U.S. patent application number 13/941411 was filed with the patent office on 2015-01-15 for dynamic sample mapping 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, Timothy Ruchti. Invention is credited to Alan Abul-Haj, Thomas George, Sandeep Gulati, Kevin H. Hazen, Timothy Ruchti.
Application Number | 20150018646 13/941411 |
Document ID | / |
Family ID | 52276852 |
Filed Date | 2015-01-15 |
United States Patent
Application |
20150018646 |
Kind Code |
A1 |
Gulati; Sandeep ; et
al. |
January 15, 2015 |
DYNAMIC SAMPLE MAPPING NONINVASIVE ANALYZER APPARATUS AND METHOD OF
USE THEREOF
Abstract
A noninvasive analyzer apparatus and method of use thereof is
described using a sample mapping phase to establish one or more
analyzer/software parameters used in a subsequent individual and/or
group specific data collection phase. For example, in the sample
mapping phase distance between incident and collected light is
varied as a function of time for collected noninvasive spectra.
Spectra collected in the sample mapping phase are analyzed to
determine a physiological property of the subject, such as dermal
thickness, hydration, collagen density, epidermal thickness, and/or
subcutaneous fat depth. Using the physiological property or measure
thereof, the analyzer is optically reconfigured for the individual
to yield subsequent spectra having enhanced features for
noninvasive analyte property determination. Similarly, in the
mapping and/or collection phase, the incident light is varied in
time in terms of any of: sample probe position, incident light
solid angle, incident light angle, depth of focus, energy, and/or
intensity.
Inventors: |
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 |
Gulati; Sandeep
George; Thomas
Ruchti; Timothy
Abul-Haj; Alan
Hazen; Kevin H. |
La Canada
La Canada
Gurnee
Mesa
Gilbert |
CA
CA
IL
AZ
AZ |
US
US
US
US
US |
|
|
Family ID: |
52276852 |
Appl. No.: |
13/941411 |
Filed: |
July 12, 2013 |
Current U.S.
Class: |
600/322 |
Current CPC
Class: |
A61B 5/14552 20130101;
A61B 5/0022 20130101; G01N 21/474 20130101; G01N 2021/4742
20130101; G01N 2021/4747 20130101; A61B 5/6801 20130101; G01J 3/42
20130101; A61B 5/14532 20130101; A61B 5/1455 20130101; G01N
2201/0826 20130101; A61B 5/1079 20130101 |
Class at
Publication: |
600/322 |
International
Class: |
A61B 5/1455 20060101
A61B005/1455; A61B 5/145 20060101 A61B005/145; A61B 5/107 20060101
A61B005/107 |
Claims
1. A method for determining a concentration of a blood borne
analyte of a subject, comprising the steps of: collecting a
plurality of mapping spectra of the subject using a noninvasive
analyzer setup in a first set of optical configurations;
calculating a metric related to skin tissue physiology of the
subject using the mapping spectra; based on the metric, setting up
said analyzer in a second set of optical configurations, the first
set of optical configurations configured to deliver light to the
subject in a manner different than the second set of optical
configurations; collecting subject specific noninvasive spectra of
the subject using the second set of optical configurations; and
post-processing the subject specific noninvasive spectra to
determine the concentration.
2. The method of claim 1, wherein said step of collecting a
plurality of mapping spectra comprises the step of: tilting an
optic of said analyzer to at least three orientations and
collecting the mapping spectra sequentially at each of the at least
three orientations of the optic.
3. The method of claim 1, wherein said step of collecting a
plurality of mapping spectra comprises the step of: sequentially
collecting a set of spectra using at least three different mean
radial distances between incident light from said analyzer entering
skin of the subject and a detection zone of detected light exiting
the skin of the subject to a detector system of said analyzer,
wherein the three different mean radial distances differ from each
other by at least ten micrometers, wherein the three mean radial
distances are each less than one millimeter.
4. The method of claim 1, wherein said step of collecting a
plurality of mapping spectra comprises the step of: sequentially
collecting a set of spectra using at least three different mean
radial distances between incident light from said analyzer entering
skin of the subject and a detection zone of detected light exiting
the skin of the subject to a detector system of said analyzer,
wherein the three different mean radial distances differ from each
other by at least one-fifth of a millimeter, wherein the three mean
radial distances are each less than four millimeters.
