U.S. patent application number 16/283798 was filed with the patent office on 2019-06-27 for device for characterization of biofluids.
This patent application is currently assigned to University of Cincinnati, a University of the Stat e of Ohio. The applicant listed for this patent is Eccrine Systems, Inc.. Invention is credited to Jason Heikenfeld, Wenjing Kang, Ian Papautsky, Michael Ratterman, Daniel P. Rose, Xiao Wang.
Application Number | 20190191999 16/283798 |
Document ID | / |
Family ID | 54396971 |
Filed Date | 2019-06-27 |
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United States Patent
Application |
20190191999 |
Kind Code |
A1 |
Heikenfeld; Jason ; et
al. |
June 27, 2019 |
DEVICE FOR CHARACTERIZATION OF BIOFLUIDS
Abstract
The invention addresses confounding difficulties involving
continuous sweat analyte measurement. Specifically, the present
invention provides: at least one component capable of monitoring
whether a sweat sensing device is in sufficient contact with a
wearer's skin to allow proper device operation; at least one
component capable of monitoring whether the device is operating on
a wearer's skin; at least one means of determining whether the
device wearer is a target individual within a probability range; at
least one component capable of generating and communicating alert
messages to the device user(s) related to: wearer safety, wearer
physiological condition, compliance with a requirement to wear a
device, device operation; compliance with a behavior requirement,
or other purposes that may be derived from sweat sensor data; and
the ability to utilize aggregated sweat sensor data that may be
correlated with information external to the device to enhance the
predictive capabilities of the device.
Inventors: |
Heikenfeld; Jason;
(Cincinnati, OH) ; Rose; Daniel P.; (Cincinnati,
OH) ; Papautsky; Ian; (Willowbrook, IL) ;
Kang; Wenjing; (Malden, MA) ; Wang; Xiao;
(Malden, MA) ; Ratterman; Michael; (South Lebanon,
OH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Eccrine Systems, Inc. |
Cincinnati |
OH |
US |
|
|
Assignee: |
University of Cincinnati, a
University of the Stat e of Ohio
Cincinnati
OH
|
Family ID: |
54396971 |
Appl. No.: |
16/283798 |
Filed: |
February 24, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15362303 |
Nov 28, 2016 |
10258262 |
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16283798 |
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PCT/US15/55756 |
Oct 15, 2015 |
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15362303 |
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62064009 |
Oct 15, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/7275 20130101;
G06F 19/00 20130101; A61B 5/0022 20130101; A61B 2562/164 20130101;
Y10T 29/49155 20150115; A61B 5/117 20130101; B05D 1/30 20130101;
A61B 5/0531 20130101; A61B 5/746 20130101; A61B 5/7475 20130101;
A61B 2562/08 20130101; G06K 9/00892 20130101; A61B 5/4266 20130101;
A61B 5/4845 20130101; B05D 3/007 20130101; A61B 5/14521 20130101;
A61B 5/112 20130101; A61B 2562/0214 20130101; B32B 37/12 20130101;
B32B 2535/00 20130101; H04Q 9/00 20130101; A61B 5/0002 20130101;
A61B 2562/0219 20130101; A61B 5/024 20130101; A61B 5/6833 20130101;
A61B 5/0205 20130101; H04L 67/18 20130101; Y02A 90/10 20180101;
Y02A 90/26 20180101; A61B 5/14546 20130101; A61B 5/742 20130101;
A61B 5/6843 20130101; A61B 2560/0252 20130101; A61B 5/14517
20130101; G16H 40/67 20180101; G16H 50/20 20180101; A61B 5/14551
20130101; A61B 5/1477 20130101; A61B 2562/125 20130101; A61B 5/0533
20130101; A61B 5/4833 20130101; G06N 5/04 20130101; G06K 2009/00939
20130101; H04Q 2209/40 20130101; A61B 5/6802 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00; A61B 5/145 20060101 A61B005/145; G16H 40/67 20060101
G16H040/67; A61B 5/053 20060101 A61B005/053; A61B 5/11 20060101
A61B005/11; A61B 5/1455 20060101 A61B005/1455; A61B 5/0205 20060101
A61B005/0205; B05D 1/30 20060101 B05D001/30; B05D 3/00 20060101
B05D003/00; B32B 37/12 20060101 B32B037/12; H04Q 9/00 20060101
H04Q009/00; A61B 5/117 20060101 A61B005/117; A61B 5/1477 20060101
A61B005/1477; G06K 9/00 20060101 G06K009/00; H04L 29/08 20060101
H04L029/08; G06N 5/04 20060101 G06N005/04 |
Claims
1. A device, comprising: a flexible substrate configured to conform
to skin, wherein a the flexible substrate includes a microfluidic
component for transporting a biofluid; and one or more sensors
supported by the flexible substrate.
2. The device of claim 1, wherein the flexible substrate is
configured to be removably adhered to the skin.
3. The device of claim 1, wherein the flexible substrate comprises
one or more of a polyimide, and a polyurethane.
4. The device of claim 1, wherein the flexible substrate has a
thickness of 20 micrometers.
5. The device of claim 1, wherein at least one of the one or more
sensors quantitatively or qualitatively monitors the biofluid.
6. The device of claim 1, wherein the one or more sensors are
configured to detect and continuously analyze one or more
biomarkers of the biofluid.
7. The device of claim 6, wherein the one or more biomarkers of the
biofluid includes ions, electrolytes, small molecules, and/or
metabolites.
8. The device of claim 1, wherein the one or more sensors are
configured to characterize a sweat rate of the biofluid.
9. The device of claim 1, wherein the one or more sensors includes
one or more of: an electrochemical sensor, an ion-selective
electrode sensor, a temperature sensor, a sweat rate sensor, a
potentiometric sensor, an amperometric sensor, an impedimetric
sensor, a capacitive sensor, an optical sensor, a chem-FET sensor,
an accelerometer, a mechanical sensor, a heart rate monitor, a
galvanic skin response sensor, a pulse oximetry sensor, or
combinations thereof.
10. The device of claim 1, further comprising a transmitter, a
receiver, and/or a transceiver.
11. The device of claim 1, further comprising a near field
communication antenna coil, a radio frequency identification
antenna coil, or a Bluetooth transceiver.
12. The device of claim 1, wherein the biofluid is sweat.
13. The device of claim 1, wherein the device has a length selected
from a range of 40 millimeters to 60 millimeters, a width selected
from a range of 25 millimeters to 70 millimeters, and a thickness
selected from a range of 1.2 millimeters to 2 millimeters.
14. The device of claim 1, wherein the device uses one or more of
heat, pressure, electricity, iontophoresis, or diffusion of one or
more chemical stimulant to cause a chemical or biological
change.
15. A method comprising: providing a device comprising a flexible
substrate configured to conform to skin and one or more sensors
supported by the flexible substrate, wherein a the flexible
substrate provides for transportation of a biofluid to the one or
more sensors; and applying the device to the skin; and obtaining
data from the one or more sensors, wherein the data provides a
quantitative or qualitative information associated with the
biofluid.
16. The method of claim 15, wherein the device is configured to
extract a fluid that includes the biofluid.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S.
Non-Provisional application Ser. No. 15/362,303, filed on Nov. 28,
2016, which is a continuation of PCT Application No.
PCT/US15/55756, filed on Oct. 15, 2015, which claims the benefit of
U.S. Provisional Application No. 62/064,009, filed on Oct. 15, 2014
and which is related to PCT Application No. PCT/US13/35092, filed
on Apr. 3, 2013. Each of these applications are hereby incorporated
by reference in their entirety and for all purposes.
BACKGROUND OF THE INVENTION
[0002] Sweat sensing technologies have enormous potential for
applications ranging from athletics to neonatology, to
pharmacological monitoring, to personal digital health, to name a
few applications. Sweat contains many of the same biomarkers,
chemicals, or solutes that are carried in blood and can provide
significant information enabling one to diagnose illness, health
status, exposure to toxins, performance, and other physiological
attributes even in advance of any physical sign. Furthermore, sweat
itself, the action of sweating, and other parameters, attributes,
solutes, or features on, near, or beneath the skin can be measured
to further reveal physiological information.
[0003] If sweat has such significant potential as a sensing
paradigm, then why has it not emerged beyond decades-old usage in
infant chloride assays for Cystic Fibrosis or in illicit drug
monitoring patches? In decades of sweat sensing literature, the
majority of practitioners in the art use the crude, slow, and
inconvenient process of sweat stimulation, collection of a sample,
transport of the sample to a lab, and then analysis of the sample
by a bench-top machine and a trained expert. This process is so
labor intensive, complicated, and costly that in most cases, one
would just as well implement a blood draw since it is the gold
standard for most forms of high performance biomarker sensing.
Hence, sweat sensing has not emerged into its fullest opportunity
and capability for biosensing, especially for continuous or
repeated biosensing or monitoring. Furthermore, attempts at using
sweat to sense "holy grails" such as glucose have not yet succeeded
to produce viable commercial products, reducing the publicly
perceived capability and opportunity space for sweat sensing.
[0004] Of all the other physiological fluids used for biological
monitoring (e.g., blood, urine, saliva, tears), sweat has arguably
the least predictable sampling rate in the absence of technology.
However, with proper application of technology, sweat can be made
to outperform other non-invasive or less invasive biofluids in
predictable sampling.
[0005] For example, it is difficult to control saliva or tear rate
without negative consequences for the user (e.g., dry eyes, tears,
dry mouth, or excessive saliva while talking). Urine is also a
difficult fluid for physiological monitoring, because it is
inconvenient to take multiple urine samples, it is not always
possible to take a urine sample when needed, and control of
biomarker dilution in urine imposes further significant
inconveniences on the user or test subject.
[0006] Many of the drawbacks and limitations stated above can be
resolved by creating novel and advanced interplays of chemicals,
materials, sensors, electronics, microfluidics, algorithms,
computing, software, systems, and other features or designs, in a
manner that affordably, effectively, conveniently, intelligently,
or reliably brings sweat sensing technology into intimate proximity
with sweat as it is generated. With such an invention, sweat
sensing could become a compelling new paradigm as a biosensing
platform.
