U.S. patent application number 17/155150 was filed with the patent office on 2021-07-29 for exudate analysis using optical signatures.
This patent application is currently assigned to Precision Healing, Inc.. The applicant listed for this patent is Precision Healing, Inc.. Invention is credited to Ira M. Herman, W David Lee, Sean P. Madden, David B. Strasfeld, Ryan Daniel Williams.
Application Number | 20210231566 17/155150 |
Document ID | / |
Family ID | 1000005403487 |
Filed Date | 2021-07-29 |
United States Patent
Application |
20210231566 |
Kind Code |
A1 |
Williams; Ryan Daniel ; et
al. |
July 29, 2021 |
EXUDATE ANALYSIS USING OPTICAL SIGNATURES
Abstract
Disclosed techniques include exudate analysis using optical
signatures. Access to a tissue exudate sample is obtained, wherein
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, wherein the illuminating comprises a
controlled photon exposure. The controlled photon exposure
comprises ambient lighting and/or one or more fluorescence
excitation light wavelength bands. Light emanating from the
immunoassay is imaged, wherein the imaging captures intensities of
light wavelengths across the light wavelength spectrum. The imaging
captures reflected light and fluorescent emanating light. A
signature for the one or more analytes is generated, based on
analysis of the intensities that were imaged. The signature
expresses a magnitude for each of the one or more analytes.
Inventors: |
Williams; Ryan Daniel;
(Somerville, MA) ; Herman; Ira M.; (Boston,
MA) ; Lee; W David; (Brookline, MA) ;
Strasfeld; David B.; (Somerville, MA) ; Madden; Sean
P.; (Arlington, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Precision Healing, Inc. |
Newton |
MA |
US |
|
|
Assignee: |
Precision Healing, Inc.
Newton
MA
|
Family ID: |
1000005403487 |
Appl. No.: |
17/155150 |
Filed: |
January 22, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62964969 |
Jan 23, 2020 |
|
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|
63132541 |
Dec 31, 2020 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 21/6428 20130101;
G16C 20/80 20190201; G16H 50/20 20180101; G16H 30/40 20180101; G16B
40/00 20190201; G16C 20/70 20190201; G01N 21/6456 20130101; G01N
2021/6439 20130101; G16B 45/00 20190201; G01N 1/405 20130101; G16H
10/40 20180101; G16H 20/10 20180101 |
International
Class: |
G01N 21/64 20060101
G01N021/64; G01N 1/40 20060101 G01N001/40; G16C 20/80 20060101
G16C020/80; G16C 20/70 20060101 G16C020/70; G16B 40/00 20060101
G16B040/00; G16B 45/00 20060101 G16B045/00; G16H 10/40 20060101
G16H010/40; G16H 50/20 20060101 G16H050/20; G16H 30/40 20060101
G16H030/40; G16H 20/10 20060101 G16H020/10 |
Claims
1. A method for exudate analysis comprising: obtaining access to a
tissue exudate sample, wherein the tissue exudate sample contains
one or more analytes representing a state of the tissue; isolating
the one or more analytes from the exudate sample on a substrate;
transferring the exudate from the substrate to an immunoassay;
illuminating the immunoassay with photons, wherein the illuminating
comprises a controlled photon exposure; imaging light emanating
from the immunoassay, wherein the imaging captures intensities of
light wavelengths across the light wavelength spectrum; and
generating a signature for the one or more analytes, based on
analysis of the intensities that were imaged.
2. The method of claim 1 wherein the signature expresses a
magnitude for each of the one or more analytes.
3. The method of claim 1 where the immunoassay is a system of
lateral flow assays, enzyme-linked immunosorbent assays (ELISA), or
multiplexed assays using encoded particles.
4. The method of claim 1 wherein the controlled photon exposure
comprises ambient lighting on the substrate.
5. The method of claim 1 wherein the imaging captures reflected
light.
6. The method of claim 1 wherein the controlled photon exposure
comprises one or more fluorescence excitation light wavelength
bands.
7. The method of claim 6 wherein the imaging captures fluorescent
emanating light.
8. The method of claim 1 wherein the tissue exudate is collected on
an absorbent material.
9. The method of claim 8 wherein the transferring of the exudate
from the substrate to an immunoassay is performed using a cartridge
to apply mechanical pressure to extract the exudate from the
substrate.
10. The method of claim 1 wherein the tissue exudate sample
comprises wound tissue, blood, infectious agents, blood serum, or
plasma.
11. The method of claim 10 further comprising generating a wound
assessment based on the signature.
12. The method of claim 11 wherein the wound assessment indicates a
wound treatment plan.
13. The method of claim 11 wherein the wound assessment includes a
wound state.
14. The method of claim 13 wherein the wound state includes a
stalled state, a healing state, a nonhealing state, an infected
state, an inflamed state, a granulating state, or an
epithelializing state.
15. The method of claim 11 wherein the wound assessment indicates a
wound topography.
16. The method of claim 15 wherein the wound topography includes a
wound center, a wound perimeter, or an array of wound zones.
17. The method of claim 1 wherein the isolating comprises
extracting both analytes and colonizing microbial agents.
18. The method of claim 1 wherein the isolating is accomplished
using a lateral flow array.
19-20. (canceled)
21. The method of claim 1 wherein the isolating enables spatial
separation of the one or more analytes.
22. The method of claim 21 wherein the spatial separation enables
tissue spatial registration.
23. The method of claim 22 wherein the tissue spatial registration
enables tracking of additional tissue exudate samples over
time.
24. The method of claim 23 wherein the tracking augments a tissue
treatment plan.
25. The method of claim 1 further comprising modeling tissue wound
healing based on the signature.
26. The method of claim 1 further comprising generating a tissue
treatment plan based on the signature.
27. The method of claim 1 wherein the substrate is integrated into
a bandage placed over the tissue.
28. The method of claim 1 wherein the exudate that was obtained is
transferred to the substrate using a transfer foam or woven
material.
29-31. (canceled)
32. A computer program product embodied in a non-transitory
computer readable medium for exudate analysis, the computer program
product comprising code which causes one or more processors to
perform operations of: obtaining access to a tissue exudate sample,
wherein the tissue exudate sample contains one or more analytes
representing a state of the tissue; isolating the one or more
analytes from the exudate sample on a substrate; transferring the
exudate from the substrate to an immunoassay; illuminating the
immunoassay with photons, wherein the illuminating comprises a
controlled photon exposure; imaging light emanating from the
immunoassay, wherein the imaging captures intensities of light
wavelengths across the light wavelength spectrum; and generating a
signature for the one or more analytes, based on analysis of the
intensities that were imaged.
33. A computer system for exudate analysis comprising: a memory
which stores instructions; one or more processors coupled to the
memory wherein the one or more processors, when executing the
instructions which are stored, are configured to: obtain access to
a tissue exudate sample, wherein the tissue exudate sample contains
one or more analytes representing a state of the tissue; isolate
the one or more analytes from the exudate sample on a substrate;
transfer the exudate from the substrate to an immunoassay;
illuminate the immunoassay with photons, wherein the illuminating
comprises a controlled photon exposure; image light emanating from
the immunoassay, wherein the imaging captures intensities of light
wavelengths across the light wavelength spectrum; and generate a
signature for the one or more analytes, based on analysis of the
intensities that were imaged.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. provisional
patent applications "Systems and Methods for Wound Care Diagnostics
and Treatment" Ser. No. 62/964,969, filed Jan. 23, 2020, and
"Multispectral Sample Analysis Using Fluorescence Signatures" Ser.
No. 63/132,541, filed Dec. 31, 2020.
[0002] Each of the foregoing applications is hereby incorporated by
reference in its entirety.
FIELD OF ART
[0003] This application relates generally to exudate analysis and
more particularly to exudate analysis using optical signatures.
BACKGROUND
[0004] People use a wide variety of materials for all kinds of
purposes. In fact, materials are pervasive throughout the world. We
wear items of clothing made from materials to protect us, to keep
us warm, and to make statements about ourselves and our beliefs. We
live in temporary or permanent structures constructed from
materials, and travel in vehicles made from materials, to name only
a very few uses of materials. A material is a substance or a
mixture of substances that make up a given object. A few often-used
examples of materials include wood, plastics, metals, fabrics, and
glass. The materials that are commonly used include naturally
occurring materials and synthetic materials. The materials can be
used in their pure form such as wood or iron, or can be used in an
"impure" or combined form. In this context, an impure form of a
material can include a compound, a composite, or a blend of
materials. A material or combination of materials can usually be
identified by studying various properties of the material in
question such as how hard the material is, what it looks like, and
how much it weighs. Material properties that are of particular
interest include physical properties such as state, where the
material state includes solid, liquid, gas, or plasma. Other
physical properties include the density of the material and
magnetic characteristics of the material. The material properties
of interest further include chemical properties such as the
chemical resistance of the material to attack by other chemicals,
and the combustibility of the material. The material properties can
further include mechanical properties such as malleability,
ductility, and strength; and electrical properties such as
conductivity and resistivity. The properties of a material can
additionally include optical properties such as transmissivity and
absorptivity. Still other properties can also be used. Because each
material has its own unique set of properties, the physical,
chemical, mechanical, electrical, optical, and other responses of a
material can be analyzed to characterize and identify unknown
materials.
[0005] Analyzing and characterizing materials is widely applied in
many industries including manufacturing, aerospace, and taxonomy,
to name but a few. The analysis and characterization of materials
is also widely used in research applications to identify a material
or materials within a sample, to characterize new alloys or
compounds of materials, and so on. The analysis and
characterization of materials can also be used to identify
materials that should not be present within a sample. Some
applications include identifying contaminants or impurities within
materials, where the contaminants cause systems made from the
materials to fail. Sophisticated tests and techniques can provide
detailed information about a material, such as identifying its
chemical composition, without which the tests and techniques would
be a very challenging task. This latter class of analysis can
require complex laboratory equipment and testing techniques. For
example, a scanning electron microscope (SEM) uses a beam of
electrons to reveal information about the surface topology and
composition of a material, while a transmission electron microscope
(TEM) can be used in crystalline defect analysis to predict
behavior and to find failure mechanisms for materials. Also, X-ray
Diffraction (XRD) is used to identify and characterize crystalline
materials. These complicated and expensive tests, techniques, and
types of equipment, usually available only in laboratories, can be
used alone or in combination to characterize and identify unknown
materials.
SUMMARY
[0006] Disclosed techniques can characterize and identify analytes
in a material sample which includes exudate by illuminating the
sample with a controlled photon exposure and imaging the light
emanating from an immunoassay of the exudate. The techniques
disclosed herein illuminate a sample with a controlled photon
exposure, where the photons can include a range of wavelengths
across the electromagnetic spectrum. The range of wavelengths
correspond to various types of light such as infrared (IR) light,
long-wavelength IR (LWIR) light, visible light, ambient light,
fluorescence excitation light wavelength bands, and so on. The
wavelengths can also include those that correspond to thermal
energy. A light source excites electrons in molecules of a compound
and causes the electrons to emit light or to fluoresce. In
addition, materials reflect and absorb light differently at
different wavelengths. Thus multispectral imaging can be used to
differentiate materials based on their spectral fluorescence
signatures, in addition to their reflection and absorption
characteristics. As disclosed, exudate analysis using optical
signatures can reduce the complexity, cost, and deployment
challenges of using specialized cameras, elaborate optical filters,
and expensive filter wheels which have orientation and alignment
sensitivities and employ fixed, lab-only equipment placement.