5. The method of claim 4, wherein said step of calculating a metric
related to skin tissue physiology comprises any of the steps of:
generating an epidermal thickness measure of the skin tissue
physiology; generating a dermis thickness measure of the skin
tissue physiology; and generating a subcutaneous fat depth measure
of the skin tissue physiology.
6. The method of claim 4, wherein said step of calculating a metric
related to skin tissue physiology comprises any of the steps of:
calculating a measure of pathlength through an aqueous medium;
calculating a measure of pathlength through a fat medium; and
calculating a measure of signal-to-noise ratio for any of the set
of spectra at the at least three different mean radial
distances.
7. The method of claim 4, wherein said step of setting up said
analyzer in the second set of optical configurations increases mean
absorbance of spectra with any of: (1) a range of 1325 to 1375 nm,
(2) a range of 1375 to 1425 nm, (3) a range of 1425 to 1475, and
(4) a range of 1475 to 1525 nanometers by at least ten percent
relative to absorbance collected using the first set of optical
configurations.
8. The method of claim 4, wherein said step of setting up said
analyzer in the second set of optical configurations increases an
average absorbance ratio of spectra at 1450 nanometers to that at
1720 nanometers relative to the mapping spectra using the first set
of optical configurations.
9. The method of claim 4, wherein a mean range of radial distance
between the incident light entering the skin and the collected
light exiting the skin is greater for said plurality of mapping
spectra than for the subject specific noninvasive spectra.
10. The method of claim 1, wherein the plurality of mapping spectra
comprise spectra collected in more optical configurations of said
analyzer than used to collect the subject specific noninvasive
spectra.
11. The method of claim 1, said step of post-processing further
comprising the step of: determining correlation between two
non-overlapping wavelength ranges of the subject specific
noninvasive spectra.
12. The method of claim 1, said step of post-processing further
comprising the steps of: defining finite width channels for the
noninvasive spectra; calculating coherence between the channels to
form a set of cross-coherence values; and selecting a subset of the
set of cross-coherence values for subsequent multivariate
analysis.
13. The method of claim 1, said step of post-processing further
comprising the step of: generating a N.times.N grid of at least one
spectrum of the subject specific noninvasive spectra, symmetrical
about a diagonal of the N.times.N grid, wherein elements of the
N.times.N grid represent a coherence estimate versus frequency,
wherein N comprises a positive integer of at least ten.
14. The method of claim 1, further comprising the step of: using a
model and said metric in said step of setting up said analyzer.
15. An apparatus for determining a concentration of a blood borne
analyte of a subject, comprising: a noninvasive analyzer,
comprising: a source configured to provide photons; a photon
transport system configured to deliver the photons to the subject;
and a detector system configured to receive the photons from the
subject, said analyzer configured to collect a plurality of mapping
spectra of the subject using said analyzer in a first set of
optical configurations; and a data processing system, said data
processing system configured to: calculate a metric related to skin
tissue physiology of the subject using the mapping spectra; and set
up said analyzer in a second set of optical configurations, the
first set of optical configurations configured to deliver light to
the subject in a manner different than the second set of optical
configurations, said analyzer configured to collect subject
specific noninvasive spectra of the subject using the second
optical configuration, and said data processing system configured
to post-process the subject specific noninvasive spectra to
determine the concentration.
16. The apparatus of claim 15, said analyzer further comprising: a
tiltable optic, said tiltable optic configured in at least three
distinct orientations during collection of the mapping spectra.
17. The apparatus of claim 15, said analyzer further comprising:
means for sequentially collecting a set of spectra using at least
three different mean radial distances between incident light from
said source entering skin of the subject and a detection zone of
detected light exiting the skin of the subject to said detector
system, wherein the three different mean radial distances differ
from each other by at least one-half millimeter, wherein the three
mean radial distances are each less than four millimeters.
18. The apparatus of claim 15, said analyzer comprising: a set of
at least three fiber optics at at least three radial positions from
a mean position of photons exiting the subject into said detector
system; and a photon delivery system configured to individually and
sequentially illuminate each of said set of at least three fiber
optics with the photons from said source.
