U.S. patent application number 13/963933 was filed with the patent office on 2015-02-12 for multiplexed noninvasive analyzer apparatus and method of use thereof.
The applicant listed for this patent is Alan Abul-Haj, Thomas George, Sandeep Gulati, Kevin H. Hazen, Vlad Novotny, Timothy Ruchti. Invention is credited to Alan Abul-Haj, Thomas George, Sandeep Gulati, Kevin H. Hazen, Vlad Novotny, Timothy Ruchti.
Application Number | 20150041656 13/963933 |
Document ID | / |
Family ID | 52276852 |
Filed Date | 2015-02-12 |
United States Patent
Application |
20150041656 |
Kind Code |
A1 |
Novotny; Vlad ; et
al. |
February 12, 2015 |
MULTIPLEXED NONINVASIVE ANALYZER APPARATUS AND METHOD OF USE
THEREOF
Abstract
A noninvasive analyzer 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. Control of illumination
times and/or patterns along with selected detection zones yields
pathlength resolved groups of spectra. Sectioned pixels and/or
zones of the detector are optionally filtered for different light
throughput as a function of wavelength. The pathlength resolved
groups of spectra are subsequently analyzed to determine an analyte
property. Optionally, in the mapping and/or collection phase,
incident light is controllably varied in time in terms of any of:
sample probe position, incident light solid angle, incident light
angle, depth of focus, energy, intensity, and/or detection angle.
Optionally, one or more physiological property and/or model
property related to a physiological property is used in the analyte
property determination.
Inventors: |
Novotny; Vlad; (Los Gatos,
CA) ; Gulati; Sandeep; (La Canada, CA) ;
George; Thomas; (La Canada, CA) ; Ruchti;
Timothy; (Gurnee, IL) ; Abul-Haj; Alan; (Mesa,
AZ) ; Hazen; Kevin H.; (Gilbert, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Novotny; Vlad
Gulati; Sandeep
George; Thomas
Ruchti; Timothy
Abul-Haj; Alan
Hazen; Kevin H. |
Los Gatos
La Canada
La Canada
Gurnee
Mesa
Gilbert |
CA
CA
CA
IL
AZ
AZ |
US
US
US
US
US
US |
|
|
Family ID: |
52276852 |
Appl. No.: |
13/963933 |
Filed: |
August 9, 2013 |
Current U.S.
Class: |
250/339.02 |
Current CPC
Class: |
A61B 5/1079 20130101;
A61B 5/14532 20130101; A61B 5/14552 20130101; G01N 2201/0826
20130101; A61B 5/6801 20130101; G01N 2021/4747 20130101; A61B
5/0022 20130101; G01N 2021/4742 20130101; G01J 3/42 20130101; A61B
5/1455 20130101; G01N 21/474 20130101 |
Class at
Publication: |
250/339.02 |
International
Class: |
G01J 3/42 20060101
G01J003/42; A61B 5/145 20060101 A61B005/145; A61B 5/1455 20060101
A61B005/1455 |
Claims
1. An apparatus for noninvasively determining an analyte
concentration of a subject, comprising: a near-infrared noninvasive
vibrational spectroscopy analyzer, comprising: a sample interface;
a photon transport system comprising at least one optic configured
for at least one: transporting photons to an illumination zone
proximate said sample interface; and collecting photons from a
detection zone proximate said sample interface; a first
two-dimensional detector array; a second two-dimensional detector
array, both said first two-dimensional detector array and said
second two-dimensional detector array positioned proximate at least
one of the illumination zone and the detection zone; and a
controller, of said analyzer, configured to receive simultaneously
collected signals from both said first two-dimensional detector
array and said second two-dimensional detector array, the signals
used in calculation of the analyte concentration.
2. The apparatus of claim 1, further comprising: a housing, said
housing substantially enclosing all of said source, said photon
transport system, and said first two-dimensional detector array,
said first two-dimensional detector array comprising an m by n
array of detector elements, wherein m and n comprise positive
integers greater than four, wherein said photon transport system
comprises optics directing photons along a z-axis to a sample
region along an x,y-plane, the x,y-plane perpendicular to the
z-axis, wherein said first two-dimensional detector array comprises
a two-dimensional near-infrared detector array.
3. The apparatus of claim 1, said first two-dimensional detector
array and said second two-dimensional detector array positioned on
opposite sides of a mean photon path center of the illumination
zone.
4. The apparatus of claim 1, said first two-dimensional detector
array positioned along a first vector from a mean optical center of
the illumination zone, said second two-dimensional detector array
positioned along a second vector from the mean optical center of
the illumination zone, said first vector and said second vector
forming an angle between twenty and two hundred degrees.
5. The apparatus of claim 1, said first two-dimensional detector
array comprising a larger number of detectors than said second
two-dimensional detector array.
6. The apparatus of claim 1, said first two-dimensional detector
array comprising a set of detectors comprising indium, gallium, and
arsenide, said second two-dimensional detector array comprising at
least one of a temperature sensor and a pressure sensor.
7. The apparatus of claim 1, a center of said first two-dimensional
detector array comprising a position along a vector from a center
of said illumination zone, said first two-dimensional detector
comprising at least one column of detectors rotated at least ten
degrees off of the vector.
8. The apparatus of claim 1, further comprising: an array of
optics, individual optical elements of said array of optics
respectively optically coupled to rows of detector elements of said
two-dimensional detector array.
9. The apparatus of claim 1, further comprising: a two-dimensional
optical transmittance filter array, wherein a first filter of said
two-dimensional optical transmittance filter array optically
couples to a first line of detector elements of said
two-dimensional detector array, wherein a second filter of said
two-dimensional transmittance filter array optically couples to a
second line of detector elements of said two-dimensional detector
array, wherein, at at least one wavelength in the range of 1500 to
1800 nm, said first filter comprises a first filter transmittance
differing from a second filter transmittance of said second filter
by at least thirty percent.
