WO2019210240A1

WO2019210240A1 - Flexible sweat sample collection and sensing devices

Info

Publication number: WO2019210240A1
Application number: PCT/US2019/029454
Authority: WO
Inventors: Gavi BEGTRUP; Jason Heikenfeld
Original assignee: Eccrine Systems, Inc.
Priority date: 2018-04-27
Filing date: 2019-04-26
Publication date: 2019-10-31

Abstract

Embodiments of the disclosed invention include flexible, body-conforming sweat sensing devices configured to measure a sweat rate, or a concentration of one or more analytes in a sweat sample that correlate to physiological conditions in the device wearer. The disclosed devices improve upon existing devices by providing determined sweat collection regions that allow measured sweat rates to be correlated to total body sweat rates or other relevant metric, and provide automatic electronic reporting of measurements taken by the device.

Description

FLEXIBLE SWEAT SAMPLE COLLECTION AND SENSING DEVICES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 62/663,568, filed April 27, 2018, and has specification that builds on U.S. Application No. 15/653,494, filed July 18, 2017, the disclosures of which are hereby incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] Sweat contains many of the same biomarkers, chemicals, or solutes that are carried in blood, which can provide significant information enabling the diagnosis of ailments, health status, toxins, performance, and other physiological attributes even in advance of any physical sign. Furthermore, sweat itself, and the action of sweating, or other parameters, attributes, solutes, or features on or near skin or beneath the skin, can be measured to further reveal physiological information. Accordingly, sweat sensing devices hold tremendous promise for use in workplace safety, athletic, military, and clinical diagnostic settings.

[0003] In particular, a sweat sensing device featuring a flexible, low profile, body-conforming form- factor may prove desirable for a number of applications, and may thereby provide useful information about the individual’s physiological state, including sweat rate, and sweat content. While practitioners in the field have proposed such devices, e.g., see PCT/US2017/037852, and US 15/625,087, which are hereby incorporated by reference herein in their entirety, none have demonstrated the ability to provide physiological sweat rate measurements or sweat analyte concentrations that correlate to physiological concentrations. What is needed, therefore, are flexible, body-conforming wearable devices configured to measure sweat rate or to measure characteristics of analytes in sweat that correlate to physiological conditions. DEFINITIONS

[0004] Before continuing with the background, a variety of definitions should be made, these definitions gaining further appreciation and scope in the detailed description and embodiments of the present invention.

[0005] As used herein,“sweat” means a biofluid that is primarily sweat, such as eccrine or apocrine sweat, and may also include mixtures of biofluids such as sweat and blood, or sweat and interstitial fluid, so long as advective transport of the biofluid mixtures (e.g., flow) is primarily driven by sweat.

[0006] “Sweat sensor” means any type of sensor that measures a state, presence, flow rate, solute concentration, or solute presence, in absolute, relative, trending, or other ways in sweat. Sweat sensors can include, for example, potentiometric, amperometric, impedance, optical, mechanical, antibody, peptide, aptamer, or other means known by those skilled in the art of sensing or biosensing.

[0007] “Analyte” means a substance, molecule, ion, or other material that is measured by a sweat sensing device.

[0008] “Measured” can imply an exact or precise quantitative measurement and can include broader meanings such as, for example, measuring a relative amount of change of something. Measured can also imply a qualitative measurement, such as‘y^es’ ^or‘^no’ tyP^e measurements.

[0009] “Chronological assurance” means the sampling rate or sampling interval that assures measurement(s) of analytes in sweat in terms of the rate at which measurements can be made of new sweat analytes emerging from the body. Chronological assurance may also include a determination of the effect of sensor function, potential contamination with previously generated analytes, other fluids, or other measurement contamination sources for the measurement(s). Chronological assurance may have an offset for time delays in the body (e.g., a well-known 5 to 30-minute lag time between analytes in blood emerging in interstitial fluid), but the resulting sampling interval (defined below) is independent of lag time, and furthermore, this lag time is inside the body, and therefore, for chronological assurance as defined above and interpreted herein, this lag time does not apply. [0010] “Analyte-specific sensor” means a sensor specific to an analyte and performs specific chemical recognition of the analyte’s presence or concentration (e.g., ion-selective electrodes (“ISE”), enzymatic sensors, electro-chemical aptamer based sensors, etc.). Sensors could also be optical, mechanical, or use other physical/chemical methods which are specific to a single analyte. Further, multiple sensors can each be specific to one of multiple analytes.