[0007] Disclosed techniques address a method for exudate analysis
using optical signatures. The disclosed techniques enable handheld,
portable, multispectral material sample analysis. Access to a
tissue exudate sample is obtained, where the tissue exudate sample
contains one or more analytes representing a state of the tissue.
The wound exudate can be obtained from a bandage associated with a
patient, beneath a film covering a wound, from a negative pressure
system, and so on. The one or more analytes are isolated from the
exudate sample on a substrate. The isolating can be used to isolate
further constituents within the exudate such as both analytes and
colonizing microbial agents. The isolating can be used to determine
which analytes are present as well as the one or more varieties of
colonizing microbial agents. Determining the analytes is critical
to diagnosing the wound state. Determining the microbial agents is
critical to effective treatment of the wound. The isolating can be
accomplished using a variety of techniques which may include using
a lateral flow assay, associating the one or more analytes to one
or more light emitting markers, and the like. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
can be a system of lateral flow assays, enzyme-linked immunosorbent
assays (ELISA), or multiplexed assays using encoded particles. The
exudate that was obtained can be transferred to the substrate using
a transfer foam or woven material. The transferring of the exudate
from the substrate to an immunoassay can be performed using a
cartridge to apply mechanical pressure to extract the exudate from
the substrate. The immunoassay is illuminated with photons, where
the illuminating comprises a controlled photon exposure. The
controlled photon exposure can include ambient lighting on the
substrate, one or more fluorescence excitation light wavelength
bands, and so on. Light emanating from the immunoassay is imaged,
where the imaging captures intensities of light wavelengths across
the light wavelength spectrum. The imaging captures reflected
light, fluorescent emanating light, etc. A signature is generated
for the one or more analytes, based on analysis of the intensities
that were imaged. The signature expresses a magnitude for each of
the one or more analytes. A wound assessment is generated based on
the signature. The signature can also be used to model tissue wound
healing, to generate a tissue treatment plan, and so on.
[0008] A method for exudate analysis is disclosed comprising:
obtaining access to a tissue exudate sample, wherein the tissue
exudate sample contains one or more analytes representing a state
of the tissue; isolating the one or more analytes from the exudate
sample on a substrate; transferring the exudate from the substrate
to an immunoassay; illuminating the immunoassay with photons,
wherein the illuminating comprises a controlled photon exposure;
imaging light emanating from the immunoassay, wherein the imaging
captures intensities of light wavelengths across the light
wavelength spectrum; and generating a signature for the one or more
analytes, based on analysis of the intensities that were
imaged.
[0009] Various features, aspects, and advantages of various
embodiments will become more apparent from the following further
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The following detailed description of certain embodiments
may be understood by reference to the following figures
wherein:
[0011] FIG. 1 is a flow diagram for exudate analysis using optical
signatures.
[0012] FIG. 2 is a flow diagram for isolating.
[0013] FIG. 3 shows a system block diagram for diagnosis and
treatment.
[0014] FIG. 4 is a table for identifying infection.
[0015] FIG. 5 is a system block diagram for infection locating.
[0016] FIG. 6 is a system block diagram for dermis healing.
[0017] FIG. 7 is a system block diagram for antibody detection.
[0018] FIG. 8 illustrates an antibody array.
[0019] FIG. 9 shows images for infection detection and analysis of
wound state.
[0020] FIG. 10 is a table showing biochromes and fluorescent
channels.
[0021] FIG. 11 is a table showing cells associated with hemostasis
and wound healing.
[0022] FIG. 12 is a table showing immune surveillance cells.
[0023] FIG. 13 shows granulation identification.
[0024] FIG. 14 illustrates water identification.
[0025] FIG. 15 shows blood vessel identification.
[0026] FIG. 16 illustrates tissue oximetry.
[0027] FIG. 17 shows a diagram for a substrate isolating analytes
from an exudate sample in one step.
[0028] FIG. 18 shows a diagram for a substrate isolating analytes
from an exudate sample in two or more steps.
[0029] FIG. 19 is a system diagram for exudate analysis using
optical signatures.
DETAILED DESCRIPTION
[0030] Techniques for exudate analysis based on optical signatures
are disclosed. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, where the illuminating comprises a
controlled photon exposure. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. A signature for the one or
more analytes is generated, based on analysis of the intensities
that were imaged. The signature expresses a magnitude for each of
the one or more analytes. A wound assessment is generated based on
the signature. Tissue wound healing is modeled based on the
signature. A tissue treatment plan is generated based on the
signature. The light emanating from the immunoassay that is imaged
can be based on fluorescence, reflection, absorption, and so
on.
[0031] Fluorophores with different emission spectra can be
distinguished based on comparison of their infrared (IR),
Red-Green-Blue (RGB), and long-wavelength IR (LWIR) emission
signals. A fluorescence signal can be spectrally resolved using
filters common to many digital imagers. The digital imagers can
include color digital imagers such as the Red, Green, and Blue
Bayer filters, IR imagers, thermal imagers, and so on. The imagers
can be integrated in typical, inexpensive sensors such as RGB
sensors that are the basis of common color digital imagers. These
sensors generally demonstrate peak blue sensitivity at 400-475 nm,
peak green sensitivity at 475-580 nm, and peak red sensitivity at
580-750 nm. One or more optical excitation sources can be provided
to the excitation light wavelength bands. In a usage example, an
optical excitation source at a wavelength is provided near the edge
of, or slightly inside or outside of, the RGB visible light
wavelength spectrum, such as at 405 nm. However, it should be noted
that the definition of the exact wavelengths of visible light is
somewhat subjective. For purposes of discussion, a visible light
wavelength range of about 425 nm-725 nm is understood herein,
although discrete wavelengths or wavelength ranges are used when
possible. The optical excitation source wavelength can, when used
to illumine a material sample, elicit a fluorescence response from
the material sample that can be detected by a sensor such as an RGB
sensor, a thermal sensor, an IR sensor, and so on. In order to
prevent cross talk from the excitation source into the spectral
channels detected by the one or more imagers, the excitation source
may be outfitted with a bandpass filter. This technique can be
especially useful if the excitation source exhibits a long
"red-side" tail into the longer wavelengths detectable by the RGB
or other sensor. Additionally, a long-pass filter placed in front
of the sensor can prevent spurious signals from the excitation
source, such as an LED, from reaching the sensor.
[0032] The low-cost, portable method of exudate analysis using
optical signatures disclosed herein can use ordinary, readily
available, sensors such as a Red-Green-Blue (RGB) sensor. The RGB
sensor typically is mass produced and has applications in low-cost
technology that endeavors to detect light waves in the visible
spectrum in a standard three-color, RGB palette suitable for
digital processing. Other low-cost sensors can include IR sensors,
thermal sensors, and so on. The RGB sensor typically employs an
integrated Bayer filter applied during the manufacturing process of
a CMOS, CCD, or similar sensor semiconductor fabrication. The Bayer
filter is completely integrated into the sensor and cannot be
removed, replaced, or adjusted. When light impinges the surface of
an RGB sensor, the underlying photosensors register a signal
related to the intensity of the impinging wavelengths as a function
of the color of the integrated sensor directly over each
photosensor device. The disclosed technology does not require
expensive filter wheels, complex optical alignments, or stationary,
non-handheld components.
[0033] FIG. 1 is a flow diagram for exudate analysis using optical
signatures. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, where the illuminating comprises a
controlled photon exposure. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. The imaging is accomplished
using an imaging sensor. A signature for the one or more analytes
is generated, based on analysis of the intensities that were
imaged. Since no filter wheels are needed to filter the response to
illumination of the immunoassay with photons, and because the
components can generally be obtained at low cost, the tissue
exudate sample analysis techniques disclosed within can be
implemented in a handheld unit.
[0034] The flow 100 includes obtaining access to a tissue exudate
sample 110, where the tissue exudate sample contains one or more
analytes representing a state of the tissue. Exudate can include a
liquid that is emitted by skin pores, a wound, and so on. The
tissue exudate sample that is obtained can contain wound tissue,
water, fibrin, glucose, immune cells, platelets, proteins, growth
factors, chemokines, cytokines, proteases, metabolic waste,
microorganisms, wound debris, dead cells, blood, infectious agents,
blood serum, plasma, and so on. The exudate can be derived from
blood and interstitial fluid. In embodiments, the tissue exudate
can be collected on an absorbent material. The exudate can include
transudate. The wound exudate can be obtained from a bandage
associated with a patient, beneath a film, from a negative pressure
system, and so on. The flow 100 includes isolating 120 the one or
more analytes from the exudate sample on a substrate. The analytes
can include cells, enzymes, proteins, mediators, chemokines,
cytokines, growth factors, proteases, inhibitors, receptors, and so
on, and can be associated with the state or condition of the wound.
Various substrates can be used. In embodiments, the substrate can
be integrated into a bandage placed over the tissue. In
embodiments, the isolating can include extracting both analytes and
colonizing microbial agents. Since the wound may be infected,
knowing which microbial agents may be colonizing the wound can help
inform treatment of the wound in general and the infection in
particular. The flow 100 includes using a lateral flow assay 126 to
accomplish the isolating. A lateral flow assay can operate based on
passing a liquid over a pad or substrate that has been treated with
reactive molecules. The isolation can occur because exudate flow in
the assay helps spatially separate the analytes and allows them to
be bound to antibodies and then fixed in position by another
antibody. The isolating can be accomplished using a variety of
techniques. In the flow 100, the isolating can be accomplished
using a single-step 122 process. Isolating analytes from an exudate
sample in one step can be accomplished using an integrated bandage,
described later. In the flow 100, the isolating can be accomplished
using a two-step 124 process. Isolating analytes from an exudate
sample in two steps can be accomplished using a cassette transfer
operation, described later. In embodiments, the isolating can
associate the one or more analytes to one or more light emitting or
light absorbing markers. Thus, the presence or absence of a given
analyte can be determined based on fluoresced, reflected, or
absorbed light from the one or more markers. In other embodiments,
the isolating can enable spatial separation of the one or more
analytes. The separation of the analytes can be used to determine
the locations of the analytes within the wound exudate sample. In
embodiments, the spatial separation can enable tissue spatial
registration. Tissue spatial separation can include a location
within a wound such as a wound edge or perimeter, a wound center, a
wound bed, and the like. In embodiments, the tissue spatial
registration can enable tracking of additional tissue exudate
samples over time. The spatial registration can enable tracking of
healing, stalled healing, or nonhealing of the wound. In
embodiments, the tracking augments a tissue treatment plan. In
embodiments, the exudate that was obtained can be transferred to
the substrate using a transfer foam or woven material.