10. The apparatus of claim 1, said near-infrared noninvasive
vibrational spectroscopy analyzer further comprising: a first
optical filter comprising transmittance of at least sixty percent
of light in a wavelength range of 1100 to 1350 nm and transmittance
of less than twenty percent in a wavelength range of 1500 to 1750
nm, said first optical filter optically coupled to a first group of
detectors of said two-dimensional detector array; and a second
optical filter comprising transmittance of at least sixty percent
of light in a wavelength range of 1500 to 1700 nm and transmittance
of less than twenty percent in a wavelength range of 1100 to 1300
nm, said second optical filter optically coupled to a second group
of detectors of said two-dimensional detector array.
11. The apparatus of claim 1, said first two-dimensional detector
array comprising: a first number of detectors in a first row; and a
second number of detectors in a second row, said second number less
than said first number.
12. The apparatus of claim 1, further comprising: a first optical
filter comprising a first transmittance profile; and a second
optical filter comprising a second transmittance profile, the
second transmittance profile different from said the first
transmittance profile, wherein said first optical filter optically
covers a first region of said first two-dimensional detector array,
and wherein said second optical filter optically covers a second
region of said first two-dimensional detector array.
13. The apparatus of claim 1, said near-infrared noninvasive
vibrational spectroscopy analyzer further comprising: a
two-dimensional transmittance filter array in an optical path of
said analyzer, comprising: a first filter comprising a first fifty
percent cut-on transmittance inflection point at a first wavelength
in a range of 1200 to 2500 nanometers; a second filter comprising a
second fifty-percent cut-on transmittance inflection at a second
wavelength, said second wavelength at least one hundred nanometers
shorter than said first wavelength, said first filter positioned
closer to the illumination zone than said second filter.
14. The apparatus of claim 13, said two-dimensional transmittance
filter array both substantially co-planar and in contact with said
two-dimensional detector array.
15. The apparatus of claim 13, further comprising: a
two-dimensional near-infrared detector optic array, each element of
said two-dimensional detector optic array optically coupled to at
least one detector element of said two-dimensional detector
array.
16. A method for noninvasively determining an analyte concentration
of a subject, comprising: providing a sample interface; using a
photon transport system comprising at least one optic for at least
one: transporting photons to an illumination zone proximate said
sample interface; collecting photons from a detection zone
proximate said sample interface; collecting a first set of signals
using a first two-dimensional detector array; collecting a second
set of signals using a second two-dimensional detector array, both
said first two-dimensional detector array and said second
two-dimensional array positioned in a common housing of a
noninvasive vibrational spectroscopy analyzer proximate at least
one of the illumination zone and the detection zone receiving, to a
processor, the first set of signals and the second set of signals;
and using the signals in calculation of the analyte
concentration.
17. The method of claim 16, further comprising the step of:
positioning both said first two-dimensional detector array and said
second two-dimensional detector array within ten centimeters of the
subject during use of said analyzer.
18. The method of claim 16, further comprising the steps of: using
a first detector gain setting for a detector element of said first
two-dimensional detector array; and simultaneously using a second
detector gain setting for a detector element of said second
two-dimensional detector array, said second gain setting at least
ten percent larger than said first detector gain setting.
19. The method of claim 16, further comprising the steps of: using
a first integration time for a first detector of said first
two-dimensional detector array; and using a second integration time
for a second detector of said first two-dimensional detector array,
said second detector positioned further from a center of said
detection zone than said first detector, said second integration
time at least ten percent larger than said first integration
time.
20. The method of claim 19, further comprising the steps of: using
a first optical filter coupled to a first sub-set of detectors of
said first two-dimensional detector array; and using a second
optical filter coupled to a second sub-set of said first
two-dimensional detector array, wherein a fifty percent cut-on
wavelength of said first filter differs from a fifty percent cut-on
wavelength of said second optical filter by at least two hundred
nanometers.
21. The method of claim 16, further comprising the steps of:
communicating the signals to a personal communication device; using
said personal communication device in a process of calculating the
analyte concentration.
22. The method of claim 16, further comprising the steps of:
extracting spectroscopic features related to optical pathlength;
and using said features in calculation of the analyte
concentration.
Description
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application: [0002] 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: [0003] U.S. provisional patent
application No. 61/672,195 filed Jul. 16, 2012; [0004] U.S.
provisional patent application No. 61/700,291 filed Sep. 12, 2012;
and [0005] U.S. provisional patent application No. 61/700,294 filed
Sep. 12, 2012; and [0006] claims the benefit of U.S. provisional
patent application No. 61/845,926 filed Jul. 12, 2013, [0007] all
of which are incorporated herein in their entirety by this
reference thereto.
TECHNICAL FIELD OF THE INVENTION
[0008] The present invention relates to a noninvasive analyzer
using a sample mapping phase to generate instrumentation setup
parameters followed by a subject specific data collection phase
using the configured instrument.
DESCRIPTION OF THE RELATED ART
[0009] Patents and literature related to the current invention are
summarized herein.
Diabetes
[0010] 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).
[0011] 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.
[0012] 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.
[0013] 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.
Skin
[0014] 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.
Fiber Optic Sample Bundle
[0015] 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.
[0016] Maruo, K., et. al., "Device for Non-Invasive Determination
of Glucose Concentration in Blood", European patent application no.
EP 0843986 B1 (Mar. 24, 2004) described 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.
Skin Thickness
[0017] 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) described the use of
near-infrared absorbance spectra to determine overall thickness of
skin tissue and layer-by-layer thickness of skin tissue.
[0018] 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.
[0019] 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.
Sample Probe/Tissue Contact
[0020] 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.
[0021] 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.
PROBLEM STATEMENT
[0022] What is needed is a noninvasive glucose concentration
analyzer having precision and accuracy suitable for treatment of
diabetes mellitus.
SUMMARY OF THE INVENTION
[0023] The invention comprises a noninvasive analyzer apparatus
having an array detector sensing a plurality of detection zones
couple to a plurality of illumination zones and a method of use
thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] 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.