[0011] “Sweat sensor data” means all of the information collected by sweat system sensor(s) and communicated via the system to a user or a data aggregation location.

[0012] “Correlated aggregated sweat sensor 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, or any other relevant data.

[0013] “Volumetric sweat rate measurement” means a measurement of sweat rate based on the time required for sweat to fill a known volume in a sweat sensing device. Devices for volumetric sweat rate measurement are disclosed in U.S. Application No. 15/653,494, which is hereby incorporated by reference herein in its entirety.

[0001] “Sweat stimulation,” means to cause sweating by known methods. For example, sweat stimulation can be achieved by thermal stimulation, chemical heating pad, infrared light, by orally administering a drug, by intradermal injection of agents such as carbachol, methylcholine or pilocarpine, and by dermal introduction of such drugs using iontophoresis, by sudo-motor-axon reflex sweating, or by other means. A device for iontophoresis may, for example, provide direct current and use large lead electrodes lined with porous material, where the positive pole is dampened with 2% pilocarpine hydrochloride or carbachol and the negative one with 0.9% NaCl solution. Sweat can also be controlled or created by asking the device wearer to conduct or increase activities or conditions that cause them to sweat.

[0014] This has served as a background for the present invention, including background technical invention needed to fully appreciate the present invention, which will now be summarized. SUMMARY OF THE INVENTION

[0015] Embodiments of the disclosed invention include flexible, body-conforming sweat sensing devices configured to measure a sweat rate, or a concentration of one or more analytes in sweat that correlate to physiological conditions in the device wearer. The disclosed devices improve upon existing devices by providing determined sweat collection regions that allow measured sweat rates to be correlated to total body sweat rates or other relevant metric, and provide automatic electronic reporting of measurements taken by the device.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The objects and advantages of the present invention will be further appreciated in light of the following detailed descriptions and drawings in which:

[0017] Figs. 1A and 1B represent a top-down view and a cross-sectional view, respectively, of a prior art device.

[0018] Fig. 2 represents a cross-sectional view of at least a portion of an embodiment of the disclosed invention.

[0019] Fig. 3 represents a cross-sectional view of at least a portion of an embodiment of the disclosed invention.

[0020] Fig. 4 represents a cross-sectional view of at least a portion of an embodiment of the disclosed invention.

[0021] Fig. 4A represents an underside view of at least a portion of an embodiment of the disclosed invention.

[0022] Fig. 5 represents a cross-sectional view of at least a portion of an embodiment of the disclosed invention.

[0023] Fig. 6 represents a top-down view of at least a portion of an embodiment of the disclosed invention. DETAILED DESCRIPTION OF THE INVENTION

[0024] Disclosed herein are flexible, body-conforming sweat sensing devices configured to measure sweat rate, or a concentration of one or more sweat analytes, that correlate to physiological conditions in the device wearer. The disclosed devices improve upon existing devices by providing determined sweat collection regions that allow measured sweat rates to be correlated to total body sweat rates or other physiological condition, and provide automatic electronic reporting of measurements taken by the device.

[0002] One skilled in the art will recognize that the various embodiments may be practiced without one or more of the specific details described herein, or with other replacement and/or additional methods, materials, or components. In other instances, well-known structures, materials, or operations are not shown or described in detail herein to avoid obscuring aspects of various embodiments of the invention. Similarly, for purposes of explanation, specific numbers, materials, and configurations are set forth herein in order to provide a thorough understanding of the invention. Furthermore, it is understood that the various embodiments shown in the figures are illustrative representations and are not necessarily drawn to scale.

[0003] Reference throughout this specification to“one embodiment” or“an embodiment” means that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention, but does not denote that they are present in every embodiment. Thus, the appearances of the phrases“in an embodiment” or“in another embodiment” in various places throughout this specification are not necessarily referring to the same embodiment of the invention. Further,“a component” may be representative of one or more components and, thus, may be used herein to mean“at least one.”

