiple sources or multiple illumination zones,
and/or multiple detectors, is optionally used to derive photon path
information in the skin.
[0125] In a first system, still referring to FIG. 2 and referring
now to FIG. 3, the photon transit system 200 of FIG. 2 is
illustrated where the photon transport system 120 irradiates the
skin of the subject 170 over a wide range of radial distances from
the detection zone, such as at least about 0.1, 0.2, 0.3, 0.4, or
0.5 millimeters from a center or edge of the detection zone to less
than about 1.0, 1.2, 1.4, 1.6, or 1.8 millimeters from a center or
edge of the detection zone. In this example, a mean photon path is
provided as a function of radial distance from the illumination
zone to the detection zone. Generally, over a range of about zero
to less than about two millimeters from the detection zone and in
the range of 1100 to 2500 nm, the mean optical path of the detected
diffusely scattered photons increases in depth as a function of
radial distance.
[0126] In the first case of the spatial resolution method,
referring now to FIG. 4, the photon transit system 200 uses a
vector or array of illumination sources 400, of the source system
110, in a spatially resolved pathlength determination system. For
example, the illumination sources are an array of fiber optic
cables, an array of light emitting diodes, light passing through an
array of optical filters, and/or an array of illumination zones. In
this example, a set of seven fiber optics 401, 402, 403, 404, 405,
406, 407 are positioned, radially along the x,y plane of the
subject 170 to provide a set of illumination zones, relative to a
detection fiber at a detection zone. As illustrated the third
illumination fiber optic 403/detector 132 combination yields a mean
photon path having a third mean depth of penetration, d.sub.3, for
a third fiber optic-to-detector radial distance, r.sub.3; the fifth
illumination fiber optic 405/detector 132 combination yields a mean
photon path having a fifth mean depth of penetration, d.sub.5, for
a fifth fiber optic-to-detector radial distance, r.sub.5; and the
seventh illumination fiber optic 407/detector 132 combination
yields a mean photon path having a seventh mean depth of
penetration, d.sub.7, for a seventh fiber optic-to-detector radial
distance, r.sub.7. Generally, for photons in the near-infrared
region from 1100 to 2500 nanometers, both a mean depth of
penetration of the photons and a total optical pathlength increases
with increasing illumination zone-to-detection zone distance, where
the illumination zone-to-detection zone distance is less than about
three millimeters.
[0127] In the second case of the spatial resolution method,
referring now to FIG. 5, the photon transit system 200 uses a
vector or array of detectors 500 in the detection system 130. For
example, an illumination zone source, such as a single fiber optic
source, sends radially distributed light to an array of staring
detectors or collection optics coupled to a set of detectors. In
this example, a set of seven detectors 501, 502, 503, 504, 505,
506, 507 are positioned radially along the x,y plane to provide a
set of detection zones relative to the illumination zone. As
illustrated the source 112/second detector 502 combination yields a
mean photon path having a second mean depth of penetration,
d.sub.2, for a second illumination zone-to-detection zone radial
distance, r.sub.2; the source 112/fourth detector 504 combination
yields a mean photon path having a fourth mean depth of
penetration, d.sub.4, for a fourth illumination zone-to-detection
zone radial distance, r.sub.4; and the source 112/sixth detector
506 combination yields a mean photon path having a sixth mean depth
of penetration, d.sub.6, for a sixth illumination-to-detection zone
radial distance, r.sub.6. Again, generally for photons in the
near-infrared region from 1400 to 2500 nanometers both the mean
depth of penetration of the photons into skin and the total optical
pathlength in skin increases with increasing illumination
zone-to-detection zone distance, where the illumination
zone-to-detection zone distance, such as a fiber optic-to-detector
distance, is less than about three millimeters. Hence, data
collected with an analyzer configured with a multiple detector
design generally corresponds to the first case of a multiple source
design, albeit with different sample volumes due to tissue layers,
tissue inhomogeneity, and tissue scattering properties.
[0128] Referring again to FIGS. 4 and 5, the number of illumination
zones, where light enters skin of the subject 170, from one or more
source elements, is optionally 1, 2, 3, 4, 5, 10, 20, 50, 100 or
more and the number of detection zones, where light exiting the
skin of the subject 170 is detected by one or more detection
elements and/or systems, such as 1, 2, 3, 4, 5, 10, 20, 50, 100,
500, 1000, 5000, 10,000, 50,000 or more detection elements.
[0129] Two Dimensional Detector Array System
[0130] Referring now to FIG. 6A, a m.times.n two-dimensional
detector array 134 is illustrated, which is an example of the
detector 132 in the detector system 130. Herein, the m.times.n
two-dimensional detector array 134 is illustrated as a matrix of m
columns by n rows, where m and n are each, not necessarily equal,
positive integers, such as greater than 1, 2, 3, 4, 5, 10, 20, 50,
100. Optionally, the two-dimensional detector array 134 is of any
geometric configuration, shape, or pattern. Preferably, but
optionally, the two-dimensional detector array 134 is positioned
perpendicular and axial to the optical light path at the detector.
Optionally, the two-dimensional detector array 134 or a portion
thereof is tilted off of the perpendicular axis, such as less than
1, 2, 3, 5, 10, or 15 degrees toward the skin of the subject 170,
which yields a range of applied pressures between the
two-dimensional detector array and the skin when the
two-dimensional detector array 134 or a layer thereon contacts the
skin.
[0131] Referring now to FIG. 6B, an optional configuration of the
two-dimensional detector array 134 is further described.
Optionally, one or more elements of the two-dimensional detector
array 134 are coated or coupled with an optical detector filter
620. In a first case, the optical detector filter 620 is uniform
across the two-dimensional detector array 134. In a second case,
the optical detector filter 620 comprises an array of filters,
where individual elements, grids, or zones of the optical filter
correspond to individual elements of the two-dimensional detector
array 134. For example, a group of at least 1, 2, 4, 9, 16, or 25
elements of the two-dimensional detector array 134 are optically
coupled with a first optical filter and a group of at least 1, 2,
4, 9, 16, or 25 elements of the two-dimensional detector array 134
are optically coupled to a second filter. Optionally, any number of
filter types are used with a single detector array, such as 1, 2,
3, 4, 5, 10, 20 or more filter types. In a preferred embodiment, a
first, second, third, fourth, and fifth filter type correspond with
peak transmittance in ranges in the 1100 to 1450 nm range, 1450 to
1900 nm range, 1100 to 1900 nm range, 1900 to 2500 nm range, or
1100 to 2500 nm range, respectively, with lower transmittances,
such as less than 50, 25, or 10 percent at higher and/or lower
frequencies. In a third case, the optical filter 134 comprises a
repeating pattern of transmittances and/or absorbances as a
function of y, z-position.
[0132] Still referring to FIG. 6B, the two-dimensional detector
array 134 is optionally coupled to a detector optic/micro-optic
layer 630. In a first case, individual optical elements of the
micro-optic layer 630 optionally: [0133] alter a focal depth of
incident light onto the two-dimensional detector array 134; [0134]
alter an incident angle of incident light onto the two-dimensional
detector array 134; [0135] focus on an individual element of the
two-dimensional detector array 134; and/or [0136] focus on groups
of detection elements of the two-dimensional detector array
134.
[0137] In a second case, individual lines, circles, geometric
shapes covering multiple detector elements, and/or regions of the
micro-optic layer optionally: [0138] alter a focal depth of
incident light onto a line, circle, geometric shape, and/or region
of the two-dimensional detector array 134; [0139] alter an incident
angle of incident light onto a line, circle, geometric shape,
and/or region of the two-dimensional detector array 134; and/or
[0140] focus onto a line, circle, geometric shape, and/or region of
a group of elements of two-dimensional detector array 134.
[0141] Further the individual optical elements of the micro-optic
layer 630 and/or the individual lines, circles, geometric shapes,
or regions of the micro-optic layer 630 optionally are controlled
by the system controller 180 to change any of the focal depth
and/or an incident angle of incident light as a function of time
within a single data collection period for a particular subject
and/or between subjects.
[0142] Still referring to FIG. 6B, the optical detector filter 620
is: [0143] optionally used with or without the detector
optic/micro-optic layer 630; and/or [0144] optionally contacts,
proximately contacts, or is separated by a detector filter/detector
gap distance from the two-dimensional detector array 134.
[0145] Similarly, the detector optic/micro-optic layer 630 is:
[0146] optionally used with or without the optical detector filter
620; and/or [0147] optionally contacts, proximately contacts, or is
separated by a micro-optic/detector gap distance 632 from the
two-dimensional detector array 134.
[0148] Referring now to FIGS. 7(A-E), optionally and preferably an
incident optic/two-dimensional detector array system 700 is
enclosed in a housing. For example, optionally and preferably, the
detector array, first optical filter array, second optical filter
array, and/or focusing optic array are sandwiched together, where
two or more of the stacked layers are substantially contacting
along an interfacing plane. The first and/or second optical filter
arrays are optionally placed along the optical axis on either side
of the focusing optic/light gathering array. The housing serves a
number of purposes, such as the ability to prevent dust/particulate
infiltration; is an enclosure sealed against moisture, allowing the
detectors to be operated below a dew point, such as via use of 2,
3, or four layers of Peltier coolers; allows use of a partial
vacuum within the enclosure;
[0149] and/or allows a substantially non-water containing gas to be
placed in the housing to minimize condensation.
[0150] Referring still to FIGS. 7(A-E), for clarity of
presentation, the incident optic/two-dimensional detector array
system 700 is illustrated in multiple representative
configurations, without loss of generality or limitation.
[0151] Referring now to FIG. 7A, a first example of the incident
optic/two-dimensional array system 700 is illustrated with the
photon transport system 120 used to deliver photons to the subject
170 proximate the two-dimensional detector array 134. In a first
example, a portion of photons from the photon transport system
diffusely scatter through skin of the subject 170 and after radial
movement emerge from the skin of the subject 170 where a portion of
the incident photons are detected by elements of the
two-dimensional detector array 134. In a first example, photons are
illustrated travelling along: (1) a first mean path, path.sub.1,
and are detected by a first detector element of the two-dimensional
detector array 134 at a first, smaller, mean radial distance from a
tissue illumination zone of the photon transport system and (2) a
second mean path, path.sub.2, are detected by a second detector
element of the two-dimensional detector array 134 at a second,
longer, mean radial distance from a tissue illumination zone of the
photon transport system relative to path.sub.1. In this first
example, optionally: [0152] a first element of the optical detector
filter 620 is preferably a filter designed for a shorter mean
tissue pathlength, such as about 0 to 1.5 millimeters, such as a
combination band optical filter with a peak transmittance in a
range of 2000 to 2500 nm; [0153] a second element of the optical
detector filter is preferably a filter designed for a longer mean
tissue pathlength, such as about 5.0 to 10 millimeters, such as a
second overtone optical filter with a peak transmittance in a range
of 1100 to 1450 nm; and [0154] a third element of the optical
detector filter is preferably a filter designed for an intermediate
mean tissue pathlength, such as about 1.5 to 5.0 millimeters, such
as a first overtone optical filter with a peak transmittance in a
range of 1450 to 1900 nm.
[0155] In the first example, [0156] a first element of the detector
optic/micro-optic layer 630 is optionally configured to preferably
collect incident skin interface light having an angle aimed back
toward the photon transport system, which yields a slightly shorter
mean tissue pathlength, such as about 0.2 to 1.7 millimeters
compared to an optic that is flat/parallel relative to the skin of
the subject 170; [0157] a first element of the detector
optic/micro-optic layer 630 is optionally configured to redirect
collected incident skin interface light back away from the photon
transport system 120 as illustrated, such as onto a center of a
detector or detector array element closer to the illumination zone;
[0158] a second element of the detector optic/micro-optic layer 630
is optionally configured to preferably collect incident skin
interface light having an angle aimed away from the incident
illumination zone of the skin, which yields a slightly shorter mean
tissue pathlength compared to an optic that is flat/parallel
relative to the skin of the subject 170; [0159] a second element of
the detector optic/micro-optic layer 630 is optionally configured
to redirect collected incident skin interface light back toward the
incident skin illumination zone, such as onto a center of a
detector or detector array element further from the illumination
zone; [0160] a third element of the detector optic/micro-optic
layer 630 is optionally flat/parallel relative to a mean plane
between the skin of the subject 170 and the two-dimensional
detector array 134.
[0161] As described, supra, the individual optical elements of the
micro-optic layer 630 and/or the individual lines, circles,
geometric shapes, or regions of the micro-optic layer 630 are
optionally dynamically controlled by the system controller 180 to
change any of a detector layer incidence acceptance angle, the
focal depth, an incident angle, and/or an emittance angle or exit
angle as a function of time within a single data collection period
for a particular subject and/or between subjects.
[0162] Still referring to FIG. 7A, an optional micro-optic
layer/detector array gap 632 is illustrated between the detector
optic/micro-optic layer 630 and elements of the two-dimensional
detector array 134, such as a gap less than 0.2, 0.5, 1, 2, 5, or
10 millimeters. Further, an optional spacer gap 121 is illustrated
between a final incident optic of the photon transport system 120
and any of the two-dimensional detector array 134, the optical
detector filter 620, and/or the detector optic/micro-optic layer
630, such as a gap of less than about 0.1, 0.2, 0.3, 0.4, 0.5,
0.75, and/or 1.0 millimeter.
[0163] Referring now to FIG. 7B, a second non-limiting example of
the incident optic/two-dimensional detector array system 700 is
illustrated with the photon transport system 120 used to deliver
photons to the subject 170 proximate a first side of the
two-dimensional detector array 134, where the array has n detector
elements, where n is a positive integer greater than three. In this
second example, ten radial distances to ten detector elements are
illustrated. In this example, some radial distances are equal, such
as a first radial distance to detector elements 1 and 5 and a
second radial distance to detector elements 2 and 4. Generally,
detector elements are optionally grouped or clustered into radial
distances relative to an illumination zone of 1, 2, 3, or more
incident light directing elements where each group or cluster is
individually associated with an average mean optical probed tissue
pathlength, subsequently used in pathlength resolution, and/or
analyte concentration estimation.