[0007] In particular, sweat sensors hold tremendous promise for use
in workplace safety, athletic, military, and health care settings.
For workplace safety and military applications, a sweat sensing
device worn on the job and connected to a computer network via a
reader device, such as a smart phone or other portable or
stationary device, could relay crucial data about physiological
conditions, or the presence of prohibited substances in the
bloodstream. In health care settings, sweat sensors may
continuously monitor the health of individuals, for example,
patients who are restricted to bed rest or participating in a
clinical trial, and communicate to a reader device or computer
network, which would then compare collected data to threshold
readings and alert caregivers if the individual is in need of
intervention.
[0008] For these applications to be effective, however, it is
crucial that a targeted individual is wearing the proper sweat
sensor device, and that the device is operational. Sweat sensor
devices may be deployed in various internal configurations, with
devices configured for detecting a specific analyte or a group of
analytes, depending on the application. If a device is placed on a
different individual than the target individual, the collected
information will be inapplicable to the target individual. Or, if a
target individual is wearing the incorrect device for a particular
application, the desired information may not be collected.
Likewise, a device that has inadequate contact with the skin, or
that is otherwise inoperable due to electronic or other
malfunction, will not effectively collect sweat and detect the
targeted analytes.
BRIEF SUMMARY OF THE INVENTION
[0009] The present invention is premised on the realization that
sweat can be effectively stimulated and analyzed in a single,
continuous, or repeated manner inside the same device. The present
invention addresses the confounding difficulties involving such
analysis by assuring that a sweat sensing device is adequately
secured to a wearer's skin, is operational, and that the wearer is
a target individual. Specifically, the present invention provides:
at least one component capable of monitoring whether a sweat
sensing device is in adequate contact with a wearer's skin to allow
proper operation of the sweat sensing device; at least one
component capable of monitoring whether a sweat sensing device is
operating on the wearer's skin; at least one means of determining
whether a device is being worn by a target individual within a
probability range; at least one component capable of generating and
communicating alert messages to the sweat device user(s) related
to: wearer safety, wearer physiological condition, compliance with
a requirement to wear a device, device operation; compliance with a
behavior requirement, or other purposes that may be derived from
the use of sweat sensor data; and the ability to utilize aggregated
sweat sensor data that may be correlated with information external
to the sweat sensing device to enhance the predictive and alert
capabilities of the sweat sensing device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The objects and advantages of the present invention will be
further appreciated in light of the following detailed descriptions
and drawings in which:
[0011] FIG. 1 is a generic representation of the present invention
including a mechanism for stimulating and analyzing sweat sensor
data on a singular, continuous or repeated basis.
[0012] FIG. 2 is an example embodiment of at least a portion of a
device of the present invention including a mechanism for
generating sweat sensor data that may be used to develop and
communicate alert messages.
[0013] FIG. 3 is an example embodiment of at least a portion of a
device of the present invention including a mechanism for
determining adequate skin contact between the device and a
wearer.
[0014] FIG. 4A is an example chart representing a method by which
the present invention may determine whether a target individual is
wearing a working device, and issue an appropriate operation and
compliance alert.
[0015] FIG. 4B is an example chart representing a subset of the
method depicted in FIG. 4A by which the present invention may
determine if a device is in adequate contact with a wearer's
skin.
[0016] FIG. 4C is an example chart representing a subset of the
method depicted in FIG. 4A by which the present invention may
determine whether a device is operating on a wearer's skin.
[0017] FIG. 4D is an example chart representing a subset of the
method depicted in FIG. 4A by which the present invention may
determine if the device wearer is a target individual.
[0018] FIG. 5 is an example chart representing a method by which
the present invention may determine if the wearer is experiencing a
health condition, and issue an appropriate alert.
[0019] FIG. 6 is an example chart representing a method by which
the present invention may determine if a wearer has been exposed to
a toxic material.
[0020] FIG. 7 is an exemplary illustration of an electronic layer
of a sweat-sensing device.
[0021] FIGS. 8a and 8b are exemplary illustrations of the one or
more layers that can be included in a sweat-sensing device.
DEFINITIONS
[0022] Sweat sensor data means all of the information collected by
sweat sensing device sensor(s) and communicated via the device to a
user or a data aggregation location.
[0023] Correlated aggregated data means sweat sensor data that has
been collected in a data aggregation location and correlated with
outside information such as time, temperature, weather, location,
user profile, other sweat sensor data, other wearables data, or any
other relevant data.
[0024] Analyte data signature means a known set of analyte levels,
ratios, or concentration trends that is correlated with a specific
individual within a probability range.
[0025] Identification metrics means the various
identification-related readings that may be used by a sweat sensing
device to indicate within a certain probability that a target
individual is wearing the device. These metrics include, without
limitation, sweat analyte data metrics, proxy identification
metrics, communication/location metrics, or other metrics.
[0026] Identification profile means a profile composed of two or
more identification metrics and associated with an individual for
use in calculating an identification probability estimate.
[0027] Identification probability estimate means the calculated
probability that a person wearing a sweat sensing device is a
target individual based on a comparison of identification metrics
with known data about the target individual.
[0028] Compliance metric means a skin contact measurement, device
operation measurement, or an identification metric.
[0029] Operation and compliance reading means the sweat sensor data
collected on at least one compliance metric.
[0030] Operation and compliance alert means a message generated by
the sweat sensing device and relayed to a user when an operation
and compliance reading indicates a device skin contact status, an
operational status, or a wearer identification status.
[0031] Safety and health reading means a measurement of at least
one sweat analyte that indicates the concentration, or
concentration trend, of the analyte in a wearer's sweat.
[0032] Safety and health alert means an alert generated by the
sweat sensing device and relayed to a user and/or a wearer, when a
safety and health reading indicates that some intervention is
recommended.
[0033] Safety profile means a known set of sweat analyte levels,
ratios, or concentration trends that indicates with a certain
probability that a wearer needs intervention, such as from a health
condition.
[0034] Behavioral profile means a known set of sweat analyte
levels, ratios, or concentration trends that indicates with a
certain probability that a wearer is in compliance with a
behavioral program, such as a drug regimen.
DETAILED DESCRIPTION OF THE INVENTION
[0035] The detailed description of the present invention will be
primarily be, but not entirely be, limited to subcomponents,
subsystems, sub methods, of wearable sensing devices, including
devices dedicated to sweat sensing. Therefore, although not
described in detail here, other essential features which are
readily interpreted from or incorporated along with the present
invention shall be included as part of the present invention. The
specification for the present invention provides examples to
portray inventive steps, but which will not necessarily cover all
possible embodiments commonly known to those skilled in the art.
For example, the described invention will not necessarily include
all obvious features needed for operation, examples being a battery
or power source which is required to power electronics, or for
example, a wax paper backing that is removed prior to applying an
adhesive patch, or for example, a particular antenna design that
allows wireless communication with a particular external computing
and information display device.
[0036] With reference to FIG. 1, a sweat sensing device 100 is
placed on or near skin 140 (shown), or in an alternate embodiment
is simply fluidically connected to skin or regions near skin
through microfluidics or other suitable techniques (not shown). A
complete enablement of such a device is described by Rose and
Heikenfeld in the article in press for publication in the journal
IEEE Transactions on Biomedical Engineering, titled "Adhesive RFID
Sensor Patch for Monitoring of Sweat Electrolytes" which is hereby
incorporated by reference in its entirety for all purposes. The
present invention applies at least to any type of sweat sensing
device that stimulates and/or measures sweat, its solutes, solutes
that transfer into sweat from skin, a property of or things on the
surface of skin, or properties or things beneath the skin, or
measures something about the surrounding; environment including
humidity, temperature, motion, or other external factors to be
measured. The present invention applies to sweat sensing devices
which can take on forms that include patches, bands, straps,
portions of clothing, wearables, or any suitable mechanism that
reliably brings sweat stimulating, sweat collecting, andlor sweat
sensing technology into intimate proximity with sweat as it is
generated. Some embodiments of the present invention utilize
adhesives to hold the device near the skin, but devices could also
be held by other mechanisms that hold the device secure against the
skin, such as a strap or embedding the device in a helmet or other
headgear. Certain embodiments of the present invention show sensors
as simple individual elements, it is understood that many sensors
such as potentiometric, amperometric, impedimetric, and others,
require two or more electrodes, reference electrodes, or additional
supporting technology or features which are not captured in the
description herein. Sensors are preferably electrical in nature,
but may also include optical, chemical, mechanical, or other known
biosensing mechanisms. Sensors can be in duplicate, triplicate, or
more, to provide improved data and readings. Sensors may be
referred to by what the sensor is measuring, for example: a sweat
sensor; an impedance sensor; a sweat volume sensor; a sweat
generation rate sensor; or a solute generation rate sensor. The
present invention includes all direct or indirect mechanisms of
sweat stimulation, including but not limited to sweat stimulation
by heat, pressure, electricity, iontophoresis or diffusion of
chemical sweat stimulants, orally or injected drugs that stimulate
sweat, stimuli external to the body, cognitive activity, or
physical activity, or other sweat responses to external stimuli.
Certain embodiments of the present invention show sub-components of
sweat sensing devices that would require additional obvious
sub-components for various applications (such as a battery, or a
counter electrode for iontophoresis). These additional
sub-components are not critical to the inventive step of the
present invention, and for purpose of brevity and focu on inventive
aspects, are not explicitly shown it1 the diagrams or described do
the embodiments of the present invention.