[0004] Certain embodiments of the invention show sensors as simple individual components. It is understood that many sensors require two or more electrodes, reference electrodes, or additional supporting technology or features that 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 sensing, for example: a sweat sensor; an impedance sensor; a fluid volume sensor; a sweat generation rate sensor; and a solute generation rate sensor. Certain embodiments of the disclosed invention show sub-components of what would be fluid sensing devices with more sub components needed for use of the device in various applications, which are obvious (such as a battery), and for purpose of brevity and focus on inventive aspects are not explicitly shown in the diagrams or described in the embodiments of the invention. As a further example, many embodiments of the invention could benefit from mechanical or other means known to those skilled in wearable devices, patches, bandages, and other technologies or materials affixed to skin, to keep the devices or sub -components of the skin firmly affixed to skin or with pressure favoring constant contact with skin or conformal contact with even ridges or grooves in skin, and are included within the spirit of the disclosed invention.

[0005] The disclosed sweat sensing device also includes computing and data storage capability sufficient to operate the device, which incorporates the ability to conduct communication among system components, to perform data aggregation, and to execute algorithms capable of generating notification messages. The device may have varying degrees of onboard computing capability (i.e., processing and data storage capacity). For example, all computing resources could be located onboard the device, or some computing resources could be located on a disposable portion of the device and additional processing capability located on a reusable portion of the device. Alternatively, the device may rely on portable, fixed or cloud-based computing resources.

[0025] The detailed description of the present invention will be primarily, but not entirely, limited to devices, methods and sub-methods using wearable sweat sensing devices. Therefore, although not described in detail here, other essential steps which are readily interpreted from or incorporated along with the present invention shall be included as part of the disclosed invention. The disclosure provides specific 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 specific invention will not necessarily include all obvious features needed for operation.

[0026] The disclosed invention incorporates by reference in their entirety the article published in the journal IEEE Transactions on Biomedical Engines ring, titled“Adhesive RFID Sensor Patch for Monitoring of Sweat Electrolytes”; and the article published in the journal AIP Biomicrofluidics, 9 031301 (2015), titled“The Microfluidics of the Eccrine Sweat Gland, Including Biomarker Partitioning, Transport, and Biosensing Implications”. The disclosed sweat sensing device may include a plurality of sensors to detect and improve detection of sweat analytes, including ISEs, a reference electrode, a pH sensor, a temperature sensor, a skin impedance sensor, a capacitive skin proximity sensor, and an accelerometer. Many of the auxiliary features of the invention may require other aspects of a sweat sensing device, including two or more counter electrodes, reference electrodes, or additional supporting technology or features, which are not captured in the description herein, such as an onboard real-time clock, onboard flash memory (i.e., 1MB minimum), Bluetooth™ or other communications hardware, and a multiplexer to process a plurality of sensor outputs.

[0027] The sweat sensing device’s data aggregation capability may include collecting all of the sweat sensor data generated by sweat sensing devices and communicated to the device. The aggregated sweat sensor data could be de-identified from individual wearers, or could remain associated with an individual wearer. Such data can also be correlated with outside information, such as the time, date, air temperature, humidity, activity performed by the individual, motion level, fitness level, mental and physical performance during the data collection, body orientation, the proximity to significant health events or stressors, age, sex, medications, drug sensitivity, medical condition, health history, or other relevant information. The reader device or companion transceiver can also be configured to correlate speed, location, environmental temperature or other relevant data with the sweat sensor data. The data collected could be made accessible via secure website portal to allow sweat system users to perform safety, compliance and/or care monitoring of target individuals. The sweat sensor data monitored by the user includes real-time data, trend data, or may also include aggregated sweat sensor data drawn from the system 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, could 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 the need to drink additional water, or to adhere to a drug regimen.

[0006] To clarify the proper numerical values or representations of sweat sampling rate and therefore chronological assurance, sweat generation rate and sweat volumes will be described in detail. From Dermatology: an illustrated color text, 5th ed., the maximum sweat generated per person per day is 10 L, which on average is 4 pL per gland maximum per day, or about 3 nL/min/gland. This is about 20X higher than the minimum sweat generation rate. The maximum stimulated sweat generation rate according to Buono 1992, J. Derm. Sci. 4, 33-37,“Cholinergic sensitivity of the eccrine sweat gland in trained and untrained men,” the maximum sweat generation rate by pilocarpine stimulation is about 4 nL/min/gland for untrained men and 8 nL/min/gland for trained (exercising often) men. Sweat stimulation data from “Pharmacologic responsiveness of isolated single eccrine sweat glands,” by K. Sato and F. Sato, Am. Physiological Society, Jul. 30, 1980, suggests a sweat generation rate up to about 5 nL/min/gland is possible with stimulation, and several types of sweat stimulating substances are disclosed (the data was for extracted and isolated monkey sweat glands, which are very similar to human ones). For simplicity, we can assume for calculations in the present disclosure (without so limiting the disclosure), that the minimum sweat generation rate is about 0.1 nL/min/gland, and the maximum sweat generation rate is about 5 nL/min/gland, which is about a 50X difference between the maximum and minimum rates.