[0164] Still referring to FIG. 7B, optionally, different clusters
of radial distances are treated optically differently, such as with
a different optical detector filter 620. Representative and
non-limiting examples include: [0165] a combination band filter for
filtering photons having mean radial distances of 0 to 1
millimeter, the combination band filter comprising: [0166] a
transmittance greater than seventy percent at 2150 nm, 2243, and/or
2350 nm, and/or [0167] an average transmittance of greater than
seventy percent from 2100 to 2400 nm and an average transmittance
of less than twenty percent from 1100 to 1900 nm and/or from 2400
to 2600 nm; [0168] a first overtone band filter for filtering
photons having mean radial distances of 0.3 to 1.5 millimeters, the
first overtone filter comprising: [0169] a transmittance greater
than seventy percent at 1550 nm, 1600, and/or 1700 nm, and/or
[0170] an average transmittance of greater than seventy percent
from 1500 to 1800 nm and an average transmittance of less than
twenty percent from 1100 to 1400 nm and/or from 2000 to 2600 nm;
[0171] a combination band/first overtone band filter for filtering
photons having mean radial distances of 0 to 1.5 millimeters, the
combination/first overtone filter comprising: [0172] a
transmittance greater than seventy percent at 1600 and 2100 nm,
and/or [0173] an average transmittance of greater than seventy
percent from 1500 to 2300 nm and an average transmittance of less
than twenty percent from 700 to 1400 nm and/or from 2500 to 2800
nm; [0174] a second overtone band filter for filtering photons
having mean radial distances of 0.5 to 3.0 millimeters, the second
overtone filter comprising: [0175] a transmittance greater than
seventy percent at 1200 nm, 1300, and/or 1400 nm, and/or [0176] an
average transmittance of greater than seventy percent from 1100 to
1400 nm and an average transmittance of less than twenty percent
from 700 to 1000 nm and/or from 1500 to 2000 nm; [0177] a first
overtone band/second overtone band filter for filtering photons
having mean radial distances of 0.5 to 3.0 millimeters, the first
overtone band/second overtone band filter comprising: [0178] a
transmittance greater than seventy percent at 1300 and 1600 nm,
and/or [0179] an average transmittance of greater than seventy
percent from 1200 to 1700 nm and an average transmittance of less
than twenty percent from 700 to 1000 nm and/or from 2000 to 3000
nm; [0180] a sloping overtone band filter or step function overtone
band filter for filtering photons having mean radial distances of
0.5 to 3.0 millimeters, the sloping overtone band filter
comprising: [0181] a mean transmittance greater than ten percent at
1300 nm, less than fifty percent at 1300 nm, and greater than
seventy percent at 1600 nm, and/or [0182] an average transmittance
between 1100 and 1300 nm in the range of ten to fifty percent and
an average transmittance between 1500 and 1700 nm of greater than
seventy percent with optional out of band blocking from 700 to 1000
nm and/or from 2500 to 3000 nm of greater than ninety percent;
and/or [0183] a luminance filter for filtering photons having mean
radial distances of 0 to 5 millimeters, the luminance filter
comprising: [0184] an optical spacing element designed to maintain
focal length; [0185] a mean transmittance greater than seventy
percent from 1100 to 1800 nm, and/or [0186] a mean transmittance
greater than seventy percent from 1100 to 2400 nm and an average
transmittance of less than twenty percent from 700 to 1100 nm
and/or from 2000 to 2600 nm.
[0187] Referring now to FIGS. 7B, 7C, and 7D, the photon transport
system 120 is illustrated as delivering light to an edge, corner,
and interior region of the two-dimensional detector array 134,
respectively. Descriptions, herein, to the edge, corner, or
interior illumination options optionally apply to the other
cases.
[0188] Referring again to FIG. 7B, the photon transport system 120
is illustrated delivering photons using at least one fiber optic
and/or through one or more optics to a point or illumination zone
along an edge of the two-dimensional detector array 134. For
clarity of presentation, in a first case, the photon transport
system 120 is illustrated delivering photons to a center of an edge
of the two-dimensional detector array 134; however, the photon
transport system 120 optionally delivers photons to any point along
the edge of the two-dimensional detector array 134 and/or at any
distance from an edge or corner of the two-dimensional detector
array.
[0189] Still referring to FIG. 7B, as illustrated the photon
transport system delivers photons that are detected with an array
of mean pathlengths and associated mean depths of penetration into
the tissue of the subject 170, at each detector element. For
example, the first detector element, 1, detects photons having a
first mean pathlength for a first illumination point, herein
denoted b.sub.(pathlength, illuminator). In the first case, using a
simplifying assumption of tissue homogeneity for clarity of
presentation, the mean probed pathlength is the same at the first
and fifth detector elements. Similarly, the mean probed pathlength
is similar and/or tightly grouped at the second and fourth detector
element. In addition, groups of detector elements observe photons
traversing similar or grouped pathlengths. For example, a first
sub-group of the first, sixth, and seventh detector elements
observe similar probed tissue pathlengths and depths of
penetration. Similarly, a second sub-group of the fifth, ninth, and
tenth detector elements observe similar probed tissue pathlengths
and depths of penetration. In this case, the first sub-group and
second sub-group are optionally placed into a single group as the
first sub-group and second sub-group observe similar, exact if the
tissue is homogenous, probed tissue pathlengths. Similarly, a first
sub-group is optionally one, two, three, or more elements of a
first column of detector elements and a second sub-group is
optionally one, two, three, or more elements of a second column of
the detector elements. Generally, the detector elements are
optionally treated individually or in sub-groups, such as by
distance from a mean sample illumination point, sub-groups of one
or more rows of detector element, sub-groups of one or more columns
of detector elements, and/or groups of sub-groups.
[0190] Still referring to FIG. 7B, any two-dimensional detector
array 134 element, sub-group, column, row, region, and/or group is
optionally individually coated or coupled to any filter, such as
the filters described supra, and/or is optionally individually
coupled with a focusing optic and/or a dynamic focusing optic, as
further described, infra.
[0191] Referring now to FIG. 7C, a second case of an illumination
optic and/or a group of illumination optics of the photon transport
system 120 used to illuminate an illumination zone relative to a
corner of the two-dimensional detector array 134 is illustrated. As
with the first side illumination case, individual elements,
sub-groups, and/or groups of detector elements observe at differing
radial distances from the illumination zone where the differing
radial distances have corresponding average observed tissue
pathlengths, depths of penetration, and/or sampled regions of skin
of the subject 170. Here, three groups or detection zones are
illustrated. The first group 710 is illustrated as detection
elements 1, 2, 3, 4, 5, and 6, where the commonality is a short
radial distance between the illumination zone and the detection
zone, such as used for the combination band spectral region and/or
for small mean depths of penetration of the photons into the tissue
of the subject 170. The second group 720 is illustrated with long
rising dashes, where the commonality is a medium radial distance
between the illumination zone and the detection zone, such as used
for the first overtone spectral region. The third group 730 is
illustrated with short falling dashes, where the commonality is a
long radial distance between the illumination zone and the
detection zone, such as used for the second overtone spectral
region. As described, supra, any detector element, sub-group,
and/or group is optionally associated with an individual filter, an
individual optic, an individual dynamic optic, and/or a group of
optics. Further, any detector element, sub-group, and/or group is
optionally associated with any position and/or wavelength of
illuminators, such as with a light-illuminating diode illumination
array.
[0192] Referring now to FIG. 7D, a third case of an illumination
optic and/or a group of illumination optics of the photon transport
system 120 used to illuminate an illumination zone within a section
within the two-dimensional detector array 134 is illustrated. As
with the first side illumination case and the second corner
illumination case, individual elements, sub-groups, and/or groups
of detector elements observe at differing radial distances from the
illumination zone where the differing radial distances have
corresponding average observed tissue pathlengths, depths of
penetration, and/or sampled regions of skin of the subject 170.
Here, two groups or detection zones are illustrated. The third
group 740 is a first section, arc, quadrant, zone, ring, square,
rectangle, and/or polygon of detection elements at a first range of
distances from the illumination zone, illustrated here with
detector elements intersecting with a long-dashed/square shape. The
fourth group 750 is a second section, arc, quadrant, zone, ring,
square, rectangle, and/or polygon of detection elements at a second
range of distances from the illumination zone, shown here with
detector elements intersecting with a short-dashed/square shape.
The fourth group 740 and fifth group 750 are illustrative of n
groups where n is a positive integer of 2, 3, 4, 5, 10 or more
where individual groups differ by 1, 2, 3, 4 or more
cross-sectional distances of a detector element. As described,
supra, any detector element, group, sub-group, and/or group is
optionally associated with an individual filter, an individual
optic, and/or an individual dynamic optic.
[0193] Still referring to FIG. 7D, in one optional filter
arrangement, optical filters are stacked. For example, a first
optical filter is a first long pass or a first short pass filter
covering a wide range of first detector elements; a second optical
filter is stacked relative to the first optical filter along the
x-axis, which is the optical axis. The second optical filter is a
second long pass, a second short pass, or a band pass filter
covering a subset of the first detector elements. For example, the
first optical filter is a long pass filter passing wavelengths
longer than 1100 nm covering all of the fourth group 740 and fifth
group 750, and the second optical filter is a long pass filter
passing wavelength longer than 1450 nm covering all of the fifth
group, which yields a first overtone filter for the fourth group
740 and a first and second overtone filter for the fifth group 750.
Combinations of stacked filters for various groups include any of
2, 3, 4, or more filters described herein, such as the combination
band filter, the first overtone band filter, the combination
band/first overtone band filter, the second overtone band filter,
the first overtone band/second overtone band filter, the sloping
overtone bands filter, and the luminance filter described, supra,
in the description of FIG. 7B. The inventor notes that cutting
larger stackable filters reduces costs and more importantly light
loss associated with placing individual filters over individual
detector elements of the two-dimensional detector array 134.
[0194] Referring now to FIG. 7E, a fourth example of multiple
illumination zones from the photon transport system 120 positioned
about and within, not illustrated, the two-dimensional detector
array 134 is illustrated. In this fourth example, a matrix of
illuminators, herein represented by a single column for clarity of
presentation, are denoted as illuminators a-z. At a given point in
time, any set or subset of the matrix of illuminators are used to
deliver photons to the tissue of the subject 170. For example, at a
first point in time, illuminators a-b are used; at a second point
in time illuminators a-d are used; at a third point time
illuminators d-g are used, and so on. As illustrated, illuminators
a-d are used and a detection element m,n is used. Generally, sets
of illuminators are optionally used as a function of time where the
illuminators define the number of photons delivered and provide a
first part of a illumination zone-to-detection zone distance and
selected detector elements as the same function of time define the
second part of the illumination zone-to-detection zone distance.
Optionally, the illumination array a light-emitting diode (LED)
array used in combination with a filter array allowing an analyzer
without use of a time-domain interferometer and/or a grating.
[0195] Referring again to FIGS. 7B-E, notably, detector elements
associated with a first sub-group or first group at a first point
in time are optionally associated with an n.sup.th sub-group or
n.sup.th group at a n.sup.th point in time when the same and/or a
different set of illuminators are used, where n is a positive
integer of 2, 3, 4, 5, 10 or more.
[0196] Multiple Two-Dimensional Detector Arrays
[0197] Referring now to FIGS. 8A-D, a multiple luminance/multiple
detector array system 800 is described. Generally, one and
preferably two or more illumination zones are provided by the
photon transport system within and/or about two or more detector
arrays, such as two or more of the two-dimensional detector arrays
134. For clarity of presentation and without loss of generality,
several examples are provided, infra, of the multiple
luminance/multiple detector array system 800.
[0198] Referring now to FIG. 8A, a first example of the photon
transport system 120 delivering light to the skin of the subject
170 at multiple illumination positions relative to two or more
detector arrays, such as a first detector array 702 and a second
detector array 704, is provided. In this first example, the photon
transport system delivers light: (1) by the side 802, (2) removed
from the side 804, (3) at the corner 806, and/or (4) around the
corner 808 of a detector array, such as the second detector array
704. As illustrated, illumination zones are provided in a first
column and in a second column relative to the side of the second
detector. The first column 802 and the second column 804 of
illuminators are illustrated proximately touching, with a first
illuminator/detector gap 812, an edge of the second detector array
704 and with a second illuminator/detector gap 814 from the first
detector array 702, where the first illuminator/detector gap 812
and the second illuminator/detector gap 814 are optionally
different by greater than ten percent and are, respectively, less
than and greater than, about 1, 1/2, 1/4, 1/8, 1/16, or 1/32 of a
millimeter.
[0199] Referring again to FIGS. 7(A-E) and 8A, any detector array
is optionally tilted along the y- and/or z-axes to yield varying
degrees of force applied to a sampled tissue sample as a function
of detector position when directly contacting the tissue or
indirectly contacting the tissue via a fronting detector layer
during sampling. The varying pressure results in data comprising
varying and/or controllable pressure for ease in subsequent data
processing, such as via binning, grouping, correlations, and/or
differential measures.
[0200] Still referring to FIGS. 7(A-E) and 8A, any detector array
is optionally differentially cooled along the y- and/or z-axes,
such as with a Peltier cooler on one side of the detector array, to
yield varying degrees of temperature as a function of detector
position when directly contacting the tissue or indirectly
contacting the tissue via a fronting detector layer during
sampling. The varying temperature results in data comprising
varying and/or controllable temperature for ease in subsequent data
processing, such as via binning, grouping, correlations, and/or
differential measures, such as for analysis of temperature
sensitive absorbance bands and/or water absorbance bands.
[0201] Multiple Pathlengths
[0202] Referring now to FIG. 8B, a second example of the photon
transport system 120 delivering light to the skin of the subject
170 at multiple illumination positions relative to two or more
detector arrays is provided.
[0203] Illuminator Arrays
[0204] In this example, an illuminator array 810 is illustrated.
Generally, the illuminator array 810 is a set of illumination
points and/or an illumination area of any geometric cross-sectional
shape along the y-, z-axes. Referring still to FIG. 8B, three
examples of illuminator arrays 810 are illustrated: a first
illuminator array 812 comprising an about circular illumination
pattern, here represented as nineteen illumination areas and/or a
rough circle of illumination; a second illuminator array 814, here
represented as twelve illumination regions and/or a subset of the
first illuminator array 812; and a third illuminator array 816,
which represents an about square and/or rectangular illumination
array, which does not overlap any of the first illuminator array
812. Additionally, a fourth illuminator array optionally overlaps a
portion of any other illuminator array as a function of time, not
illustrated.
[0205] Detector Arrays
[0206] Still referring to FIG. 8B, an illustrative example of a
three illuminator area system coupled to a four area detection
system is described, where the four area detection system
comprises: a first detector array 702, a second detector array 704,
a third detector array 706, and a fourth detector array 708. In
this second example, four detector arrays are illustrated about the
three illumination arrays 812, 814, 816, which are representative
of any number of illumination elements and/or any number of
illumination arrays. For ease of presentation, this section refers
to a center mean illumination point for each of the three
illumination arrays 812, 814, 816, which in the present case is the
center of the symmetrically illustrated light illumination arrays
labeled X, Y, and Z, respectively.
[0207] Still referring to FIG. 8B and now referring to the first
detector array 702 and the first illumination array 812 having
center X, the inventor notes that the first row of the detector
array contains detector elements at three optical pathlengths from
the center of the illumination array. A first pathlength, b.sub.1,
is observed at the center element of the first row of detector
elements. A second pathlength, b.sub.2, is observed with each of
the detector elements, in the first row of the detector array,
adjacent the center detector element in the first row of the first
detector array 702. Data collected at the redundant pathlengths
comprise multiple uses, such as precision determination, outlier
detection, tissue variation estimation, and/or tissue mapping, as
described infra. A third pathlength, b.sub.3, is observed with each
of the detector elements at the outer ends of the first row of the
first detector array 702. Similarly, the second row of the detector
array observes three additional pathlengths, described here as the
fourth, fifth, and sixth pathlengths, b.sub.4, b.sub.5, N.
Similarly, the third, fourth, and fifth rows of the detector array
contains fifteen additional detector elements observing an
additional three pathlengths per row or nine additional
pathlengths, b.sub.7-b.sub.15. The inventor notes that the first
detector array 702, represented as a 5.times.5 matrix of detector
elements, is optionally an m.times.n array of detector elements, as
described in relation to FIG. 6A, with a corresponding number of
observed mean optical pathlengths and mean optical depths.
[0208] Still referring to FIG. 8B, as described, supra, in relation
to FIG. 5 and further described, infra, as the median pathlength of
the probing photons increases, the depth of penetration of the mean
photon increases for each wavelength in the range of 1100 to 2500
nm until an absorbance limit of detection is reached. Thus, as
illustrated, the first detector array 702 is configured to observe
fifteen pathlengths, three per row, where ten of the pathlengths
are observed twice with intentionally separated sample tissue
volumes.