[0035] Embodiments include transferring the exudate from the
substrate to an immunoassay. An immunoassay can include a
biochemical test that can measure the concentration of or the
presence of a molecule. The molecule can include a macromolecule, a
small molecule, and so on. The detected molecule or analyte can be
detected based on techniques that include using antibodies or
perhaps antigens. In embodiments, the immunoassay can be a system
of lateral flow assays, enzyme-linked immunosorbent assays
(ELISAs), immunohistochemistry assays, Western blot assays, flow
cytometry assays, dot blot assays, multiplexed assays using encoded
particles, and so on. The transferring can be accomplished using a
variety of techniques. In embodiments, the transferring of the
exudate from the substrate to an immunoassay is performed using a
cartridge to apply mechanical pressure to extract the exudate from
the substrate. The flow 100 includes extracting unbound non-analyte
molecules 130 from the substrate. The unbound non-analyte molecules
can include molecules unassociated with a wound such as debris in
the wound. The extracting the non-analyte molecules can be
accomplished using one or more techniques. In embodiments, the
extracting can include magnetic or electrostatic extraction. Such a
technique can be useful for removing non-analyte molecules that are
magnetic or electrostatically charged. In other embodiments, the
extracting can include fluidic washing. In the flow 100, the
extraction is accomplished using a series of proteases 132. A
protease is an enzyme that can be used to break down proteins and
peptides. In embodiments, a protease can be specific to a single
amino acid sequence and can be activated by a parameter associated
a wound. The wound parameters can include biochemical species such
as cells, enzymes, proteins, mediators, chemokines, cytokines,
growth factors, proteases, inhibitors, receptors, and so on, as
well as healing stages such as hemostasis, infected, inflamed,
granulating, epithelializing, remodeling, and so on.
[0036] The flow 100 includes illuminating the immunoassay with
photons 140, where the illuminating comprises a controlled photon
exposure. The photos that are used to illuminate the immunoassay
can include photons from one or more optical excitation light
wavelength bands. The optical excitation light wavelength bands can
include infrared (IR) bands, visible light bands (e.g., red, green,
blue, or RGB), long-wavelength IR (LWIR) bands, thermal bands, and
so on. In embodiments, a first band of the plurality of optical
excitation light wavelength bands can include wavelengths
substantially in the range of 325 nm to 375 nm, a second band of
the plurality of optical excitation light wavelength bands can
include wavelengths substantially in the range of 350 nm to 400 nm,
and a third band of the plurality of optical excitation light
wavelength bands can include wavelengths substantially in the range
of 375 nm to 425 nm. Other bands can also be used. In other
embodiments, a fourth band of the plurality of optical excitation
light wavelength bands comprises wavelengths substantially in the
range of 400 nm to 450 nm. The optical excitation light wavelength
bands can include wide bands or narrow bands. In embodiments, the
plurality of optical excitation light wavelength bands can include
narrow bands substantially at 350 nm, 375 nm, 400 nm, 425 nm, 450
nm, 500 nm, 525 nm, 550 nm, 575 nm, 600 nm, and 625 nm. In
embodiments, the controlled photon exposure can include ambient
lighting on the substrate. The ambient light can include visible
light or RGB light. In other embodiments, the controlled photon
exposure can include one or more fluorescence excitation light
wavelength bands such as the fluorescence excitation light
wavelength band described previously.
[0037] The flow 100 includes imaging light emanating from the
immunoassay 150, One or more sensors, such as an IR or LWIR sensor,
an RGB sensor, a thermal sensor, etc., can be used to detect the
light emanating from the immunoassay. In embodiments, the imaging
captures reflected light, where the reflected light can include
light within any of the bandwidths mentioned throughout. In other
embodiments, the imaging captures fluorescent emanating light. The
imaging light can be based on fluoresced, reflected, or absorbed
light. The light that is emitted can be associated with light
emitting markers. In embodiments, the one or more light emitting
markers emit photons in a fluorescent or a phosphorescent manner.
In the flow 100, the imaging captures intensities of light
wavelengths across the light wavelength spectrum 152. The light
wavelength spectrum can include IR light, long-wavelength IR (LWIR)
light, visible light, RGB light, UV light, and so on. The
electromagnetic radiation emanating from the immunoassay can
include heat.
[0038] The flow 100 includes generating a signature 160 for the one
or more analytes, based on analysis of the intensities that were
imaged. The signature can be based on numerical values, a range of
values, ratios, percentages, qualitative evaluations, and so on. In
embodiments, the signature expresses a magnitude for each of the
one or more analytes. The signature that is generated can be
applied to a variety of purposes. The flow 100 includes generating
a wound assessment 162 based on the signature. The wound assessment
can include a severity of the wound such as minor, moderate, or
severe; a healing state for the wound such as healing, stalled
healing, or nonhealing; an infection state for the wound such as
infected or not infected; and so on. In embodiments, the wound
state includes a stalled state, a healing state, a nonhealing
state, an infected state, an inflamed state, a granulating state,
or an epithelializing state. The assessment can also include other
parameters such as surgery indicated, drug therapy required, etc.
The flow 100 further includes modeling tissue wound healing 164
based on the signature. The modeling can simulate wound healing.
The flow 100 includes generating a tissue treatment plan 166 based
on the signature. The tissue treatment plan can include recommended
cleaning and bandaging techniques, surgical recommendations, drug
therapy recommendations, and the like. Embodiments can include
regenerating the output signature over time. The regenerating the
output signature can be performed based on updated parameter values
associated with a wound, changes in fluorescence response, changes
in absorption response, and the like. The regenerating the output
signature over time can be used to determine whether a wound is
healing properly, is healing slowly, is not healing, and so on. In
embodiments, the regenerating the output signature over time can
inform a wound care treatment plan. The wound care treatment plan
can include therapies such as medicinal therapies, surgery, and so
on.
[0039] Various steps in the flow 100 may be changed in order,
repeated, omitted, or the like without departing from the disclosed
concepts. Various embodiments of the flow 100 can be included in a
computer program product embodied in a non-transitory computer
readable medium that includes code executable by one or more
processors.
[0040] FIG. 2 is a flow diagram for isolating. Wound tissue exudate
can contain analytes, colonizing microbial agents, and so on.
Various isolation techniques can be used to isolate one or more
analytes, microbes, etc., from a tissue exudate sample on a
substrate. The isolating enables identification of the analytes,
microbes, and other constituents within the exudate for purposes
including wound assessment, infection type identification, wound
treatment, and so on. The one or more isolating techniques enable
exudate analysis using optical signatures. Access to a tissue
exudate sample is obtained. The tissue exudate sample contains
analytes representing a state of the tissue. The analytes are
isolated from the substrate to an immunoassay. The immunoassay is
illuminated with a controlled exposure to photons. Light emanating
from the immunoassay is imaged using an image sensor. The imaging
captures intensities of light wavelengths across the light
wavelength spectrum. A signature for the one or more analytes is
generated. The signature expresses a magnitude for each of the
analytes.
[0041] The flow 200 includes isolating the one or more analytes 210
from the exudate sample on a substrate. In the context of analytes
within an exudate associated with a wound, the analytes can include
molecules of interest such as saccharides and proteins. The
saccharides and proteins can include glucan, IL1.beta., IL6, TNF,
pH, MMP1, MMP2, MMP8, MMP9, MMP13, TGF.beta.1, Angiopoietin-1,
Angiopoietin-2, Angiogenin, endostatin, CD105, CD31, GM-CSF,
TIMP1-4, hyaluronic acid, Collagens I/III/IV, IL10, VEGF, HB-EGF,
EGF, PDGF, and so on. In embodiments, the isolating can be
accomplished using a lateral flow array. In the flow 200, the
isolating comprises extracting both analytes and colonizing
microbial agents 220. A wound, particularly a wound that is healing
slowly or not healing, may or may not be infected. To determine
whether a wound is infected and if so by what, determination of the
colonizing microbial agents is critical to planning an appropriate
treatment for the wound. In the flow 200, the isolating is
accomplished using a series of proteases 222. A protease is an
enzyme that can be used to break down proteins and peptides. In
embodiments, a protease can be specific to a single amino acid
sequence and can be activated by a parameter associated a wound.
The wound parameters can include biochemical species such as cells,
enzymes, proteins, mediators, chemokines, cytokines, growth
factors, proteases, inhibitors, receptors, and so on, as well as
healing stages such as hemostasis, infected, inflamed, granulating,
epithelializing, remodeling, and so on.
[0042] The flow 200 includes using a series of fluorescent
reporters 224. A fluorescent reporter can be used to measure gene
expression in a cell or in a series of cells. A fluorescent
reporter can be specific to a single protease and can be acted on
by the single protease. The protease can change the magnitude of
the fluorescent component of the reporter and the polarization
anisotropy signal of the reporter. In the flow 200, the absorption
and emission channels for each reporter within the series of
reporters are chosen so that each reporter can be spectrally
resolved 226 to augment analysis. Spectral resolution includes
choosing reporters that absorb and emit light within excitation
bands that are sufficiently separated to be clearly identified. The
flow 200 includes enabling binding of analytes to a substrate 228.
The binding of analytes to a substrate can be accomplished using
one or more substrate adhesion molecules (SAMs). A SAM can include
a protein that binds a cell to a substrate. Some of the amino acids
that make up the SAM bind to the cell, while other amino acids bind
to the substrate. In the flow 200 an array comprising an antibody
membrane 230 captures and identifies target molecules or molecules
of interest. In embodiments, the capturing and identifying can
include extracting unbound non-analyte molecules from the
substrate. The extracting the unbound non-analyte molecules from
the substrate can be accomplished by fluidic washing. In other
embodiments, the extracting can include magnetic or electrostatic
extraction.
[0043] Discussed through, assaying of exudate obtained from a wound
can be used to determine a state of the wound, whether or not the
wound is infection, and a treatment plan for a wound. Note however
that different locations within a wound can heal at different
rates. As a result, assaying two or more locations associated with
a wound can further inform wound treatment. In the flow 200, the
isolating enables spatial separation 232 of the one or more
analytes. The spatial separation of the analytes can indicate the
presence or the absence of one or more analytes at various
locations within the wound. Thus, successful treatment of the wound
can be augmented by determining the locations of the analytes
within the wound. In embodiments, the spatial separation can enable
tissue spatial registration. In the flow 200, the tissue spatial
registration enables tracking of additional tissue exudate samples
234 over time. The amount of time can include a testing period such
as hours, days, or weeks; a series of medical appointments at which
exudate samples can be collected; and so on. In embodiments, the
tracking augments a tissue treatment plan. Through spatial
registration, various locations and/or features of a wound (or
other tissue) can be tracked over time to determine healing
trajectories for those particular locations and/or features.
[0044] Various steps in the flow 200 may be changed in order,
repeated, omitted, or the like without departing from the disclosed
concepts. Various embodiments of the flow 200 can be included in a
computer program product embodied in a non-transitory computer
readable medium that includes code executable by one or more
processors.
[0045] FIG. 3 shows a system block diagram for diagnosis and
treatment. Discussed throughout, signatures such as optical
signatures associated one or more analytes can be generated based
on scanning one or more light wavelength bands on a material sample
such as a wound sample. The signatures can be generated to enable
exudate analysis. The exudate analysis can include determining a
wound location, assaying the exudate from the wound to identify
infection, determining healing progress, and so on. Using optical
signatures enables exudate analysis. Access to a tissue exudate
sample is obtained, where the tissue exudate sample contains one or
more analytes representing a state of the tissue. The one or more
analytes are isolated from the exudate sample on a substrate. The
exudate is transferred from the substrate to an immunoassay. The
immunoassay is illuminated with photons, where the illuminating
comprises a controlled photon exposure. Light emanating from the
immunoassay is imaged, where the imaging captures intensities of
light wavelengths across the light wavelength spectrum. A signature
for the one or more analytes is generated, based on analysis of the
intensities that were imaged.