[0007] Based on the assumption of a sweat gland density of 100/cm², a sensor that is 0.55 cm in radius (1.1 cm in diameter) would cover about 1 cm² area, or approximately 100 sweat glands. Next, assume a sweat volume under a skin- facing sensor (space between the sensor and the skin) of 100 pm average height or 100E-4 cm, and that same 1 cm² area, which provides a sweat volume of 100E-4 cm³ or about 100E-4 mL or 10 pL of volume. With the maximum sweat generation rate of 5 nL/min/gland and 100 glands, it would require a 20 minutes to fully refresh the sweat volume (using first principles/simplest calculation only). With the minimum sweat generation rate of 0.1 nL/min/gland and 100 glands, it would require 1000 minutes or -17 hours to refresh the sweat volume. Because the flow is not precisely centered, according to Sonner, et al, in Biomicrofluidics, 2015 May 15;9(3):031301. doi: 10.1063/1.4921039, the time to fully refresh the sweat volume (i.e., new sweat replaces all old sweat) could be 6X longer or more. For slow sweat flow rates, back-diffusion of analytes and other confounding factors could make the effective sampling interval even larger. Clearly, conventional wearable sweat sensing approaches with large sweat volumes and slow sampling rates would find continuous sweat sample monitoring to be a significant challenge.

[0028] With reference to Fig. 1A, a prior art sweat sensing device lOa configured to be worn on an individual’s skin 12 is depicted. The sweat sensing device comprises a flexible substrate 150 that is secured to the skin via an adhesive layer (not shown). Sweat enters the device through an inlet 130, and progresses to one or more channels 132, which routes the sweat to one or more sensing areas 120. The sensing area 120 contains an analyte sensor (not shown), such as a colorimetric or enzymatic sensor for pH, an electrolyte, glucose, lactate or other sweat analyte. The device may also include an RFID antenna coil to facilitate communication (not shown). With reference to Fig. 1B, the device lOb is a cross-section of the device lOa shown in Fig. 1 A. Here the device is shown attached to skin 12 via an adhesive layer l80b. As the wearer sweats, a certain amount of sweat 14 will enter the inlet 130 from skin located substantially beneath the inlet. From other areas covered by the flexible substrate, sweat 16 will either move toward the inlet 130, or will remain uncollected by the device. Because the sweat collection area of the prior art device is ill-defined, the device is incapable of consistently measuring a physiological sweat rate. Therefore, what is needed are improvements to allow a flexible sweat sensing device, such as the prior art device, to consistently measure physiological sweat rates.

[0029] With reference to Fig. 2, a flexible sweat sensing device 20 is placed on a wearer’s skin 12. The device comprises a flexible substrate 250, that is removably attached to the skin 12 via an adhesive 280. The substrate includes an inlet 230 that is in fluidic communication with a biofluid channel 232, and one or more sensing areas 220 (one is shown), or a volumetric sweat rate measurement channel (see, e.g., Fig. 6). The device further includes a seal 236, that surrounds the inlet 230, and encloses a defined collection region, e.g., having a surface area of 1 cm². The seal is, for example, a flexible rubber o-ring, an inflexible or stiffened polymer ridge, a gel with density sufficient to displace the substrate and/or adhesive layer, or other suitable material for creating a seal between the skin and the substrate. In this embodiment, the seal 236 is placed between the adhesive layer 280 and the substrate 250. Upon application to the skin, the seal pushes down on the skin, causing a portion of the skin in the collection region to bulge upward toward the inlet. When the wearer begins to sweat, substantially only sweat from within the defined collection region enters the inlet 230 to be measured by the device.

[0030] With reference to Fig. 3, which features like numerals to refer to like structures from Fig. 2, an alternative embodiment of the disclosed invention is depicted. In this embodiment of the device 30, the layer of adhesive 380 does not pass beneath the seal 336 as depicted in Fig. 2, but instead contacts an outer perimeter of the seal. The seal accordingly contacts the skin 12 directly when the device is being worn.