[0025] FIG. 1 illustrates an analyzer;
[0026] FIG. 2 illustrates diffusely reflecting optical paths;
[0027] FIG. 3 illustrates probing tissue layers using a spatial
distribution method;
[0028] FIG. 4 illustrates varying illumination zones relative to a
detector;
[0029] FIG. 5 illustrates varying detection zones relative to an
illuminator;
[0030] FIG. 6A illustrates an end view of an array detector and
FIG. 6B illustrates a side view of the array detector;
[0031] FIGS. 7(A-E) illustrate a coupled source detector array
system, FIG. 7A; a side illuminated array detector system, FIG. 7B;
a corner illuminated array detector system, FIG. 7C; a within array
illumination system, FIG. 7D; and an array illuminated detector
array system, FIG. 7E;
[0032] FIGS. 8(A-D) illustrate a first example of a multiple
two-dimensional array detector system, FIG. 8A; a second example of
a multiple two-dimensional array detector system, FIG. 8B; a third
example of a multiple two-dimensional array detector system, FIG.
8C; and a fourth example of a multiple two-dimensional array
detector system, FIG. 8D;
[0033] FIGS. 9(A-D) illustrate temporal resolution gating, FIG. 9A;
probabilistic optical paths for a first elapsed time, FIG. 9B;
probabilistic optical paths for a second elapsed time, FIG. 9C; and
a temporal distribution method, FIG. 9D;
[0034] FIGS. 10(A-C) illustrate a fiber optic bundle, FIG. 10A; a
first example sample interface end of the fiber optic bundle, FIG.
10B; and a second example sample interface end of the fiber optic
bundle, FIG. 10C;
[0035] FIG. 11A illustrates a third example sample interface end of
the fiber optic bundle and FIG. 11B illustrates a mask;
[0036] FIG. 12 illustrates a mask selection wheel;
[0037] FIG. 13A illustrates a position selection optic; FIG. 13B
illustrates the position selection optic selecting position; FIG.
13C illustrates solid angle selection using the position selection
optic; and FIG. 13D illustrates radial control of incident light
relative to a detection zone;
[0038] FIGS. 14(A-B) illustrate a pathlength resolved sample
interface for (1) a first subject, FIG. 14A and (2) a second
subject, FIG. 14B;
[0039] FIG. 15 provides a method of use of a data processing
system; and
[0040] FIG. 16 provides a method of using a sample mapping phase
and a subsequent subject specific data collection phase.
[0041] 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
[0042] The invention comprises a noninvasive analyzer apparatus and
method of use thereof using a plurality of two-dimensional
near-infrared detector arrays.
[0043] In 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.
[0044] In still another 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.
[0045] 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.
[0046] 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 of more focusing depths.
[0047] In still another embodiment, an analyzer using light
interrogates the sample using one or more of: [0048] a spatially
resolved system; [0049] an incident light radial distance resolved
system; [0050] a controllable and variable incident light solid
angle system; and [0051] a controllable and variable incident light
angle system; [0052] a time resolved system, where the times are
greater than about 1, 10, 100, or 1000 microseconds; [0053] a
picosecond timeframe resolved system, where times are less than
about 1, 10, 100, or 1000 nanoseconds; [0054] collection of spectra
with varying radial distances between incident light entering skin
and detected light exiting the skin; [0055] an incident angle
resolved system; and [0056] a collection angle resolved system.
[0057] Data from the analyzer is analyzed using a data processing
system capable of using the information inherent in the resolved
system data.
[0058] 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.
[0059] 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.
[0060] In still yet another embodiment, a data processing system
uses information related to contact pressure on a tissue sample
site.
[0061] In another embodiment, a data processing system uses a
combination of any of: [0062] spatially resolved information;
[0063] temporally resolved information on a time scale of longer
than about one microsecond; [0064] temporally resolved information
on a sub one hundred picosecond timeframe; [0065] incident photon
angle information; [0066] photon collection angle information;
[0067] interrelationships of spectral absorbance and/or intensity
information; [0068] environmental information; [0069] temperature
information; and [0070] information related to contact pressure on
a tissue sample site.
[0071] 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.
Axes
[0072] 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.
[0073] Herein, when referring to the analyzer, an x, y, z-axes
analyzer coordinate system is defined relative to the analyzer. The
x-axis is the 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.
[0074] 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.
Analyzer
[0075] Referring now 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. 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.
Patient/Reference
[0076] 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 patient. In practice, the analyzer 100 is used by a
user to analyze the user, referred to as the subject 170, the
subject 170 and is used by a medical professional to analyze a
patient.
Controller
[0077] Still referring to FIG. 1 and referring now to FIG. 5, the
analyzer 100 optionally includes a system controller 180. 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 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 hard wired communication system
198. For example, the remote system includes a data processing
system, a data storage system, and/or a data organization
system.
[0078] 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.
[0079] 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,
and/or physical routing of photons from the source 110 using a
position controller 126.
[0080] Still referring to FIG. 1, for clarity of presentation the
optional outside system 190 is illustrated as using a smart phone
192. However, the smart phone 192 is optionally a cell phone, a
tablet computer, a computer network, and/or a personal computer.
Similarly, the smart phone 192 also refers to a feature phone, a
mobile phone, a portable phone, and/or a cell phone. Generally, the
smart phone 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 smart
phone 192 includes a user interface system, a memory system, a
communication system, and/or a global positioning system. Further,
the smart phone 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 in noninvasively determining a glucose concentration
of the subject 170 is performed using the smart phone 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 smart phone 192, where the
auxiliary sensor is not integrated into the analyzer 100.
Optionally data from the analyzer 100 is processed in the cloud.
Optionally, the smart phone 192 is used as a portal between the
analyzer 100 and the cloud.
Source
[0081] 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.
Photon/Skin Interaction
[0082] Light interacts with skin through laws of physics to scatter
and transmit through skin voxels also referred to as volume
pixels.
[0083] 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 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: [0084] at
a first radial distance, photons penetrate with a mean maximum
depth of penetration into an epidermal layer of a subject; [0085]
at a second larger radial distance, photons penetrate with a mean
maximum depth of penetration into a dermal layer of the subject;
and [0086] at a third still larger radial distance, photons
penetrate with a mean maximum depth of penetration into a
subcutaneous fat layer of the subject.