[0037] With further reference to FIG. 1, the arrangement and
description of the device is an example embodiment only, and other
obvious configurations and applications are included within spirit
of the present invention. The device 100 is in wired communication
110 or wireless communication 120 with an AC or battery-powered
reader device 130, and placed on skin 140. In one embodiment of the
present invention, the reader device 130 would be a smart phone, or
other portable electronic device. In another embodiment, the reader
device is a companion transceiver placed at bedside, mounted in a
commercial or military vehicle, or widely distributed in locations
that are supplied with electrical power. In another embodiment, the
reader device is a portable electronic device or companion
transceiver capable of secure two-way communication with the sensor
and secure two-way communication with a computer network, such as a
local area network or the Internet via a wireless router and/or a
cellular data network. In alternate embodiments the device 100 and
device 130 can be combined (not shown).
[0038] The device may include RFID, or may include wireless
protocol such as Bluetooth, or the device may use alternate
communication or power strategies to communicate with a reader
device in proximity to the device. The sensor can include a thin
layer battery and provide its own power source, and thus not rely
on RFID. Both RFID and Bluetooth can be used in conjunction, where
RFID can charge the battery when provided the proper near field
communications. The device may also include means of signal
amplification to improve signal quality communicated to the reader
device, and to improve transmission distance to the reader device.
Other biomarker sensing methods and sweat transport methods may be
included, so long as they provide the same capability of continuous
or semi-continuous monitoring of sweat biomarkers.
[0039] The sweat sensing device disclosed herein also includes
computing and data storage capability sufficient to operate the
device, which incorporates the ability to conduct communication
among device components, to perform data aggregation, and to
execute algorithms capable of analyzing data and generating alert
messages. This computing capability may be fully or partially
located on the device, on the reader device, or on a connected
computer network.
[0040] The sweat sensing device may also include data aggregation
and monitoring capability. Such data aggregation may include
collecting all of the sweat sensor data generated by sweat sensing
devices. The aggregated data may be de-identified from individual
wearers, or may remain associated with an individual wearer. Such
data may also be correlated with outside information, such as the
time, date, weather conditions, activity performed by the
individual, the individual's mental and physical performance during
the data collection, the proximity to significant health events
experienced by the individual, the individual's age or sex, the
individual's health history, data from other wearable devices, such
as those measuring galvanic skin response, pulse oximetry, heart
rate, etc., or other relevant information. The data collected may
be made accessible via secure website portal to allow sweat device
users to perform safety, compliance and/or care monitoring of
target individuals. In an alternative embodiment, the data may be
made accessible via application programming interface ("API"),
which would allow sweat sensor data to be integrated with a user's
existing safety, compliance and care monitoring systems, such as an
employer's on-shift monitoring system. The sweat sensor data
monitored by the user may include real-time data, trend data, or
may also include aggregated sweat sensor data drawn from the device
database and correlated to a particular user, a user profile (such
as age, sex or fitness level), weather condition, activity,
combined analyte profile, or other relevant metric. Trend data,
such as a target individual's hydration level over time, may be
used to predict future performance, or the likelihood of an
impending physiological event. Such predictive capability can be
enhanced by using correlated aggregated data, which would allow the
user to compare an individual's historical analyte and external
data profiles to a real-time situation as it progresses, or even to
compare thousands of similar analyte and external data profiles
from other individuals to the real-time situation. Sweat sensor
data may also be used to identify wearers that are in need of
additional monitoring or instruction, such as to maintain the
proper hydration levels, or to adhere to a drug regimen. Sweat
sensor data may be used to supply information for incentive systems
by tracking an individual wearer's performance on various metrics.
For example, an athletic coach may track a player's efforts to
maintain proper hydration or electrolyte levels, or an employer may
track positive safety results over one or more incentive cycles.
Incentive system information could then be relayed to supervisory
management and tied to financial incentives for the target
individual. The disclosed uses of aggregated data are for
illustration purposes only, and do not limit other potential
sources or applications available for such data, which are within
the spirit of the present invention.
[0041] FIG. 2 is an example embodiment of at least a portion of a
device of the present invention capable of ensuring device security
and compliance through the use of various means. As shown in FIG.
2, a sweat sensing device 2 positioned on skin 240 by an adhesive
layer 200 bonded to fluid impermeable substrate 210. Substrate 210
holds electronics 270, one or more sensors 220 (one shown), a
microfluidic component 230, coupled to one or more sweat pads 242,
244, 246. Each pad has a source of chemical sweat stimulant, such
as pilocarpine, and independently controlled iontophoresis
electrode(s) 252, 254, 256. There is also one or more counter
electrode(s) 260. The sweat sensor 220 can be a gate-exposed SiCMOS
chip having three or more identical chem-FETs per biomarker.
Sub-micron SiCMOS allow for MHz impedance spectroscopy. Sensors are
separated spatially into subgroups of identical sensors, or large
sensor arrays can be formed using techniques such as
photo-initiated chemical patterning. Arrays of biomarker-specific
sensors allow for continuous monitoring of multiple physiological
conditions. Thus, in operation, the electronics 270 would activate
one or more electrodes 252, 254, 256. This will cause the skin to
generate sweat, which will be transferred through the microfluidic
structures 230, directed to the sensor 220.
[0042] In addition to sweat generation, the electrodes 252, 254,
256, with counter electrode 260 may also be used to measure skin
and/or body impedance in order to determine whether the device is
in adequate contact with the skin. In other embodiments, the device
2 may be configured with two or more skin facing electrodes
dedicated to determining skin and/or body impedance (not shown), as
are known to those skilled in the art of electrophysiology.
Similarly, in other embodiments, at least one capacitive sensor
electrode (not shown), also as known in the art of
electrophysiology, may be placed on selected locations on the
skin-facing side of the device, and would convey information about
the distance between the sensor and the skin. The skin proximity
readings generated by the capacitive sensor(s) would therefore
indicate whether the device is in adequate contact with a wearer's
skin.
[0043] FIG. 3 is applicable to any of the devices of FIGS. 1-2. If
electrode/pad contact to the skin is or becomes inadequate, this
can be detected as an increase in impedance and the sweat sensing
device can send an alert message to the user. The sweat sensing
device 3 affixed to skin 340 by adhesive 300 senses impedance of
the contact of the electrode 350 (with chemical stimulant source
330 and microfluidic component 320) with the skin 340 or the
contact of counter electrode 360 with the skin 340 where "contact"
refers to direct contact or indirect contact but which has adequate
and/or uniform electrical conduction with the skin. Measurement of
electrical impedance includes obvious related measures such as
voltage or current, which also give a measure of impedance. If the
impedance exceeds a preset limit by circuit 370, the device sends
an alert to the user.
[0044] With reference to FIGS. 4A to 4D, the sweat sensing device
described above may generate operation and compliance alerts to
inform the device user whether a sweat sensing device (1) is in
adequate contact with a wearer's skin, (2) is operating on the
wearer's skin, or (3) the wearer is a target individual. Alerts may
be communicated to the user via email, SMS messaging, pager,
automated phone call, or callbacks to other systems. The device may
conduct continuous or periodic operation and compliance readings to
determine if the device is in contact with the skin, or to
determine if the device is functioning on the skin of the target
individual. If the sweat sensing device determines that the device
is not adequately contacting the skin, the device could relay a
signal to user directly or via computer network. Likewise, if the
sweat sensor data, or other data, did not match a profile
indicating operation on the skin, the device could relay that
information. The sweat sensing device user would accordingly
receive an alert message that a device is no longer operative. The
device may also conduct identification readings using any of the
herein disclosed means to determine the identification probability
estimate for the target individual. If the sweat sensing device
determined that the identification probability estimate were below
a certain threshold, it could generate an operation and compliance
alert that the target individual is not wearing the device.
[0045] Various means may be used to determine the appropriate time
to initiate operation and compliance readings. These may be
conducted continuously whenever a device is detected to be in use
by the device, or if the device determines that a target individual
should be wearing a device at a particular time. For example, the
reader device may employ an API to communicate with an employer's
on-shift system to determine if a target employee is on the job,
and therefore ought to be wearing a device. In another example, a
trucking company's sweat sensing device could determine through
changing location data sensed by a companion transceiver that a
target employee was operating a tractor-trailer, triggering the
initiation of operation and compliance readings. The sweat sensing
device could also integrate other data to determine whether to
issue an operation and compliance alert, such as the current
weather, the time of day, or the day of the week.
[0046] With reference to FIG. 4B, the sweat sensing device uses
onboard impedance or capacitive sensors to determine if the device
is in adequate contact with the wearer's skin to allow proper
device function. Inadequate contact can indicate that the device
has been removed by the user, or has become detached from the skin
for other reasons. Additionally, inadequate skin contact can cause
undesirable effects upon the skin or with the function of the
device. If the device is not in adequate contact with the wearer's
skin, the device will send a negative operation and compliance
alert. If the device measurements indicate that the device is
adequately secured to skin, an operation and compliance alert
conveying that information may be sent, and the sweat sensing
device will proceed to verify the other operation and compliance
elements. The device may be programmed to record and track the
time(s) at which a sweat sensor is in contact with the skin, as
well as the time(s) at which the sweat sensor is no longer in skin
contact. The device can also be programmed to sense skin contact
continuously, or periodically, for example, on a daily or hourly
basis.
[0047] With reference to FIG. 4C, once the device confirms it has
adequate contact with a wearer's skin, it may assess whether the
device is operating on the wearer's skin. When the device begins
operation, it will be able to determine if the device is actually
generating sweat data. For example, the device could determine
whether sweat is present by taking a measurement of galvanic skin
response or by measuring sweat generation rate. Additionally, sweat
analyte measurements can be used to distinguish genuine sweat data
from counterfeit data. Sweat analytes change in predictable ways to
increases or decreases in sweat rate. For example, when sweat rate
increases, Na.sup.+ and concentrations in sweat typically increase,
while K.sup..+-. concentrations stay relatively constant with sweat
rate. These trending measurements would be difficult to reproduce
artificially, for example, if a wearer were trying to avoid
compliance by introducing other fluids to the sweat sensing device.