19. The apparatus of claim 15, said photon transport system
comprising: at least one optic configured to deliver a mean path of
the photons to the subject at at least three positions separated
from each other by at least one-twentieth of a millimeter as a
function of time.
20. The apparatus of claim 15, said photon transport system
comprising: at least one optic configurable to at least three focal
lengths as a function of time.
21. The apparatus of claim 15, said analyzer further comprising: a
time resolved gating system configured to detect the photons in a
pulse mode from the source in time periods greater than one
femtosecond and less than one hundred milliseconds after the
photons leave the source.
22. The apparatus of claim 15, said photon transport system
comprising: at least one optic configurable to deliver the photons
to the subject, during a single sampling period of less than one
minute, at at least three mean incident angles relative to a plane
normal to the subject, wherein the at least three mean incident
angles differ from each other by greater than five degrees as a
function of time.
23. The apparatus of claim 15, said data processing system
configured to: calculate a set of coherence values between finite
width channels of elements of the noninvasive spectra; and use said
set of coherence values in determination of the concentration of
the blood borne analyte of the subject.
Description
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application is: [0002] a continuation-in-part of U.S.
patent application Ser. No. 13/941,389 filed Jul. 12, 2013, which:
[0003] is a continuation-in-part of U.S. patent application Ser.
No. 13/941,369 filed Jul. 12, 2013, which claims the benefit of
U.S. provisional patent application No. 61/672,195 filed Jul. 16,
2012; and [0004] claims the benefit of U.S. provisional patent
application No. 61/700,291 filed Sep. 12, 2012; and [0005] claims
the benefit of U.S. provisional patent application No. 61/700,294
filed Sep. 12, 2012 [0006] all of which are incorporated herein in
their entirety by this reference thereto.
TECHNICAL FIELD OF THE INVENTION
[0007] 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
[0008] Patents and literature related to the current invention are
summarized herein.
Diabetes
[0009] 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).
[0010] 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.
[0011] 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.
[0012] 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
[0013] 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
[0014] 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.
[0015] 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
[0016] 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.
[0017] 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.
[0018] 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
[0019] 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.
[0020] 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
[0021] What is needed is a noninvasive glucose concentration
analyzer having precision and accuracy suitable for treatment of
diabetes mellitus.
SUMMARY OF THE INVENTION
[0022] The invention comprises a noninvasive analyzer apparatus
having dynamic control of distance between a plurality of
irradiation zones and a detection zone and a method of use
thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] 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.
[0024] FIG. 1 illustrates an analyzer;
[0025] FIG. 2 illustrates diffusely reflecting optical paths;
[0026] FIG. 3 illustrates probing tissue layers using a spatial
distribution method;
[0027] FIG. 4 illustrates varying illumination zones relative to a
detector;
[0028] FIG. 5 illustrates varying detection zones relative to an
illuminator;
[0029] FIG. 6(A-D) illustrate temporal resolution gating, FIG. 6A;
probabilistic optical paths for a first elapsed time, FIG. 6B;
probabilistic optical paths for a second elapsed time, FIG. 6C; and
a temporal distribution method, FIG. 6D;
[0030] FIG. 7(A-C) illustrate a fiber optic bundle, FIG. 7A; a
first example sample interface end of the fiber optic bundle, FIG.
7B; and a second example sample interface end of the fiber optic
bundle, FIG. 7C;
[0031] FIG. 8A illustrates a third example sample interface end of
the fiber optic bundle and FIG. 8B illustrates a mask;
[0032] FIG. 9 illustrates a mask selection wheel;
[0033] FIG. 10A illustrates a position selection optic; FIG. 10B
illustrates the position selection optic selecting position; FIG.
10C illustrates solid angle selection using the position selection
optic; and FIG. 10D illustrates radial control of incident light
relative to a detection zone;
[0034] FIG. 11(A-B) illustrate a pathlength resolved sample
interface for (1) a first subject, FIG. 11A and (2) a second
subject, FIG. 11B;
[0035] FIG. 12 provides a method of use of a data processing
system; and
[0036] FIG. 13 provides a method of using a sample mapping phase
and a subsequent subject specific data collection phase.