[0087] Referring still to FIG. 2 and referring now to FIG. 5, a
photon transit system 200 through skin layers of the subject 170 is
illustrated. 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 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 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 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 entering the skin
that are detected by the detection system 130. In the
illustrations, optical pathlengths are illustrated as straight
lines and/or curved lines for clarity of presentation; light
travels in straight lines between multiple scattering events.
Pathlength
[0088] Herein, for clarity, without loss of generality, and without
limitation, Beer's Law is used to described 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, and/or absorbance out of a
linear range of the analyzer 100.
[0089] Beer's Law, equation 1, states that:
A.alpha.bC (eq. 1)
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.
Algorithm
[0090] 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 provide, 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 detection zone. 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.
Spatial Resolution
[0091] 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 optical sample photons paths
and/or depth information. Still further, a combination of the first
two cases, such as multiple sources and multiple detectors, is
optionally used to derive photon path information in the skin.
[0092] In the first system, Referring now to FIG. 3, the photon
transit system 200 of FIG. 2 is illustrated where the photon
transport system 110 irradiates the skin of the subject 170 over a
wide range of radial distance from the detection zone, such as at
least about 0.1, 0.2, 0.3, 0.4, or 0.5 millimeters from the
detection zone to less than about 1.0, 1.2, 1.4, 1.6, or 1.8
millimeters from 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, the mean optical path of the detected diffusely scattering
photons increases in depth for photons in the near-infrared
traveling through skin.
[0093] 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. 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 illuminations 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 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 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 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
fiber optic-to-detector distance, where the fiber optic-to-detector
distance is less than about three millimeters.
[0094] 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, a single fiber optic source is used, which 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 an illumination zone. As illustrated the source
112/second detector 502 combination yields a mean photon path
having a second depth of penetration, d.sub.2, for a second
source-to-detector radial distance, r.sub.2; the source 112/fourth
detector 504 combination yields a mean photon path having a fourth
depth of penetration, d.sub.4, for a fourth source-to-detector
radial distance, r.sub.4; and the source 112/sixth detector 506
combination yields a mean photon path having a sixth depth of
penetration, d.sub.6, for a sixth source-to-detector radial
distance, r.sub.6. Again, generally for photons in the
near-infrared region from 1100 to 2500 nanometers both the mean
depth of penetration of the photons into skin and the total optical
pathlength in skin increases with increasing fiber
optic-to-detector distance, where the 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.
[0095] Referring again to FIGS. 4 and 5, the number of source
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, is optionally 1, 2, 3, 4, 5, 10, 20, 50,
100, 500, 1000, 5000, 10,000, 50,000 or more.
Two-Dimensional Array Systems
[0096] 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 array detector 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 array detector 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 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.
[0097] Referring now to FIG. 6B, the two-dimensional detector array
134 is further described. Optionally, one or more elements of the
two-dimensional array is 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 two-dimensional array
detector 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 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.
[0098] 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: [0099] alter a focal depth of
incident light onto the two-dimensional detector array 134; [0100]
alter an incident angle of incident light onto the two-dimensional
detector array 134; and/or [0101] focus on an individual element of
the two-dimensional detector array 134.
[0102] In a second case, individual lines, circles, geometric
shapes covering multiple detector elements, and/or regions of the
micro-optic layer optionally: [0103] alter a focal depth of
incident light onto a line, circle, geometric shape, and/or region
of the two-dimensional detector array 134; [0104] 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
[0105] focus onto a line, circle, geometric shape, and/or region of
a group of elements of two-dimensional detector array 134.
[0106] 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 the incident angle as a function of time within a single
data collection period for a particular subject and/or between
subjects.
[0107] Still referring to FIG. 6B, the optical detector filter 620
is: [0108] optionally used with or without the detector
optic/micro-optic layer 630; and/or [0109] optionally contacts,
proximately contacts, or is separated by a detector filter/detector
gap distance from the two-dimensional detector array 134.
[0110] Similarly, the detector optic/micro-optic layer 630 is:
[0111] optionally used with or without the optical detector filter
620; and/or [0112] optionally contacts, proximately contacts, or is
separated by a micro-optic/detector gap distance 632 from the
two-dimensional detector array 134.
[0113] Referring now to FIGS. 7A-E, for clarity of presentation, an
incident optic/two-dimensional detector array system 700 is
illustrated in multiple representative configurations, without loss
of generality or limitation.
[0114] 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 they are
detected by elements of the two-dimensional detector array 134. In
a first example, photons are illustrated travelling along: (1) a
mean first path, path.sub.1, and are detected by a first detector
element of the two-dimensional detector array 134 at a first,
smaller, radial distance from a tissue illumination zone of the
photon transport system and (2) a mean second path, path.sub.2, and
are detected by a second detector element of the two-dimensional
detector array 134 at a second, longer, radial distance from a
tissue illumination zone of the photon transport system relative to
path.sub.1. In this first example, optionally: [0115] 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; [0116] 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 [0117] 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.
[0118] In the first example, [0119] 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 longer
shorter mean tissue pathlength, such as about 0.2 to 1.7
millimeters compared to an optic that is flat relative to the skin
of the subject 170; [0120] 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;
[0121] 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 relative to the
skin of the subject 170; [0122] 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; [0123] a
third element of the detector optic/micro-optic layer 630 is
optionally flat relative to a mean plane between the skin of the
subject 170 and the two-dimensional detector array 134.
[0124] 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 controlled by the system controller 180 to change any of
a detector layer incidence acceptable 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.
[0125] 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 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 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 millimeter.
[0126] Referring now to FIG. 7B, a second non-limiting 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 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.