[0209] Still referring to FIG. 8B and referring now to the second
detector array 704 and still referring to the first illuminator
array 812, the second detector array 704 is rotated about the
x-axis relative to the first detector array 702 placing a corner of
the second detector array closet to the mean illumination point of
the first illumination array, X, as opposed to the first detector
array 702 having a side closest to the mean illumination point, X.
Rotation of the second detector array 704 allows another set of
observed pathlengths, even when a duplicate detector array design
is used. For example, as illustrated the corner of the second
detector array 704 represents a sixteenth pathlength, b.sub.16.
Similarly, the second diagonal of the second detector array 704
contains two additional detector elements observing a seventeenth
pathlength, b.sub.17, in duplicate due to symmetry about a line
through the center of the first illuminator array 812 and nearest
corner of the second detector array 704. Similarly, the third to
ninth diagonal of the second detector array 704 contain twenty-two
additional detector elements observing thirteen additional
pathlengths, b.sub.18-b.sub.30.
[0210] Still referring to FIG. 8B and referring now to the third
detector array 706 and still referring to the first illuminator
array 812, the third detector array 706 is positioned opposite the
second detector array 704. The symmetrical positioning of the third
detector array 704 relative to the second detector array 704 and
the first illuminator array 812 yields pathlengths mirroring those
observed using the second detector array; particularly, pathlengths
sixteen to thirty, b.sub.16-b.sub.30. The mirrored pathlengths
allows repetitive data for an internal check of results, validation
of results, outlier detection, concentration estimation bounding,
and/or additional algorithmic uses. Notably, by merely shifting a
detector array and/or a source array along the y-z-axes, instead of
repeated pathlengths, the new illuminator/detector combination will
observe new pathlengths; twenty-five new pathlengths for the
illustrated 5.times.5 detector element array.
[0211] Still referring to FIG. 8B and referring now to the fourth
detector array 708 and still referring to the first illuminator
array 812, the fourth detector array 708 is rotated an angle theta
relative to the first detector array 702. The rotation of the
fourth detector array 708 breaks symmetry along a line from the
center of the first illuminator array 812, X, and a center of the
fourth detector array 708. Now, intentionally, lacking rotational
symmetry the fourth 5.times.5 detector array observes twenty-five
additional pathlengths, b.sub.31-b.sub.55, compared with the
fifteen pathlengths observed by the first detector array 702 and
fifteen distinct pathlengths observed using the second detector
array 704.
[0212] Still referring to FIG. 8B and now referring to the second
illuminator array 814, the center of the second illuminator array
814, Y, is offset along the y-z-axes relative to the center of the
first illuminator array, X, which breaks symmetry relative to each
of the four detector arrays 702, 704, 706, 708. The intentional
breaking of the symmetry allows the four detector arrays 702, 704,
706, 708 to observe one hundred (25.times.4) new pathlengths by
merely changing an optical illumination configuration. Similarly,
now referring to the third illuminator array 816, moving the center
of illumination to a third point, Z, yields an additional one
hundred new observed pathlengths (25.times.4). To illustrate the
number of observed pathlengths still further, use of four
50.times.50 detector arrays without symmetry relative to five
illumination patterns yields 50,000 (2500 detectors/array.times.4
arrays.times.5 illumination zones) observed pathlengths. Detector
arrays of m.times.n dimension where m and/or n are independently
any positive integer of 1, 2, 3, 5, 10, 100, 500, 100 or more thus
yields tens, hundreds, thousands, and/or millions of detector
elements. Hence, with a two-dimensional detector array, even using
one detector design, and an illumination source, even statically
positioned, may readily yield hundreds of thousands or millions of
observed pathlengths in a period of less than 1, 2, 3, 4, 5, 10,
20, or 30 seconds as the detectors are optionally used in
parallel.
[0213] Filters
[0214] Herein, optical filters optically coupled with elements of
the detector arrays are described.
[0215] Longpass Filters
[0216] Referring now to FIG. 9A, a series of longpass filters are
described. A longpass filter is an optical interference and/or
coloured glass filter that attenuates and/or blocks shorter
wavelengths and transmits and/or passes longer wavelengths over a
range of wavelengths. Longpass filters optionally have a high slope
described by a cut-on wavelength at a wavelength passing fifty
percent of peak transmission. Herein, longpass filters refer to
filters comprising a fifty percent cut-on wavelength in the range
of 900 to 2300 nm. More preferably, for analysis of tissue spectra,
the inventor has determined that longpass filters complementing
water absorbance bands offer multiple advantages relating to
detector dynamic range.
[0217] Referring still to FIG. 9A and referring now to FIG. 9B, a
first longpass filter 912 is illustrated comprising a fifty percent
cut-on wavelength in the range of 1850 to 2050 nm, such as at about
1900, 1950, or 2000 nm. The first longpass filter 912 is designed
to transmit photons in a region referred to herein as a
`combination band region` 950, which comprises a first region of
low water absorbance and three glucose absorbance bands. The
inventor has determined that by having the sharp, often temperature
sensitive and/or difficult to analyze region due to rapid changes
in transmittance as a function of wavelength, cut-on wavelength in
the wavelength range of the large water absorbance band spectral
feature, that the filter weaknesses are masked by the water
absorbance band while the filter strengths are optimize, as
described herein. First, the first longpass filter 912 transmits a
high percentage of light, such as greater than 70, 80, or 90
percent, in the desirable range of 2100 to 2350 nm where water
absorbance 1310 and scattering combine to yield detected photons in
the glucose rich dermis layer of skin and where glucose has three
prominent absorbance bands at 2150, 2272, and 2350 nm. Second, the
first longpass filter 912 has a transition cut-on range, that
hinders analysis due to the rapid change in transmittance as a
function of wavelength and is susceptible to temperature induced
spectral shifts, that is placed in a region where water absorbance
prevents detection of photons penetrating into the dermis, thereby
eliminating the problem. Third, the first longpass filter 912 has a
blocking range from a detector cut-on of about 700 nm to about 1900
nm, which blocks photons otherwise filling a dynamic range of an
element of the detector array, which allows an enhanced
signal-to-noise ratio, using proper detector gain electronics
and/or integration time, in the desirable range of 2100 to 2350 nm.
The inventor notes that the water absorbance band at circa 2500 nm
functions as a natural shortpass filter, which combines with the
first longpass filter 912 to form a combination band bandpass
filter.
[0218] Referring still to FIG. 9A and FIG. 9B, a second longpass
filter 914 is illustrated comprising a fifty percent cut-on
wavelength in the range of 1350 to 1490 nm, such as at about 1375,
1400, 1425, 1450, or 1475 nm. The second longpass filter 914 is
designed to transmit photons in a region referred to herein as a
`first overtone region` 960, which comprises a second region of low
water absorbance and three glucose absorbance bands. As with the
first longpass filter 912, the second longpass filter 914 is
designed to function in a complementary manner with water
absorbance of tissue. Particularly, the second longpass filter 914
transmits three prominent glucose bands in the first overtone
region centered at circa 1640, 1692, and 1730 nm, which are in a
region where the dominant absorber water and tissue scattering
combine to yield detectable photons having sampled the glucose rich
dermal layer of tissue in diffuse reflectance mode. Further, the
second longpass filter blocks/substantially blocks light from about
700, 800, 900, 1000, and/or 1100 to 1450 nm, which would otherwise
contribute to filling a dynamic range of a detector array element.
Blocking the second overtone light, described infra, thus allows
full use of a dynamic range of a detector in the first overtone
region and a correlated enhancement in a signal-to-noise ratio of
the three first overtone glucose absorbance bands. Still further,
the second longpass filter 914 benefits from the water absorbance
band at 1950 nm, which functions as a natural shortpass filter to
the second longpass filter 914 forming a first overtone bandpass
filter from about 1450 to 2000 nm or a spectral region therein.
[0219] The inventor notes that traditional spectroscopic analysis
of tissue using near-infrared light does not: (1) combine light
from the combination band region 950 with light from the first
overtone region 960 using separate detectors, which are optionally
individually optimized for a spectral region, or (2) use separate
longpass filters, bandpass filters, or optics coupled to the
multiple detectors to simultaneously enhance spectral quality of
the first overtone region and combination band region.
[0220] The inventor has determined that the three glucose
absorbance bands in the combination band region are linked at an
atomic/chemical energy level to the three glucose absorbance bands
in the first overtone region. Hence, detection of signals from
corresponding bands of the combination band region and first
overtone region are optionally compared to enhance glucose
concentration estimations.
[0221] Referring still to FIG. 9A and FIG. 9B, a third longpass
filter 916 is illustrated comprising a fifty percent cut-on
wavelength in the range of 700 to 1200 nm, such as at about 800,
900, 1000, or 1100 nm. The third longpass filter 916 is designed to
transmit photons in a region referred to herein as a `second
overtone region` 970 from about 1000 or 1100 to 1400 nm. Similar to
the first and second longpass filters 912, 914, the third longpass
filter 916 is designed to optimize signal-to-noise ratios in the
second overtone region, function with the use of water absorbance
bands at 1450 and 1900 nm as natural shortpass filters, and to be
used with detector array elements observing photons having sampled
at least the dermis skin layer. It is noted that the first, second,
and third longpass filters 912, 914, 916 are illustrated with
differing maximum light throughput for clarity of presentation, but
each optionally function as a longpass filter as described
supra.
[0222] Shortpass Filters
[0223] Referring now to FIG. 10, a series of shortpass filters are
illustrated. A shortpass filter is an optical interference and/or
coloured glass filter that attenuates and/or blocks longer
wavelengths of light and transmits and/or passes shorter
wavelengths of light over a spectral range. Herein, shortpass
filters refer to filters comprising a fifty percent cut-off
wavelength in the range of 1400 to 3000 nm. More preferably, for
analysis of tissue spectra, the inventor has determined that
shortpass filters complementing water absorbance bands offer
multiple advantages relating to detector dynamic range. A shortpass
filter preferable passes greater than 60, 70, 80, or 90 percent of
light in the passed spectral region and transmits less than 1, 5,
10, 20, 30, or 40 percent of the light in the attenuated spectral
region.
[0224] Referring again to FIG. 10 and referring now to FIG. 11A, a
first shortpass filter 1012 is illustrated comprising a fifty
percent cut-off wavelength in the range of 2350 to 3000 or more
nanometers. The first shortpass filter 1012 is designed to transmit
photons in the second overtone 970, first overtone 960, and/or
combination band region 950. The first shortpass filter 1012 is
designed to block infrared heat at wavelengths greater than about
2350 nm, where otherwise transmitted heat would alter temperature
of parts of the tissue and result in shifting of oxygen-hydrogen
water band positions. Preferably, the first shortpass filter 1012
is combined with a longpass filter, such as with the first longpass
filter 912 to form a combination band bandpass filter 1130 for the
combination band region, with the second longpass filter 914 to
form a bandpass filter for the first overtone/combination band
spectral region, or with the third longpass filter 916 to form a
second overtone/first overtone/combination band bandpass
filter.
[0225] Referring again to FIG. 10 and FIG. 11A, a second shortpass
filter 1014 is illustrated comprising a fifty percent cut-off
wavelength in the range of 1800 to 2100 nm, such as at about 1900,
1950, or 2000 nanometers. The second shortpass filter 1014 is
designed to transmit photons in the second overtone 970 and first
overtone 960 regions. The second shortpass filter 1014 is designed
to block infrared heat at wavelengths greater than about 2000 nm,
where otherwise transmitted heat would alter temperature of parts
of the tissue and result in shifting of oxygen-hydrogen water band
absorbance positions of molecules in the skin. Preferably, the
second shortpass filter 1014 is combined with a longpass filter,
such as with the second longpass filter 914 to form a first
overtone bandpass filter 1120 for the first overtone region or with
the third longpass filter 916 to form a second overtone/first
overtone bandpass filter.
[0226] Referring again to FIG. 10 and FIG. 11A, a third shortpass
filter 1016 is illustrated comprising a fifty percent cut-off
wavelength in the range of 1300 to 1600 nm, such as at about 1400,
1450, or 1500 nanometers. The third shortpass filter 1016 is
designed to transmit photons in the second overtone 970 and
optionally part of the first overtone 960 spectral regions. The
third shortpass filter 1130 is designed to block photons from about
1600 to 2500 nm than would otherwise contribute to filling a
detector well depth and/or dynamic range of a near-infrared
detector, such as an indium/gallium/arsenide detector. Preferably,
the third shortpass filter 1016 is combined with a longpass filter,
such as with the third longpass filter 916, to form a second
overtone bandpass filter 1110 for the second overtone region and/or
a portion of the first overtone region, such as about 1500 to 1580
nm.
[0227] As illustrated in FIG. 11A, the fifty percent cut-off of the
shortpass filter is preferably in a region of strong water
absorbance to maximize transmitted photons while minimizing
detection of out of band photons by using the water absorbance
properties of skin.
[0228] Referring now to FIG. 11B, narrowband bandpass filters or
bandpass filters are optionally used to enhance the signal-to-noise
ratio in a narrow spectral region, such as about 25, 50, 100, 150,
or 200 nm wide. Optionally, the bandpass filters are associated
with a light intensity limiting sample constituent, such as water.
For example, in the combination band spectral region 950, a minimum
water absorbance is observed at about 2270 with higher water
absorbances observed at both longer and shorter wavelengths, such
as at about 2150 or 2350 nm. Without an optical filter or an
independent wavelength selection device, a multiplexed signal, such
as obtained using a Fourier transform near-infrared spectrometer,
will dominantly fill a well of a detector with photons from the
spectral region transmitting more light, such as at about the water
absorbance minimum, while obtaining fewer photons from spectral
regions of higher absorbance. Thus, the signal-to-noise ratio in
regions of higher water absorbance is degraded compared to use of
the narrowband bandpass filter in a region of higher water
absorbance and/or total observed absorbance. A narrowband bandpass
filter or a set of narrowband bandpass filters in combination with
multiple detectors, such as a two-dimensional detector array allows
for each region to fully use a dynamic range of the detector
elements, if properly matched with amplifier circuitry and
integration time. For example, a first narrowband bandpass filter
1150 is optionally used at a first set of wavelengths correlated
with a larger water absorbance. Similarly, a second narrowband
bandpass filter 1160 and/or a third narrowband bandpass filter 1170
are optionally used at spectral regions of intermediate and low
water absorbance, respectively. Generally, n narrowband bandpass
filters are optionally used, where n is a positive integer of 2, 3,
4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 50 or more. Combined, signals
collected, preferably simultaneously, with the set of narrowband
bandpass filters allows coverage of large regions of the
near-infrared region where signal-to-noise ratios are significantly
enhanced for given subsets of the near-infrared spectral region
associated with each narrowband bandpass filter.
[0229] The narrowband filters are optionally used in combination
with an array of LEDs, where LED wavelength regions are optionally
radially configured relative to the associated filter in the filter
arrays as a function of water absorbance. For instance, a first LED
illuminating at a wavelength where water absorbance in skin is high
is positioned close to one or more filters passing light emitted by
the first LED, such as within about 0.2 to 0.75 millimeters.
Similarly, a second LED illuminating at a wavelength where water in
skin has medium absorbance is positioned at an intermediate
distance from the one or more filters passing light emitted by the
second LED, such as within about 0.5 and 1.5 millimeters.