[0046] The wound healing process is complex. There are in excess of
13 critical parameters local to the wound that control the healing
process, and if not at correct levels can stall healing
indefinitely. These parameters include but are not limited to:
collagens, glucan, IL1.beta., IL6, TNF, pH, MMP1, MMP2, MMP8, MMP9,
MMP13, TGF.beta.1, Angiopoietin-1, Angiopoietin-2, Angiogenin,
endostatin, CD105, CD31, GM-CSF, TIMP1-4, hyaluronic acid,
Collagens I/III/IV, IL10, VEGF, HB-EGF, EGF, PDGF, fibroblasts,
water, hyaluronic acid, interleukins, angiogenesis factors,
porphyrins, pyoverdines, lipofuscin, and metabolic factors such as
NADH and FAD. Because the process is dynamic, these parameters
change over time. In addition, the wound is not homogenous, and the
parameters vary by location, as well.
[0047] Wounds will not heal properly or at all if there is an
infection. In general, infections are caused by microbes that can
populate the wound and grow at an exponential rate. While these
microbes are present to some degree in all wounds and skin
surfaces, they are harmful to wound healing when they reach a
critical population and virulence that they begin to induce injury
in the host. That is, infection is not just the presence of
bacteria, but also the presence of a host response and injury. It
is this inflammatory response that can interrupt the native healing
process, allow further propagation of the microbe or pathogen, and
result in deterioration of the wound to an acute or chronic state.
This deterioration process can cascade, with the initial infection
allowing the wound to decline to a point where additional microbes
can contaminate, colonize, and infect the wound. As a result, the
compromised wound is trapped in a state of chronic nonhealing or
further deterioration. Currently, there is no clinical technique
for determining the presence, abundance and/or location of
infecting microbes and the resulting host inflammatory responses.
Technology that could identify the site of infection and
inflammation and help assess the presence or absence of infecting
microbes would meet an unmet need in the clinic.
[0048] Host responses like what is seen with infection can also be
caused by autoimmune disorders (no infecting microbes) such as
pyoderma gangrenosum. Pyoderma gangrenosum is thought to be an
immune response to injury, and the treatment (immune suppression)
is different from microbial infections and therefore requires
careful diagnosis. Once the infection has been identified and
treated, over 50% of all chronic wounds still do not heal, even
when there is no infection. This is because one of more of the
critical wound parameters or vital signs is not in the correct
range. Disruptions to the wound healing process may be related to
excess or lack of biochemical species. For example, fibroblasts may
be producing collagen only for it to be destroyed by an excess of
collagenase created by another cell or biochemical process,
resulting in stalled healing. A precise balance of cells,
extra-cellular matrix, and biochemicals are necessary for wound
healing. Accurately measuring the relative abundance of these
components can call for targeted treatments to repair the
underlying healing mechanisms.
[0049] Precision medicine techniques for skin diagnostics can be
used to identify whether one or more critical parameters such as
wound parameters are within ranges which enable healing or not. The
one or more wound parameters are associated with the skin
diagnostics. Based on the assessed parameters, one or more
treatments can be recommended that address results of diagnostics
such as wound locating, wound treatment, treatment efficacy, and so
on. The system block diagram 300 includes an infection screener
310. The infection screener can include an imaging component which
can be used to locate infection. The infection can include a skin
infection, a respiratory infection, residual cancer, and so on. In
embodiments, the infection can include a COVID-19 infection. The
system block diagram 300 can include an assay component such as an
exudate analyzer 320. The assay component can include a lab-based
component, a bedside component, and so on. In the block diagram
300, data associated with the infection screener and data
associated with the exudate analyzer can be provided to a precision
treatment platform 330. The precision treatment platform can use
the imaging data from the infection screener to perform infection
location 332. The infection location can be associated with skin,
sinuses, or lungs; a wound; and the like. The precision treatment
platform can use the exudate analysis data to generate a wound
biology model 334. Based on the infection location and the wound
biology model, an infection treatment component 340 can be used to
propose infection treatment. The proposed infection treatment can
be presented as an array (described below). The infection treatment
component can rank treatments to determine a most appropriate
treatment for an individual patient.
[0050] Infection location can be accomplished non-invasively using
a combination of fluorescence and reflectance images generated at
specific excitation and emission wavelengths. Cellular and
molecular species exist in the wound and peri-wound areas. The
fluorescence and reflectance images can exhibit spectral
signatures, where the spectral signatures can be compared to known
spectral signatures. The spectral signatures can be extracted,
calculated, and analyzed, and can be used to identify signatures
including infection signatures, healing signatures, nonhealing
signatures, and the like. A variety of techniques can be used for
locating infection, whether the infection is associated with a
wound, a respiratory infection, a COVID-19 infection, residual
cancer detection, and so on. Discussed above and throughout,
infection detection can be accomplished using a handheld device, a
cart-based device, etc. The detection can be based on fluorescence
measurements, absorption measurements, reflection measurements,
and/or transmission measurements, or any combination of
measurements thereof. The detection can further be based on
absorption and reflection of various excitation light wavelength
bands by tissue such as wound tissue, and it can be augmented by
fluorescence measurements.
[0051] With regard to wound healing measurements, it is important
to note that about half of chronic wounds are not infected. These
wounds are chronic and slow healing due to an imbalance of healing
factors, mostly related to poor blood supply and elevated protease
activity, which destroys needed proteinaceous signals required for
healing. There are numerous treatments that attempt to address
this, but there can be ten to twenty factors that work together to
foster healing. Further, no single treatment addresses all of them.
Key wound factors, signaling pathways, and immigrant and resident
dermal cells coordinating reparative and regenerative responses
post-injury are discussed below. The imager can assess a number of
key biomarkers, but additional analysis may be necessary to fully
assess a wound. The analysis can require extraction and assessment
of wound exudate.
[0052] FIG. 4 is a table for identifying infection. Identifying
that an infection is present, and determining the type of
infection, can be critical to treating the infection, promoting
healing of a wound, and so on. Identifying infection is based on
exudate analysis, where the exudate analysis is based on optical
signatures. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate, and the exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, and light emanating from the
immunoassay is imaged. A signature for the one or more analytes is
generated, based on analysis of the intensities that were
imaged.
[0053] Table 400 shows example wound parameters that can be
determined based on scanning a material sample such as a skin
sample using a plurality of optical excitation light wavelength
bands. The table can include one or more parameters 410 and values
412 associated with the one or more parameters. The parameters can
include temperature, porphyrin, vasculature/blood flow, collagen,
cellular activity, pH, and so on. The values associated with the
one or more parameters can include a numerical value, a range of
values, a percentage, a quality, an assessment, and so on. Table
400 shows qualitative values or assessments assigned to the one or
more parameters. Based on the optical excitation light wavelength
scans of the skin sample, infection can be determined from high
temperature, high porphyrin, low vasculature/blood flow, low
collagen, high cellular activity, high pH, etc.
[0054] FIG. 5 is a system block diagram for infection locating. A
patient can present with one or more indications that can be
associated with an infection. Locating the infection can be
critical to providing appropriate care to the patient to help her
recover from the infection. Locating an infection can be associated
with locating a wound or other damage to the skin of the patient.
Other infections, such as respiratory infections and COVID-19
infections, and detection of residual cancer, among others, can be
harder to locate or identify because the infections or residual
cancer are likely not visible. In these and other cases, optical
techniques may be applied to infection locating. The infection
locating enables exudate analysis using optical signatures. Access
to a tissue exudate sample is obtained, where the tissue exudate
sample contains one or more analytes representing a state of the
tissue. The one or more analytes are isolated from the exudate
sample on a substrate. The exudate is transferred from the
substrate to an immunoassay. The immunoassay is illuminated with
photons, where the illuminating comprises a controlled photon
exposure. Light emanating from the immunoassay is imaged, where the
imaging captures intensities of light wavelengths across the light
wavelength spectrum. A signature for the one or more analytes is
generated, based on analysis of the intensities that were
imaged.
[0055] The system block diagram 500 includes a hyperspectral or
multispectral imager 510. The multispectral imager can be based on
a handheld component, a mobile cart-based component, and so on. The
multispectral imager can receive data from one or more cameras
(discussed below) and can measure fluorescence, absorption, and
reflection of wound tissue at a variety of optical excitation light
wavelength bands. The multispectral imager can be coupled to a
processor 512. The processor can control illumination sources,
filters, cameras, sensors, and so on. The processor or processors
can execute code, where the code can perform various operations
associated with the infection detection. The code can include code
for control, image processing, data analysis, etc. The processor
can be used to isolate signals from biochromes associated with
infection. The signal isolation from biochromes associated with
infection can be accomplished by scanning a material sample with
one or more optical excitation light wavelength bands. The
excitation wavelength can be held constant while one or more
signals are collected from progressively longer wavelength emission
bands. In embodiments, the multispectral imager can collect and
isolate signals associated with nicotinamide adenine dinucleotide
plus hydrogen (NADH) and flavins by collecting 440-500 and 500-550
nm emission photons, respectively, and scanning excitation (325-375
nm, 350-400 nm, 375-425 nm, 400-450 nm).
[0056] The multispectral imager can be used to locate infection
associated with a patient 520. The infection can include an
infection associated with a material sample such as skin, a
respiratory infection, a particular infection such as a COVID-19
infection, residual cancer detection, and so on. The infection
location can be accomplished using a handheld scanner, a cart-based
scanner, and the like, as discussed throughout. The multispectral
imager can be coupled to a variety of components including
illumination sources, filters, cameras, and so on. The system block
diagram 500 includes a visible light camera and filters 530. The
camera can include an imaging sensor, where the imaging sensor can
detect wavelengths within the visible light band. The visible light
band can include one or more wavelengths between 380 nm and 700 nm.
The visible light filters can include one or more of a red filter,
a green filter, a blue filter, etc. The system block diagram 500
includes an infrared light camera and filters 532. The infrared
camera, which can be based on an infrared imaging sensor, can
detect wavelengths within the infrared band. The infrared band can
include wavelengths between 780 nm and 1 mm. The infrared filters
can be used to capture or isolate one or more wavelength bands
within the infrared band. The system block diagram 500 can include
illumination and filters 534. The illumination can be based on a
plurality of optical excitation light wavelength bands, where the
light wavelength bands can include visible light, IR light, long
wavelength infrared (LWIR) light, and so on. The filters can
include one or more filters which can be used to provide specific
optical excitation light wavelengths. The system block diagram 500
can include a thermal (LWIR) camera 536. As noted throughout,
detection of infection can include detection of elevated
temperature or a "hot spot" on a material sample such as a skin
sample. In the system block diagram 500, the illumination and
filters can be used to provide a plurality of optical excitation
light wavelength bands that can be scanned on a material sample.
The material sample, such as a skin sample, a body part, a limb,
exudate, and so on, can be associated with the patient 520.
[0057] FIG. 6 is a system block diagram for dermis healing. Dermis
healing can be based on performing wound healing measurements,
where the wound healing measurements can be based on exudate
analysis. While some chronic wounds may not be infected, they can
remain chronic or can be slow to heal. The slow healing can be due
a variety of factors such as poor blood supply, elevated protease
activity, and so on. The latter can destroy proteinaceous signals
that are required for healing. The dermis healing can be improved
by exudate analysis using optical signatures. Access is obtained to
a tissue exudate sample that contains one or more analytes
representing a state of the tissue. The analytes are isolated from
the exudate sample on a substrate, and the exudate is transferred
from the substrate to an immunoassay. The immunoassay is
illuminated with photons, and light emanating from the immunoassay
is imaged. A signature is generated for the one or more analytes,
based on analysis of the imaged intensities.