[0127] 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: [0128] a combination band filter for
filtering photons having mean radial distances of 0 to 1
millimeter, the combination band filter comprising: [0129] a
transmittance greater than seventy percent at 2150 nm, 2243, and/or
2350 nm, and/or [0130] 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; [0131] a first overtone band filter for filtering
photons having mean radial distances of 0.3 to 1.5 millimeters, the
first overtone filter comprising: [0132] a transmittance greater
than seventy percent at 1550 nm, 1600, and/or 1700 nm, and/or
[0133] 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;
[0134] 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: [0135] a
transmittance greater than seventy percent at 1600 and 2100 nm,
and/or [0136] 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; [0137] a second overtone band filter for filtering photons
having mean radial distances of 0.5 to 3.0 millimeters, the second
overtone filter comprising: [0138] a transmittance greater than
seventy percent at 1200 nm, 1600, and/or 1300 nm, and/or [0139] 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; [0140] 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: [0141] a
transmittance greater than seventy percent at 1300 and 1600 nm,
and/or [0142] 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 2500 to 3000
nm; [0143] a sloping overtone bands filter for filtering photons
having mean radial distances of 0.5 to 3.0 millimeters, the sloping
overtone bands filter comprising: [0144] 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 [0145]
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 [0146] a luminance filter for filtering
photons having mean radial distances of 0 to 5 millimeters, the
luminance first comprising: [0147] an optical spacing element
designed to maintain focal length; [0148] a mean transmittance
greater than seventy percent from 1100 to 1800 nm, and/or [0149] a
mean transmittance greater than seventy percent from 1100 to 2400
nm and an average transmittance of less than twenty percent from
1100 to 1400 nm and/or from 2000 to 2600 nm.
[0150] 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.
[0151] Referring again to FIG. 7B, the photon transport system 120
is illustrated delivering photons using and/or through one or more
optics to a point 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.
[0152] Still referring to FIG. 7B, as illustrated the photon
transport system delivers photons that are detected with an array
of 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
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.
[0153] 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.
[0154] 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, group,
sub-group, and/or group is optionally associated with an individual
filter, an individual optic, and/or an individual dynamic
optic.
[0155] 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 relative to 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.
[0156] 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 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.
[0157] 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 used as a function of time where the
illuminators define the number of photons delivered and provide a
first part of a illuminator-to-detector element distance and
selected detector elements as the same function of time define the
second part of the illuminator-to-detector distance.
[0158] 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.
[0159] 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.
[0160] 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 (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.
[0161] 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, such as a first detector array 702 and a second
detector array 704, is provided. In this second example, four
detector arrays are illustrated about a single illumination array.
In this second example, the first detector array 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. 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 a second detector
array 704, a third detector array 706, and a fourth detector array
706 positioned about the illumination zone from the photon
transport system 120, the inventor notes that the same five filters
positioned in different configuration 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 yields a plurality of
additional pathlengths. For brevity and clarity of presentation,
only the first filter, filter 1, is addressed. In the first
detector array 702, 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
array filter 704 monitors two additional mean pathlengths from the
mean illumination zone using the first filter and individual
detector elements. The third detector array 706 could measure the
same mean pathlengths as the second detector array 704; however,
preferably the third detector array 706 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 708 optionally measures a number of yet still
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 array 702, 704, 706, 708
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 702, 704, 706, 708 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.
[0162] Referring now to FIG. 8C, additional examples of
two-dimensional detector arrays are provided. Referring now to the
first detector array 702 and the second detector array 704, the
second detector array 704 relative to the first detector array
illustrates: [0163] 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 [0164] 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.
[0165] Referring now to the third detector array 706, 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 708, the two-dimensional detector array is 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 distances 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 702, 704, 706, 708, an optional range of
illuminator/detector gaps are illustrated 121, 123, 125, 127 for
the first through fourth detector arrays 702, 704, 706, 708,
respectively.
[0166] Referring now to FIG. 8D, yet another example of a multiple
two-dimensional detector array system is provided. In this example,
a first detector array 702 is configured with zones of regularly
shaped filters over multiple individual detector element sizes. For
example, a first filter, 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 a second optic,
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 fifth
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 702 in
this example is designed to optionally readout in rows, which
allows different rows to comprise different sizes of detector
elements.
[0167] Referring still to FIG. 8D, a second detector array 704 is
presented in a rotated configuration about the x-axis relative to
the first detector array 702. The rotation of the second detector
array 704 yields a continuum of pathlength ranges for a row of
detectors. For example, in the first detector array 702, 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
array 704 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 704 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 702 due to the rotation of the
second detector array in the y,z-plane relative to a line from a
center of the second array detector to a center of the illumination
zone.
[0168] Referring again to FIGS. 7 and 8, 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.
[0169] Still referring to FIGS. 7 and 8, 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.
Temporal Resolution
[0170] 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.
[0171] Referring now to FIGS. 9A-D, an example of a temporally
resolved gating system 900 is illustrated. Generally, in the
temporal gating system 900 the time of flight of a photon is used
to determine the pathlength, b. Referring now to FIG. 9A, at an
initial time, t.sub.0, an interrogation pulse 910 of one or more
photons is introduced to the sample, which herein is skin of the
subject 170. The interrogation pulse 910 is also referred to as a
pump pulse or as a flash of light. At one or more subsequent gated
detection times 920, after passing through the sample the
interrogation pulse 910 is detected. As illustrated, the gated
detection times are at a first time 922, t.sub.1; a second time
924, t.sub.2; a third time 926, t.sub.3; and at an n.sup.th time
928, t.sub.n, where n is a positive number. Optionally, the gated
detection times 920 overlap. For the near-infrared spectral region,
the elapsed time used to detect the interrogation photons 910 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)
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.
[0172] Referring now to FIG. 9B, illustrative paths of the photons
for the first gated detection time 922 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.
[0173] Referring now to FIG. 9C, illustrative paths of the photons
for the second gated detection time 924 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 924 is twice as long as the first gated detection
time 922, then the second pathlength, p.sub.2, for the second gated
detection time 924 is twice as long as the first pathlength,
p.sub.1, for the first gated detection time 922. 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.2a, 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.
[0174] Referring now to FIG. 9D, 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.
Spatial and Temporal Resolution
[0175] 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.