Similarly, a third LED illuminating at a wavelength where water in
skin has low absorbance is positioned at a still further distance
from the one or more filters passing light emitted by the third
LED, such as within about 1.0 and 2.5 millimeters. Generally, the
distance between an LED and a filter configuration passing light of
the LED is a function of absorbance and/or scattering, such as
according to equation 2,
distance ~ 1 abs * 1 scattering ( eq . 2 ) ##EQU00001##
[0230] where a correlation with the function is at least 0.4, 0.5,
0.6, 0.7,0.8, or 0.9, where abs is absorbance of the sample at the
given wavelength, such as approximated by water absorbance at the
given wavelength, and scattering is the scattering coefficient
and/or relative scattering coefficient at the given wavelength
relative to neighboring wavelengths.
[0231] Referring now to FIG. 12 and referring again to FIG. 11B, a
step-function bandpass filters is described. In this example, a
first step-function bandpass filter 1140 is illustrated with a
large percent transmittance in the first overtone spectral region
960 and a lower transmittance, such as about 10, 20, 30, 40, or 50
percent transmittance, in the second overtone spectral regions 970.
A major benefit of the first step-function bandpass filter 1140 is
simultaneous collection of light from the first and second overtone
spectral regions 960, 970, where the lower transmittance of the
first overtone region 960, relative to the second overtone region
970, is compensated for by the greater transmittance in the first
overtone region 960, relative to the second overtone region 970, of
the first step-function bandpass filter and the difference in
detectivity, D*, between the two regions. As illustrated in FIG.
12, the first step-function bandpass filter is optionally a
combination of a shortpass and longpass filter, such as the second
shortpass filter 1014 and a fourth longpass filter 918, where the
fourth longpass filter 918 intentionally leaks light, such as less
than 30, 20, 10, or 5 percent, at wavelengths shorter than about
1450 nm. Generally, the step-function bandpass filter has any
transmittance profile. However, preferably, sections of 25, 50,
100, 200, or more nanometers of the step-function bandpass filter
are anti-correlated with water absorbance, scattering, or a
combination thereof, with a correlation coefficient of less than
about -0.9, -0.8, -0.7, or -0.6.
[0232] Referring now to FIGS. 13A, 13B, 14A, and 14B, narrowband
filters are illustrated relative to absorbance features of blood
and/or skin constituents. In FIG. 13A, a first analyte narrowband
bandpass filter is illustrated; overlaid with fat absorbance bands
in FIG. 13B. In FIG. 14A, a second analyte narrowband bandpass
filter is illustrated; overlaid with a glucose absorbance bands in
FIG. 14B. Generally, a set of n individual filters, where each
filter passes wavelengths dominated by a limited number of sample
constituents, are optionally used. Optionally and preferably the n
individual filters are associated with individual detectors or
groups of detectors of the two-dimensional detector array 134, as
described infra. Notably, since the analyte narrowband filters,
such as in FIGS. 13A, 13B, 14A, and 14B, occur at different
wavelengths where the total absorbance, dominated by water
absorbance and/or scattering, varies, preferably the detector array
uses different gain settings and/or integration times for different
detector elements, within the two-dimensional detector array 134,
associated with different optical filters.
[0233] Detector Array/Filter Array Combinations
[0234] Referring now to FIG. 15, a detector array/filter array
assembly 1500 is illustrated. For clarity of presentation and
without limitation, the detector array/filter array assembly 1500
is illustrated and described as a single unit. However, optionally,
the one or more two-dimensional filter arrays are optionally
proximate the two-dimensional detector array 134, such as within
less than 5, 2, 1, or 0.5 millimeters or are well removed from the
two-dimensional detector array 134, such as at any position in the
optical train between the source system 110 and the detector system
130. Further, for clarity of presentation and without limitation,
two two-dimensional filter arrays are described, which are
representative of 1, 2, 3, 4, 5, or more filter arrays. Still
further, the two-dimensional filter arrays presented are optionally
presented in reverse or any order in the optical train.
[0235] Still referring to FIG. 15, a first example of the detector
array/filter array assembly 1500 is described, which is a form of
the incident optic/two-dimensional array system 700. In this
example, the two-dimensional detector array 134 is combined with 1,
2, 3, 4 or more two-dimensional optical filter arrays, such as a
first optical filter array 1510 and a second optical filter array
1520. Several features of the detector array/filter array assembly
1500 are noted.
[0236] First, optionally individual detector elements, A, B, C,
optically align with individual filters of the first optical filter
array 1510, i, ii, iii, and/or optically align with individual
filters of the second optical filter array 1520, 1, 2, 3. Second,
optionally two or more detector elements, D, E, F, optically align
with a single filter element of the first optical filter array
1510, iv, which aligns with two or more elements of the second
optical filter array 1520, 4, 5. Third, optionally, a single
optical filter element of the first optical filter array 1510, iv,
optically aligns with two or more elements of the second optical
filter array 1520, 4, 5. Fourth, optionally, a single optical
filter element of the second optical filter array 1520, 5,
optically aligns with two or more elements of the first optical
filter array 1520, iv, vi. Fifth, optionally columns and or rows of
detector elements, (D, E, F), (F, I, L) align with a column optic,
iv, or row optic, 5, respectively. Fifth, a single two-dimensional
filter array, such as the first two-dimensional optical filter
array 1510, optionally contains 2, 3, 4, 5, 10, 20, 50, or more
filter types. Sixth, a single two-dimensional filter array, such as
the first two-dimensional optical filter array 1510, optionally
contains 2, 3, 4, 5, 10, 20, 50, or more filter shapes.
[0237] Referring now to FIG. 16, a multiple illumination
zone/multiple detection zone system 1600 is illustrated. For
example, an array of illumination points delivered from the photon
transport system 120 is illustrated launching photons out of the
page along the x-axis into the skin of the subject 170, not
illustrated. An array of detection zones are achieved, monitoring
photons moving into the page along the x-axis, using the
two-dimensional detector array 134 and as illustrated the optional
first optical filter array 1510. Similar to the systems described
supra when referring to FIG. 8B, the illustrated illumination array
optionally illuminates all illuminators; a single illuminator, such
as element A, B, or C; and/or subsets of illuminators, such as
elements A and B or A, B, and C. As described, supra, the
optionally varying position of illumination coupled with the
two-dimensional detector array 134 yields discrete pathlength and
depth of penetration information about the optically sampled skin
tissue of the subject 170 for each detector element of the
two-dimensional detector array 134. As illustrated, the first
two-dimensional optical filter array 1510 provides additional
insight as to the sampled skin by selectively filtering: (1)
regions, such as the combination band region 950, the first
overtone region 960, and/or the second overtone region 970; (2)
analytes, such as through use of the narrowband analyte filters;
and/or (3) based on intensity of the observed signal, such as
through narrowband filters designed for a narrow range of
absorbances of the sample tissue, where detector gain elements
and/or integration times are optionally individually configured for
each element or group of elements, such as along a column or row,
of the two-dimensional detector array 134.
[0238] Detector
[0239] Physical and tissue constraints limit a sample interface
size between the analyzer 100 and subject 170. As such, minimizing
use of non-optical parameters in the sample interface is
beneficial. In one embodiment, a readout element of a CCD array is
place on an outer perimeter of the sample interface area or outside
of the perimeter. If two or more detector arrays are used, the
readout elements of the detector arrays are optionally on opposite
sides of the sample interface or on adjacent sides of the sample
interface, such as at about ninety degrees from each other.
Similarly, if three of more detector arrays are utilized, the
readout positions of the multiple detector arrays optional
circumferentially surround the sample interface area. Further,
having multiple detector arrays allows a more rapid readout of the
data as the readouts are optionally at least partially in parallel.
Parallel readout of the gathered signal allows: (1) faster readout,
(2) timing of readout corresponding to an expected signal-to-noise
ratio, and/or (3) an ability to start calculations before all data
is received, such as initiation of a tissue-specific tissue map
and/or part of a rolling glucose concentration estimation. Still
further, columns/rows of a traditional CCD array are optionally
configured along arcs, chords, circles, and/or along an arc
allowing detector elements to be positioned in concentric rings or
other non-rectangular patterns. Still further, optionally the
individual rows, columns, and/or curved sets of detector elements
are optionally read out individually allowing an inner set,
relative to an illuminator, where absorbance is smallest to be read
out first and/or more often than outer detector sets, where larger
absorbance of tissue leads to longer sample integration times.
[0240] Multiple Two-Dimensional Detector Arrays
[0241] Referring now to FIG. 17, a multiple two-dimensional
detector array system 1700 is illustrated. As illustrated, the
photon transport system 120 delivers photons proximate a plurality
of two-dimensional detector arrays denoted here as a first detector
array 1702, a second detector array 1704, a third detector array
1706, and a fourth detector array 1708. Generally, any number of
two-dimensional detector arrays are optionally used, such as 2, 3,
4, 5, 10, 20, or more detector arrays. Configurations of the
detector arrays 1702, 1704, 1706, 1708 are described, infra.
[0242] Referring still to FIG. 17 and referring now to the first
detector array 1702, the first detector array is optionally
positioned with an edge of the first detector array 1702 proximate
an outer border or edge of an illumination point, zone, or array of
the photon transport system 120. In this example, first detector
array 1702 is optically and/or physically coupled to a series of
filters, such as: a first filter, 1, coupled to a first detector
element row; a second filter, 2, coupled to a second detector row;
a third filter, 3, coupled to a third detector row; a fourth
filter, 4, coupled to a fourth detector row; and a fifth filter, L,
coupled to a fifth detector row. Here the first, second, third,
fourth, and fifth filter, 1, 2, 3, 4, L, are optionally a
combination band filter, a first overtone filter, a first and
second overtone filter, a second overtone filter, and luminance
filter, respectively. Similarly, the first, second, third, fourth,
and fifth filter, 1, 2, 3, 4, L, are optionally an analyte
narrowband bandpass filter, a spectral region filter, a first
overtone filter, a second narrowband analyte filter, and luminance
filter, respectively. Generally, the individual filters are any
optical filter. The individual filters optionally cover a column,
row, geometric sector, and/or two-dimensional region of the
two-dimensional detector array 134. Optionally, physical edges of
the optical filters fall onto unused detector elements, such as a
column, row, or line of filter elements.
[0243] Referring still to FIG. 17 and referring now to the second
detector array 1704, additional detector/filter configurations are
described. First, the second detector array 1704 is optionally
positioned with a corner proximate the outer border or edge of an
illumination point, zone, or array of the photon transport system
120. Rotation of the second detector array 1704 relative to the
first detector array 1702 yields a second set of distinct
pathlengths and correlated depths of penetration compared to those
observed using the first detector array, as described supra.
Second, the same filter elements, as used on the first detector
array 1702, are optionally used on the second detector array 1704,
which reduces manufacturing costs and research and development time
understanding finer points, such as temperature stability of the
filters. However, the physical mounting configuration of the
filters are optionally different, which yields an additional set of
measures of state of the subject 170. For example, the first
filter, 1, as illustrated is positioned along two diagonals of the
second detector array 1704, which yields three optical
filter/detector combinations not observed with the first detector
array 1702 where the three new combinations relate to three
additional sampled pathlengths and depths of penetration of the
subject 170. Similarly, the second, third, fourth, and fifth
filters, 2, 3, 4, L, are positioned along diagonals across the
second detector array 1704 yielding, as illustrated, eighteen
additional measurements of the state of the subject 170. Further,
in this example, one set of detector elements are not associated
with a filter, which yields yet another set of measurements of the
state of the subject 170.
[0244] Referring still to FIG. 17 and referring now to the third
detector array 1706, additional detector/filter configurations are
described. First, the first, second, third, and fourth filters, 1,
2, 3, 4, are orientated in yet another set of configurations
relative to the photon transport system 120. Notably, in this
example, some of the source/detector element distances are
intentionally redundant yielding internal precision, outlier,
sample inhomogeneity checks, and/or sample interface 150 contact
checks. For example, three elements of the second and third
detector array 1704, 1706 have redundant positions of the first
filter, 1. In addition, one detector element of the third detector
array 1706 uses the first filter, 1, in a position not used with
the first or second detector arrays 1702, 1704 yielding yet another
measure of the state of the subject 170. Similarly, the second
filter, 2, is configured with both redundant positions, relative to
those used with the second detector array 1704, and with new
positions, relative to those used with the second detector array
1704. In this example, the third filter and fourth filter, 3, 4,
are configured at larger distances from a mean point of the
illumination zone relative to the filter positions configurations
of the second detector array 1704. In practice, some of the third
and fourth filter/detector positions are optimally probing the
glucose containing dermal region 174, while others will yield
information on the intervening and underlying epidermis and
subcutaneous fat regions, respectively. Generally, the range of
information gathered is used in post-processing to generate more
accurate and precise analyte concentration information, such as
through development and use of the same data used to form a person
specific tissue map.
[0245] Referring still to FIG. 17 and referring now to the fourth
detector array 1708, still additional detector/filter
configurations are described. In this example, still further
illumination zone to detection zone distances are illustrated for
the first, second, and third filters, 1, 2, 3. As illustrated, the
second and third filters, 2, 3, such as a first overtone and a
second overtone filter, extend to still greater radial distances
from the illumination zone yielding still yet another set of
measures of the state of the subject 170. Further, in this example,
the fourth detector array 1708 is rotated to a non-symmetric
orientation relative to the illumination zone, which yields an
entirely new set of pathlengths and depths of penetration, as
described supra.
[0246] Referring still to FIG. 17, for clarity of presentation and
without limitation a particular filter/detector combination of the
first filter, 1, is described. Here the first filter, 1, is a
combination band filter used for short distances between the
illumination zone and detection zone. As described supra in the
description of the first, second, third, and fourth detector arrays
1702, 1704, 1706, 1708 multiple short distances between the
illumination zone and detection zone are probed, some of which will
optimally probe the glucose containing dermal layer 174 of the
subject 170, some of which will primarily probe the epidermis 173
of the subject 170, and some of which probe into the subcutaneous
fat layer 176 of the subject 170. The availability of multiple
measures of the state of the subject allows post-processing to
derive information about the tissue layer thicknesses, tissue
homogeneity, probed pathlengths, probed tissue depth, and/or
analyte concentration of the subject 170 with optional use of
redundant information, exclusion of outlier information, exclusion
of non-optimally sampled tissue, and/or inclusion of optimally
measured tissue. Similarly, use of the second, third, fourth, and
fifth filter, 2, 3, 4, L, along with use of no filter at a variety
of intelligently selected radial distances from the illumination
zone based on scattering and absorbance properties of the tissue of
the subject 170 yield additional complementary and optionally
simultaneous information on the state of the subject 170.