[0037] 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
[0038] The invention comprises an apparatus and method of use
thereof for acquisition of noninvasive mapping spectra of skin and
to reconfigure the apparatus based upon the mapping spectra for
subsequent subject specific data collection.
[0039] 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.
[0040] In 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.
[0041] In still another embodiment, an analyzer using light
interrogates the sample using one or more of: [0042] a spatially
resolved system; [0043] an incident light radial distance resolved
system; [0044] a controllable and variable incident light solid
angle system; and [0045] a controllable and variable incident light
angle system; [0046] a time resolved system, where the times are
greater than about 1, 10, 100, or 1000 microseconds; [0047] a
picosecond timeframe resolved system, where times are less than
about 1, 10, 100, or 1000 nanoseconds; [0048] collection of spectra
with varying radial distances between incident light entering skin
and detected light exiting the skin; [0049] an incident angle
resolved system; and [0050] a collection angle resolved system.
[0051] Data from the analyzer is analyzed using a data processing
system capable of using the information inherent in the resolved
system data.
[0052] 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.
[0053] 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.
[0054] In still yet another embodiment, a data processing system
uses information related to contact pressure on a tissue sample
site.
[0055] In another embodiment, a data processing system uses a
combination of any of: [0056] spatially resolved information;
[0057] temporally resolved information on a time scale of longer
than about one microsecond; [0058] temporally resolved information
on a sub one hundred picosecond timeframe; [0059] incident photon
angle information; [0060] photon collection angle information;
[0061] interrelationships of spectral absorbance and/or intensity
information; [0062] environmental information; [0063] temperature
information; and [0064] information related to contact pressure on
a tissue sample site.
[0065] 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
[0066] 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.
[0067] 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.
[0068] 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
[0069] 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
[0070] 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
[0071] Still referring to FIG. 1, 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 smart phone
192, 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.
[0072] 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.
[0073] 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.
[0074] 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.
Source
[0075] 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
[0076] Light interacts with skin through laws of physics to scatter
and transmit through skin voxels.
[0077] 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 and for some temperatures, that mean photon depth of
penetration increases with mean radial distance between a photon
illumination zone and a photon detection zone.
[0078] Referring still to FIG. 2, 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, or 1/4mm.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.
Pathlength
[0079] 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.
[0080] 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
[0081] 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
[0082] 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.
[0083] 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.
[0084] 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.
[0085] 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.
[0086] 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.
Temporal Resolution
[0087] 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.
[0088] Referring now to FIGS. 6A-D, an example of a temporally
resolved gating system 600 is illustrated. Generally, in the
temporal gating system 600 the time of flight of a photon is used
to determine the pathlength, b. Referring now to FIG. 6A, at an
initial time, t.sub.0, an interrogation pulse 610 of one or more
photons is introduced to the sample, which herein is skin of the
subject 170. The interrogation pulse 610 is also referred to as a
pump pulse or as a flash of light. At one or more subsequent gated
detection times 620, after passing through the sample the
interrogation pulse 610 is detected. As illustrated, the gated
detection times are at a first time 622, t.sub.1; a second time
624, t.sub.2; a third time 626, t.sub.3; and at an n.sup.th time
628, t.sub.n, where n is a positive number. Optionally, the gated
detection times 620 overlap. For the near-infrared spectral region,
the elapsed time used to detect the interrogation photons 610 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 ) ##EQU00001##
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.
[0089] Referring now to FIG. 6B, illustrative paths of the photons
for the first gated detection time 622 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.
[0090] Referring now to FIG. 6C, illustrative paths of the photons
for the second gated detection time 624 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 624 is twice as long as the first gated detection
time 622, then the second pathlength, p.sub.2, for the second gated
detection time 624 is twice as long as the first pathlength,
p.sub.1, for the first gated detection time 622. Knowledge of
anisotropy is optionally used to decrease the probability spread of
paths observed in the second set of pathlengths, p.sub.2a,
p.sub.2b, p.sub.2c. Similarly a-priori knowledge of approximate
physiological thickness of varying tissue layers, such as an
epidermal thickness of a patient, an average epidermal thickness of
a population, a dermal thickness of a patient, and/or an average
dermal thickness of a population is optionally used to reduce error
in an estimation of pathlength, a product of pathlength and a molar
absorptivity, and/or a glucose concentration by limiting bounds of
probability of a photon traversing different pathways through the
skin layers and still returning to the detection element with the
elapsed time. Similarly, knowledge of an index of refraction of one
or more sample constituents and/or a mathematical representation of
probable indices of refraction is also optionally used to reduce
error in estimation of a pathlength, molar absorptivity, and/or an
analyte property concentration estimation. Still further, knowledge
of an incident point or region of light entering she skin of the
subject relative to a detection zone is optionally used to further
determine probability of a photon traversing dermal or subcutaneous
fat layers along with bounding errors of pathlength in each
layer.