[0058] In order to determine a treatment that is best suited to a
wound such as an infected wound, a variety of factors can be
determined. These factors, which in embodiments can include ten to
twenty factors, can work together to promote healing. Typically, no
one treatment addresses all of the factors. The system block
diagram 600 shows a basic overview of key factors associated with a
wound, signaling pathways, and immigrant and resident dermal cells
that can coordinate reparative and regenerative responses of wound
healing. A wound image can be analyzed and wound exudate can be
analyzed to determine one or more biomarkers. The wound exudate can
be obtained from a bandage associated with a patient, beneath a
film, present in a negative pressure system, and so on. The wound
exudate can be analyzed in a laboratory, a bed-side assay, etc. In
embodiments, an assay array can be used to detect molecules of
interest to determine wound healing. The molecules of interest can
include key saccharides and proteins such as glucan, IL1.beta.,
IL6, TNF, pH, MMP1, MMP2, MMP8, MMP9, MMP13, TGF.beta.1,
Angiopoietin-1, Angiopoietin-2, Angiogenin, endostatin, CD105,
CD31, GM-CSF, TIMP1-4, hyaluronic acid, Collagens I/III/IV, IL10,
VEGF, HB-EGF, EGF, PDGF, and so on.
[0059] In the system block diagram 600, an individual's insult and
resulting innate and adaptive immune responses can stimulate
microvascular leakage, signaling neutrophils and
monocyte/macrophages to a wound site 610. Glucan synthesis 620 can
occur and support inflammatory macrophages 622. In addition,
hyaluronic acid synthesis 640 can occur and repair macrophages are
borne 642. Transforming growth factor beta (TGF B) can be released
from repair macrophages 630 and affect fibroblasts at the wound
site. Platelets, fibroblasts, and vascular cells contribute to
platelet-derived growth factor (PDGF) 628 and several other growth
factor production, e.g. FGF, VEGF, etc. Fibroblasts, vascular
cells, and macrophages produce protease matrix metalloproteinases
(MMPs) 626, which are affected by the local pH 624. The fibroblasts
and vascular cells can also influence hyaluronic acid synthesis 640
and the production of collagen 638. The pH 634 can also affect
microbial proliferation, oxygen (O2) 636 levels, which have a
bearing on collagen synthesis, and basement membrane assembly (when
pH is optimal for healing). The collagen 638 affects blood vessels
646 as well. Repair macrophages 642 can in turn affect both PDGF
628 and vascular endothelial growth factor (VEGF) 644. Thus even
the basic overview dermis healing system block diagram 600 shows
how complex the process is.
[0060] FIG. 7 is a system block diagram for antibody detection. An
array such as the array shown in 700 can be used for antibody
detection. Antibody detection can be used to identify molecules
such as glucan, IL1.beta., IL6, TNF, pH, MMP1, MMP2, MMP8, MMP9,
MMP13, TGF.beta.1, Angiopoietin-1, Angiopoietin-2, Angiogenin,
endostatin, CD105, CD31, GM-CSF, TIMP1-4, hyaluronic acid,
Collagens I/III/IV, IL10, VEGF, HB-EGF, EGF, PDGF, and so on. The
molecules can also be detected using other techniques including
mass spectrometry, nuclear magnetic resonance (NMR),
chromatography, fluorescence spectroscopy, absorption spectroscopy,
antibody assays, polarization anisotropy assays, zymography,
fluorescence-activated cell sorting (FACS), gel electrophoresis,
and the like. Antibody detection enables exudate analysis using
optical signatures. Access to a tissue exudate sample is obtained,
where the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, where the illuminating comprises a
controlled photon exposure. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. A signature for the one or
more analytes is generated, based on analysis of the intensities
that were imaged.
[0061] The system block diagram for antibody detection 700 includes
a light source 710. The light source can include a plurality of
optical excitation light wavelength bands, where the wavelength
bands can include visible light, IR light, LWIR light (heat), and
so on. Bioluminescence can be created using horseradish peroxidase
(HRP) and hydrogen peroxide. The bioluminescence can be detected by
a camera, photographic film, etc. Streptavidin 720 can be used to
bind to a biotin 730 with strong affinity. A detection antibody 740
can be in a specific and known location on a material sample such
as skin, on a patient's body part, and so on. Thus, light due to
bioluminescence or the emission from a fluorophore can be emitted
from the specific and known location can indicate that a target
analyte 750 has been captured 760. In embodiments, indication that
the target antibody has been captured can be based on parameters
such as vital signs associated with the wound (WVS). A blocked
membrane 770 can be used to support the antibody detection array.
The blocked membrane can be used to capture and identify target
molecules.
[0062] FIG. 8 illustrates an antibody array. An antibody array can
show one or more wound parameters or vital signs associated with a
wound. The antibody array can be determined for one or more
locations associated with a wound such as a wound perimeter, a
wound center, etc. The antibody array enables exudate analysis
using optical signatures. Access to a tissue exudate sample that
contains one or more analytes representing a state of the tissue is
obtained. The analytes are isolated from the exudate sample on a
substrate, and the exudate is transferred from the substrate to an
immunoassay. The immunoassay is illuminated with a controlled
exposure of photons. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. A signature for the one or
more analytes is generated, based on analysis of the intensities
that were imaged.
[0063] Antibody arrays are shown for a wound center 800 and a wound
perimeter 802. The antibody arrays can be based on analysis results
of wound fluid or exudate, i.e., a liquid biopsy collected from the
wound center 810, wound perimeter 850, and so on. Such assays can
be performed to determine the state of healing of a wound based on
the absence or presence, together with the relative abundance of
one or several wound controllers, classifiers or variables
controlling healing stages and wound state. Such assays are useful
for gauging healing of a wound such as a slow-healing wound,
because the rate of healing of the wound can vary across the wound.
Fourteen parameters are shown for the example assays of exudate at
the wound center and the wound perimeter. More or fewer parameters
may be used for the comparison of assay results. The parameters can
include Activin A 812 and 852; Angiopoietin 1 and Ang 2 814 and
854; and Amphiregulin 816 and 856. Note the difference between the
assay results 816 and 856. This difference can indicate that the
perimeter of the wound is healing while the center of the wound is
not healing or is only slowly healing. The parameters can further
include Endostatin/Collagen XVIII 818 and 858; Fibroblast Growth
Factors (FGF) FGF 1 and FGF 2 820 and 860; Glial cell line-derived
neurotrophic factors (GDNF) and Granulocyte-macrophage
colony-stimulating factors (GM-CSF) 822 and 862. The factors can
further include Heparin-binding epidermal growth factor-like
(HB-EGF) factors 824 and 864; Insulin-like growth factor-binding
proteins (IGFBP) IGFBP 1 and IGFBP 2 826 and 866; Interleukin 1
Beta 828 and 868; and Transforming growth factor betas (TGFb-1) 830
and 870. The factors can also include Monocyte chemoattractant
protein 1 (MCP-1) 832 and 872; Matrix metalloproteinases (MMPs)
MMP8 and MMP9 834 and 874; Tissue inhibitors of metallopeptidase
(TIMP) TIMP1 and TIMP4 836 and 876; and Vascular endothelial growth
factors (VEGF) 838 and 878. As noted above, one or more factors can
be present or absent at a wound location such as a wound center, a
wound perimeter, and so on. Note further that the magnitude of a
given parameter can vary across the wound, temporally and
spatially, and that these amplitude modulations influence the stage
of healing and the wound state, while classifying each. Such
differences in magnitude can also be indicative of causes for a
wound to be slow healing or nonhealing.
[0064] FIG. 9 shows images for infection detection and analysis of
wound state. An image or a series of images can be obtained and
analyzed for infection detection. The images can be based on
fluorescence, reflection, absorption, and so on, of a material
sample such as tissue scanned with one or more optical excitation
light wavelength bands. The images enable exudate analysis using
optical signatures. Access to a tissue exudate sample is obtained,
where the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, wherein the illuminating comprises a
controlled photon exposure. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. A signature is generated for
the one or more analytes, based on analysis of the intensities that
were imaged.
[0065] Images which have been collected and analyzed can be used
for infection detection 900. The images can be based on
fluorescence response wavelengths, absorption response wavelengths,
and so on, where the response wavelengths can be emitted by the
material sample in response to exposer by the various optical
excitation light wavelength bands. Note that the emitted response
wavelengths can be different from the excitation light wavelengths
scanned on the material sample. In embodiments, a first band of the
plurality of optical excitation light wavelength bands can include
wavelengths substantially in the range of 325 nm to 375 nm, a
second band of the plurality of optical excitation light wavelength
bands can include wavelengths substantially in the range of 350 nm
to 400 nm, and a third band of the plurality of optical excitation
light wavelength bands can include wavelengths substantially in the
range of 375 nm to 425 nm. Other bands of optical excitation light
wavelength bands can further be used. In embodiments, a fourth band
of the plurality of optical excitation light wavelength bands can
include wavelengths substantially in the range of 400 nm to 450 nm.
An output signature can be interpreted from emission detected from
the scanned material sample. In embodiments, the interpreting can
be based on measured wavelengths substantially in the range of 400
nm to 460 nm. Other fluorescence excitation light wavelength bands
can be used to expose the material sample. Further embodiments
include exposing the material sample to a fluorescence excitation
light wavelength band comprising wavelengths substantially in the
315 nm to 375 nm range to augment the interpreting. Image 910 can
be based on 375 nm excitation with 430 nm emission, where the 430
nm emission or output signature can be indicative of the presence
of collagen.
[0066] Image 912 can be based on 375 nm excitation with 470 nm
output signature can be indicative of the presence of nicotinamide
adenine dinucleotide plus hydrogen (NADH) and flavins. An image can
include photograph 914. The photograph can be based on visible
light, where visible light can include wavelengths substantially
within the approximate range of 380 nm and 750 nm. The images can
be based on absorption. Image 916 can be based on 570 nm
absorption, where the 570 nm absorption can be indicative of
hemoglobin. The images can further be based on narrow bands. In
embodiments, the plurality of optical excitation light wavelength
bands can include narrow bands substantially at 350 nm, 375 nm, 400
nm, 425 nm, 450 nm, 500 nm, 525 nm, 550 nm, 575 nm, 600 nm, and 625
nm. Other embodiments can include exposing the material sample to a
narrow fluorescence excitation light wavelength band comprising
wavelengths substantially at 400 nm to augment the interpreting.
The interpreting can be based on additional measured wavelengths.
In embodiments, the interpreting can be based on measured
wavelengths substantially in the range of 600 nm to 660 nm and 675
nm to 725 nm. Image 918 can be based on 425 nm excitation and 650
nm emission which can be analyzed to generate an output signature.
In embodiments, the output signature can be indicative of the
presence of porphyrins. Longer wavelengths can also be used to
analyze the material sample. Image 920 can be based on the
magnitude of photons between 7 and 15 microns that are detected,
which can create a monochromatic image where intensity is converted
into temperature, and where the intensity represents a thermal
profile of the wound. In embodiments, the interpreting is based on
excitation wavelengths from 380 nm to 420 nm and measured
wavelengths substantially in the range of 500 nm to 550 nm and 550
nm to 600 nm. In embodiments, the output signature is indicative of
the presence of pyoverdine, based on a ratio of output values from
the range of 550 nm to 600 nm to output values from the range of
500 nm to 550 nm.