In some embodiments, the device may also determine if the device
has been placed on a body location that is appropriate for the
particular device application sought by the device user. Eccrine
sweat pore distribution varies throughout the body, as does the
readiness with which body locations begin sweating in response to
stimulus, as is discussed in further detail in Z. Sonner, et al.,
"The microfluidics of the eccrine sweat gland, including biomarker
partitioning, transport, and biosensing implications,"
Biomicrofluidics 9, 031301 (2015); doi: 10.1063/1.4921039.
Therefore, sweat rates and volumes as detected by a sweat sensing
device may used to determine if a device has been applied to the
correct area of the body.
[0048] With reference to FIG. 4D, in an example embodiment, the
device may also determine whether a device wearer is likely a
target individual from whom the device user desires to collect
sweat data. The sweat sensing device would take readings on a
selected identification metric, and would then compare that
measurement to an identification signature used for the target
individual. Based on this comparison, the device would calculate an
identification probability estimate characterizing the probability
that the wearer is the target individual. If the desired certainty
about the wearer's identity has not been reached, and the device
has another identification metric available, the device will
measure another identification metric and calculate a new
identification probability estimate. The process would continue
until either the device has exhausted all of its available
identification metrics, or the wearer has been positively or
negatively identified as the target individual with sufficient
certainty for the application. The device would then send an
operation and compliance alert indicating whether or not the wearer
is the target individual.
[0049] A unique identification signature for a target individual
may be developed by using a sweat sensing device to generate
readings for at least one of the identification metrics discussed
herein. A device user would collect sufficient data on the
identification metric to build a robust signature characteristic of
the individual, such as a characteristic sweat RNA content. For the
development of the identification signature, it will be
particularly important to ensure that the target individual is
actually wearing the sweat sensing device and that the collected
data is accurate. For example, the device(s) used to develop the
identification signature may be applied under supervision, and the
target individual may need to wear the device under controlled
physical conditions optimized for accurate reading, such as a
climate-controlled room, or while performing set physical or mental
tasks. The sweat sensing device may calculate an identification
signature at the time of first use of a sweat sensor, or over
multiple sweat sensor uses. The user may also develop the
identification signature by some combination of the above methods.
In alternative embodiments, the sweat sensing device may not
develop a unique identification signature for a target individual,
but instead would use an identification signature composed of
relevant known general characteristics of the target individual,
such as age, fitness level, or sex.
[0050] When the sweat sensing device has more than one
identification metric available, the device will combine the
identification probability estimates for each metric to calculate a
new combined identification probability estimate. The device will
use an algorithm to perform a weighted aggregation of the separate
identification probability estimates, thereby increasing the
overall probability of identification. The use of multiple
identification metrics, therefore, will greatly increase the
device's ability to determine if a wearer is a target individual,
even where each identification metric alone is of limited value for
distinguishing among individuals. The higher identification
probability estimate will correlate with increased certainty that a
target individual is, or is not, wearing the device and
correspondingly reduce the incidence of false warnings generated by
the device.
[0051] Designing an algorithm capable of performing an aggregation
of separate identification probability estimates is known by
persons skilled in the art of statistical analysis and computer
programming. The probability that a given event may occur is
calculated by dividing the number of desired outcomes by the number
of possible outcomes in a given population. For example, assume the
target individual is a male with a low basal cortisol level (less
than 11 nMol/L). The probability that the wearer will be male out
of the general U.S. population with a female-to-male ratio of 1.07
is P(male)=48.3%. The probability that the wearer will have low
cortisol given that (hypothetically) 1 of 25 individuals in a
population typically has a basal cortisol level under 11 nMol/L is
P(low cortisol)=4%. The combined probability that two independent
events would occur randomly, is calculated by multiplying the
probabilities. If two identification metrics taken on the wearer
indicate that the wearer is a male with low basal cortisol, the
probability that a random member of the population would have both
identification metrics is 0.4830.04=1.9%. Therefore, the
identification probability estimate that the wearer is the target
individual is 98.0%.
[0052] For further refinement of the method, each probability
estimate may then be weighted appropriately considering each
estimate's reliability within the context of the sweat sensing
device's capabilities and operation. For example, an analyte trend
reading calculated with a limited number of data points would be
weighed less than a similar reading calculated from many data
points. Similarly, a BMI measurement by body impedance sensors may
suffer inaccuracies due to the number of sensors used, the wearer's
level of dehydration, or the time proximity of the measurement to
food consumption or strenuous exercise by the wearer. As a
component of an identification probability estimate, therefore, a
BMI measurement would be weighed less than other more reliable
metrics. Weighted aggregation of the separate identification
probability estimates, then, is a dynamic process, considering, for
example, the hydration level of the wearer, sweat rate at the time
of measurement, the functionality of sensors, number of operating
sensors, number of readings taken, and other relevant factors.
[0053] Several identification metrics are available for use with a
sweat sensing device, including metrics derived from sweat
analytes, metrics derived from other characteristics of the wearer,
and metrics derived from data originating outside the wearer's
body, such as device communication characteristics or location.
[0054] Perhaps the most reliable of these metrics are ones derived
from the sweat sensing device's sweat analyte measurements.
Accordingly, the device may be configured to create an analyte data
signature based on individual differences in analyte concentrations
and ratios that emerge in sweat. This analyte data signature may
comprise all or part of the target individual's identification
signature. The concentrations of different sweat analytes, whether
commonly or rarely found in sweat, or the comparative ratios of
such analytes, may be a strong indicator of identity. In the
simplest case, a sweat sensing device may detect sweat
concentrations or ratios of sex hormones, such as estradiol or
testosterone, to determine a wearer's sex. In other embodiments, a
wearer's resting concentration of Na.sup.+ (common) or chromium
(less common); a wearer's ratio of common electrolytes, such as the
resting ratio of K.sup.+ to Na.sup.t; or a wearer's trend profile
of K.sup.+ to Na.sup.+ when stress sweating or when sweating due to
physical exertion, may prove to be effective identifiers of the
individual. In other embodiments, apocrine sweat sex-specific
pheromones may be used to identify a wearer.
[0055] In another embodiment of the invention, the sweat sensing
device may be configured to create an analyte signature based on
biological oligomers, such as nucleotides, that are excreted in
eccrine sweat. DNA fragments, RNA fragments, micro RNA, peptides,
and similar oligomers emerge in eccrine sweat, and perform various
extracellular signaling functions. In particular, micro RNA appears
to play a significant role in exosomic endocrine modulation and
mediation of tissue crosstalk, facilitating immune response, among
other functions. The concentrations of micro RNA, and/or other
biological oligomers in sweat, or the comparative ratios of such
oligomers, or the ratios of such oligomers to other analytes, may
be a strong indicator of identity.
[0056] In an alternative embodiment, a target individual could be
administered a tracer compound that can be used to determine if a
device wearer is a target individual, for example by incorporating
expected tracer-related sweat molecule concentrations into the
individual's analyte data profile. After being administered, the
tracer molecule or its metabolite(s) are excreted in sweat and
detected by the sweat sensing device. The tracer compound may be a
substance that is easily detectible in sweat, with known and
predictable metabolizing qualities. The tracer compound may be
selected with a half-life that is appropriate to the length of time
the sweat sensor is to be worn by the user, or the tracer compound
may be administered at regular intervals suitable for the duration
of sweat sensor use. The sweat sensing device detects the tracer
compound in the sweat and compares the detected levels to the
expected levels based on the administered dose and/or the
half-life. By confirming that the tracer molecule is detected at
the expected concentrations in the sweat, the sweat sensing device
will be able to calculate a higher identification probability
estimate.
[0057] Several other techniques that do not rely on sweat analyte
data may also prove useful for identifying a user with a sweat
sensing device. For example, in another embodiment of the
invention, the sweat sensing device may be configured to combine
sweat sensing device measurements with data from other wearable
sensors currently known in the art, such as an accelerometer, gait
analysis sensor, heart rate monitor, sensors measuring
electrodermal activity, such as galvanic skin response, pulse
oximetry, and others. For example, a sweat sensing device may take
analyte measurements of Na.sup.t, Cl.sup.- and K.sup.t
concentrations as they emerge in a wearer's sweat. The device then
uses the trending ratio of Cl.sup.- to K.sup.t and corrects for
sweat rate by using the Na.sup.t concentration trend. The device
then compares these analyte values to the analyte signature
assigned to a target individual. The device determines that the
measured values correspond to the analyte signature, giving a
(hypothetical) 70% probability that the wearer is the target
individual. The device then accounts for measurements from a gait
analysis device, which determines that the wearer's gait matches
that of the target individual with a (hypothetical) probability of
70%. The sweat sensing device then calculates a weighted average of
the two probabilities to calculate a combined probability estimate
of 91% that the wearer is the target individual.
[0058] In other embodiments, a sweat sensing device may use
impedance electrodes to calculate the body mass index (BMI) or body
composition of a device wearer. BMI readings vary from individual
to individual depending on their sex, age and fitness level, among
other factors. In some cases, the composition or thickness of
layers of fat under skin could be measured by impedance, since the
resistance to electricity varies between adipose, muscular and
skeletal tissue. A body composition reading could be used to
determine whether a child, a middle-aged adult, or an older adult
was likely wearing a device, or if a male or female, or someone who
is generally fit, or someone who is overweight is wearing it. A
sweat sensing device or other means may be used to develop a BMI
signature that comprises all or part of a target individual's
identification signature. The individual may also be periodically
reassessed to ensure the BMI signature is accurate. A device may
then accomplish a BMI measurement on a wearer, and compare the
measurement to the BMI signature on file for a target individual to
determine the identification probability estimate for the
wearer.
[0059] Similarly, in other embodiments, the sweat sensing device
may be configured to calculate the skin age or skin pigmentation of
the individual wearing the device using skin impedance readings. An
optical sensor could also be used to detect skin pigmentation,
using hardware in some cases similar to that used for pulse
oximetry. Skin impedance readings vary predictably according to an
individual's age with the amount of scarring of tissue over time,
with hydration, with increase in skin roughness, change in the
level of function of eccrine sweat glands, or other known factors.