[0091] Referring now to FIG. 6D, 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
[0092] 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
[0093] 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)
[0094] 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
[0095] 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.
[0096] Referring now to FIG. 7A, an example of a fiber optic
interface system 700 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 714 of a fiber optic bundle
710. The fiber optic illumination bundle 714 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 716 of the fiber optic bundle 710 contacts the
subject 170 at the sample site 178. In a second case, the sample
interface tip 716 of the fiber optic bundle 710 proximately
contacts the subject 170 at the sample site 178, but leaves a gap
720 between the sample interface tip 716 of the fiber optic bundle
710 and the subject 170. In one instance, the gap 720 is filled
with a contact fluid and/or an optical contact fluid. In a second
instance, the gap 720 is filled with air, such as atmospheric air.
Light transported by the fiber optic bundle 710 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 718, which is
optionally and preferably integrated into the fiber optic bundle
710. As illustrated, a single collection fiber 718 is used. The
collection fiber 718 transports collected light to the detector 132
of the detection system 130.
[0097] Referring now to FIG. 7B, a first example of a sample side
light collection end 716 of the fiber optic bundle 710 is
illustrated. In this example, the single collection fiber 718 is
circumferentially surrounded by an optional spacer 730, where the
spacer has an average radial width of less than about 200, 150,
100, 50, or 25 micrometers. The optional spacer 730 is
circumferentially surrounded by a set of fiber optic elements 713.
As illustrated, the set of fiber optic elements 713 are arranged
into a set of radial dispersed fiber optic rings, such as a first
ring 741, a second ring 742, a third ring 743, a fourth ring 744,
and an n.sup.th ring 745, where n comprises a positive integer of
at least 2, 3, 4, 5, 6, 7, 8, 9, or 10. Optionally, the fiber optic
elements 713 are in any configuration, such as in a close-packed
configuration about the collection fiber 718 or in an about
close-packed configuration about the collection fiber 718. The
distance of each individual fiber optic of the set of fiber optic
elements 713, or light collection element, from the center of the
collection fiber 718 is preferably known.
[0098] Referring now to FIG. 7C, a second example of the sample
side light collection end 716 of the fiber optic bundle 710 is
provided. In this example, the centrally positioned collection
fiber 718 is circumferentially surrounded by a set of spacer fibers
750. 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 750 are
circumferentially surrounded by the radially dispersed fiber optic
rings, such as the first ring 741, the second ring 742, the third
ring 743, the fourth ring 744, and the n.sup.th ring 745.
Optionally, fiber diameters of the spacer fibers 750 are at least
ten, twenty, or thirty percent larger or smaller than fiber
diameters of the set of fiber optic elements 713. Further,
optionally the fiber optic elements 713 are arranged in any spatial
configuration radially outward from the spacer fibers 750. More
generally, the set of fiber optic elements 713 and/or spacer fibers
750 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
[0099] Referring now to FIG. 8A, FIG. 8B and FIG. 9, and FIGS. 10
A-D a system for spatial illumination 800 of the sample site 178 of
the subject 170 is provided. The spatial illumination system 800 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
[0100] Referring now to FIG. 8A, a third example of the sample side
light collection end 716 of the fiber optic bundle 710 is provided.
In this example, the collection fiber 718 or collection optic is
circumferentially surrounded by the set of fiber optic elements 713
or irradiation points on the skin of the subject 170. For clarity
of presentation and without loss of generality, the fiber optic
elements 713 are depicted in a set of rings radially distributed
from the collection fiber 718. However, it is understood that the
set of fiber optics 713 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 713 from the collection fiber 718 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.