[0031 ] With reference to Figs. 4 and 4A, where like numerals depict like structures from Fig. 2, another alternate embodiment is depicted. In this embodiment, the device uses patterned adhesive with an adhesive seal to provide a predictable sampling area. As shown in Fig. 4, the flexible substrate 450 is coated on its skin-facing side with a patterned adhesive 482 surrounding the inlet 430, and a perimeter adhesive 480 extending from the collection region toward the outer edge of the device. During sweating conditions, sweat originating from under open areas 434 will flow to the inlet 430, while sweat 14 originating under the patterned adhesive 482 will tend to flow toward or away from the inlet 430. This arrangement provides an approximate collection surface area A_c, as well as an adhesive covered area having a perimeter surface area A_a (not shown). Sweat 16 originating under the perimeter adhesive 480 will either flow toward or away from the inlet 430, and as a result, the area under the perimeter adhesive cannot be relied upon to consistently supply to the inlet all of the sweat generated beneath it. The ratio of A_c to A_a will be designed to provide an adequate amount of device adhesion to the skin, so that the device is securely (but removably) attached to the skin while minimizing error due to less predictable sweat contribution from under the perimeter adhesive 480. In some embodiments, A_c is maximized relative to A_a. In other embodiments, the ratio of A_c to A_a is greater than (>) IX, >l.5X, >2X, >5X, or >10C. [0032] Fig. 4A represents an underside view of the embodiment depicted in Fig. 4. As depicted, the patterned adhesive 482a is arranged in a concentric circular pattern with gaps 434a that allow for the passage of sweat toward the inlet 430a. While the pattern depicted is concentric circles, the invention is not so limited, and can be other suitable patterns that facilitate adhesion to the skin, while allowing sweat to efficiently reach the inlet from the collection surface area A_c.

[0033] Another drawback facing prior art devices is the requirement that outputs be read either visually by the user, e.g., by taking a photo with a smartphone, or by using a smartphone to read sensors through RFID induction. Each of these output acquiring means compromises physiologically relevant data because the time at which optical or enzymatic sensors are read is critical. For example, with further reference to Fig. 1A, assume the sensing area 120 contains a colorimetric sensor for glucose. As the area fills with sweat sample, the sensor will begin to change color in response to glucose in the sweat. However, the color change will not be complete until the entire area 120 is filled with sweat, at which point the sensor should be read. Immediately after this point, the colorimetric sensor will begin to fade. Therefore, there is a brief window, after the sensing area is filled but before the sensor begins to fade, during which such a sensor can be properly read without introducing error. Unfortunately, a device user is unlikely to observe the device and take a reading during the window, since doing so consistently would be highly impractical, especially if multiple devices are in use simultaneously. Similarly, if the sensing area 120 contains an enzymatic sensor for glucose, the sensor will begin to register a current when the area begins to fill with sweat. This will register as a sharp peak in current, followed by a decrease in current as the sensor consumes the glucose. For enzymatic sensors, therefore, there is an ideal time to take a reading (e.g., several seconds after sensor exposure to sweat), which will prove impractical for a user to consistently perform. The inability to consistently and conveniently acquire timely readings will prevent or greatly hinder such systems from deriving physiologically relevant readings from sweat. In addition to this deficiency in acquiring physiologically correlated data, such visual or smartphone reading methods also pose limitations that render impractical uses beyond individual consumer applications. A primary issue is the inability to automatically report out measurements. Since the prior art devices require someone to visually check the sensor, or to place a smartphone in proximity to the sensor, acquiring outputs from the device would consequently rely on self-reporting or close supervision or the wearer, either of which would be incompatible with compliance-type applications, such as adherence to a dehydration protocol. Further, to the extent a device must be uncovered for visual reading, it is incompatible with some protective equipment and uniforms. Therefore what is needed is an output collecting and transmitting component to enable automatic and timely collection of sweat sensor data.