[0247] Referring still to FIG. 17, for clarity and without loss of
generalization another example of the photon transport system 120
delivering light to the skin of the subject 170 at multiple
illumination positions relative to two or more detector arrays is
provided. In this example, the first detector array 1702 is
illustrated with a plurality of filters along rows of detector
elements. For example, a first filter, illustrated as filter 1, is
optionally a combination band filter; a second filter, illustrated
as filter 2, is optionally a first overtone filter; a third filter,
illustrated as filter 3, is optionally a first and second overtone
filter; a fourth filter, illustrated as filter 4, is optionally a
second overtone filter; and a fifth filter, illustrated as filter
L, is optionally a luminance filter/intensity filter. The inventor
notes that the filters are arranged in readily manufactured rows,
provide a spread of radial distances within a row, and fall in an
order of wavelength inversely correlating with mean pathlength as a
function of radial distance from the illuminator. Referring now to
the second detector array 1704, the third detector array 1706, and
the fourth detector array 1708 positioned about the illumination
zone from the photon transport system 120, the inventor notes that
the same five filters positioned in different configurations and/or
orders as a function of radial distance from the illumination zone
and/or as a function of rotation angle of the detector array yield
a plurality of additional pathlengths. For brevity and clarity of
presentation, only the first filter, filter 1, is addressed. In the
first detector array 1702, the first filter represents three
distinct mean pathlengths from a mean illumination zone using the
1.sup.st and 5.sup.th detector elements, the 2.sup.nd and 4.sup.th
detector elements, and the 3.sup.rd detector element. Similarly,
the second detector array filter 1704 monitors two additional mean
pathlengths from the mean illumination zone using the first filter
and individual detector elements. The third detector array 1706
could measure the same mean pathlengths as the second detector
array 1704; however, preferably the third detector array 1706
measures still two more mean pathlengths using two pairs of
detector elements with differing distances from the mean
illumination zone. Similarly, the fourth detector array 1708
optionally measures a number of yet still further distinct mean
pathlengths, such as by binning all six detector elements, or by
binning rows of detector elements. Thus, at a first point in time,
the four detector arrays 1702, 1704, 1706, 1708 optionally monitor
at least eight mean pathlengths using only the first filter. At a
second point in time, an additional distinct eight pathlengths are
optionally monitored by illuminating a second pattern of the
illustrated illumination points. The inventor notes that even
illuminating all of the illumination points or only the first and
second rings of illumination points, despite having the same mean
point of illumination, will yield eight additional mean pathlengths
in the tissue due to tissue inhomogeneity. Clearly, simultaneous
use of the other four filters allows for simultaneous collections
of spectra having at least forty pathlengths (8.times.5). Further,
filter 1, is optionally different, in terms of a filter parameter
such as a cut-on wavelength or a cut-off wavelength, for each
detector array 1702, 1704, 1706, 1708 without complicating
manufacturing, which yields still additional simultaneously probed
optical tissue pathlengths. Generally, any number or detector
elements, any number of detector arrays, any number of filters,
and/or any geometry of filter layout are optionally used to obtain
a desired number of simultaneously probed sample pathlengths.
Optionally, signal from groups of common detector elements are
binned to enhance a given signal-to-noise ratio.
[0248] Further, the two-dimensional detector arrays described
herein optionally contain 1, 2, 3, or more detector materials 134
and/or types. For example, a single two-dimensional detector array
134 optionally contains 1.7, 1.9, 2.2, and/or 2.6 .mu.m
indium/gallium/arsenide detectors. For example, the 2.6 micrometer
indium/gallium/arsenide detector is optionally optically coupled
with longpass, shortpass and/or bandpass filters for the
combination band 950 spectral region and/or the 1.7, 1.9, 2.2 .mu.m
indium/gallium/arsenide detectors are optionally coupled with
longpass, shortpass, and/or bandpass filters for the first overtone
region 960. Optionally and preferably, different detector types are
joined along a joint and/or a seal, where the seal optionally
corresponds with a joint or seal between two filter types or simply
a set, such as a column, of unused detector elements.
[0249] Referring now to FIG. 18A, a multiple detector array system
1800 is described, which is a further example of a multiple
two-dimensional detector array system. In this example, multiple
detector types are optionally used, as described infra. Further, in
this example, multiple detector sizes are optionally used, as
described infra.
[0250] Referring still to FIG. 18A, additional examples of
two-dimensional detector/filter arrays are provided. Referring now
to the first detector array 1702 and the second detector array
1704, the second detector array 1704 relative to the first detector
array illustrates: [0251] that two detector arrays optionally vary
in length and/or width by at least 5, 10, or 20 percent, which
results in an ability to miniaturize a sample probe head and/or to
enhance collection efficiency of delivered photons by increasing
overall skin surface coverage by the detectors; and [0252] that the
row and/or columns of detector elements optionally have different
single element sizes, which allows control over range of
pathlengths monitored with a given detector element.
[0253] Referring now to the third detector array 1706, the
two-dimensional detector array 134 optionally contains sensors
and/or optics to measure a range of parameters, such as a local
tissue temperature, T.sub.1, a local tissue pressure, P.sub.1,
and/or a local illumination, I.sub.1. Referring now to the fourth
detector array 1708, the two-dimensional detector array 134 is
optionally designed to be read out in columns or sideways as rows,
which allows each row to have a different detector element size.
Increasing the detector element size as a function of radial
distance away from an illuminator allows an enhanced/tuned
signal-to-noise ratio as the detector aperture is larger as the
number of photons exiting the skin with increased radial distance
decreases. The larger aperture sizes of the detectors enhances
signal-to-noise ratios as baseline noise remains constant and
thermal noise increases at a smaller, less than linear, rate
compared to the linear increase in signal with increased
integration time. Referring now to the first through fourth
detector arrays 1702, 1704, 1706, 1708, an optional range of
illuminator/detector gaps are illustrated 121, 123, 125, 127 for
the first through fourth detector arrays 1702, 1704, 1706, 1708,
respectively.
[0254] Referring now to FIG. 18B, yet another example of a multiple
two-dimensional detector/filter array system is provided. In this
example, a first detector array 1702 is configured with zones of
regularly shaped filters over multiple individual detector element
sizes. For example, the first filter, 1, such as a first overtone
filter, covers two rows of detector elements, which aids in filter
costs, alignment, masks, and/or installation. The first row of
detector elements comprises smaller dimensions than the second row
of detector elements, which enhances signal-to-noise ratios in each
row as the time to fill detector wells in the first row of detector
elements is less than the time to fill detector wells in the second
row of detector elements due to the light transport/scattering
properties in the 1450 to 1900 nm spectral region. The larger
aperture of the second row detector elements gathers more light as
a function of time compared to the first row detector elements as
an area of a detector element in the second row is at least 2, 3,
4, 5, 6, 7, 8, 9, or 10 times larger than an area of a detector
element in the first row. Similarly, the third and fourth rows of
detector elements are optionally associated with the second optic,
2, such as the first overtone/second overtone band filter. The
third row of detector elements are larger than the first row of
detector elements due to fewer photons from an illumination zone
exiting the skin at greater distances from the illumination zone
and smaller than the second row of detector elements due to the
enlarged spectral bandwidth of the first overtone/second overtone
band filter. The fifth row of detector elements optionally uses a
third, 3, filter, such as a second overtone filter. Generally, the
area of detector elements is preferably manufactured to inversely
match light density exiting the skin of the subject 170 in each
optically filtered wavelength range. Here, the first detector array
1702 in this example is designed to optionally readout in rows,
which allows different rows to comprise different sizes of detector
elements. Optionally, filters at one or more detector elements
positions are matched to wavelengths of an LED of a set of
LEDs.
[0255] Referring still to FIG. 18B, a second detector array 1704 is
presented in a rotated configuration about the x-axis relative to
the first detector array 1702. The rotation of the second detector
array 1704 yields a continuum of pathlength ranges for a row of
detectors. For example, in the first detector array 1702, the first
row of detectors monitor four average pathlengths of illuminated
tissue due to C2 symmetry of the detector elements in the first
row, where for example the inner two detector elements observe a
single first mean pathlength and the outer two detector elements
observe a single second mean pathlength. However, in stark
contrast, the first row of detector elements in the second
detector/filter array 1704 monitor eight different mean optical
pathlengths of light delivered by the photon transport system 120.
Similarly, each row of detector elements in the second detector
array 1704 observe, simultaneously, more mean pathlengths of
photons from the photon transport system 120 compared to a
corresponding row of detector elements in the first detector array
1702 due to the rotation of the second detector array in the
y,z-plane relative to a line from a center of the second detector
array to a center of the illumination zone.
[0256] Detector Array/Guiding Optical Array Combinations
[0257] Referring now to FIG. 19A and FIG. 19B, a two-dimensional
detector array/guiding optic array assembly 1900 is illustrated
proximate output of the photon transport system 120, illustrated as
an array of incident light optics proximate skin tissue, where the
skin is not illustrated. For clarity of presentation and without
limitation, the detector array/guiding optic array assembly 1900 is
illustrated and described as a single assembled detector/optic unit
1930. However, optionally, the two-dimensional guiding optic array
1920 is optionally proximate the two-dimensional detector array
134, such as within less than 20, 10, 5, 2, 1, or 0.5 millimeters
or is well removed from the two-dimensional detector array 134,
such as at any position in the optical train between the skin of
the subject 170 and the detector system 130. Further, the
two-dimensional guiding optic arrays is optionally on either
optical train side of one or more of the optional two-dimensional
filter arrays.
[0258] Still referring to FIGS. 19A and FIG. 19B, varying optional
detector shape/optical filter combinations are described.
[0259] In a first case, two or more detector elements of the
two-dimensional detector array 134 are optically coupled with a
single optic. For example, the first column of detectors in the
two-dimensional detector array 134 are coupled with a single optic,
O.sub.1. The single optic, O.sub.1, is optionally a pathlength
extending optic, which redirects light to include a vector
component back toward the illumination zone resulting in a longer
mean pathlength and/or depth of penetration. The pathlength
extending optic is optionally and preferably used close to the
illumination zone, in this case to the left of the
two-dimensional/guiding optic array assembly 1900, to yield
additional photons in sampling the dermis region and fewer photons
sampling solely the epidermis region, as described supra in
relation to FIG. 7A. The extending optic is particularly useful
with a combination band source/combination band filter/detector
combination.
[0260] In a second case, 1, 2, 3, 4, or more individual detector
elements of the two-dimensional detector array 134 are optionally
each optically coupled with discrete individual optics of the
two-dimensional optic array 1920. For example, as illustrated, the
second column of detectors comprise combination band detectors,
C.sub.2(a-f), each coupled with standard focusing optics and/or
optics redirecting light to comprise a vector back toward the mean
radial axis of detected incident photons, C.sub.2b,2e. Optionally,
the further from the mean radial axis of the detected incident
photons, the greater the magnitude of the induced vector component
redirecting photons back toward the mean radial axis,
C.sub.2a,2f.
[0261] In a third case, light gathering areas of individual optics
in the two-dimensional optic array 1920 are optionally larger with
increasing distance from an illumination zone proximate incident
light entering skin of the subject 170 from the photon transport
system 120. For example a sixth optic, O.sub.6, optionally has a
larger surface area along the y/z-plane compared to a fourth optic,
O.sub.4, which has a larger area than a third optic, O.sub.3, which
has a larger area than a second optic, O.sub.2a. For a noninvasive
near-infrared spectral measurement, the generally, but not
absolutely, larger collection areas as a function of radial
distance from the illumination zone aid signal-to-noise ratios due
to fewer photons reaching the larger radial distances. The optic
size matched to spectral region is further described, infra.
[0262] In a fourth case, light gathering areas along the y/z-plane
are chosen to enhance signal-to-noise ratios for varying spectral
regions, such as the combination band region 950, the first
overtone region 960, the second overtone region 970, and/or one or
more narrowband analyte specific regions. For example, observed
light intensity generally decreases with increased radial distance
from an illumination zone in the spectral region of 1100 to 2500
nm. Further, the radial distance needed to obtain quality/high
signal-to-noise ratio spectra using dermal layer probing photons
generally varies with radial distance from the illumination zone.
The inventor has determined that a series of detector types,
optical filters, and/or light gathering areas are preferentially
used, such as: a combination band region detector, C.sub.2a, at
close radial distance to the source with a first optic collection
area, O.sub.2a; a first overtone detector, 1, at an intermediate
radial distance to the source with a second optic collection area,
O.sub.3; a first and second overtone detector, 1 and 2, at a still
further radial distance from the illumination zone with a third
collection optic area, O.sub.4; and/or a second overtone detector,
2, at a yet still further radial distance from the illumination
zone with a fourth optic collection area, O.sub.6.
[0263] In a fifth case, the two-dimensional detector area 134
contains a greater or first number of detector elements in a given
area at a first radial distance from the illumination zone and a
lesser or second number of detector elements in a second equally
sized area at a second greater radial distance from the
illumination zone. For example, the first number of detector
elements is optionally 10, 20, 30, 40, 50, 100, 150, 200, or more
percent larger than the second number of detector elements.
[0264] In a sixth case, more than one optic size, in the y/z-plane
is used for a single column or row of detector elements of the
two-dimensional detector array 134, such as the fourth and fifth
optic, O.sub.4 and O.sub.5, associated with the fourth detector
column in the provided example.
[0265] In a seventh case, one or more filters are optically coupled
to one or more corresponding elements of the two-dimensional
detector array 132 and/or to one or more corresponding elements of
the two-dimensional optic array 1920.
[0266] In an eighth case, one or more detector elements of the
two-dimensional detector array are optically coupled to one or more
luminance filters.
[0267] Two-Dimensional Detector/Optical Filter/Guiding Optic
Combinations
[0268] Referring now to FIGS. 20(A&B) and FIGS. 21(A&B),
various exemplary combinations of the two-dimensional detector
array 134/the two-dimensional filter array 1510/two-dimensional
optic array 1920 are provided. Herein, examples are provided for
clarity of presentation and without limitation. Generally, the
examples represent any combination and/or permutation of the
two-dimensional detector array 134, the two-dimensional filter
array 1510, and/or the two-dimensional optic array 1920. Further,
for clarity of presentation and without limitation, the
two-dimensional filter array 1510 is depicted as two optional
arrays, a two-dimensional longpass filter array 1512 and a
two-dimensional shortpass filter array 1514. Still further, the
two-dimensional detector array 134, the two-dimensional longpass
filter array 1512, the two-dimensional shortpass filter array 1514,
and the two-dimensional optic array 1920 are optionally
individually spaced from one another, are optionally contacting
each other as in a detector/filter/optic assembly 2050, and/or have
gaps between one or more of the individual two-dimensional
arrays.
[0269] Referring now to FIG. 20A and FIG. 20B, a first example of a
two-dimensional detector/filter/optic system 2000 is described. In
this first example, the two-dimensional detector array 134 contains
a plurality of detectors in any geometric pattern, of one or more
sizes. Further, the optional two-dimensional filter array 1510 is
depicted as layers of longpass filter elements and/or shortpass
filter elements, such as the two-dimensional longpass filter array
1512 and/or the two-dimensional shortpass filter array 1514. The
two-dimensional longpass filter array 1512 is optionally 1, 2, 3,
or more filter types, LP.sub.1, LP.sub.2, LP.sub.3. Similarly, the
two-dimensional shortpass filter array 1514 is optionally 1, 2, 3,
or more filter types, SP.sub.1, SP.sub.2, SP.sub.3. Optionally,
elements of the two-dimensional shortpass filter array 1514 are
present in the two-dimensional longpass filter array 1512 and
vise-versa. Still further, the optional two-dimensional optic layer
1920 contains 1, 2, 3, or more optic sizes and/or types, O.sub.1,
O.sub.2, O.sub.3. Optionally, one or more of the longpass and/or
shortpass filters overlap one or more detectors or optics of the
two-dimensional detector array 132 and two-dimensional optic array
1920, respectively. Optionally, one or more edges of a longpass
filter element of the two-dimensional longpass filter array 1512 do
not align with one or more edges of a shortpass filter of the
two-dimensional shortpass filter array 1514 or vise-versa.
Generally, multiple configurations of the two-dimensional
detector/filter/optic system 2000 are useful in a noninvasive
analyte concentration determination, such as a noninvasive spectral
determination of glucose concentration. One exemplary configuration
is provided, infra.
[0270] Referring now to FIG. 21A and FIG. 21B, a second example of
the two-dimensional detector/filter/optic system 2000 is described.