[0101] Referring now to FIG. 8B, an example of a light input end
712 of the fiber optic bundle 710 is provided. In this example,
individual fibers of the set of fiber optics 713 having the same or
closely spaced radial distances from the collection fiber 718 are
grouped into a set of fiber optic bundles or a set of fiber optic
bundlets 810. As illustrated, the seven fibers in the first ring
circumferentially surrounding the collection fiber 718 are grouped
into a first bundlet 811. Similarly, the sixteen fibers in the
second ring circumferentially surrounding the collection fiber 718
are grouped into a second bundlet 812. Similarly, the fibers from
the third, fourth, fifth, and sixth rings about the collection
fiber 718 at the sample side illumination end 716 of the fiber
bundle 710 are grouped into a third bundlet 813, a fourth bundlet
814, a fifth bundlet 815, and a sixth bundlet 816, respectively.
For clarity of presentation, the individual fibers are not
illustrated in the second, third, fourth, fifth, and sixth bundlets
812, 813, 814, 815, 816. Individual bundles and/or individual
fibers of the set of fiber optic bundlets 810 are optionally
selectively illuminated using a mask 820, described infra.
[0102] Referring now to FIG. 9 and FIG. 7A, a mask wheel 830 is
illustrated. Generally, the mask wheel 830 rotates, such as through
use of a wheel motor 820. As a function of mask wheel rotation
position, holes or apertures through the mask wheel 830 selectively
pass light from the source system 110 to the fiber optic input end
712 of the fiber optic bundle 710. 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 712 of the fiber optic bundle or (2) individual bundlets
of the set of fiber optic bundlets 810. Optionally an encoder or
marker section 840 of the mask wheel 830 is used for tracking,
determining, and/or validating wheel position in use.
[0103] Still referring to FIG. 9, an example of use of the mask
wheel 830 to selectively illuminate individual bundlets of the set
of fiber optic bundlets 810 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, 821 is
illustrated at about the seven o'clock position. The first mask
position 821 figuratively illustrates an aperture passing light
from the source system 110 to the first bundlet 811 while blocking
light to the second through sixth bundlets 812-816. At a second
point in time, the mask wheel 830 is rotated such that a second
mask position, p.sub.2, 822 is aligned with the input end 712 of
the fiber optic bundle 710. As illustrated, at the second point in
time, the mask wheel 830 passes light from the illumination system
110 to the second bundlet 812, while blocking light to the first
bundlet 811 and blocking light to the third through six bundlets
813-816. Similarly, at a third point in time the mask wheel uses a
third mask position, p.sub.3, 823 to selectively pass light into
only the fifth bundlet 815. Similarly, at a fourth point in time
the mask wheel uses a fourth mask position, p.sub.4, 824 to
selectively pass light into only the sixth bundlet 816.
[0104] Still referring to FIG. 9, 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 830 is rotated such that a
fifth mask position, p.sub.5, 825 is aligned with the input end 712
of the fiber optic bundle 710. As illustrated, at the fifth point
in time, the mask wheel 830 passes light from the illumination
system 110 to all of (1) the second bundlet 812, (2) the third
bundlet 813, and (3) the fourth bundlet 814, while blocking light
to all of (1) the first bundlet 811, (2) the fifth bundlet 815, and
(3) the sixth bundlet 816. Similarly, at a sixth point in time a
sixth mask position, p.sub.6, 826 of the mask wheel 830 passes
light to the second through fifth bundlets 812-815 while blocking
light to both the first bundlet 811 and sixth bundlet 816.
[0105] In practice, the mask wheel 830 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 713 and/or (2) bundlets 810 of the set of fiber optic
optics 713. 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 713. 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
[0106] Referring now to FIG. 10, a dynamically positioned optic
system 1000 for directing incident light to a radially changing
position about a collection zone is provided.
[0107] Referring now to FIG. 10A, a mirror 1010 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.
[0108] 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: [0109] x-axis position of the incident
light on the subject 170; [0110] y-axis position of the incident
light on the subject 170; [0111] solid angle of the incident light
on a single fiber of the fiber bundle 710; [0112] solid angle of
incident light on a set of fibers of the fiber bundle 710; [0113] a
cross-sectional diameter or width of the incident light; [0114] 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; [0115] focusing of the
incident light; and/or [0116] depth of focus of the incident light
on the subject 170.