Analyzer and Subject Variation
[0176] 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, .epsilon., term,
as shown in equation 3:
A=.epsilon.bC (eq. 3)
[0177] 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 or determination are
provided infra.
Spatially Resolved Analyzer
[0178] 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.
[0179] Referring again to FIG. 1 and referring now to FIG. 10A, an
example of a fiber optic interface system 1000 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 1014
of a fiber optic bundle 1010. The fiber optic illumination bundle
1014 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 1016 of the fiber optic bundle 1010
contacts the subject 170 at the sample site 178. In a second case,
the sample interface tip 1016 of the fiber optic bundle 1010
proximately contacts the subject 170 at the sample site 178, but
leaves a sample interface gap 1020 between the sample interface tip
1016 of the fiber optic bundle 1010 and the subject 170. In one
instance, the sample interface gap 1020 is filled with a contact
fluid and/or an optical contact fluid. In a second instance, the
sample interface gap 1020 is filled with air, such as atmospheric
air. Light transported by the fiber optic bundle 1010 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 1018,
which is optionally and preferably integrated into the fiber optic
bundle 1010. As illustrated, a single collection fiber 718 is used.
The collection fiber 1018 transports collected light to the
detector 132 of the detection system 130.
[0180] Referring now to FIG. 10B, a first example of a sample side
light collection end 1016 of the fiber optic bundle 1010 is
illustrated. In this example, the single collection fiber 1018 is
circumferentially surrounded by an optional spacer 1030, where the
spacer has an average radial width of less than about 200, 150,
100, 50, or 25 micrometers. The optional spacer 1030 is
circumferentially surrounded by a set of fiber optic elements 1013.
As illustrated, the set of fiber optic elements 1013 are arranged
into a set of radial dispersed fiber optic rings, such as a first
ring 1041, a second ring 1042, a third ring 1043, a fourth ring
1044, and an n.sup.th ring 1045, where n comprises a positive
integer of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10. Optionally, the
fiber optic elements 1013 are in any configuration, such as in a
close-packed configuration about the collection fiber 1018 or in an
about close-packed configuration about the collection fiber 1018.
The distance of each individual fiber optic of the set of fiber
optic elements 1013, or light collection element, from the center
of the collection fiber 1018 is preferably known.
[0181] Referring now to FIG. 10C, a second example of the sample
side light collection end 1016 of the fiber optic bundle 1010 is
provided. In this example, the centrally positioned collection
fiber 1018 is circumferentially surrounded by a set of spacer
fibers 1050. 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
1050 are circumferentially surrounded by the radially dispersed
fiber optic rings, such as the first ring 1041, the second ring
1042, the third ring 1043, the fourth ring 1044, and the n.sup.th
ring 1045. Optionally, fiber diameters of the spacer fibers 1050
are at least ten, twenty, or thirty percent larger or smaller than
fiber diameters of the set of fiber optic elements 1013. Further,
optionally the fiber optic elements 1013 are arranged in any
spatial configuration radially outward from the spacer fibers 1050.
More generally, the set of fiber optic elements 1013 and/or spacer
fibers 1050 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.
Radial Distribution System
[0182] Referring now to FIG. 11A, FIG. 11B and FIG. 12, and FIGS.
13 A-D a system for spatial illumination 1100 of the sample site
178 of the subject 170 is provided. The spatial illumination system
1100 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.
Radial Position Using Fiber Optics
[0183] Referring now to FIG. 11A, a third example of the sample
side light collection end 1016 of the fiber optic bundle 1010 is
provided. In this example, the collection fiber 1018 or collection
optic is circumferentially surrounded by the set of fiber optic
elements 1013 or irradiation points on the skin of the subject 170.
For clarity of presentation and without loss of generality, the
fiber optic elements 1013 are depicted in a set of rings radially
distributed from the collection fiber 1018. However, it is
understood that the set of fiber optics 1013 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 1013 from the collection fiber
1018 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.
[0184] Referring now to FIG. 11B, an example of a light input end
1012 of the fiber optic bundle 1010 is provided. In this example,
individual fibers of the set of fiber optics 1013 having the same
or closely spaced radial distances from the collection fiber 1018
are grouped into a set of fiber optic bundles or a set of fiber
optic bundlets 1110. As illustrated, the seven fibers in the first
ring circumferentially surrounding the collection fiber 1018 are
grouped into a first bundlet 1111. Similarly, the sixteen fibers in
the second ring circumferentially surrounding the collection fiber
1018 are grouped into a second bundlet 1112. Similarly, the fibers
from the third, fourth, fifth, and sixth rings about the collection
fiber 1018 at the sample side illumination end 1016 of the fiber
bundle 1010 are grouped into a third bundlet 1113, a fourth bundlet
1114, a fifth bundlet 1115, and a sixth bundlet 1116, respectively.
For clarity of presentation, the individual fibers are not
illustrated in the second, third, fourth, fifth, and sixth bundlets
1112, 1113, 1114, 1115, 1116. Individual bundles and/or individual
fibers of the set of fiber optic bundlets 1110 are optionally
selectively illuminated using a mask 1120, described infra.
[0185] Referring now to FIG. 12 and FIG. 10A, a mask wheel 1130 is
illustrated. Generally, the mask wheel 1130 rotates, such as
through use of a wheel motor 1120. As a function of mask wheel
rotation position, holes or apertures through the mask wheel 1130
selectively pass light from the source system 110 to the fiber
optic input end 1012 of the fiber optic bundle 1010. 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 1012 of the fiber optic bundle or (2) individual
bundlets of the set of fiber optic bundlets 1110. Optionally an
encoder or marker section 1140 of the mask wheel 1130 is used for
tracking, determining, and/or validating wheel position in use.