Likewise, the ratio of pigment molecules to other molecules
contained in the skin varies from individual to individual. As in
the case of BMI, a skin type signature may be developed to
contribute to a target individual's identification signature.
[0060] In another embodiment of the present invention, a sweat
response signature may be developed for a target individual based
on their typical sweat response to a stimulus. The target
individual's sweat response signature would be compared to the
sweat response metric generated while the wearer performed a test
designed to elicit an electro-physical response, such as a math
test or having the wearer count backwards from 100. Sweat response
is largely influenced by sweat gland density at the anatomical
location of the device's application. In addition, individual sweat
rate can change based on the individual's sweat threshold, which
may be influenced by physical activity levels or climate. These
variations can influence the time it takes to evoke a physiological
response to stimulus, as well as the volumetric rate of the
response. A target individual may be given multiple tests of this
nature to develop a more accurate sweat response signature value,
or the individual may be periodically reassessed to update the
signature. As with other methods disclosed herein, a target
individual's sweat response signature may comprise all or part of
the individual's identification signature.
[0061] In other embodiments of the present invention, the sweat
sensor device may use data originating outside the target
individual's body, such as computer network connectivity, or Global
Positioning System location data, to create an identification
signature. For example, the sweat sensor may be in wireless
communication with a reader device, such as a smart phone or other
portable electronic device, or a companion transceiver. The reader
device is programmed to operate the sweat sensor and to detect the
RFID, or other firmware signature of the sweat sensor. The sweat
sensor's RFID device or other firmware, is programmed with a unique
identification code that indicates the sensor is part of a certain
group, or lot, of sensors. The particular lot of sensors may, for
example, all serve a particular purpose, or may have been
distributed to a specific individual. The sweat sensor, when
communicating data to the reader device, would transmit the
identification code along with the sensor data. The reader device
could then determine if the sweat sensor is part of the correct lot
of sensors for the particular individual or application.
[0062] Similarly, the sweat sensor may be in wireless communication
with a reader device through a wireless protocol such as Bluetooth
or other communication strategy. The reader device can determine
the signal strength of the sweat sensor, and thereby determine
approximate distance from the reader device to the sweat sensor as
it is being worn by an individual. The reader device may be
associated with an individual or group of individuals. By
calculating the approximate distance from the reader device to the
target individual, it can be determined if a sweat sensor is being
worn in proximity to a device that is associated with a particular
individual, thereby increasing the probability that the wearer is
the target individual.
[0063] In another embodiment, the reader device could determine its
approximate location via GPS application, network access location,
or other means. When the reader device is in wireless communication
with the sweat sensor, it could determine the approximate location
of the sweat sensor as an individual is wearing it. By calculating
the individual's approximate location, and comparing the calculated
location with the target's individual's known approximate location,
the sweat sensing device can ensure the device is being worn by the
target individual.
[0064] In another embodiment of the present invention, a trained
professional could apply the sweat sensing device to the target
individual and the device would then be activated. If the device
were subsequently removed from the target individual, the sweat
sensing device could detect the change in impedance indicating
device removal.
[0065] With reference to FIG. 5, the sweat sensing device could
also generate safety and health alerts to warn the device user or
the wearer that analyte concentrations, analyte ratios, or trend
data for such measurements indicate the need for intervention. As
with the operation and compliance alerts, these messages could be
communicated in various formats. The device may conduct continuous
or periodic safety and health readings to determine if the wearer's
detected analytes indicate the need for intervention. Once the
device detects a predetermined analyte threshold or trend, the
device would generate a safety and health alert, which would be
relayed to the device user or to the wearer. Depending on the
application, the sweat sensing device user may set threshold or
trend criteria for the target individual's hydration level, blood
alcohol content, blood sugar levels, level of physiological stress,
or other measures within the capability of the sweat sensor device
in use. The sweat sensing device could also integrate other
aggregated sweat sensor and external data, such as the current
weather, the time of day, the individual's previous day exertion
level, the number of continuous days the individual was on the job,
the individual's historical analyte profiles, and etc., to
determine whether to issue a safety and health alert. For example,
the sweat sensing device may have access to aggregated data on
thousands of individuals of similar age that experienced an analyte
profile similar to the wearer under similar environmental
conditions. The device could use the aggregated data to predict how
long the wearer may have until intervention is required and issue
an appropriate alert. The device may also report data to safety,
compliance or care managers to identify a wearer that is in need of
additional instruction or monitoring as to obtaining optimal
physical and mental performance, hydration maintenance, adherence
to a drug regimen, or other appropriate applications.
[0066] In another embodiment of the present invention, the sweat
sensing device could be configured for use in clinical trials to
provide improved safety monitoring without the need for blood
draws, and to ensure compliance with drug regimens. The devices may
be customized for use with a specific drug, or may be for general
application to clinical trials.
[0067] To monitor safety, the sweat sensor devices may be
internally configured to monitor a suite of analytes useful in such
trials for safety purposes, such as Na.sup.t, Cl.sup.-, K.sup.-,
Ca.sup.+2, cortisol, glucose, and ammonium, to name a few.
Alternatively, the sensor may be configured to monitor specific
analytes indicative of side effects identified during earlier
clinical studies or animal trials. In addition, the sensor could be
configured to monitor the health of specific organs during
treatment through sweat detection of metabolic, renal or other
similar commonly used blood test panels. The device may also
monitor for specific analytes associated with the side-effects or
safety implications of a particular drug. For example, drug safety
could be monitored by developing an analyte safety profile. The
safety profile would consist of analytes that, when analyzed
together, indicate with high probability that a test subject needs
intervention. A safety profile for a particular drug may be
predicted using correlated aggregated sweat sensor data, or it may
need to be developed by the device as it is being used during a
clinical trial. A safety profile developed for a drug during its
clinical trials could then be used to monitor safety
post-approval.
[0068] To monitor compliance with a drug regimen, the sensor device
may be internally configured to detect metabolites or other
analytes that are associated with the trial drug, or with a tracer
compound having metabolic properties similar to the trial drug. For
example, compliance could be monitored by developing a behavioral
profile. The behavioral profile would consist of analytes that,
when taken together, indicate with high probability that a test
subject is, or is not, following a drug regimen. The analytes in
the profile may be metabolites of the drug itself, a tracer
compound, or they might be other analytes that are indirectly
affected by the drug. When a drug is taken, the concentration of
various analytes in the bloodstream may change in reaction to the
drug. The device could monitor the concentrations of these
analytes, the ratio of these analytes to each other, and could
develop trend data showing changes in their relative
concentrations. The behavioral profile would then be a known set of
analyte levels, ratios, or concentration trends that is unique to
compliance with a particular drug regimen. A behavioral profile for
a particular drug may be predicted using correlated aggregated
sweat sensor data, or it may need to be developed by the device as
it is being used during a clinical trial. A behavioral profile
developed for a drug during its clinical trials could then be used
to monitor compliance post-approval.
[0069] If the analytes monitored for safety purposes indicated the
need for intervention, the device could generate and communicate a
safety and health alert. Similarly, if detected analyte readings
differed significantly from the drug's behavioral profile, the
device would determine that the target individual had not taken a
required dose, and could generate and communicate a safety and
health alert.
[0070] With reference to FIG. 6, in another embodiment of the
present invention, the sweat sensing device could be configured to
enhance workplace safety by providing continuous or near-continuous
monitoring for the presence of workplace-related toxins in a
wearer's bloodstream. Sweat has been identified as a preferential
means of monitoring for the presence of toxic metals, metalloids,
petrochemicals and other substances, since bioaccumulation levels
of such toxins may be underrepresented in blood and urine. The
devices may therefore be internally configured to detect toxins
that are widely encountered in workplace settings, or may be
customized to detect toxins that are unique to a particular
workplace. As with safety monitoring in other contexts, for
workplace safety a device may be configured to monitor for specific
analytes associated with exposure to a particular toxin, or group
of toxins. For example, workplace safety could be monitored by
developing an analyte safety profile for the workplace. The safety
profile would consist of analytes that, when taken together,
indicate with high probability that an employee needs intervention
from exposure to toxins. A safety profile for a particular
workplace may be developed using correlated aggregated sweat sensor
data, or it may need to be developed by the device as it is being
used. Further, an individual's toxin exposure data may be stored
and monitored over time, and factored into future safety and health
alerts for that individual.
[0071] Wearable digital health devices are dominantly found in
rigid form factors such as bracelets and pucks. An adhesive RFID
sensor bandage (patch) is reported, which can be made completely
intimate with human skin, a distinct advantage for chronological
monitoring of biomarkers in sweat. In this demonstration, a
commercial RFID chip is adapted with minimum components to allow
potentiometric sensing of solutes in sweat, and surface
temperature, as read by an Android.TM. smart-phone app with 96%
accuracy at 50 mM Na+ (in-vitro tests). All circuitry is
solder-reflow integrated on a standard Cu/polyimide
flexible-electronic layer including an antenna, but while also
allowing electroplating for simple integration of exotic metals for
sensing electrodes. Optional paper microfluidics wick sweat from a
sweat porous adhesive allowing flow to the sensor, or the sensor
can be directly contacted to the skin. The wearability of the patch
has been demonstrated for up to 7 days, and includes a protective
textile which provides a feel and appearance similar to a standard
Band-Aid.RTM.. Applications include hydration monitoring, but the
basic capability is extendable to other mM ionic solutes in sweat
(Cl-, K+, Mg2+, NH4+, Zn2+). The design and fabrication of the
patch is provided in full detail, as the basic components could be
useful in the design of other wearable sensors.