In this second example, for clarity of presentation particular
detector types, filter parameters, spectral regions, and/or optics
are described that are representative of many possible detector,
filter, and/or optical configurations. In this second example,
filters and optics for varying spectral regions are provided in
Table 1.
TABLE-US-00001 TABLE 1 Simultaneous Multiple Region Analysis Long-
Short- pass pass Detector Filter Filter Detector(s) Type* (.mu.m)
(.mu.m) Optic Region 1-6 2.5 1.9 2.5 Pathlength Combination
Extending Band 7-12 2.5 1.9 2.5 Standard Combination Band 13-15 2.5
1.9 2.5 Focusing Combination Band 16 2.5 1.4 2.5 Focusing
Combination Band and 1.sup.st Overtone 17 1.9 1.4 1.9 Focusing
1.sup.st Overtone 18 1.9 1.0 1.9 Focusing 1.sup.st and 2.sup.nd
Overtone 19 2.5 1.0 2.5 Pathlength Broadband Reducing 20 1.9 1.0
1.9 Pathlength 1.sup.st and 2.sup.nd Reducing Overtone 21 1.7 1.0
1.4 Pathlength 2.sup.nd Overtone Reducing *non-limiting examples of
InGaAs detector cut-off wavelengths
[0271] From Table 1, it is observed that optionally multiple
spectral regions are simultaneously observed with a single
two-dimensional detector array. It is further noted that observed
mean sampled pathlengths and observed mean sampled depths of
penetration correspond with filter types changing as a function of
relative radial distance from an illumination zone; the
illumination zone to the left of the illustrated two-dimensional
detector and associated optics. Still further, if additional
emphasis is desired for a particular spectral region, more
detectors are simply used with the appropriate filter combination.
For example, if more first overtone spectra are desired, the area
of optics associated with detector 17 is optionally expanded along
the y-axis for similar pathlengths and/or along the z-axis for
longer and/or shorter mean pathlengths.
[0272] Multiple combinations of filter types and/or optic types are
optionally used in the noninvasive analyte spectral determination
process. Table 2 shows an exemplary configuration for a noninvasive
analysis performed using the first overtone 960 and second overtone
970 spectral regions. From Table 2, it is again observed that,
optionally, multiple spectral regions are simultaneously observed
with a single two-dimensional detector array optically coupled to
an array of filter types and/or an array of light directing
optics.
TABLE-US-00002 TABLE 2 Simultaneous Multiple Region Analysis Long-
Short- pass pass Detector Filter Filter Column (.mu.m) (.mu.m)
Optic Region 1 1.4 1.9 Pathlength First Overtone Extending 2 1.6
1.4 Standard Analyte Band 3 1.4 1.9 Focusing First Overtone 4 1.6
1.4 Focusing Analyte Band 5 1.1 1.9 Standard 1.sup.st and 2.sup.nd
Overtone 6 1.1 1.9 Focusing 1.sup.st and 2.sup.nd Overtone 7 1.0
1.7 Focusing Extended 2.sup.nd Overtone 8 1.0 1.4 Focusing 2.sup.nd
Overtone 9 1.0 1.4 Pathlength 2.sup.nd Overtone Reducing
[0273] Temporal Resolution
[0274] The second method of temporal resolution is optionally
performed in a number of manners. For clarity of presentation and
without limitation, a temporal resolution example is provided where
photons are timed using a gating system and the elapsed time is
used to determine photon paths in tissue.
[0275] Referring now to FIGS. 22(A-D), an example of a temporally
resolved gating system 2200 is illustrated. Generally, in the
temporal gating system 2200 the time of flight of a photon is used
to determine the pathlength, b. Referring now to FIG. 22A, at an
initial time, t.sub.0, an interrogation pulse 2210 of one or more
photons is introduced to the sample, which herein is skin of the
subject 170. The interrogation pulse 2210 is also referred to as a
pump pulse or as a flash of light. At one or more subsequent gated
detection times 2220, after passing through the sample the
interrogation pulse 2210 is detected. As illustrated, the gated
detection times are at a first time 2222, t.sub.1; a second time
2224, t.sub.2; a third time 2226, t.sub.3; and at an n.sup.th time
2228, t.sub.n, where n is a positive number. Optionally, the gated
detection times 2220 overlap. For the near-infrared spectral
region, the elapsed time used to detect the interrogation photons
2210 is on the order of picoseconds, such as less than about 100,
10, or 1 picosecond. The physical pathlength, b, is determined
using equation 2:
OPD = c n ( b ) ( eq . 2 ) ##EQU00002##
[0276] where OPD is the optical path distance, c is the speed of
light, n is the index of refraction of the sample, and b is the
physical pathlength. Optionally, n is a mathematical representation
of a series of indices of refraction of various constituents of
skin and/or skin and surrounding tissue layers. More generally,
observed pathlength is related to elapsed time between photon
launch and photon detection where the pathlength of photons in the
sample is related to elapsed time, optionally with one or more
additional variables related to one or more refractive indices.
[0277] Referring now to FIG. 22B, illustrative paths of the photons
for the first gated detection time 2222 are provided. A first path,
p.sub.1a; second path, p.sub.1b; and third path, p.sub.1c, of
photons in the tissue are illustrated. In each case, the total
pathlength, for a constant index of refraction, is the same for
each path. However, the probability of each path also depends on
the anisotropy of the tissue and the variable indices of refraction
of traversed tissue voxels.
[0278] Referring now to FIG. 22C, illustrative paths of the photons
for the second gated detection time 2224 are provided. A first
path, p.sub.2a; second path, p.sub.2b; and third path, p.sub.2c, of
photons in the tissue are illustrated. Again, in each case the
total pathlength for the second elapsed time, t.sub.2, is the same
for each path. Generally, if the delay to the second gated
detection time 2224 is twice as long as the first gated detection
time 2222, then the second pathlength, p.sub.2, for the second
gated detection time 2224 is twice as long as the first pathlength,
p.sub.1, for the first gated detection time 2222. Knowledge of
anisotropy is optionally used to decrease the probability spread of
paths observed in the second set of pathlengths, p.sub.2a,
p.sub.2b, p.sub.2c. Similarly a-priori knowledge of approximate
physiological thickness of varying tissue layers, such as an
epidermal thickness of a patient, an average epidermal thickness of
a population, a dermal thickness of a patient, and/or an average
dermal thickness of a population is optionally used to reduce error
in an estimation of pathlength, a product of pathlength and a molar
absorptivity, and/or a glucose concentration by limiting bounds of
probability of a photon traversing different pathways through the
skin layers and still returning to the detection element with the
elapsed time. Similarly, knowledge of an index of refraction of one
or more sample constituents and/or a mathematical representation of
probable indices of refraction is also optionally used to reduce
error in estimation of a pathlength, molar absorptivity, and/or an
analyte property concentration estimation. Still further, knowledge
of an incident point or region of light entering she skin of the
subject relative to a detection zone is optionally used to further
determine probability of a photon traversing dermal or subcutaneous
fat layers along with bounding errors of pathlength in each
layer.
[0279] Referring now to FIG. 22D, mean pathlengths and trajectories
are illustrated for three elapsed times, t.sub.1, t.sub.2, t.sub.3.
As with the spatially resolved method, generally, for photons in
the near-infrared region from 1100 to 2500 nanometers, both a mean
depth of penetration of the photons, d.sub.n; the total radial
distance traveled, r.sub.m; and the total optical pathlength
increases with increasing time, where the fiber optic-to-detector
distance is less than about three millimeters. Preferably, elapsed
times between a pulse of incident photon delivery and time gated
detection are in a range between 100 nanoseconds and 100
picoseconds, such as about 1, 5, 10, and 50 picoseconds.
[0280] Spatial and Temporal Resolution
[0281] Hence, both the spatial resolution method and temporal
resolution method yield information on pathlength, b, which is
optionally used by the data processing system 140 to reduce error
in the determined concentration, C.
[0282] Analyzer and Subject Variation
[0283] As described, supra, Beer's Law states that absorbance, A,
is proportional to pathlength, b, times concentration, C. More
precisely, Beer's Law includes a molar absorbance, E, term, as
shown in equation 3:
A=.epsilon.bC (eq. 3)
[0284] Typically, spectroscopists consider the molar absorbance as
a constant due to the difficulties in determination of the molar
absorbance for a complex sample, such as skin of the subject 170.
However, information related to the combined molar absorbance and
pathlength product for skin tissue of individuals is optionally
determined using one or both of the spatially resolved method and
time resolved method, described supra. In the field of noninvasive
glucose concentration determination, the product of molar
absorbance and pathlength relates at least to the dermal thickness
of the particular individual or subject 170 being analyzed.
Examples of spatially resolved analyzer methods used to provide
information on the molar absorbance and/or pathlength usable in
reduction of analyte property estimation and/or uncertainty
determination are provided infra.
[0285] Spatially Resolved Analyzer
[0286] Herein, an analyzer 100 using fiber optics is used to
describe obtaining spatially resolved information, such as
pathlength and/or molar absorbance, of skin of an individual, which
is subsequently used by the data processing system 140. The use of
fiber optics in the examples is used without limitation, without
loss of generality, and for clarity of presentation. More
generally, photons are delivered in quantities of one or more
through free space, through optics, and/or off of reflectors to the
skin of the subject 170 as a function of distance from a detection
zone.
[0287] Referring again to FIG. 1 and referring now to FIG. 23A, an
example of a fiber optic interface system 2300 of the analyzer 100
to the subject 170 is provided, which is an example of the sample
interface system 150. Light from the source system 110 of the
analyzer 100 is coupled into a fiber optic illumination bundle 2314
of a fiber optic bundle 2310. The fiber optic illumination bundle
2314 guides light to a sample site 178 of the subject 170. The
sample site 178 has a surface area and a sample volume. In a first
case, a sample interface tip 2316 of the fiber optic bundle 2310
contacts the subject 170 at the sample site 178. In a second case,
the sample interface tip 2316 of the fiber optic bundle 2310
proximately contacts the subject 170 at the sample site 178, but
leaves a sample interface gap 2320 between the sample interface tip
2316 of the fiber optic bundle 2310 and the subject 170. In one
instance, the sample interface gap 2320 is filled with a contact
fluid and/or an optical contact fluid. In a second instance, the
sample interface gap 2320 is filled with air, such as atmospheric
air. Light transported by the fiber optic bundle 2310 to the
subject 170 interacts with tissue of the subject 170 at the sample
site 178. A portion of the light interacting with the sample site
is collected with one or more fiber optic collection fibers 2318,
which is optionally and preferably integrated into the fiber optic
bundle 2310. As illustrated, a single collection fiber 2318 is
used. The collection fiber 2318 transports collected light to the
detector 132 of the detection system 130.
[0288] Referring now to FIG. 23B, a first example of a sample side
light collection end 2316 of the fiber optic bundle 2310 is
illustrated. In this example, the single collection fiber 2318 is
circumferentially surrounded by an optional spacer 2330, where the
spacer has an average radial width of less than about 200, 150,
100, 50, or 25 micrometers. The optional spacer 2330 is
circumferentially surrounded by a set of fiber optic elements 2313.
As illustrated, the set of fiber optic elements 2313 are arranged
into a set of radial dispersed fiber optic rings, such as a first
ring 2341, a second ring 2342, a third ring 2343, a fourth ring
2344, and an n.sup.th ring 2345, where n comprises a positive
integer of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10. Optionally, the
fiber optic elements 2313 are in any configuration, such as in a
close-packed configuration about the collection fiber 2318 or in an
about close-packed configuration about the collection fiber 2318.
The distance of each individual fiber optic of the set of fiber
optic elements 2313, or light collection element, from the center
of the collection fiber 2318 is preferably known.
[0289] Referring now to FIG. 23C, a second example of the sample
side light collection end 2316 of the fiber optic bundle 2310 is
provided. In this example, the centrally positioned collection
fiber 2318 is circumferentially surrounded by a set of spacer
fibers 2350. The spacer fibers combine to cover a radial distance
from the outside of the collection fiber of less than about 300,
200, 150, 100, 75, 60, 50, or 40 micrometers. The spacer fibers
2350 are circumferentially surrounded by the radially dispersed
fiber optic rings, such as the first ring 2341, the second ring
2342, the third ring 2343, the fourth ring 2344, and the n.sup.th
ring 2345. Optionally, fiber diameters of the spacer fibers 2350
are at least ten, twenty, or thirty percent larger or smaller than
fiber diameters of the set of fiber optic elements 2313. Further,
optionally the fiber optic elements 2313 are arranged in any
spatial configuration radially outward from the spacer fibers 2350.
More generally, the set of fiber optic elements 2313 and/or spacer
fibers 2350 optionally contain two, three, four, or more fiber
optic diameters, such as any of about 40, 50, 60, 80, 100, 150,
200, or more micrometers. Optionally, smaller diameter fiber
optics, or light collection optics, are positioned closer to any
detection fiber and progressively larger diameter fiber optics are
positioned, relative to the smaller diameter fiber optics, further
from the detection fiber.
[0290] Radial Distribution System
[0291] Referring now to FIG. 24A, FIG. 24B, FIG. 25, and FIGS. 26
A-D a system for spatial illumination 2400 of the sample site 178
of the subject 170 is provided. The spatial illumination system
2400 is used to control distances between illumination zones and
detection zones as a function of time. In a first case, light is
distributed radially relative to a detection zone using a fiber
optic bundle. In a second case, light is distributed radially
relative to a detection zone using a reflective optic system and/or
a lens system. Generally, the first case and second case are
non-limiting examples of radial distribution of light about one or
more detection zones as a function of time.
[0292] Radial Position Using Fiber Optics
[0293] Referring now to FIG. 24A, a third example of the sample
side light collection end 2316 of the fiber optic bundle 2310 is
provided. In this example, the collection fiber 2318 or collection
optic is circumferentially surrounded by the set of fiber optic
elements 2313 or irradiation points on the skin of the subject 170.
For clarity of presentation and without loss of generality, the
fiber optic elements 2313 are depicted in a set of rings radially
distributed from the collection fiber 2318. However, it is
understood that the set of fiber optics 2313 are optionally close
packed, arranged in a random configuration, or arranged according
to any criterion. Notably, the distance of each fiber optic element
of the set of fiber optic elements 2313 from the collection fiber
2318 is optionally determined using standard measurement techniques
through use of an algorithm and/or through use of a dynamically
adjustable optic used to deliver light to the sample, such as
through air. Hence, the radial distribution approach, described
infra, is optionally used for individual fiber optic elements
and/or groups of fiber optic elements arranged in any
configuration. More generally, the radial distribution approach,
described infra, is optionally used for any set of illumination
zone/detection zone distances using any form of illuminator and any
form of detection system, such as through use of the spatially
resolved system and/or the time resolved system.
[0294] Referring now to FIG. 24B, an example of a light input end
2312 of the fiber optic bundle 2310 is provided. In this example,
individual fibers of the set of fiber optics 2313 having the same
or closely spaced radial distances from the collection fiber 2318
are grouped into a set of fiber optic bundles or a set of fiber
optic bundlets 2410. As illustrated, the seven fibers in the first
ring circumferentially surrounding the collection fiber 2318 are
grouped into a first bundlet 2411. Similarly, the sixteen fibers in
the second ring circumferentially surrounding the collection fiber
2318 are grouped into a second bundlet 2412. Similarly, the fibers
from the third, fourth, fifth, and sixth rings about the collection
fiber 2318 at the sample side illumination end 2316 of the fiber
bundle 2310 are grouped into a third bundlet 2413, a fourth bundlet
2414, a fifth bundlet 2415, and a sixth bundlet 2416, respectively.