[0067] FIG. 10 is a table showing biochromes and fluorescent
channels. A fluorophore is a chemical compound that when excited by
light re-emits light. Biochromes include substances such as
chemical compounds which present a color based on selective
absorption of other colors. The colors are associated with
wavelengths of light. Biochromes and fluorescent channels support
exudate analysis using optical signatures. Access to a tissue
exudate sample that contains one or more analytes representing a
state of the tissue is obtained. The analytes are isolated from the
exudate sample on a substrate. The exudate is transferred from the
substrate to an immunoassay. The immunoassay is illuminated with
photons, where the illuminating includes a controlled photon
exposure. Light emanating from the immunoassay is imaged, and a
signature for the one or more analytes is generated, based on
analysis of the intensities that were imaged.
[0068] A table based on biochromes and fluorescent channels is
shown 1000. The table includes skin fluorophores and biochromes
1010. Each of the skin fluorophores and biochromes can correspond
to a factor associated with healing. Each of the factors can
further be associated with one or more biomolecules or cell
localizations 1012. The various skin fluorophores and biochromes
can be excited by an optical excitation light wavelength band 1014.
The excited fluorophores and biochromes generate an emission
response 1016 by the scanned material sample. In embodiments, the
material sample can include cells, tissues, and organs. The
material sample can include skin, lungs, and so on. The emission
response can be indicative of infection such as infection of a
wound, respiratory infection such as a COVID-19 infection or
influenza infection, residual cancer detection, and so on.
[0069] FIG. 11 is a table showing cells associated with hemostasis
and wound healing. A wound to skin, an organ, and so on, can cause
prodigious bleeding. The first step to healing the wound is to
stanch the bleeding. Hemostasis is a process that stops bleeding
and prevents further bleeding based on blood platelet function and
coagulation of blood, where coagulation includes transforming blood
from a liquid to a gel. The coagulating or clotting of the blood is
dependent on functional blood platelets, which become activated,
releasing many factors that control downstream effectors, which
influence vascular leakage, immune responses and the
reparative/regenerative responses needed for healing. Hemostasis
and wound healing can be analyzed using exudate analysis using
optical signatures. Access to a tissue exudate sample is obtained,
where the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate. The exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, where the illuminating comprises a
controlled photon exposure. Light emanating from the immunoassay is
imaged, where the imaging captures intensities of light wavelengths
across the light wavelength spectrum. A signature is generated for
the one or more analytes, based on analysis of the intensities that
were imaged.
[0070] Table 1100 shows various cells that can be associated with
hemostasis and the various stages and state of wound healing. The
table shows resident cells 1110, where the resident cells can be
present in blood, tissue, and so on. The resident cells can produce
key products 1112, where the key products can signal and modulate
healing. The healing can include healing of a wound such as a
tissue wound or an organ wound; recovery from an infection such as
an infection of the skin or organ, or a respiratory infection such
as COVID-19 or influenza; detection to facilitate removal of
residual cancer; and so on. The key products can be associated with
target cell or cell function 1114. The target cell or cells can be
associated with wound healing, infection recovery, and the
like.
[0071] FIG. 12 is a table showing immune surveillance cells. The
immune system associated with an individual fights "foreign
invaders" to their body. The foreign invaders can include bacteria,
fungi, viruses, tumors, and so on. The immune system identifies and
attempts to eliminate the invading pathogen(s), whether fungi,
bacteria, viruses, etc. based on immune surveillance. For example,
a tumor can include cells that are based on transformed normal
cells. The transformed cells associated with tumor-expressed
antigens, where the expressed antigens are not found in normal
cells. As a result, the body attacks with immune cells the
self-antigens as `foreign` antigens. Immune surveillance can be
analyzed using exudate analysis using optical signatures. Access to
a tissue exudate sample is obtained, where the tissue exudate
sample contains analytes representing a state of the tissue. The
analytes are isolated from the exudate sample on a substrate, and
the exudate is transferred from the substrate to an immunoassay.
The immunoassay is illuminated with a controlled photon exposure. A
signature for the one or more analytes is generated, based on
analysis of the intensities that were imaged.
[0072] A table showing immune surveillance cells, key products, and
one or more target cells is shown 1200. Some symptoms or conditions
presented by a patient can appear similar to those caused by
infection, but can actually be caused by autoimmune disorders, as
above. One identifier that differentiates between an infection and
an autoimmune disorder can include an absence of infecting microbes
or non-specific inflammation, e.g., vasculitis, which is associated
with the autoimmune disorder (e.g. gangrenosum pyoderma). Careful
diagnosis can be required to differentiate between an autoimmune
disorder, which may be treated with an immune suppression
technique, and an infection which may be treated by boosting
immunity, prescribing antibiotics, and so on. Various immune
surveillance cells are shown 1210. The cells can be associated with
one or more key products 1212. The key products can be used to
elicit effector or target cell function 1214, where the target
cells can be attacked, used to fight infection, used to rebuild
tissue, and so on.
[0073] FIG. 13 shows granulation identification. Granulation
identification can enable exudate analysis using optical
signatures. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate, and the exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, and light emanating from the
immunoassay is imaged. A signature for the one or more analytes is
generated, based on analysis of the intensities that were
imaged.
[0074] In the graph 1300, an x-axis indicating wavelength 1310 is
provided. Increasing wavelength from left to right indicates
decreasing frequency of light waves and a traversal from the
ultraviolet spectrum, approximately sub-400 nm, through the blue,
green, and red wavelength regions, roughly 450 nm, 550 nm, and 650
nm, respectively, to the infrared wavelength band, which is roughly
greater than 750 nm. It should be noted that an exact wavelength
definition of a particular color is somewhat arbitrary and is
dependent on the sensor type. For example, the cones of a human eye
roughly sense RGB signals using three cone types, but they are
generally distributed differently from a typical CMOS RGB sensor's
output. However, maintaining a consistent definition for a given
system is generally required in order to provide consistent sample
indications. The graph 1300 also includes a left y-axis of
absorption amount 1312 and a right y-axis of transmission amount
1314.
[0075] The graph 1300 includes absorption characteristics, such as
absorption characteristic 1322, typical for the presence of
collagen, absorption characteristic 1324, typical for the presence
of hemoglobin (Hgb), and absorption characteristic 1326, typical
for the presence of oxygenated hemoglobin (oxyHb). The typical
absorption characteristics 1322, 1324, and 1326 can be used as
reference signals as is, or they can be compensated to enable
generation of an indication of material composition. A granulation
output signature is isolated by quantifying the dip in the Hgb
spectrum at 450 nm, illustrated in highlight circle 1342. Tissue
that is mostly collagen will not have a dip, whereas granulation
tissue will have a dip that resides roughly halfway between the
typical Hgb characteristic 1324 and/or 1326 and the typical
collagen characteristic 1322. The intensity of the dip can be
quantified by taking the ratio or difference of the absorption
intensity at 1336 and/or 1338 and comparing it to the absorption
intensity at 1334 and/or 1332.
[0076] The graph 1300 shows signals indicative of filter
characteristics, including signals 1332, 1334, 1336, and 1338.
Signal 1332 represents a light wavelength centered at about 488 nm
with a bandwidth of about 10 nm and a relative transmission
amplitude of about 0.7 out of 1. Signal 1334 represents a light
wavelength centered at about 520 nm with a bandwidth of about 40 nm
and a relative transmission amplitude of almost 1.0 out of 1.
Signal 1336 represents a light wavelength centered at about 550 nm
with a bandwidth of about 10 nm and a relative transmission
amplitude of about 0.6 out of 1. Signal 1338 represents a light
wavelength centered at about 570 nm with a bandwidth of about 10 nm
and a relative transmission amplitude of about 0.5 out of 1. It is
to be understood that the characteristics and signals illustrated
herein have substantially the values shown in graph 1300, but that
normal, typical variations and equipment calibration may provide a
delta to the characteristics and signals, such as a five percent
delta.
[0077] FIG. 14 illustrates water identification. Water
identification can enable exudate analysis using optical
signatures. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate, and the exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, and light emanating from the
immunoassay is imaged. A signature for the one or more analytes is
generated, based on analysis of the intensities that were
imaged.
[0078] In the graph 1400, an x-axis indicating wavelength 1410 is
provided. Increasing wavelength from left to right indicates
decreasing frequency of light waves and a traversal from the
ultraviolet spectrum, roughly sub-400 nm, through the blue, green,
and red wavelength regions, roughly 450 nm, 550 nm, and 650 nm,
respectively, to the infrared wavelength band, which is roughly
greater than 750 nm. It should be noted that an exact wavelength
definition of a particular color is somewhat arbitrary and
dependent on the sensor type. For example, the cones of a human eye
roughly sense RGB signals using three cone types, but they are
generally distributed differently from a typical CMOS RGB sensor's
output. However, maintaining a consistent definition for a given
system is generally required in order to provide consistent sample
indications. The graph 1400 also includes a left y-axis of
absorption amount 1412 and a right y-axis of transmission amount
1414.
[0079] The graph 1400 includes absorption characteristics, such as
absorption characteristic 1422, indicative of the presence of
collagen, absorption characteristic 1424, indicative of the
presence of hemoglobin (Hgb), absorption characteristic 1426,
indicative of the presence of oxygenated hemoglobin (oxyHb), and
absorption characteristic 1428, indicative of the presence of
water. The typical absorption characteristics 1422, 1424, 1426, and
1428 can be used as reference signals as is, or they can be
compensated to enable generation of an indication of material
composition. A water output signature is isolated by irradiating a
material sample (wound or other) with broad-band white light and
comparing the absorption at 960 nm (or similar) and 800 nm (or
similar). In the graph 1400, broad-band white light is passed by a
long-pass filter, shown as signal 1434, which cuts off wavelengths
of light below 450 nm (in the ultraviolet range), and allows
visible light above 450 nm with a relative transmission amplitude
of about 0.9 out of 1. Light emanating from the sample can be
measured at two or more points at successively longer wavelengths,
as shown by signals 1436 and 1438. Signal 1436 represents an
optical filter centered at about 800 nm with a bandwidth of about
20 nm and a relative amplitude of about 0.85 out of 1. Signal 1438
represents a light wavelength centered at about 960 nm with a
bandwidth of about 100 nm and a relative amplitude of about 0.85
out of 1. The output signature of water will be substantially
higher at the longer wavelength sample point. As shown in graph
1400, this is not true for the absorption characteristics of
collagen 1422 and hemoglobin 1424 and 1426 as sampled at 800 nm and
960 nm. It is to be understood that the characteristics and signals
have substantially the values illustrated in graph 1400, but that
normal, typical variations and equipment calibration may provide a
delta to the characteristics and signals, such as a five percent
delta.
[0080] FIG. 15 shows blood vessel identification. Blood vessel
identification can enable exudate analysis using optical
signatures. Access to a tissue exudate sample is obtained, where
the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate, and the exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, and light emanating from the
immunoassay is imaged. A signature for the one or more analytes is
generated, based on analysis of the intensities that were
imaged.