I. Introduction
[0072] Sweat is one of few examples of non-invasively accessed
biofluids, with potential advantages in measurement of inflammatory
biomarkers compared to saliva and potentially superior
time-resolved (chronological) readings of biomarker concentrations
compared to saliva and urine. Sweat access can be locally
stimulated using FDA-approved iontophoresis (Wescor Macroduct), and
recent tattoo-like sweat-sensing demonstrations further include
measurement of lactate, ammonium, and sodium [2-4]. A particularly
attractive application could be hydration and heat-stress
monitoring through electrolyte balance (e.g., Na+, K+) for
athletes, military personnel, first-responders, and others working
in extreme-conditions. Electrolyte sensing is of further value,
because the high salinity of sweat can confound other biomarker
readings, hence electrolyte concentrations need to be base-lined.
Realizing such wearable sensors could be achieved several ways,
including wearable textiles, tattoos, and form-factors such as
those seen commercially in digital bracelet products such as
Nike+.TM. and Fitbit.TM.. However, a complete wireless sensor with
wearability comparable to a simple Band-Aid.RTM. that is low cost,
robust, communicates with smart phones and exhibits a design which
automatically lends itself to maximum time-resolved readings of
sweat has not yet been demonstrated.
[0073] A wearable, medical-grade adhesive RFID enabled sensor patch
is reported, which is conformal to the shape of the human body, and
therefore minimizes dead volumes of sweat which would otherwise
limit chronological measurements. Adaptation of a commercial RFID
chip is achieved with minimum components to allow potentiometric
sensing of electrolytes in sweat as well as skin surface
temperature, and could be of use for hydration and heat-stress
monitoring. The patch is battery-free, powered and read wirelessly
by an Android smart phone and custom-app. From in-vitro solution to
smart-phone readout, a dynamic range of 235 mV to 255 mV is
achieved with 20 mM to 70 mM range and 96% accuracy in the
detection of Na+ concentration. All circuitry is solder-reflow
integrated on a standard Cu/polyimide flexibleelectronic layer
including conventional components such as an antenna, but also
allowing electroplating for simple integration of exotic metals for
ion-selective sensing electrodes. The sensing electrodes can be
folded over to be in direct contact with skin, or paper
microfluidics can be used to wick sweat from the skin and to the
sensors. The wearability of the patch has been shown up to 7 days,
and includes a protective textile which provides a feel and
appearance similar to a standard Band-Aid or transdermal patch.
This work outlines a complete integration of the key materials,
electronics, microfluidics, and ergonomics, required for a wearable
sweat sensing patch, paving the way for future wearable sweat
sensor development and in-vivo testing. Applications include
hydration monitoring, but the basic capability is extendable to
other mM solutes in sweat (Cl-, K+, Mg2+, NH4+, Zn2+). Full details
of the design and fabrication of the patch are reported, as the
basic components could be of use to other wearable sensor
applications. A preliminary version of this work has been initially
accepted as proceedings of IEEE EMBC'14.
II. Top-Level Design Considerations
[0074] A. Patch Size
[0075] Two patch sizes were chosen and demonstrated. The smaller
size (.about.25.times.60 mm) of a typical Band-Aid was used for
high user acceptance. A larger 70.times.40 mm patch was also
demonstrated, a size similar to bandage that might be placed over a
knee. To allow a maximally thin form factor, potentially longer
shelf-life, and low cost, the patch was designed for battery-free
RFID (radio-frequency ID, inductively powered) operation. RFID
requires .about.10-20 loops of a coiled antenna to power the
electronics (depending on patch size). The resulting area interior
to the coil is more than sufficient for placement of the necessary
electronics and the sensor electrodes (as visible in FIG. 7). The
larger of the two patch antenna sizes was found to be more
resilient to variations in antenna fabrication (antenna resonance),
and provides greater reliability in communication. Patches even
smaller than those demonstrated here are possible (see online
supplemental file on antenna design).
[0076] B. Communication
[0077] For communication, most modern smartphones have, or will
have, the capability to establish wireless connections and transfer
data via a near-field communication RFID protocol. The patch is
designed to operate on the standard ISO-15693 as a vicinity device.
This provides the desired versatility in communication through
stand-alone RFID readers as well as customizable applications
(`apps`) for RFID-enabled Android smartphones. The ubiquity of
smartphones provides an easily accessible computing platform with
increased memory/storage capabilities, thereby eliminating the need
for on-patch data logging and the additional circuitry, cost, size
it would require.
[0078] C. Flexible & Wearable
[0079] Flexibility is of paramount concern in wearable electronics,
along with strength and durability. The flexible printed circuit
board (PCB) is built from Dupont Pyralux--a combination of
flexible, conformal polyimide 812 and a thin copper foil 816. The
high heat tolerance of the polyimide allows for electronics to be
attached by solder reflow. Furthermore, solder reflow allows
surface-mount packaging which eliminates need for throughholes that
would result in protrusions that would cause discomfort when the
patch is worn. For packaging and skin adhesion, a survey of
numerous medical-grade textiles from 3M.TM. was conducted to
determine which materials would provide maximum adhesion to the
wearer's skin and high durability to protect the patch itself.
Double sided medical adhesive tape was used below the patch,
whereas above the patch, a medical textile covering was added to
protect the patch and improve visual aesthetics (all shown in FIG.
8).
[0080] D. Basic Electronics and Programming Functionality
[0081] The system level block diagram illustrates the system level
layout of the patch functionality beginning and ending with
communication between the reader device and the patch. The reader
device initiates the communication and requests identification from
the patch. The patch responds by load modulating the inductive
coupling between itself and the RFID reader. Custom commands for
programming include reading, writing to memory registers, sensor
configuration, power management, and other functionalities not
required for this present work.
[0082] The primary chip in the patch is a small Melexis MLX90129
RFID transponder chip which has both basic sensor and energy
harvesting capabilities. The chip functionality is explained in
detail here, because its use could be adapted to a large variety of
other sensor applications. A significant amount of programming
development was required to enable a smart phone to turn the RFID
chip into an electrolyte sensor. The sensor protocol manages tasks
assigned to the MLX90129's sensor pins such as input connections,
voltage output to external sensors, and enabling the internal
temperature sensor. Four input pins provide differential
measurement of potential from externally connected sensors (e.g.
ion selective electrodes in this work). Two internal connections
can enable the output of the onboard temperature sensor to be used
as input into the multiplexer. Configuration of the multiplexer
determines which inputs are passed to the first programmable gain
amplifier (PGA). If enabled, the digital to analog converter (DAC)
can set the offset used in the optional second PGA. The 12-bit ADC
converts the amplified sensor outputs for storage in digital memory
until the DAC converts the digital measurements for analog
transmission to the reader.
[0083] Battery-free operation is achieved by utilizing energy
harvesting circuitry of the MLX90129, 724 (FIG. 7) which utilizes
the induced current of the incoming electromagnetic waves from the
reader to power the entire patch. To facilitate the power demands
of the various IC processes, an external capacitor 712 and diode
716 are added for charge storage. The siphoned charge is used to
complete low power processes during brief interruptions or absences
of induced current from the reader device. Battery independence
improves the potential shelf-life of such patches.
III. Detailed Fabrication--Electronics
[0084] 1) Flexible Circuit Board
[0085] Fabrication begins at the flexible electronic circuit board
(FIG. 7) with a sheet of Dupont Pyralux AC (18 .mu.m thick Cu foil
clad to 12 .mu.m Kapton). A 127.times.101.6 mm substrate is first
cut from the bulk Pyralux roll. As the integrity of the copper
surface is imperative, great care must be taken to minimize
creases, dimples, and other surface imperfections. Therefore even
during substrate cleaning, the substrate is supported by a rigid
silicon carrier. The substrate is cleaned of any residual oils,
fingerprints or other contaminants by submerging it in a
120.degree. C. alkaline solution of Na2CO3 (9.2 wt %), 50% NaOH
(4.6 wt %), Triton X-100 (surfactant, 0.2 wt %) and reverse osmosis
(RO) H2O (86.0 wt %). The sample is left in the solution for a
minimum of 10 min and agitated approximately every 2 to 3 min, and
then rinsed thoroughly in RO water. Once rinsed and dried in N2,
the substrate is then placed in a bath of reagent grade H2SO4 (10
wt %) for 5 min to remove the manufacturer's anti-tarnish coating
and prepare the sample for lithography. As before, the copper is
thoroughly rinsed in RO water and dried in N2.
[0086] To pattern the Cu, Shipley S1818 positive tone, liquid
photoresist is coated on the copper substrate using traditional
spin-coat techniques. For the spin-coat process, the substrate is
bonded to 6 inch silicon wafer using a droplet of water, smoothed
via a plastic blade for uniform pressure, and held in place by
capillary adhesion.
[0087] The S1818 resist is spun first at 500 rpm for 30 s and then
at 2500 rpm for 60 s to achieve a target thickness between 2 to 2.5
.mu.m (a thicker resist is more durable during the etching
process). The substrate and the Si carrier are then "soft" baked in
an oven set at 100.degree. C. for 150 s. The carrier and copper
substrate are removed from the oven and allowed to cool briefly
before masking and 365 nm UV exposure at 150 mJ/cm2 for 25 s.
Developing of the resist is accomplished by placing the substrate
and carrier for 45 s into an agitated .about.21.degree. C. bath of
Microposit 351 photoresist developer diluted with RO to a 1:4 (v/v)
ratio. This solution is slightly more aggressive than the more
common 1:5 ratio, however, the higher concentration developer
performs better at removing the exposed photoresist from the
non-uniform features of the copper surface and therefore results in
a more consistent etch time and cleaner etch results. During
development of the photoresist the Si carrier detaches from the
substrate so that great care must be taken during rinsing and
drying of the substrate after development.
[0088] Etching of the exposed copper is accomplished by an air
bubble agitated acid bath in which the substrate is secured with
PTFE screws to a plastic acrylic carrier and submerged vertically
positioned for 30 s. The acid bath is comprised of a diluted
reagent HCl solution (30 wt %) and diluted solution of 30% H2O2 (3
wt %) combined at a ratio of 2:1 by volume. After etching is
complete, the substrate and carrier are thoroughly rinsed in a
spray of RO water for a minimum of 60 s and dried using compressed
N2. The substrate is then carefully removed from the acrylic
carrier and placed on the Si wafer for photoresist stripping. The
S1818 photoresist is removed by submerging the sample and Si
carrier in a bath of full concentration Shipley 351 photoresist
developer. The bath is manually agitated once every 30 s for 5 min
or until all the photoresist has been removed from the Cu surface.