For clarity of presentation, the individual fibers are not
illustrated in the second, third, fourth, fifth, and sixth bundlets
2412, 2413, 2414, 2415, 2416. Individual bundles and/or individual
fibers of the set of fiber optic bundlets 2410 are optionally
selectively illuminated using a mask 2420, described infra.
[0295] Referring now to FIG. 25 and FIG. 23A, a mask wheel 2430 is
illustrated. Generally, the mask wheel 2430 rotates, such as
through use of a wheel motor 2420. As a function of mask wheel
rotation position, holes or apertures through the mask wheel 2430
selectively pass light from the source system 110 to the fiber
optic input end 2312 of the fiber optic bundle 2310. In practice,
the apertures through the mask wheel are precisely located to align
with (1) individual fiber optic elements of the set of fiber optics
at the input end 2312 of the fiber optic bundle or (2) individual
bundlets of the set of fiber optic bundlets 2410. Optionally an
encoder or marker section 2440 of the mask wheel 2430 is used for
tracking, determining, and/or validating wheel position in use.
[0296] Still referring to FIG. 25, an example of use of the mask
wheel 2430 to selectively illuminate individual bundlets of the set
of fiber optic bundlets 2410 is provided. Herein, for clarity of
presentation the individual bundlets are each presented as uniform
size, are exaggerated in size, and are repositioned on the wheel.
For example, as illustrated a first mask position, p.sub.1, 2421 is
illustrated at about the seven o'clock position. The first mask
position 2421 figuratively illustrates an aperture passing light
from the source system 110 to the first bundlet 2411 while blocking
light to the second through sixth bundlets 2412-2416. At a second
point in time, the mask wheel 2430 is rotated such that a second
mask position, p.sub.2, 2422 is aligned with the input end 2312 of
the fiber optic bundle 2310. As illustrated, at the second point in
time, the mask wheel 2430 passes light from the illumination system
110 to the second bundlet 2412, while blocking light to the first
bundlet 2411 and blocking light to the third through six bundlets
2413-2416. Similarly, at a third point in time the mask wheel uses
a third mask position, p.sub.3, 2423 to selectively pass light into
only the fifth bundlet 2415. Similarly, at a fourth point in time
the mask wheel uses a fourth mask position, p.sub.4, 2424 to
selectively pass light into only the sixth bundlet 2416.
[0297] Still referring to FIG. 25, thus far the immediately prior
example has only shown individual illuminated bundlets as a
function of time. However, combinations of bundlets are optionally
illuminated as a function of time. In this continuing example, at a
fifth point in time, the mask wheel 2430 is rotated such that a
fifth mask position, p.sub.5, 2425 is aligned with the input end
2312 of the fiber optic bundle 2310. As illustrated, at the fifth
point in time, the mask wheel 1130 passes light from the
illumination system 110 to all of (1) the second bundlet 2412, (2)
the third bundlet 2413, and (3) the fourth bundlet 2414, while
blocking light to all of (1) the first bundlet 2411, (2) the fifth
bundlet 2415, and (3) the sixth bundlet 2416. Similarly, at a sixth
point in time a sixth mask position, p.sub.6, 2426 of the mask
wheel 2430 passes light to the second through fifth bundlets
2412-2415 while blocking light to both the first bundlet 2411 and
sixth bundlet 2416.
[0298] In practice, the mask wheel 2430 contains an integral number
of n positions, where the n positions selectively illuminate and/or
block any combination of: (1) the individual fibers of the set of
fiber optics 2313 and/or (2) bundlets 2410 of the set of fiber
optic optics 2313. Further, the filter wheel is optionally of any
shape and uses any number of motors to position mask position
openings relative to selected fiber optics. Still further, in
practice the filter wheel is optionally any electro-mechanical
and/or electro-optical system used to selectively illuminate the
individual fibers of the set of fiber optics 2313. Yet still
further, in practice the filter wheel is optionally any
illumination system that selectively passes light to any
illumination optic or illumination zone, where various illumination
zones illuminate various regions of the subject 170 as a function
of time. The various illumination zones alter the effectively
probed sample site 178 or region of the subject 170.
[0299] Radial Position Using a Mirror and/or Lens System
[0300] Referring now to FIGS. 26(A-D), a dynamically positioned
optic system 2300 for directing incident light to a radially
changing position about a collection zone is provided.
[0301] Referring now to FIG. 26A, a mirror 2610 is illustrative of
any mirror, lens, mirror system, and/or lens system used to
dynamically and positionally direct incident light to one or more
illumination zones of the subject 170 relative to one or more
detection zones and/or volumes monitored by the photon transport
system 120 and/or the detector system 130.
[0302] Still more generally, the data processing system 140 and/or
the system controller 180 optionally control one or more optics,
figuratively illustrated as the mirror 2310, to dynamically control
incident light 2311 on the subject 170 relative to a detection zone
on the subject 170 that combine to form the sample site 178 through
control of one or more of: [0303] x-axis position of the incident
light on the subject 170; [0304] y-axis position of the incident
light on the subject 170; [0305] solid angle of the incident light
on a single fiber of the fiber bundle 2410; [0306] solid angle of
incident light on a set of fibers of the fiber bundle 2410; [0307]
a cross-sectional diameter or width of the incident light; [0308]
an incident angle of the incident light on the subject 170 relative
to an axis perpendicular to skin of the subject 170 where the
incident light interfaces to the subject 170; [0309] focusing of
the incident light; and/or [0310] depth of focus of the incident
light on the subject 170.
[0311] Several examples are provided, infra, to further illustrate
the use of the system controller 180 to control shape, position,
and/or angle of the incident light 2311 reaching a fiber optic
bundle, skin of the subject 170, and/or an element of the photon
transport system 120.
[0312] Referring again to FIG. 26A, an example is provided of light
directed by the photon transport system 120 from the source system
110 to the subject directly, through one or more fiber optic of the
fiber optic bundle 2410, and/or through the photon transport system
120. However, orientation of the mirror 2610 is varied as a
function of time relative to an incident set of photons pathway.
For example, the mirror 2610 is translated along the x-axis of the
mean optical path, is rotated about the y-axis of the mean optical
path, and/or is rotated about the z-axis of the mean optical path
of the analyzer 100. For example, a first mirror movement element
2622, such as a first spring or piezoelectric device, and a second
mirror movement element 2624, such as a second spring, combine to
rotate the mirror about a first axis, such as the y-axis as
illustrated. Similarly, a third mirror movement element 2626, such
as a third spring, and a fourth mirror movement element 2628, such
as a fourth spring, combine to rotate the mirror about a second
axis, such as the z-axis as illustrated, in the second time
position, t.sub.2, relative to a first time position, t.sub.1.
[0313] Referring now to FIG. 26B, an example of the dynamically
positioned optic system 2600 directing the incident light 2311 to a
plurality of positions as a function of time is provided. As
illustrated, the mirror 2610 directs light to the light input end
2312 of the fiber bundle 2310. Particularly, the incident light
2311 is directed at a first time, 6, to a first fiber optic 2351
and the incident light 2311 is directed at a second time, t.sub.2,
to a second fiber optic 2352 of a set of fiber optics 2350.
However, more generally, the dynamically positioned optic system
2600 directs the incident light using the mirror 2600 to any y-,
z-axis position along the x-axis of the incident light as a
function of time, such as to any optic and/or to a controlled
position of skin of the subject 170.
[0314] Referring now to FIG. 26C, an example of the dynamically
positioned optic system 2300 directing the incident light to a
plurality of positions with a controllable and varying as a
function of time solid angle is provided. Optionally, the solid
angle is fixed as a function of time and the position of the
incident light 2311 onto the light input end 2312 of the fiber
bundle 2310 is varied as a function of time. As illustrated, the
mirror 2610 directs light to the light input end 2312 of the fiber
bundle 2310 where the fiber bundle 2310 includes one or more
bundlets, such as the set of fiber optic bundlets 2410. In this
example, the incident light incident light is directed at a first
time 6, with a first solid angle to a first fiber optic bunch or
group, such as the first bundlet 2411, described supra, and at a
second time, t.sub.2, with a second solid angle to a second fiber
optic bunch, such as the second bundlet 2412, described supra. In
one case, the first solid angle and second solid angle do not
overlap, such as at the fiber optic interface. In another case, the
first solid angle and the second solid angle overlap by less than
20, 40, 60, or 80 percent. However, more generally, the dynamically
positioned optic system 2600 directs the incident light to any y-,
z-axis position along the x-axis of the incident light as a
function of time at any solid angle or with any focusing angle,
such as to any optic, any group of optics, and/or to a controlled
position and/or size of skin of the subject 170 relative to a
detection zone.
[0315] Referring now to FIG. 26D, an example is provided of the
dynamically positioned optic system 2600 directing the incident
light to a plurality of positions with a varying incident angle
onto skin of the subject 170. As illustrated, the mirror 2610
directs light directly to the subject 170 without an optic touching
the subject 170 or without touching a coupling fluid on the subject
170. However, alternatively the light is redirected after the
mirror 2610, such as with a grins lens on a fiber optic element of
the fiber optic bundle 2310. In this example, the incident light is
directed at a first time, t.sub.1, with a first incident angle,
.theta..sub.1, and at a second time, t.sub.2, with a second
incident angle, .theta..sub.2. However, more generally, the
dynamically positioned optic system 2600 directs the incident light
to any y-, z-axis position along the x-axis of the incident light
as a function of time at any solid angle, with any focusing depth,
and/or an any incident angle, such as to any optic and/or to a
controlled position and/or size of skin of the subject 170 relative
to a detection zone. In this example, the detection zone is a
volume of the subject monitored by the photon transport system 120
and/or a lens or mirror of the photon transport system 120 as
interacting with the detector system 130 and a detector
therein.
[0316] Adaptive Subject Measurement
[0317] Delivery of the incident light 2311 to the subject 170 is
optionally varied in time in terms of position, radial position
relative to a point of the skin of the subject 170, solid angle,
incident angle, depth of focus, energy, and/or intensity. Herein,
without limitation a spatial illumination system is used to
illustrate the controlled and variable use of incident light.
[0318] Referring now to FIG. 27A and FIG. 27B, examples of use of a
spatial illumination system 2700 are illustrated for a first
subject 171 and a second subject 172. However, while the examples
provided in this section use a fiber optic bundle to illustrate
radially controlled irradiation of the sample, the examples are
also illustrative of use of the dynamically positioned optic system
2600 for directing incident light to a radially changing position
about a collection zone. Still more generally the photon transport
system 120 in FIGS. 27A and 27B is used in any spatially resolved
system and/or in any time resolved system to deliver photons as a
function of radial distance to a detector and/or to a detection
zone.
[0319] Referring now to FIG. 27A and FIG. 25, an example of
application of the spatial illumination system 2400 to the first
subject 171 is provided. At a first point in time, the first
position, p.sub.1, 2421 of the filter wheel 2430 is aligned with
the light input end 2312 of the fiber bundle 2310, which results in
the light from the first bundlet 2411, which corresponds to the
first ring 2341, irradiating the sample site 178 at a first radial
distance, r.sub.1, and a first depth, d.sub.1, which as illustrated
in FIG. 24A has a mean optical path through the epidermis.
Similarly, at a second point in time, the filter wheel 2430 at the
second position 2422 passes light to the second bundlet 2412, which
corresponds to the second ring, irradiating the sample site 178 at
a second increased distance and a second increased depth, which as
illustrated in FIG. 27A has a mean optical path through the
epidermis and dermis. The dynamically positioned optic system 2600
is optionally used to direct light as a function of time to the
first position 2421 and subsequently to the second position 2422.
Similarly, results of interrogation of the subject 170 with light
passed through the six illustrative fiber illumination rings in
FIG. 24A is provided in Table 3. The results of Table 3 demonstrate
that for the first individual, the prime illumination rings for a
blood analyte concentration determination are rings two through
four as the first ring, sampling the epidermis, does not sample the
blood filled dermis layer; rings two through four probe the blood
filled dermis layer; and rings five and six penetrate through the
dermis into the subcutaneous fat where photons are lost and the
resultant signal-to-noise ratio for the blood analyte
decreases.
TABLE-US-00003 TABLE 3 Subject 1 Illumination Deepest Tissue Layer
Ring Probed 1 Epidermis 2 Dermis 3 Dermis 4 Dermis 5 Subcutaneous
Fat 6 Subcutaneous Fat
[0320] Referring now to FIG. 27B and FIG. 24A, an example of
application of the spatial illumination system 2400 to the second
subject 172 is provided. Again, the dynamically positioned optic
system 2600 is optionally used to deliver light to the spatial
illumination system 2400. Results of interrogation of the subject
170 with light passed through the six illustrative fiber
illumination rings in FIG. 24A is provided in Table 4. For the
second subject, it is noted that interrogation of the sample with
the fifth radial fiber ring, f.sub.5, results in a mean optical
path through the epidermis and dermis, but not through the
subcutaneous fat. In stark contrast, the mean optical path using
the fifth radial fiber ring, f.sub.5, for the second subject 172
has a deepest penetration depth into the dermis 174. Hence, the
fifth radial fiber ring, f.sub.5, yields photons probing the
subcutaneous fat 176 for the first subject 171 and yields photons
probing the dermis 174 of the second subject 172. Hence, for a
water soluble analyte and/or a blood borne analyte, such as
glucose, the analyzer 100 is more optimally configured to not use
both the fifth fiber ring, f.sub.5, and the sixth fiber ring,
f.sub.6, for the first subject 171. However, analyzer 100 is more
optimally configured to not use only the sixth fiber ring, f.sub.6,
for the second subject 172, as described infra.
TABLE-US-00004 TABLE 4 Subject 2 Illumination Deepest Tissue Layer
Ring Probed 1 Epidermis 2 Dermis 3 Dermis 4 Dermis 5 Dermis 6
Subcutaneous Fat
[0321] In yet another example, light is delivered with known radial
distance to the detection zone, such as with optics of the
analyzer, without use of a fiber optic bundle and/or without the
use of a filter wheel. Just as the illumination ring determines the
deepest tissue layer probed, control of the irradiation
zone/detection zone distance determines the deepest tissue layer
probed.
[0322] Incident Light Control
[0323] Referring again to FIGS. 26A-D, the dynamically positioned
optic system 2600 is optionally used as a function of time to
control one or more of: [0324] delivery of the incident light 2311
to a single selected fiber optic of the fiber optic bundle 2310;
[0325] delivery of the incident light 2311 to a selected bundlet of
the set of fiber optic bundlets 2410, such as to the first bundlet
2411 at a first point in time and to the second bundlet 2412 at a
second point in time; [0326] variation of solid angle of the
incident light 2311 to an optic and/or to the subject 170; [0327]
variation of radial position of delivery of the incident light 2311
relative to a fixed location, such as a center of an optic, a
target point on skin of the subject 170, or a center of the sample
site 178; [0328] incident angle of the incident light 2311 relative
to a plane tangential to the skin of the subject 170 and/or an axis
normal to the skin of the subject 170 at the sample site 178;
[0329] apparent focus depth of the incident light 2311 into the
skin of the subject 170; [0330] energy; and [0331] intensity, such
as number of photon per second varying from one point in time to
another by greater than 1, 10, 50, 100, 500, 1000, or 5000
percent.