[0081] In the graph 1500, an x-axis indicating wavelength 1510 is
provided. Increasing wavelength from left to right indicates
decreasing frequency of light waves and a traversal from the
ultraviolet spectrum, roughly sub-400 nm, through the blue, green,
and red wavelength regions, roughly 450 nm, 550 nm, and 650 nm,
respectively, to the infrared wavelength band, which is roughly
greater than 750 nm. It should be noted that an exact wavelength
definition of a particular color is somewhat arbitrary and
dependent on the sensor type. For example, the cones of a human eye
roughly sense RGB signals using three cone types, but they are
generally distributed differently from a typical CMOS RGB sensor's
output. However, maintaining a consistent definition for a given
system is generally required in order to provide consistent sample
indications. The graph 1500 also includes a left y-axis of
absorption amount 1512 and a right y-axis of transmission amount
1514.
[0082] The graph 1500 includes absorption characteristics, such as
absorption characteristic 1522, indicative of the presence of
hemoglobin (Hgb), and absorption characteristic 1524, indicative of
the presence of oxygenated hemoglobin (oxyHb). The typical
absorption characteristics 1522 and 1524 can be used as reference
signals as is, or they can be compensated to enable generation of
an indication of material composition. A blood vessel signal is
isolated based on the absorption of Hgb at 523 nm and 660 nm. Light
from two different light emitting diodes (LEDs) is used to illumine
a material sample. In the graph 1500, signal 1532 represents the
typical output spectrum of a 523 nm LED, and signal 1534 represents
the typical output spectrum of a 660 nm LED. As can be seen in
graph 1500, the absorption characteristics of Hgb 1522 and oxyHb
1524 are very similar at about 523 nm. However, an order of
magnitude difference is observed when comparing absorption
characteristics 1522 and 1524 at 660 nm. The low absorption in the
red band is indicative of oxygenated hemoglobin, which is typically
found in active blood vessels, but not found in pooled blood due to
bruising or other wound-related phenomena. It is to be understood
that the characteristics and signals have substantially the values
illustrated in graph 1500, but that normal, typical variations and
equipment calibration may provide a delta to the characteristics
and signals, such as a five percent delta.
[0083] FIG. 16 illustrates tissue oximetry. Tissue oximetry can
enable exudate analysis using optical signatures. Access to a
tissue exudate sample is obtained, where the tissue exudate sample
contains one or more analytes representing a state of the tissue.
The one or more analytes are isolated from the exudate sample on a
substrate, and the exudate is transferred from the substrate to an
immunoassay. The immunoassay is illuminated with photons, and light
emanating from the immunoassay is imaged. A signature for the one
or more analytes is generated, based on analysis of the intensities
that were imaged.
[0084] In the graph 1600, an x-axis indicating wavelength 1610 is
provided. Increasing wavelength from left to right indicates
decreasing frequency of light waves and a traversal from the
ultraviolet spectrum, roughly sub-400 nm, through the blue, green,
and red wavelength regions, roughly 450 nm, 550 nm, and 650 nm,
respectively, to the infrared wavelength band, which is roughly
greater than 750 nm. It should be noted that an exact wavelength
definition of a particular color is somewhat arbitrary and
dependent on the sensor type. For example, the cones of a human eye
roughly sense RGB signals using three cone types, but they are
generally distributed differently from a typical CMOS RGB sensor's
output. However, maintaining a consistent definition for a given
system is generally required in order to provide consistent sample
indications. The graph 1600 also includes a left y-axis of
absorption amount 1612 and a right y-axis of transmission amount
1614.
[0085] The graph 1600 includes absorption characteristics, such as
absorption characteristic 1622, indicative of the presence of
hemoglobin (Hgb), and absorption characteristic 1624, indicative of
the presence of oxygenated hemoglobin (oxyHb). The typical
absorption characteristics 1622 and 1624 can be used as reference
signals as is, or they can be compensated to enable generation of
an indication of material composition. An oxygenated tissue output
signature is isolated by comparing absorption at 960 nm, where
oxyHb absorption dominates, to 650 nm, where Hgb absorption
dominates. In the graph 1600, broad-band white light is passed by a
long-pass filter, shown as signal 1634, which cuts off wavelengths
of light below 450 nm (in the ultraviolet range), and allows
visible light above 450 nm with a relative transmission amplitude
of about 0.9 out of 1. Light emanating from the sample can be
measured at two or more points at successively longer wavelengths,
as shown by signals 1636 and 1638. Signal 1636 represents an
optical filter centered at about 650 nm with a bandwidth of about
100 nm and a relative amplitude of about 0.95 out of 1. Signal 1638
represents a light wavelength centered at about 960 nm with a
bandwidth of about 100 nm and a relative amplitude of about 0.85
out of 1. The output signature of oxygenated tissue will show
higher absorption at the longer wavelength sample point. It is to
be understood that the characteristics and signals have
substantially the values illustrated in graph 1600, but that
normal, typical variations and equipment calibration may provide a
delta to the characteristics and signals, such as a five percent
delta.
[0086] FIG. 17 shows a diagram for a substrate isolating analytes
from an exudate sample in one step. Isolating analytes from an
exudate sample in one step can enable exudate analysis using
optical signatures. Access to a tissue exudate sample is obtained,
where the tissue exudate sample contains one or more analytes
representing a state of the tissue. The one or more analytes are
isolated from the exudate sample on a substrate, and the exudate is
transferred from the substrate to an immunoassay. The immunoassay
is illuminated with photons, and light emanating from the
immunoassay is imaged. A signature is generated for the one or more
analytes, based on analysis of the intensities that were
imaged.
[0087] One step diagram 1700 shows a wound bed 1710 within skin
1712 or some other tissue structure. The wound bed 1710 is covered
by an absorbent material 1722, such as a bandage, a woven material,
a foam material, and so on. The absorbent material 1722 is in
contact with the wound bed 1710, which allows exudate from the
wound to flow from the wound bed 1710 through the absorbent
material 1722, through an opening in hydrophobic polymer 1713 and
1714, into lateral flow assay 1742, and finally into absorbent
material 1740 and 1741 at the end of the lateral flow immunoassay
1742, as indicated by exudate flow arrows 1724 and 1726. Included
in absorbent material 1740 can be pH indicator 1746. Included in
absorbent material 1741 can be pH indicator 1744. Transparent
windows 1736 and 1738 can allow optical analysis of the exudate as
it flows through the assay 1742, driven by capillary forces as well
as the hydrostatic pressure of the wound. Reagent for the assay can
be added via reagent port 1734 or by reagent reservoirs embedded in
the hydrophobic polymer 1713 and 1714 (not shown). Thus, a
substrate comprising absorbent material 1722, hydrophobic polymer
1713 and 1714, lateral flow assay 1742, absorbent material 1740 and
1741, optional pH indicators 1744 and 1746, reagent port 1734, and
transparent windows 1736 and 1738 can enable isolating analytes
from an exudate sample in one step. The time elapsed for the
process of exudate flow and assay isolation will vary based on the
patient, the wound type, the exact materials and pore size, etc.,
but it can be in the range of 5 to 30 minutes. The absorbent
material will carry many times its weight in exudate. The analytes
that are isolated in lateral flow assay 1742 can then be optically
analyzed through transparent windows 1736 and 1738. Of course, it
is to be appreciated that the one step diagram 1700 represents a
vertical cross-sectional view, and that the wound bed, substrate,
and described features exist in three-dimensions. Isolating
analytes from an exudate sample in one step can comprise an
integrated, or "smart", bandage for exudate analysis using optical
signatures.
[0088] FIG. 18 shows a diagram for a substrate isolating analytes
from an exudate sample in two or more steps. Isolating analytes
from an exudate sample in two or more steps can enable exudate
analysis using optical signatures. Access to a tissue exudate
sample is obtained, where the tissue exudate sample contains one or
more analytes representing a state of the tissue. The one or more
analytes are isolated from the exudate sample on a substrate, and
the exudate is transferred from the substrate to an immunoassay.
The immunoassay is illuminated with photons, and light emanating
from the immunoassay is imaged. A signature is generated for the
one or more analytes, based on analysis of the intensities that
were imaged.
[0089] Multistep diagram 1800 illustrates the first step of the
multistep process and shows a wound bed 1810 within skin 1812 or
some other tissue structure. The wound bed 1810 is covered by an
absorbent material 1822, such as a foam material, although other
absorbent materials are possible. The absorbent material 1822 is in
contact with the wound bed 1810, which allows exudate from the
wound to flow from the wound bed 1810 to the absorbent material
1822 as illustrated by arrows 1824. Region 1826 of illustrates that
an amount of exudate has been transferred from the wound bed 1810
to the absorbent material 1822. The exudate flow illustrated in
diagram 1800 can be driven by capillary forces as well as by the
hydrostatic pressure of the wound. Other methods to enhance exudate
flow into the absorbent material, such as negative pressure
(suction) over the wound bed and absorbent material, are possible.
A soaking time of several minutes to more than an hour might be
necessary to allow enough exudate to penetrate the absorbent
material. However, a typical time for soaking can be about ten
minutes. After sufficient soaking time, absorbent material 1822 can
be taken off of wound bed 1810.
[0090] Multistep diagram 1802 illustrates a second step of the
multistep process, whereby soaked absorbent material 1832 is
carefully placed in a cassette 1814, so as not to prematurely
squeeze the exudate 1834 out of the soaked absorbent material 1832.
The impermeable (or semi-impermeable) and rigid (or semi-rigid)
cassette allows the soaked absorbent material 1832 to transfer
exudate 1834 to a lateral flow immunoassay 1842 through opening
1818 of cassette top piece 1816, as indicated by exudate flow
arrows 1826. The flow of exudate 1834 into the lateral flow assay
1842 is facilitated by pressing cassette top piece 1816 into
cassette 1814, as illustrated. The lateral flow assay 1842 can be
attached to cassette top piece 1816 to further facilitate exudate
flow. In due time, lateral flow assay 1842 can be appropriately
positioned for optical analysis as described herein, either by
removing lateral flow assay 1842 from cassette top piece 1816, or
by removing cassette top piece 1816 from cassette 1814 with lateral
flow assay 1842 still attached, or by positioning cassette 1814
with cassette top piece 1816 and lateral flow assay 1842 still in
place. The time elapsed for the process of exudate flow and assay
isolation will vary based on the amount of exudate 1834 collected
in the soaked absorbent material 1832, the amount of pressure
applied to the cassette top piece 1816 and or lateral flow assay
1842, the material properties of the assay, and so on. A typical
time for analyte isolation by the assay can be in the range of 3 to
10 minutes.
[0091] FIG. 19 is a system diagram for exudate analysis using
optical signatures. The system 1900 can include one or more
processors 1910, which are attached to a memory 1912 which stores
instructions. The system 1900 can further include a display 1914
coupled to the one or more processors 1910 for displaying data,
indications of sample analysis, directions, input requests, control
options, excitation wavelengths, filter options, compensation
options, data forwarding options, and so on. Embodiments of the
system 1900 comprise a computer system for exudate analysis
comprising: one or more processors 1910 that are coupled to the
memory 1912 which stores instructions, wherein the one or more
processors, when executing the instructions which are stored, are
configured to: obtain access to a tissue exudate sample, wherein
the tissue exudate sample contains one or more analytes
representing a state of the tissue; isolate the one or more
analytes from the exudate sample on a substrate; transfer the
exudate from the substrate to an immunoassay; illuminate the
immunoassay with photons, wherein the illuminating comprises a
controlled photon exposure; image light emanating from the
immunoassay, wherein the imaging captures intensities of light
wavelengths across the light wavelength spectrum; and generate a
signature for the one or more analytes, based on analysis of the
intensities that were imaged.