[0186] Still referring to FIG. 12, an example of use of the mask
wheel 1130 to selectively illuminate individual bundlets of the set
of fiber optic bundlets 1110 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, 1121 is
illustrated at about the seven o'clock position. The first mask
position 1121 figuratively illustrates an aperture passing light
from the source system 110 to the first bundlet 1111 while blocking
light to the second through sixth bundlets 1112-1116. At a second
point in time, the mask wheel 1130 is rotated such that a second
mask position, p.sub.2, 1122 is aligned with the input end 1012 of
the fiber optic bundle 1010. As illustrated, at the second point in
time, the mask wheel 1130 passes light from the illumination system
110 to the second bundlet 1112, while blocking light to the first
bundlet 1111 and blocking light to the third through six bundlets
1113-1116. Similarly, at a third point in time the mask wheel uses
a third mask position, p.sub.3, 1123 to selectively pass light into
only the fifth bundlet 1115. Similarly, at a fourth point in time
the mask wheel uses a fourth mask position, p.sub.4, 1124 to
selectively pass light into only the sixth bundlet 1116.
[0187] Still referring to FIG. 12, 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 1130 is rotated such that a
fifth mask position, p.sub.5, 1125 is aligned with the input end
1012 of the fiber optic bundle 1010. 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 1112, (2)
the third bundlet 1113, and (3) the fourth bundlet 1114, while
blocking light to all of (1) the first bundlet 1111, (2) the fifth
bundlet 1115, and (3) the sixth bundlet 1116. Similarly, at a sixth
point in time a sixth mask position, p.sub.6, 1126 of the mask
wheel 1130 passes light to the second through fifth bundlets
1112-1115 while blocking light to both the first bundlet 1111 and
sixth bundlet 1116.
[0188] In practice, the mask wheel 1130 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 1013 and/or (2) bundlets 1110 of the set of fiber
optic optics 1013. 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 1013. 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.
Radial Position Using a Mirror and/or Lens System
[0189] Referring now to FIG. 13, a dynamically positioned optic
system 1000 for directing incident light to a radially changing
position about a collection zone is provided.
[0190] Referring now to FIG. 13A, a mirror 1310 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.
[0191] 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 1010, to dynamically control
incident light 711 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: [0192] x-axis position of the incident
light on the subject 170; [0193] y-axis position of the incident
light on the subject 170; [0194] solid angle of the incident light
on a single fiber of the fiber bundle 710; [0195] solid angle of
incident light on a set of fibers of the fiber bundle 710; [0196] a
cross-sectional diameter or width of the incident light; [0197] 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; [0198] focusing of the
incident light; and/or [0199] depth of focus of the incident light
on the subject 170.
[0200] 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 711 reaching a fiber optic
bundle, skin of the subject 170, and/or an element of the photon
transport system 120.
[0201] Referring again to FIG. 13A, 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 710, and/or through the photon transport system
120. However, orientation of the mirror 1310 is varied as a
function of time relative to an incident set of photons pathway.
For example, the mirror 1310 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
1322, such as a first spring or piezoelectric device, and a second
mirror movement element 1324, such as a second spring, combine to
rotate the mirror about the y-axis as illustrated. Similarly, a
third mirror movement element 1326, such as a third spring, and a
fourth mirror movement element 1328, such as a fourth spring,
combine to rotate the mirror about the z-axis as illustrated in the
second time position, t.sub.2, relative to a first time position,
t.sub.1.
[0202] Referring now to FIG. 13B, an example of the dynamically
positioned optic system 1300 directing the incident light 1011 to a
plurality of positions as a function of time is provided. As
illustrated, the mirror 1310 directs light to the light input end
1012 of the fiber bundle 1010. Particularly, the incident light
1011 is directed at a first time, t.sub.1, to a first fiber optic
1051 and the incident light 1011 is directed at a second time,
t.sub.2, to a second fiber optic 1052 of a set of fiber optics
1050. However, more generally, the dynamically positioned optic
system 1300 directs the incident light using the mirror 1300 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.
[0203] Referring now to FIG. 13C, an example of the dynamically
positioned optic system 1000 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 1011 onto the light input end 1012 of the fiber
bundle 1010 is varied as a function of time. As illustrated, the
mirror 1310 directs light to the light input end 1012 of the fiber
bundle 1010 where the fiber bundle 1010 includes one or more
bundlets, such as the set of fiber optic bundlets 1110. In this
example, the incident light is directed at a first time, t.sub.1,
with a first solid angle to a first fiber optic bunch or group,
such as the first bundlet 1111, 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 1112, described supra. However,
more generally, the dynamically positioned optic system 1300
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.
[0204] Referring now to FIG. 13D, an example is provided of the
dynamically positioned optic system 1300 directing the incident
light to a plurality of positions with a varying incident angle
onto skin of the subject 170. As illustrated, the mirror 1310
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 1310, such as with a grins lens on a fiber optic element of
the fiber optic bundle 1010. 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 1300 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.
Adaptive Subject Measurement
[0205] Delivery of the incident light 1011 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.
[0206] Referring now to FIG. 14A and FIG. 14B, examples of use of a
spatial illumination system 1400 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
1300 for directing incident light to a radially changing position
about a collection zone. Still more generally the photon transport
system 120 in FIGS. 14A and 14B 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 or to a detection
zone.
[0207] Referring now to FIG. 14A and FIG. 12, an example of
application of the spatial illumination system 1100 to the first
subject 171 is provided. At a first point in time, the first
position, p.sub.1, 1121 of the filter wheel 1130 is aligned with
the light input end 1012 of the fiber bundle 1010, which results in
the light from the first bundlet 1111, which corresponds to the
first ring 1041, 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. 11A has a mean optical path through the epidermis.
Similarly, at a second point in time, the filter wheel 1130 at the
second position 1122 passes light to the second bundlet 1112, 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. 14A has a mean optical path through the
epidermis and dermis. The dynamically positioned optic system 1300
is optionally used to direct light as a function of time to the
first position 1121 and subsequently to the second position 1122.