[0332] Time Resolved Spectroscopy
[0333] In still yet another example, referring again to time
resolved spectroscopy, instead of delivering light through the
filter wheel to force radial distance, photons are optionally
delivered to the skin and the time resolved gating system is used
to determine probably photon penetration depth. For example, Table
5 shows that at greater elapsed time to the n.sup.th gated
detection period, the probability of the deepest penetration depth
reaching deeper tissue layers increases.
TABLE-US-00005 TABLE 5 Time Resolved Spectroscopy Elapsed Time
Deepest Tissue Layer (picoseconds) Probed 1 Epidermis 10 Dermis 50
Dermis 100 Subcutaneous Fat
[0334] Data Processing
[0335] Referring now to FIG. 28, the data processing system 140 is
further described. The data processing system 140 optionally uses a
step of post-processing 2820 to process a set of collected data
2810. The post-processing step 2420 optionally operates on data
collected as a function of any of: radial distance of the incident
light 2311 to a reference point, such as a detector; solid angle of
the incident light 2311 relative to the subject 170; angle of the
incident light 2311 relative to skin of the subject 170; and/or
depth of focus of the incident light 2311 relative to a surface of
the skin of the subject 170.
[0336] Two-Phase Measurement(s)
[0337] Referring now to FIG. 29, in another embodiment, the
analyzer 100 is used in two phase system 2900: (1) a sample mapping
phase 2910, such as a subject or group mapping phase and (2) a
subject specific data collection phase 2930/data analysis phase. In
one example, in the first mapping phase 2910, skin of the subject
170 is analyzed with the analyzer 100 using a first optical
configuration. Subsequently, the mapping phase spectra are analyzed
2920. In the second subject specific data collection phase 2930,
the analyzer 100 is setup in a second optical configuration based
upon data collected in the sample mapping phase 2910. The second
optical configuration is preferably configured to enhance
performance of the analyzer 100 in terms of accuracy and/or
precision of estimation and/or determination of an analyte
property, such as a noninvasive glucose concentration. Examples
provided, infra, use a single subject 170. However, more generally
the sample mapping phase 2910 is optionally used to classify the
subject into a group or cluster and the analyzer 100 is
subsequently setup in a second optical configuration for the group
or cluster, which represents a subset of the human population, such
as by gender, age, skin thickness, water absorbance, fat
absorbance, protein absorbance, epidermal thickness, dermal
thickness, depth of a subcutaneous fat layer, and/or a model fit
parameter. For clarity of presentation, several examples are
provided, infra, describing use of a sample mapping phase 2910 and
a subsequent subject specific data collection phase 2930.
[0338] In a first example, referring again to FIG. 27A and FIG.
27B, a first optional two-phase measurement approach is herein
described. Optionally, during the first sample mapping phase 2910,
the photon transport system 120 provides interrogation photons to a
particular test subject at controlled, but varying, radial
distances from the detection system 130. One or more spectral
markers, or an algorithmic/mathematical representation thereof, are
used to determine the radial illumination distances best used for
the particular test subject. An output of the first phase is the
data processing system 140 selecting how to illuminate/irradiate
the subject 170. Subsequently, during the second subject specific
data collection phase 130, the system controller 180 controls the
photon transport system 120 to deliver photons over selected
conditions and/or optical configuration to the subject 170.
[0339] In a second example, a first spectral marker is optionally
related to the absorbance of the subcutaneous fat 176 for the first
subject 171. During the first sample mapping phase 2710, the fifth
and sixth radial positions of the fiber probe illustrated in FIG.
24A, yield collected signals for the first subject 171 that contain
larger than average fat absorbance features, which indicates that
the fifth and sixth fiber rings of the example fiber bundle should
not be used in the subsequent second data collection phase, which
more generally establishes an outer radial distance for subsequent
illumination. Still in the first sample mapping phase 130, probing
the tissue of the subject with photons from the fourth fiber ring
yields a reduced signal for the first spectral marker and/or a
larger relative signal for a second spectral marker related to the
dermis 174, such as a protein absorbance band or an
algorithmic/mathematical representation thereof. Hence, the data
processing system 140 yields a result that the fifth and sixth
radial fiber optic rings or distance of the fiber bundle 170 should
not be used in the second subject specific data collection phase
2930 and that the fourth radial fiber optic ring or distance should
be used in the second subject specific data collection phase 2930.
Subsequently, in the second subject specific data collection phase
2930, data collection for analyte determination ensues using the
first through fourth radial positions of the fiber bundle, which
yields a larger signal-to-noise ratio for dermis constituents, such
as glucose, compared to the use of all six radial positions of the
fiber bundle. Optionally, data already collected in the mapping
phase is subsequently re-used in the data analysis phase.
[0340] In a third example, the first sample mapping phase 2910 of
the previous example is repeated for the second subject 172. The
first sample mapping phase 2910 indicates that for the second
subject, the sixth radial illumination ring of the fiber bundle
illustrated in FIG. 24A should not be used, but that the fourth and
fifth radial illumination ring should be used.
[0341] In a fourth example, the first mapping phase 2910 determines
positions on the skin where papillary dermis ridges are closest to
the skin surface and positions on the skin where the papillary
dermis valleys are furthest from the skin surface. In the
subsequent subject specific data collection phase 2930, the
incident light is optionally targeted at the papillary dermis
valleys, such as greater than 50, 60, or 70 percent of the incident
light is targeted at the papillary dermis valley and less than 30,
40, or 50 percent of the incident light is targeted at the
papillary dermis ridge. The increased percentage of the incident
light striking the papillary dermis valley increases the number of
photons sampling the underlying dermis layer, where blood borne
analytes reside, which increases the signal-to-noise ratio of
collected data and lowers resultant errors in blood borne analyte
property determination.
[0342] Generally, a particular subject is optionally probed in a
sample mapping phase 2910 and results from the sample mapping phase
2910 are optionally used to configure analyzer parameters in a
subsequent subject specific data collection phase 2930. While for
clarity of presentation, and without loss of generality, radial
distance was varied in the provided examples, any optical parameter
of the analyzer is optionally varied in the sample mapping phase
2910, such as sample probe position, incident light solid angle,
incident light angle, focal length of an optic, position of an
optic, energy of incident light, and/or intensity of incident
light. Optionally, the sample mapping phase 2910 and sample
specific data collection phase 2930 occur within less than 1, 5,
10, 20, or 30 seconds of each other. Optionally, the subject 170
does not move away from the sample interface 150 between the sample
mapping phase 2910 and the subject specific data collection phase
130. Further, generally each of the spatial and temporal methods
yield information on pathlength, b, and/or a product of the molar
absorptivity and pathlength, which is not achieved using a standard
spectrometer.
[0343] In yet another embodiment, the sample interface tip 2316 of
the fiber optic bundle 2310 includes optics that change the mean
incident light angle of individual fibers of the fiber optic bundle
2316 as they first hit the subject 170. For example, a first optic
at the end of a fiber in the first ring 1041 aims light away from
the collection fiber optic 2318; a second optic at the end of a
fiber in the second ring 2342 aims light nominally straight into
the sample; and a third optic at the end of a fiber in the third
ring 2342 aims light toward the collection fiber 2318. Generally,
the mean direction of the incident light varies by greater than 5,
10, 15, 20, or 25 degrees.
[0344] In still another embodiment, the two-dimensional detector
array is used in the mapping phase to determine positions of best
signal and/or positions of interference, such as a hair follicle.
In the data analysis phase, the determined sub-optimal regions,
such as those related to the detected hair follicle, are not used
in the analyte determination phase.
[0345] Data Processing System
[0346] The data processing system 140 is further described herein.
Generally, the data processing system uses an instrument
configuration analysis system 2940 to determine an optical
configuration of the analyzer 100 and/or a software configuration
of the analyzer 100 while the sample property analysis system 2950
is used to determine a chemical, a physical, and/or a medical
property, such as an analyte concentration, measured or represented
by collected spectra. Further, the data processing system 140
optionally uses a preprocessing step and a processing step to
determine an instrument configuration and/or to determine an
analyte property.
[0347] In one embodiment, the data processing system 140 uses a
preprocessing step to achieve any of: lower noise and/or higher
signal. Representative and non-limiting forms of preprocessing
include any of: use of a digital filter, use of a convolution
function, use of a derivative, use of a smoothing function, use of
a resampling algorithm, and/or a form of assigning one or more
spectra to a cluster of a whole. The data processing system
subsequently uses any multivariate technique, such as a form of
principal components regression, a form of partial least squares,
and/or a form of a neural network to further process the
pre-processed data.
[0348] In another embodiment, the data processing system 140 and/or
the sample property analysis system 2950 operates on spectra
collected by the analyzer 100, such as in the subject specific data
collection phase 2930, using a first step of defining finite width
channels and a second step of feature extraction, which are each
further described, infra.
[0349] Finite Width Channels
[0350] In one example, the sample property analysis system 2950
defines a plurality of finite width channels, where the channels
relate to changes in an optical parameter, software setting of the
analyzer 100, a chemical condition, a physical property, a
distance, and/or time. Still further, the channels optionally
relate to radial distance between the incident light from the
analyzer 100 entering skin of the subject 170 and detected light
exiting the skin of the subject 170 and detected by the detector
system 130, a focal length of an optic, a solid-angle of a photon
beam from the source system 110, an incident angle of light onto
skin of the subject, and/or a software setting, such as control
over spectral resolution. For clarity of presentation, the channels
are described herein in terms of wavelength channels. For example,
a spectrum is collected over a range of wavelengths and the finite
width channels represent finite width wavelength channels within
the spectrum. Generally, the channels are processed to enhance
localized signal, to decrease localized noise, and/or are processed
using a cross-wavelet transform.
[0351] In one case, the sample property analysis system 2950
defines a plurality of finite width wavelength channels, such as
more than 3, 5, 10, 15, 20, 30, 40, or 50 wavelength channels
contained in a broader spectral region, such as within a spectrum
from 900 to 2500 nanometers or within a sub-range therein, such as
within 1100 to 1800 nanometers. The plurality of multiple finite
width wavelength channels enhance accessibility to content related
to: (1) a target analyte, such as a glucose concentration, and (2)
a measurement context, such as the state of skin of the subject
170, which is used as information in a self-correcting
background.
[0352] Feature Extraction
[0353] In one case, feature extraction determines and/or calculates
coherence between channels, which is referred to herein as
cross-coherence, to identify and/or enhance information common to
the analytical signal, such as frequency, wavelength, shift, and/or
phase information. Subsequently, cross-coherence terms are selected
using a metric, such as to provide maximum contrast between: (1)
the target analyte or signal and (2) the measurement context or
background. Examples of background include, but are not limited to:
spectral interference, instrument drift impacting the acquired
signal, spectral variation resultant from physiology and/or tissue
variation, temperature impact on the analyzer, mechanical
variations in the analyzer as a function of time, and the like.
[0354] Generally, the cross-coherence terms function to reduce
toward or to monotonicity detected variation as a function of
analyte concentration. In a particular instance, an N.times.N grid
is generated per spectrum, which is symmetric about the diagonal of
the N.times.N grid, with each grid element representing an M term
coherence estimate versus frequency, where N is a positive integer
of at least three.
[0355] Model
[0356] Typically, a model, such as a nonlinear model, is
constructed to map the extracted features to the analyte property,
such as a glucose concentration. For example, the total
differential power of the cross-coherence estimate is determined
between features related to the analyte versus the background and a
separate nonlinear function is calculated for multiple analyte
ranges.
[0357] Absorbance Spectra
[0358] The data processing system 140 optionally uses absorbance
spectra of skin and/or blood constituents, such as water absorbance
peaks at about 1450 nm or in the range of 1350 to 1500 nm.
[0359] Personal Communication Device
[0360] Herein, a personal communication device comprises any of a
wireless phone, a cell phone, a smart phone, a tablet, a phablet, a
wearable internet connectable accessory, a wearable internet
connectable garment, and/or a smart wearable accessory, such as a
watch with internet and/or phone communication ability. Optionally,
the analyzer 100 has no display screen and results are transmitted
to a personal communication device of the user, which allows a
smaller analyzer 100 and/or the analyzer to be semi-continuously
worn in a non-conspicuous location, such as under a shirt or around
the torso of the individual.
[0361] Optionally, the personal communication device and/or the
analyzer communicate with a data processing center. For example,
the data processing center received data from the analyzer 100
through use of at least one wireless step, processes the data, and
sends a result and/or a model parameter to the personal
communication device of the user, resulting in one or more of: a
displayed analyte concentration, a description of detection of an
analyzer error, and/or an alert, such as a rapidly falling glucose
concentration, an abnormally high glucose concentration, and/or a
request for use of an alternative glucose determination method.
[0362] Still yet another embodiment includes any combination and/or
permutation of any of the analyzer and/or sensor elements described
herein.
[0363] The particular implementations shown and described are
illustrative of the invention and its best mode and are not
intended to otherwise limit the scope of the present invention in
any way. Indeed, for the sake of brevity, conventional
manufacturing, connection, preparation, and other functional
aspects of the system may not be described in detail. Furthermore,
the connecting lines shown in the various figures are intended to
represent exemplary functional relationships and/or physical
couplings between the various elements. Many alternative or
additional functional relationships or physical connections may be
present in a practical system.
[0364] In the foregoing description, the invention has been
described with reference to specific exemplary embodiments;
however, it will be appreciated that various modifications and
changes may be made without departing from the scope of the present
invention as set forth herein. The description and figures are to
be regarded in an illustrative manner, rather than a restrictive
one and all such modifications are intended to be included within
the scope of the present invention. Accordingly, the scope of the
invention should be determined by the generic embodiments described
herein and their legal equivalents rather than by merely the
specific examples described above. For example, the steps recited
in any method or process embodiment may be executed in any order
and are not limited to the explicit order presented in the specific
examples. Additionally, the components and/or elements recited in
any apparatus embodiment may be assembled or otherwise
operationally configured in a variety of permutations to produce
substantially the same result as the present invention and are
accordingly not limited to the specific configuration recited in
the specific examples.
[0365] Benefits, other advantages and solutions to problems have
been described above with regard to particular embodiments;
however, any benefit, advantage, solution to problems or any
element that may cause any particular benefit, advantage or
solution to occur or to become more pronounced are not to be
construed as critical, required or essential features or
components.
[0366] As used herein, the terms "comprises", "comprising", or any
variation thereof, are intended to reference a non-exclusive
inclusion, such that a process, method, article, composition or
apparatus that comprises a list of elements does not include only
those elements recited, but may also include other elements not
expressly listed or inherent to such process, method, article,
composition or apparatus. Other combinations and/or modifications
of the above-described structures, arrangements, applications,
proportions, elements, materials or components used in the practice
of the present invention, in addition to those not specifically
recited, may be varied or otherwise particularly adapted to
specific environments, manufacturing specifications, design
parameters or other operating requirements without departing from
the general principles of the same.
[0367] Herein, a set of fixed numbers, such as 1, 2, 3, 4, 5, 10,
or 20 optionally means at least any number in the set of fixed
number and/or less than any number in the set of fixed numbers.
[0368] Herein, specific wavelengths are used to facilitate
communication of key spectroscopic points. However, the specific
wavelengths presented are optionally plus and/or minus 10, 20, 30,
40, 50, 75, or 100 nm.
[0369] Although the invention has been described herein with
reference to certain preferred embodiments, one skilled in the art
will readily appreciate that other applications may be substituted
for those set forth herein without departing from the spirit and
scope of the present invention. Accordingly, the invention should
only be limited by the Claims included below.
* * * * *