A final rinse and dry step is performed and electrical continuity
tests are used to verify the integrity of the antenna coil 704
traces, sensor electrode traces and other critical connections.
[0089] 2) Plating of Sensor Electrodes
[0090] The sensors are fabricated in two steps, one before and one
after the electronic chip attachment. In the first step, the
working and reference electrodes of the sensor (FIG. 8a) are
fabricated by electrodeposition of Pd and Ag on the
previously-defined bare copper electrodes 728 (FIG. 7). This is
accomplished using plating solutions from Technic, Inc. and
deposition at .about.5 mA/cm2 anodic current for 90 s with a Pt
wire auxiliary electrode to sustain the current. The reference
electrode fabrication is then completed by chloridization of the Ag
layer in 1 M KCl with a 3 mA/cm2 anodic current for 30 s to form
the reference.
[0091] 3) Chip Attachment
[0092] Before chip attachment, the inductance of the antenna coil
is measured to determine the needed values of the tuning capacitors
712 shown in FIG. 7. An alloy of Sn/Ag (96.5/3.5%) noclean solder
paste (Superior Flux & Mfg. Co. P/N: 3033-85) is applied to
each pad using an air-metered syringe dispenser, or higher volume
fabrication by stencil printing. The chips are then placed, and
also an insulated jumper wire 708 (Fig.7) is placed to connect to
the outer loop of the coil 704. The flex circuit board is then
placed in a programmable, convection reflow oven that applies a
heating profile according to the solder supplier specification. The
reflow oven is connected to a pressurized N2 gas supply, which is
used to purge the sample chamber and prevent oxidation of the Cu
surfaces.
[0093] 4) Hermetic Sealing of Electronics
[0094] In applications where fluid contact could occur, such as
sweat sensing, the electronics must be hermetically sealed. This is
easily achieved by masking the sensor electrodes with Kapton Tape
(silicone adhesive), and conformally coating the flexible circuit
and electronics with 10 s of .mu.m of Parylene C polymer dielectric
using a Specialty Coating Systems 2010 Lab Coater. Ideally this is
performed before sensor functionalization, to ensure the Kapton
masking tape does not damage or contaminate the final sensor
surfaces.
[0095] 5) Sensor Functionalization
[0096] Onto the plated sensor electrodes, the polymer ionophore
(ion-selective) membrane is cast. This is performed after chip
attachment because the high temperature required for chip solder
reflow would damage the polymer membranes. The membrane solution
was cast carefully over the working electrode using a modified
screen printing process. The membrane was made from a cocktail of
sodium ionophore X, bis(2-ethylhexyl) sebacate (DOS), potassium
tetrakis (pchlorophenyl) borate (KTpClPB), PVC, and cyclohexanone,
then manually mixed together until the PVC was fully dissolved. The
cast membranes were left to air dry for 8 hours, then coated 2 more
times to ensure adequate coverage of the electrodes and to
passivate any pores in the membrane that could cause shorting to
the electrodes.
[0097] The Na+ sensor is based on a traditional ion selective
electrode (ISE), but which has been miniaturized in this work. The
Na+ selective ionophore membrane establishes a difference in
potential across the electrode-ionophore barrier corresponding to
the Na+ concentration, enabling a simple potentiometric
measurement. The level of Na+ in the solution is given by the
Nernst equation: E=E0+S log(X), where E is the measured electrode
potential, E0 is the reference electrode potential, S is the
sensitivity, and Xis the concentration of Na+ ions in solution.
Although in this work only sensing of Na+ is demonstrated, sensing
of other ions in sweat (Cl-, K+, Mg2+, NH4+, Zn2+) could be
demonstrated using appropriate commercially available ionophores
from Sigma Aldrich.
[0098] 6) Substrate Cutting
[0099] The patch is a wearable sensor, and therefore all unused
portions of gas/liquid impermeable polyimide substrate film should
be removed to provide skin access, and to improve breathability of
the final patch. Cutting is performed using a Universal Laser
Systems VLS3.50 CO2 laser cutter. The areas that are trimmed
include area outside the antenna coil, and the unused interior
portion, including the electroplating leads 720 (FIG. 7).
IV. Integration--Electronics, Textiles, Skin Adhesives, and
Microfluidics
[0100] As shown in FIG. 8, the final device (800) integration
involves from the bottom up: skin adhesives 808, electronics 812,
816, and 820, paper microfluidics 832, and a vapor porous top
adhesive textile 824. All of these layers are laser cut. The
bottom, double-sided adhesive layer is 3M.TM. Double Coated
Polyester Tape (P/N: 1567) and cut to a 1 mm offset larger than the
trimmed flex circuit layer. An array of circular pores is also
laser cut in the bottom adhesive layer to facilitate sweat 828
transmission to the sensor. The microfluidic paper layer is
interior to the coil and surrounds the sensor electrodes and
electronics. If the sensors are placed face-up (away from skin 804)
then they are covered by the paper layer to bring sweat to the
sensors. Extensive wearability studies have not been performed with
the patch in this initial demonstration, and in the event that
further breathability is needed by skin areas covered by flexible
circuit substrate, then the paper-microfluidics layer can simply be
integrated beneath the electronics layer to provide horizontal
transport of vapor or fluid. The top protective layer is cut from
3M.TM. Tan Polyurethane Tape (P/N: 9834T) with single-sided
adhesive. This layer is cut to the same outer dimensions as the
bottom adhesive layer to provide an edge sealed seam for the
completed patch.
[0101] Multi-layer integration is assisted by a custom alignment
jig and vacuum forming/bonding table (1 atm. pressure). The bottom
layer is affixed to a waxed paper carrier. The flex circuit's
sensor electrodes are then folded back and underneath its traces so
that the active area of the sensor will be facing the skin. The
flex circuit is placed on top of the bottom adhesive layer using
the vacuum placement tool. Next, the microfluidic paper layer is
placed between the coil and the rest of the circuitry. Finally, the
top protective layer is aligned and placed by vacuuming; sealing
the circuit and sensor within. A final communication test with the
RFID reader is performed to verify operation, and the sweat sensor
is ready for programming and use.
V. Experimental Testing and Results
[0102] A. Wearable Antenna Performance
[0103] The assembled RFID circuit was tested to ensure that the
resonate frequency was near enough to the target frequency of 13.56
MHz that the device would communicate with the reader. A
supplemental information document is provided with the online
materials for this paper, detailing the finer details of the
antenna design and tuning. To confirm antenna tuning, a vector
network analyzer (VNA) was connected to an ISO standard calibration
loop-probe, per ISO10373-7, to enable contactless measurement of
the patch's frequency response. The VNA displays the loop-probe's
reflection coefficient by measuring the S-parameter S11 as a
function of frequency. A reduction in the reflection measured by
the VNA correlates to an increase in transmission of the
electromagnetic waves at a specific frequency, via absorption of
the radiated energy by a tuned and coupled device. Successful
tuning of the flexible RFID circuit was confirmed by a reduction of
S11 by -2.9 dB at 13.56 MHz. With a reader RF power of .about.0.5 W
this tuning was also shown to be adequate to inductively power the
electronics and enable RF communication. Patch communication was
shown in wearable format, including arm placement which induces
curvature on the entire patch.
[0104] B. Sensor and Electronics Performance
[0105] The patch and sensors were characterized in-vitro by
pipetting of various NaCl concentration solutions onto the patch
sensor. FIG. 8a-8b illustrates sensor response as Na+ concentration
increased from 20 mM to 70 mM. As expected, the sensor output
increased with analyte concentration, exhibiting stable response at
each concentration. At each concentration change, the sensor
responded rapidly, with approx. 30 s response time. The standard
curve, developed by measuring response of a stand-alone sensor in
the 20-70 mM Na+ range against the commercial ISE from Denver
Instruments (300741.1) exhibited a correlation coefficient of 0.99
(data not shown). These results clearly suggest that our sensor
exhibits acceptable and predictable behavior for measurement of
Na+. As expected, the patch-integrated sensors exhibited a
predictable linear response, with the correlation coefficient of
0.92. The range of 10 mM to 90 mM was chosen to ensure the
detection range would be +/-10 mM beyond physiologically relevant
ranges for hydration monitoring.
[0106] Sensitivity of the sensor in the integrated patch was 0.3
mV/mM, which was slightly lower than that the commercial sensor
sensitivity of 0.5 mV/mM or approx. 25 mV/decade of Na+
concentration. While at first glance this suggests a sub-Nernstian
behavior, we tested the stand-alone sensors, and obtained
sensitivity of approximately 57 mV/decade of Na+ in the 10-90 mM
concentration range, indicating that the sensor exhibits Nernstian
behavior. Similar results have been reported for Na+ ISEs by
others. Thus, the apparent lower sensitivity of the
patch-integrated sensors appears to be due to the limitations of
the ADC on the RFID patch. The ADC reference voltage is set by the
MLX90129's internal regulator, from which two values may be
selected--normal reference of 3.1 V, or low-volt reference of 2.1
V. The minimum voltage of the chip's coil input is such that
provided the chip powers on, the internal regulator will supply a
stable reference to the ADC. However, since the sampling rate for
the converter is slow (<3 Hz) for the desired accuracy the
stabilization of the reference electrode on a specific voltage is
impaired. The sampling rate used in FIG. 7 is approximately 3 Hz to
achieve maximum resolution, while the maximum sampling rate of the
device is approx. 435 Hz at the lowest conversion resolution.