[0117] 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.
[0118] Referring again to FIG. 10A, 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 1010 is varied as a
function of time relative to an incident set of photons pathway.
For example, the mirror 1010 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
1022, such as a first spring, and a second mirror movement element
1024, such as a second spring, combine to rotate the mirror about
the y-axis as illustrated. Similarly, a third mirror movement
element 1026, such as a third spring, and a fourth mirror movement
element 1028, 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.
[0119] Referring now to FIG. 10B, an example of the dynamically
positioned optic system 1000 directing the incident light 711 to a
plurality of positions as a function of time is provided. As
illustrated, the mirror 1010 directs light to the light input end
712 of the fiber bundle 710. Particularly, the incident light 711
is directed at a first time, t.sub.1, to a first fiber optic 751
and the incident light 711 is directed at a second time, t.sub.2,
to a second fiber optic 752 of a set of fiber optics 750. However,
more generally, the dynamically positioned optic system 1000
directs the incident light using the mirror 1000 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.
[0120] Referring now to FIG. 10C, 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 711 onto the light input end 712 of the fiber bundle
710 is varied as a function of time. As illustrated, the mirror
1010 directs light to the light input end 712 of the fiber bundle
710 where the fiber bundle 710 includes one or more bundlets, such
as the set of fiber optic bundlets 810. 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 811, 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 812, described supra. However, more generally,
the dynamically positioned optic system 1000 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.
[0121] Referring now to FIG. 10D, an example is provided of the
dynamically positioned optic system 1000 directing the incident
light to a plurality of positions with a varying incident angle
onto skin of the subject 170. As illustrated, the mirror 1010
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 1010, such as with a grins lens on a fiber optic element of
the fiber optic bundle 710. 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 1000 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 an lens or mirror of the photon transport system 120 as
interacting with the detector system 130 and a detector
therein.
Adaptive Subject Measurement
[0122] Delivery of the incident light 711 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.
[0123] Referring now to FIG. 11A and FIG. 11B, examples of use of a
spatial illumination system 1100 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
1000 for directing incident light to a radially changing position
about a collection zone. Still more generally the photon transport
system 120 in FIGS. 11A and 11B 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.
[0124] Referring now to FIG. 11A and FIG. 9, an example of
application of the spatial illumination system 800 to the first
subject 171 is provided. At a first point in time, the first
position, p.sub.1, 821 of the filter wheel 830 is aligned with the
light input end 712 of the fiber bundle 710, which results in the
light from the first bundlet 811, which corresponds to the first
ring 741, 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 830 at the
second position 822 passes light to the second bundlet 812, 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. 11A has a mean optical path through the
epidermis and dermis. The dynamically positioned optic system 1000
is optionally used to direct light as a function of time to the
first position 821 and subsequently to the second position 822.
Similarly, results of interrogation of the subject 170 with light
passed through the six illustrative fiber illumination rings in
FIG. 8A 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
[0125] Referring now to FIG. 11B and FIG. 8A, an example of
application of the spatial illumination system 800 to the second
subject 172 is provided. Again, the dynamically positioned optic
system 1000 is optionally used to deliver light to the spatial
illumination system 800. 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
[0126] 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
[0127] Referring again to FIGS. 10A-D, the dynamically positioned
optic system 1000 is optionally used as a function of time to
control one or more of: [0128] delivery of the incident light 711
to a single selected fiber optic of the fiber optic bundle 710;
[0129] delivery of the incident light 711 to a selected bundlet of
the set of fiber optic bundlets 810, such as to the first bundlet
811 at a first point in time and to the second bundlet 812 at a
second point in time; [0130] variation of solid angle of the
incident light 711 to an optic and/or to the subject 170; [0131]
variation of radial position of delivery of the incident light 711
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; [0132] incident angle of the incident light 711 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;
[0133] apparent focus depth of the incident light 711 into the skin
of the subject 170; [0134] energy; and [0135] 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
[0136] 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
[0137] Referring now to FIG. 12, the data processing system 140 is
further described. The data processing system 140 is optionally
uses a step of post-processing 1120 to process a set of collected
data 1210. The post-processing step 1120 optionally operates on
data collected as a function of any of: radial distance of the
incident light 711 to a reference point, such as a detector; solid
angle of the incident light 711 relative to the subject 170; angle
of the incident light 711 relative to skin of the subject 170;
and/or depth of focus of the incident light 711 relative to a
surface of the skin of the subject 170.