[0092] The system 1900 can include an obtaining component 1920. The
obtaining component 1920 can be used to obtain access to a tissue
exudate sample, where the tissue exudate sample contains one or
more analytes representing a state of the tissue. The tissue
exudate sample can be obtained using a variety of techniques
including gathering exudate from a bandage that may have been
covering a wound, swabbing the wound, extracting liquid from the
wound, extracting liquid from below a film covering the wound,
using a negative pressure device, and so on. The tissue exudate
sample that is obtained can contain wound tissue, water, fibrin,
glucose, immune cells, platelets, proteins, growth factors,
metabolic waste, microorganisms, wound debris, dead cells, blood,
infectious agents, blood serum, plasma, and so on. The exudate can
be derived from blood and interstitial fluid. In embodiments, the
exudate that was obtained can be transferred to a substrate using a
transfer foam or woven material. The system 1900 can include an
isolating component 1930. The isolating component 1930 can be used
to isolate the one or more analytes from the exudate sample on a
substrate. The isolating can be used to isolate further
constituents within the exudate. In embodiments, the isolating can
include extracting both analytes and colonizing microbial agents.
The isolating can be used to determine which analytes are present
as well as which of the one or more varieties of colonizing
microbial agents are present. Determining the microbial agents is
critical to effective treatment of the wound. Further embodiments
include extracting unbound non-analyte molecules from the
substrate. A variety of techniques can be used for the extracting.
In embodiments, the extracting can include magnetic or
electrostatic extraction. Chemical and liquid techniques can also
be used for the extracting. In embodiments, the extracting can
include fluidic washing.
[0093] The isolating can be accomplished using a variety of
techniques. In embodiments, the isolating can be accomplished using
a lateral flow array. In a lateral flow array, liquid is passed
across a material such as a pad on which reactive molecules have
been placed. The reactive molecules are used to indicate a visual
result, such as a positive result or a negative result. In
embodiments, the isolating can associate the one or more analytes
to one or more light emitting markers. Thus, a given light marker
can include the presence or absence of an analyte. The markers can
produce light based on one or more physical or chemical techniques.
In embodiments, the one or more light emitting markers can emit
photons in a fluorescent or a phosphorescent manner. In order for
the markers to be detected or seen more easily, the markers can be
distributed across the isolating pad. In embodiments, the isolating
enables spatial separation of the one or more analytes. As a
further benefit of the isolating, the spatial separation enables
tissue spatial registration.
[0094] The system 1900 can include a transferring component 1940.
The transferring component 1940 can be used to transfer the exudate
from the substrate to an immunoassay. The transferring can be
accomplished using one or more techniques. In embodiments, the
transferring of the exudate from the substrate to an immunoassay
can be performed using a cartridge. The cartridge can be used to
apply mechanical pressure to the substrate to extract the exudate
from the substrate. In order to extract the exudate from the
substrate, the exudate must first have been transferred to the
substrate. An immunoassay can include a biochemical test that can
measure the concentration of or the presence of a molecule. The
molecule can include a macromolecule, a small molecule, and so on.
The detected molecule or analyte can be detected based on
techniques that include using antibodies or perhaps antigens. The
system 1900 can include an illuminating component 1950. The
illuminating component 1950 can be used to illuminate the
immunoassay with photons, wherein the illuminating comprises a
controlled photon exposure. Various types of lights, wavelengths
and bands of light, and so on can be used for the controlled photon
exposure. In embodiments, the controlled photon exposure can
include ambient lighting on the substrate. The ambient lighting can
be based on visible light. In other embodiments, the controlled
photon exposure can include one or more fluorescence excitation
light wavelength bands.
[0095] The system 1900 can include an imaging component 1960. The
imaging component 1960 can be used to image light emanating from
the immunoassay, where the imaging captures intensities of light
wavelengths across the light wavelength spectrum. The imaging can
be accomplished using an imaging sensor, where the imaging sensor
can include an IR sensor, a long-wavelength IR (LWIR) sensor, an
RGB sensor, a thermal sensor, and so on. In embodiments, the
imaging captures reflected light. The reflected light can result
from the controlled photon exposure based on ambient lighting. In
other embodiments, the imaging captures fluorescent emanating
light. The fluorescent emanating light can result from the
controlled photon exposure comprising one or more fluorescence
excitation light wavelength bands. The system 1900 can include a
generating component 1970. The generating component 1970 can be
used to generate a signature for the one or more analytes, based on
analysis of the intensities that were imaged. The signature that is
generated can be used for a variety of purposes. In embodiments,
the signature can express a magnitude for each of the one or more
analytes. The magnitudes of the analytes can be used to determine
various wound parameters or wound "vital signs". Further
embodiments can include generating a wound assessment based on the
signature. The wound assessment can be used for a variety of
wound-related assessments, treatments, and so on. In embodiments,
the wound assessment can indicate a wound treatment plan. The wound
treatment plan can include cleaning and rebandaging protocols, drug
therapies, surgery, etc. In other embodiments, the wound assessment
can include a wound state. A wound state can include a condition of
a wound, a rate of healing of the wound, whether the wound is
healing, and so on. In embodiments, the wound state includes a
stalled state, a healing state, a nonhealing state, an infected
state, an inflamed state, a granulating state, or an
epithelializing state. The wound assessment can further indicate
the size and shape of the wound. In embodiments, the wound
assessment can indicate a wound topography. In embodiments, the
wound topography can include a wound center, a wound perimeter, or
an array of wound zones.
[0096] The system 1900 can include a computer program product
embodied in a non-transitory computer readable medium for exudate
analysis, the computer program product comprising code which causes
one or more processors to perform operations of: obtaining access
to a tissue exudate sample, wherein the tissue exudate sample
contains one or more analytes representing a state of the tissue;
isolating the one or more analytes from the exudate sample on a
substrate; transferring the exudate from the substrate to an
immunoassay; illuminating the immunoassay with photons, wherein the
illuminating comprises a controlled photon exposure; imaging light
emanating from the immunoassay, wherein the imaging captures
intensities of light wavelengths across the light wavelength
spectrum; and generating a signature for the one or more analytes,
based on analysis of the intensities that were imaged.
[0097] Each of the above methods may be executed on one or more
processors on one or more computer systems. Embodiments may include
various forms of distributed computing, client/server computing,
and cloud-based computing. Further, it will be understood that the
depicted steps or boxes contained in this disclosure's flow charts
are solely illustrative and explanatory. The steps may be modified,
omitted, repeated, or re-ordered without departing from the scope
of this disclosure. Further, each step may contain one or more
sub-steps. While the foregoing drawings and description set forth
functional aspects of the disclosed systems, no particular
implementation or arrangement of software and/or hardware should be
inferred from these descriptions unless explicitly stated or
otherwise clear from the context. All such arrangements of software
and/or hardware are intended to fall within the scope of this
disclosure.
[0098] The block diagrams and flowchart illustrations depict
methods, apparatus, systems, and computer program products. The
elements and combinations of elements in the block diagrams and
flow diagrams, show functions, steps, or groups of steps of the
methods, apparatus, systems, computer program products and/or
computer-implemented methods. Any and all such functions--generally
referred to herein as a "circuit," "module," or "system"--may be
implemented by computer program instructions, by special-purpose
hardware-based computer systems, by combinations of special purpose
hardware and computer instructions, by combinations of
general-purpose hardware and computer instructions, and so on.
[0099] A programmable apparatus which executes any of the
above-mentioned computer program products or computer-implemented
methods may include one or more microprocessors, microcontrollers,
embedded microcontrollers, programmable digital signal processors,
programmable devices, programmable gate arrays, programmable array
logic, memory devices, application specific integrated circuits, or
the like. Each may be suitably employed or configured to process
computer program instructions, execute computer logic, store
computer data, and so on.
[0100] It will be understood that a computer may include a computer
program product from a computer-readable storage medium and that
this medium may be internal or external, removable and replaceable,
or fixed. In addition, a computer may include a Basic Input/Output
System (BIOS), firmware, an operating system, a database, or the
like that may include, interface with, or support the software and
hardware described herein.
[0101] Embodiments of the present invention are limited to neither
conventional computer applications nor the programmable apparatus
that run them. To illustrate: the embodiments of the presently
claimed invention could include an optical computer, quantum
computer, analog computer, or the like. A computer program may be
loaded onto a computer to produce a particular machine that may
perform any and all of the depicted functions. This particular
machine provides a means for carrying out any and all of the
depicted functions.
[0102] Any combination of one or more computer readable media may
be utilized including but not limited to: a non-transitory computer
readable medium for storage; an electronic, magnetic, optical,
electromagnetic, infrared, or semiconductor computer readable
storage medium or any suitable combination of the foregoing; a
portable computer diskette; a hard disk; a random access memory
(RAM); a read-only memory (ROM), an erasable programmable read-only
memory (EPROM, Flash, MRAM, FeRAM, or phase change memory); an
optical fiber; a portable compact disc; an optical storage device;
a magnetic storage device; or any suitable combination of the
foregoing. In the context of this document, a computer readable
storage medium may be any tangible medium that can contain or store
a program for use by or in connection with an instruction execution
system, apparatus, or device.
[0103] It will be appreciated that computer program instructions
may include computer executable code. A variety of languages for
expressing computer program instructions may include without
limitation C, C++, Java, JavaScript.TM., ActionScript.TM., assembly
language, Lisp, Perl, Tcl, Python, Ruby, hardware description
languages, database programming languages, functional programming
languages, imperative programming languages, and so on. In
embodiments, computer program instructions may be stored, compiled,
or interpreted to run on a computer, a programmable data processing
apparatus, a heterogeneous combination of processors or processor
architectures, and so on. Without limitation, embodiments of the
present invention may take the form of web-based computer software,
which includes client/server software, software-as-a-service,
peer-to-peer software, or the like.
[0104] In embodiments, a computer may enable execution of computer
program instructions including multiple programs or threads. The
multiple programs or threads may be processed approximately
simultaneously to enhance utilization of the processor and to
facilitate substantially simultaneous functions. By way of
implementation, any and all methods, program codes, program
instructions, and the like described herein may be implemented in
one or more threads which may in turn spawn other threads, which
may themselves have priorities associated with them. In some
embodiments, a computer may process these threads based on priority
or other order.
[0105] Unless explicitly stated or otherwise clear from the
context, the verbs "execute" and "process" may be used
interchangeably to indicate execute, process, interpret, compile,
assemble, link, load, or a combination of the foregoing. Therefore,
embodiments that execute or process computer program instructions,
computer-executable code, or the like may act upon the instructions
or code in any and all of the ways described. Further, the method
steps shown are intended to include any suitable method of causing
one or more parties or entities to perform the steps. The parties
performing a step, or portion of a step, need not be located within
a particular geographic location or country boundary. For instance,
if an entity located within the United States causes a method step,
or portion thereof, to be performed outside of the United States
then the method is considered to be performed in the United States
by virtue of the causal entity.
[0106] While the invention has been disclosed in connection with
preferred embodiments shown and described in detail, various
modifications and improvements thereon will become apparent to
those skilled in the art. Accordingly, the foregoing examples
should not limit the spirit and scope of the present invention;
rather it should be understood in the broadest sense allowable by
law.
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