[0107] Accuracy is an important characteristic for a sensor and
measures how close the sensor is able to determine the true value
of a given concentration. To measure accuracy of our RFID Na+
sensor, we repeatedly measured 50 mM of NaCl (n=7), which was
expected to yield 185 mV based on the calibration curve. Response
of our patch was measured to be 177+/-5 mV. These results show that
at 50 mM NaCl, our patch sensor exhibits 96% accuracy. Precision is
another important characteristic for a sensor and in essence it
illustrates sensor variability. From the experimental data, the
patch sensor exhibited 28% precision. However, precision is not
provided for commercial ISEs, and the needed values will depend on
application. Even simple measurement of trending (increase or
decrease) of Na+ itself is valuable, as Na+ concentration predicts
sweat rate as it increases by 10's of mM in concentration with
increasing sweat rate. This patch therefore can be utilized even in
its current form as an athletic exertion sensor, for example.
[0108] To further explore the potential for continuous monitoring
in sweat, concentration of NaCl was varied repeatedly every 4 min
from 20 mM to 70 mM over a period of 45 min. Na+ concentration in
sweat can vary from 20 mM to 70 mM depending on body hydration
status. As shown in FIG. 7, the sensor exhibited good repeatability
and stability during this measurement. The average high measurement
was 255 mV, which corresponds to 70 mM based on the calibration
curve. The coefficient of variation across the 6 high concentration
measurements was CV=0.1%, indicating excellent repeatability.
Similarly, the 5 low concentration measurements yielded
approximately 237 mV, with CV=0.8%. The response time at low
concentration was slower, and is a function of the mass transport
across the sensor ionselective membrane. As with most
electro-chemical sensors, stability of the reference electrode can
be an issue and can lead to the inability to collect stable data.
Our sensor exhibited only a slight drift (+/-3 mV/5 mM), however by
increasing sampling frequency and averaging the values we were able
to compensate for this difference. Future work will involve further
stabilizing of the Ag/AgCl reference electrode to increase
stability of the measured values. Collectively, these results
suggest that the developed sensor is suitable for sweat electrolyte
monitoring.
[0109] VI. Discussion and Conclusions
[0110] The primary objective of this work was to demonstrate the
complete integration of the components and functionality needed for
a low-cost and highly self-contained sweat sensor. A collection of
key performance data and cost-estimates is provided in Table 1. The
most expensive single component, is the Melexis RFID chip, at
<$2 in volume purchasing right now. The remainder of the
components and fabrication procedures for the patch are rather
simple and implementable on most flexible and printed electronics
manufacturing lines. Therefore the basic patch presented here could
be speculated at this time to meet the economic considerations of a
disposable commercial product.
[0111] The key question in the applied value for this work is in
terms of performance. The performance for the existing patch is
shown to be adequate and accurate for basic sensing at
physiological relevant levels in sweat, and would increase in
performance with higher sampling frequency, improved power
management, sensor signal conditioning and conversion efficiency of
the analog sensor inputs. Establishing the basic functionality
shown in this paper is important, because numerous other ionophores
and ion selective electrodes, or measurements, could be integrated
with the patch, allowing a broader range of applications for the
sensor. The current sensor measures Na+, and using the second
sensor port to measure K+ would be intended to explore ratios of
electrolytes in relation to hydration (hence the term, `electrolyte
balance`). Other ions of interest include Cl-, Mg2+, NH4+, which
expand the physiological readings that could be made from human
sweat. Devices such as this, and others, could mark the beginning
of an entirely new way of monitoring human physiology and
performance. Wearable and wireless devices that are unobtrusive to
the user fill a critical gap in the technology needed to collect
real time data on the health status of our most precious
assets--people.
[0112] The following examples are provided to help illustrate the
present invention, and are not comprehensive or limiting in any
manner These examples serve to illustrate that although the
specification herein does not list all possible device features or
arrangements or methods for all possible applications, the
invention is broad and may incorporate other useful methods or
aspects of materials, devices, or other embodiments that are
readily understood and obvious for the broad applications of the
present invention.
[0113] EXAMPLE 1: A sweat sensor device is used by an employee in a
mining operation. When the employee arrives at work for his shift,
he applies a sweat sensor device that is coded with a unique
identifier assigned to him. After the employee clocks in, the
employer's on-shift system determines that he is on the job and the
device takes an operation and compliance reading. The device
communicates to the device user that the employee's device is in
good skin contact. Then the device initiates sweat measurements,
and determines that the device is operating on the employee's skin
because Na.sup.+ and IC' concentration trends are as expected for
the measured sweat rate. The device also calculates an
identification probability estimate by comparing the identification
metrics to an identification signature on file for the employee,
and determines that the correct person is wearing the device. Four
hours into the employee's shift, the device generates a safety and
health alert based on the employee's hydration level and trend
data. The employee receives the alert via companion transceiver
located in his work area, and the supervisor receives an email at
his workstation. The employee stops work to rehydrate, and the
supervisor schedules the employee for safety training because this
was the third instance of serious dehydration the employee
experienced in the past month.
[0114] EXAMPLE 2: A professional cyclist is participating in a
multi-stage race, and is wearing a sweat sensor device during a 100
mile climbing stage. The device communicates via Bluetooth to a
companion transceiver, which in turn communicates via cellular
network with the team chase car. During the latter portion of the
stage, the sweat sensing device initiates an operation and
compliance reading, and determines the device is in good contact
with the cyclist's skin. Then the device takes a reading on a group
of selected analytes to measure fatigue, hydration level, and
inflammation. The device compares the readings to predetermined
thresholds representing optimal performance, then creates trend
data by comparing the readings to the cyclist's prior readings
during that stage. The device then compares the cyclist's current
analyte profile and trend data with the cyclist's historical
analyte profiles and trend data for similar stages of past races.
The sweat device data is then used to generate a safety and health
alert to the chase car. The cyclist's chase team then recommends an
optimal pace, water and nutrient intake to the cyclist to optimize
performance.
[0115] EXAMPLE 3: A group of soldiers in a hot climate is
attempting to secure a dangerous area in order to protect a group
of civilians, and they are using sweat monitoring devices to
measure their physical and mental stresses through sweat
electrolytes, cortisol and cytokine biomarker measurements. Each
soldier carries a companion transceiver integrated into their
equipment. The companion transceiver communicates with the device,
and communicates via secure datalink to the patrol leader and the
unit commander. The soldiers have been on patrol for several hours,
and sweat readings for two of the soldiers are trending toward
dehydration and high stress. The device issues a safety and health
alert for dehydration and high stress levels for the two affected
soldiers and communicates the alert to the unit commander, the
patrol leader and the two soldiers. The commander instructs the
sweat devices to increase the sampling rate for the two distressed
soldiers. The soldiers increase their water consumption. The patrol
leader factors the condition of the two soldiers into her decision
about whether extend the mission duration.
[0116] EXAMPLE 4: A transplant patient is taking an antirejection
medication (immunosuppressant) and his attending physician is
utilizing the sweat sensing device to monitor the drug levels in
the patient's body through the drug metabolites excreted in sweat.
The patient is to wear the device 24 hours a day, replacing it only
as needed. The sweat sensing device takes periodic readings of the
drug metabolites and other relevant analytes in the patient's
sweat. The sweat device compares the patient's analyte readings to
a standard analyte profile based on aggregated data collected on
other individuals who have taken the drug. The device also
constructs a profile of the analyte levels of other individuals
that share relevant characteristics with the patient and develops a
more customized behavioral signature for the patient. The device
also builds an individual behavioral signature for the patient over
several days of collecting sweat sensor data. The device then
compares the detected analyte levels and ratios to one or more of
the behavioral signatures developed for the patient. Several days
into the treatment regimen, the sweat sensor performs a reading
that detects analyte ratios and trend data that significantly
differ from the patient's behavioral signature. The device
generates a safety and health alert that the patient has missed a
dose of medication and communicates the alert to the patient and
the patient's attending physician.
[0117] EXAMPLE 5: A cruise ship captain is about to embark with his
ship carrying 900 passengers. According to company protocol,
captains are required to wear a sweat sensor device while on duty
to monitor performance Unfortunately, the captain spent the
previous evening at a bar, and consumed too much alcohol to legally
operate the ship. Instead of wearing his device, he instructs his
first officer to wear one of his assigned devices and he retires to
quarters. The device communicates via Bluetooth with various
companion transceivers located throughout the ship, and the
transceivers in turn communicate with the cruise ship dispatch
center. Upon application by the first officer, the device initiates
an operation and compliance reading and then compares the reading
with the identification signature on file for the captain. While
the device ID is positively associated with the captain, several
other identification metrics analyzed by the device diverge from
the captain's identification signature, and the identification
probability estimate is below the acceptable threshold. The device
issues an operation and compliance alert that the wearer is not the
captain and communicates it to the cruise ship dispatch center.
[0118] EXAMPLE 6: To determine if a sweat sensing device wearer is
a target cancer patient, the device measures the wearer's sweat
testosterone concentration, which is an identification metric for
sex. The device detects testosterone concentrations that correlate
with the wearer being male. In this context, male and female
individuals are evenly distributed, so the corresponding
identification probability estimate is 50%. The sweat sensing
device then measures a second identification metric, which is
resting sweat concentration of Na.sup.+. The measured Na.sup.+
concentration corresponds to the target patient's resting rate with
a 75% probability. The device then weighs the two measurements,
taking into account the testosterone sensor's inherent accuracy of
+/-5% of actual sweat concentration, and the daily variability of
testosterone for the target individual's age, as well as the
Na.sup.t measurement's stronger accuracy rating derived from the
Na.sup.t sensor's inherent accuracy of +/-2% of actual sweat
concentration, its stability over time, and the consistency of the
concentration value over 10 different samples at comparable sweat
rates. The device then combines the two probability estimates to
calculate a combined identification probability estimate of 85%
that the wearer is the target patient, which is above the desired
probability threshold. The device then sends an operation and
compliance message indicating that the wearer is the target
patient.
[0119] This has been a description of the present invention along
with a preferred method of practicing the present invention,
however the invention itself should only be defined by the appended
claims.
* * * * *