Two-Phase Measurement(s)
[0138] Referring now to FIG. 13, in another embodiment, the
analyzer 100 is used in two phase system 1300: (1) a sample mapping
phase 1310, such as a subject or group mapping phase and (2) a
subject specific data collection phase 1330. In one example, in the
first mapping phase 1310, skin of the subject 170 is analyzed with
the analyzer 100 using a first optical configuration. Subsequently,
the mapping phase spectra are analyzed 1320. In the second subject
specific data collection phase 1330, the analyzer 100 is setup in a
second optical configuration based upon data collected in the
sample mapping phase 1310. 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 1310 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 1310 and a subsequent subject specific data collection phase
1330.
[0139] In a first example, referring again to FIG. 11A and FIG.
11B, a first optional two-phase measurement approach is herein
described. Optionally, during the first sample mapping phase 1310,
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.
[0140] 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 1310, the fifth
and sixth radial positions of the fiber probe illustrated in FIG.
8A, 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
1330 and that the fourth radial fiber optic ring or distance should
be used in the second subject specific data collection phase 1330.
Subsequently, in the second subject specific data collection phase
1330, 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.
[0141] In a third example, the first sample mapping phase 1310 of
the previous example is repeated for the second subject 172. The
first sample mapping phase 1310 indicates that for the second
subject, the sixth radial illumination ring of the fiber bundle
illustrated in FIG. 8A should not be used, but that the fourth and
fifth radial illumination ring should be used.
[0142] In a fourth example, the first mapping phase 1310 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 1330, 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.
[0143] Generally, a particular subject is optionally probed in a
sample mapping phase 1310 and results from the sample mapping phase
1310 are optionally used to configure analyzer parameters in a
subsequent subject specific data collection phase 1330. 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
1310, 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 1310 and sample
specific data collection phase 1330 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 1310 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.
[0144] In yet another embodiment, the sample interface tip 716 of
the fiber optic bundle 710 includes optics that change the mean
incident light angle of individual fibers of the fiber optic bundle
716 as they first hit the subject 170. For example, a first optic
at the end of a fiber in the first ring 741 aims light away from
the collection fiber optic 718; a second optic at the end of a
fiber in the second ring 742 aims light nominally straight into the
sample; and a third optic at the end of a fiber in the third ring
742 aims light toward the collection fiber 718. Generally, the mean
direction of the incident light varies by greater than 5, 10, 15,
20, or 25 degrees.
Data Processing System
[0145] The data processing system 140 is further described herein.
Generally, the data processing system uses an instrument
configuration analysis system 1340 to determine an optical
configuration of the analyzer 100 and/or a software configuration
of the analyzer 100 while the sample property analysis system 1350
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.
[0146] 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.
[0147] In another embodiment, the data processing system 140 and/or
the sample property analysis system 1350 operates on spectra
collected by the analyzer 100, such as in the subject specific data
collection phase 1330, 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
[0148] In one example, the sample property analysis system 1350
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.
[0149] In one case, the sample property analysis system 1350
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
[0150] 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
[0151] 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
[0152] 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.
[0153] In one example, a method for determining a concentration of
a blood borne analyte of a subject, includes the steps of: (1)
collecting a plurality of mapping spectra of the subject using a
noninvasive analyzer setup in a first set of optical
configurations, (2) calculating a metric related to skin tissue
physiology of the subject using the mapping spectra, (3) based on
the metric, setting up the analyzer in a second set of optical
configurations, the first set of optical configurations is
configured to deliver light to the subject in a manner different
than the second set of optical configurations, (4) collecting
subject specific noninvasive spectra of the subject using the
second set of optical configurations; and (5) post-processing the
subject specific noninvasive spectra to determine the
concentration.
[0154] Still yet another embodiment includes any combination and/or
permutation of any of the analyzer and/or sensor elements described
herein.
[0155] 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.
[0156] 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.
[0157] 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.
[0158] 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.
[0159] 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.
* * * * *