Similarly, results of interrogation of the subject 170 with light
passed through the six illustrative fiber illumination rings in
FIG. 11A is provided in Table 1. The results of Table 1 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-00001 TABLE 1 Subject 1 Illumination Ring Deepest Tissue
Layer Probed 1 Epidermis 2 Dermis 3 Dermis 4 Dermis 5 Subcutaneous
Fat 6 Subcutaneous Fat
[0208] Referring now to FIG. 14B and FIG. 11A, an example of
application of the spatial illumination system 1100 to the second
subject 172 is provided. Again, the dynamically positioned optic
system 1300 is optionally used to deliver light to the spatial
illumination system 1100. Results of interrogation of the subject
170 with light passed through the six illustrative fiber
illumination rings in FIG. 8A is provided in Table 2. 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-00002 TABLE 2 Subject 2 Illumination Ring Deepest Tissue
Layer Probed 1 Epidermis 2 Dermis 3 Dermis 4 Dermis 5 Dermis 6
Subcutaneous Fat
[0209] 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.
Incident Light Control
[0210] Referring again to FIGS. 13A-D, the dynamically positioned
optic system 1300 is optionally used as a function of time to
control one or more of: [0211] delivery of the incident light 1011
to a single selected fiber optic of the fiber optic bundle 1010;
[0212] delivery of the incident light 1011 to a selected bundlet of
the set of fiber optic bundlets 1110, such as to the first bundlet
1111 at a first point in time and to the second bundlet 1112 at a
second point in time; [0213] variation of solid angle of the
incident light 1011 to an optic and/or to the subject 170; [0214]
variation of radial position of delivery of the incident light 1011
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; [0215] incident angle of the incident light 1011 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;
[0216] apparent focus depth of the incident light 1011 into the
skin of the subject 170; [0217] energy; and [0218] 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.
Time Resolved Spectroscopy
[0219] 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
3 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-00003 TABLE 3 Time Resolved Spectroscopy Elapsed Time
(picoseconds) Deepest Tissue Layer Probed 1 Epidermis 10 Dermis 50
Dermis 100 Subcutaneous Fat
Data Processing
[0220] Referring now to FIG. 15, the data processing system 140 is
further described. The data processing system 140 optionally uses a
step of post-processing 1520 to process a set of collected data
1510. The post-processing step 1120 optionally operates on data
collected as a function of any of: radial distance of the incident
light 1011 to a reference point, such as a detector; solid angle of
the incident light 1011 relative to the subject 170; angle of the
incident light 1011 relative to skin of the subject 170; and/or
depth of focus of the incident light 1011 relative to a surface of
the skin of the subject 170.
Two-Phase Measurement(s)
[0221] Referring now to FIG. 16, in another embodiment, the
analyzer 100 is used in two phase system 1600: (1) a sample mapping
phase 1610, such as a subject or group mapping phase and (2) a
subject specific data collection phase 1630. In one example, in the
first mapping phase 1610, skin of the subject 170 is analyzed with
the analyzer 100 using a first optical configuration. Subsequently,
the mapping phase spectra are analyzed 1620. In the second subject
specific data collection phase 1630, the analyzer 100 is setup in a
second optical configuration based upon data collected in the
sample mapping phase 1610. 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 1610 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 1610 and a subsequent subject specific data collection phase
1630.
[0222] In a first example, referring again to FIG. 14A and FIG.
14B, a first optional two-phase measurement approach is herein
described. Optionally, during the first sample mapping phase 1610,
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.
[0223] 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 1610, the fifth
and sixth radial positions of the fiber probe illustrated in FIG.
11A, 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
1630 and that the fourth radial fiber optic ring or distance should
be used in the second subject specific data collection phase 1630.
Subsequently, in the second subject specific data collection phase
1630, 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.
[0224] In a third example, the first sample mapping phase 1610 of
the previous example is repeated for the second subject 172. The
first sample mapping phase 1610 indicates that for the second
subject, the sixth radial illumination ring of the fiber bundle
illustrated in FIG. 11A should not be used, but that the fourth and
fifth radial illumination ring should be used.
[0225] In a fourth example, the first mapping phase 1610 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 1630, 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.
[0226] Generally, a particular subject is optionally probed in a
sample mapping phase 1610 and results from the sample mapping phase
1610 are optionally used to configure analyzer parameters in a
subsequent subject specific data collection phase 1630. 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
1610, 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 1610 and sample
specific data collection phase 1630 occur within thirty seconds of
each other. Optionally, the subject 170 does not move away from the
sample interface 150 between the sample mapping phase 1610 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.
[0227] In yet another embodiment, the sample interface tip 1016 of
the fiber optic bundle 1010 includes optics that change the mean
incident light angle of individual fibers of the fiber optic bundle
1016 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 1018; a second optic at the end of a
fiber in the second ring 1042 aims light nominally straight into
the sample; and a third optic at the end of a fiber in the third
ring 1042 aims light toward the collection fiber 1018. Generally,
the mean direction of the incident light varies by greater than 5,
10, 15, 20, or 25 degrees.
Data Processing System
[0228] The data processing system 140 is further described herein.
Generally, the data processing system uses an instrument
configuration analysis system 1640 to determine an optical
configuration of the analyzer 100 and/or a software configuration
of the analyzer 100 while the sample property analysis system 1650
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.
[0229] 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.
[0230] In another embodiment, the data processing system 140 and/or
the sample property analysis system 1650 operates on spectra
collected by the analyzer 100, such as in the subject specific data
collection phase 1630, using a first step of defining finite width
channels and a second step of feature extraction, which are each
further described, infra.
Finite Width Channels
[0231] In one example, the sample property analysis system 1650
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.
[0232] In one case, the sample property analysis system 1650
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.
Feature Extraction
[0233] 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.
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.
Model
[0234] 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.
Absorbance Spectra
[0235] 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.
Personal Communication Device
[0236] Herein, a personal communication device comprises any of a
wireless phone, a cell phone, a smart phone, a tablet, and/or a
wearable internet connectable accessory, a wearable internet
connectable garment.
[0237] Still yet another embodiment includes any combination and/or
permutation of any of the analyzer and/or sensor elements described
herein.
[0238] 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.
[0239] 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.
[0240] 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.
[0241] 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.
[0242] 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.
[0243] 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.
* * * * *