[0034] With reference to Fig. 5, where like numbers represent like features from Fig. 2, a flexible sweat sensing device is described, having automatic reading of colorimetric, fluorescent, chemiluminescent, other optical sensors, or a volumetric sweat rate channel. As with previous embodiments, the device includes a flexible substrate 550 that adheres to skin 12 via an adhesive layer 580. The substrate creates one or more biofluid channels 532 that carries sweat samples to one or more sensing areas 520. The sensing area includes a colorimetric sensor or optical enzymatic sensor to measure a characteristic of an analyte, e.g. , lactate, in sweat. Configured to have electromagnetic communication with the sensing area 520 is an output reader 522, which includes one or more light sources 524, e.g., a light- emitting diode (LED), paired with a photodetector 526, e.g., a miniaturized camera, a photodiode, a photovoltaic sensor, a photoelectric sensor, a thermal sensor, a photochemical sensor, or a polarization sensor. Some embodiments include a single color LED, while other embodiments may contain a combination of LED colors, e.g., red, green, and blue. Similarly, some embodiments may use a single photodiode, while others include a photodiode array, depending on the needs of the application. LED colors will be chosen to optimize readings from the particular colorimetric sensor, e.g., if a sensor produces a yellow color in the presence of an analyte, the chosen LED(s) would optimize light reflected to the photodiode to improve sensitivity or other measurement characteristic. In other embodiments, the wavelengths of transmitted and/or detected light are altered by a filter (not shown) so that transmission or detection is optimized.

[0035] In operation, the sweat sensing device will begin to fill with sweat 14 through the inlet 530, then sweat fills into the channel 532, and begins to fill the sensing area 520. The light source 524 will emit light substantially continuously, or periodically, toward the sensing area, which is reflected and collected by the photodetector 526. As the sensing area fills with sweat, the intensity of reflected light collected by the photodetector increases until a peak is reached, at which point the sensing area is substantially full, and then will begin to decline as the colorimetric sensor fades. The device records the peak intensity read by the photodetector, which serves as a measurement of lactate concentration. The time required to fill the sensing area is also recorded, and can be used to measure sweat rate, or improve the concentration measurement. In other embodiments, there may be multiple light sources, which would allow the photodetector to collect color spectrum data, which can also be used to interpret color changes by the colorimetric sensor, and hence measure concentration. For embodiments with multiple sensing areas, the device may be configured to route sweat to different sensing areas sequentially. In such configurations, the time required to fill each sensing area can be aggregated, which along with the known channel and sensing area volume will yield a sweat rate. In addition, concentration measurements from sequentially filled sensing areas may be compared to develop chronologically assured measurements of analyte concentration.

[0036] In other embodiments employing electrochemical enzymatic sensors to measure sweat analyte concentrations, the output reader(s) 522 will be in electrical communication with the enzymatic sensor, and will detect the electrical signals generated by the enzymatic sensors upon exposure to the sweat analyte. In operation, as sweat reaches the sensing area 520, the enzymatic sensor will begin producing a voltage, which will rapidly peak and then decline as the analyte is consumed by the sensor. In order to reduce measurement error, the device will record the voltage peak, and then use readings from an interval after the voltage peak, usually a few seconds, to determine concentration.

[0037] With reference to Fig. 6, flexible, low-profile device for measuring and reporting a volumetric sweat rate is depicted. In this embodiment, the flexible substrate 650 contains a biofluid channel 632 for measuring a volumetric sweat rate. The channel 632 has a known volume, e.g., several nL, and is in optical communication with a plurality of optical sensors 622 that are spaced at known intervals along the channel. These sensors may be embedded in another substrate layer (not shown) that covers the biofluid channel, as is depicted in Fig. 5. The channel is also in fluidic communication with an inlet 630 at a first end and an outlet 636 at a second end. The inlet receives sweat from a defined surface area of the device wearer’s skin, said defined area being created by an o-ring type seal or a patterned adhesive seal (not shown). As a sweat sample moves through the channel 632 from the channel’s first end to its second end, the sweat sample will pass the sensors 622 in sequence at measured intervals. The time required for sweat to reach each sensor, coupled with the volume of the channel section(s) proceeding the sensor, yields a measurement of sweat rate. Some embodiments may include a dye within the channel to improve the detection of sweat by the sensors 622. In other embodiments, volumetric sweat rate and sweat analyte sensing may be combined in the same device.

[0038] In order to maintain the low-profile, flexible form factor of the disclosed sweat sensing devices, circuitry may be deformable or flexible, as is known in the art of wearable sensors. Computing capability may be miniaturized, or located off the device. Similarly, communication means will be optimized to improve flexibility, and reduce weight, bulk, and power consumption, e.g., an RFID antenna coil, or miniaturized Bluetooth antenna. Operational power may be supplied by battery, energy harvesting technology, or induction coil transfer from a smartphone.

[0039] In other embodiments, the device may include components for stimulating sweat (not shown), such as iontophoresis electrodes, sweat stimulating chemicals (e.g., carbachol, pilocarpine), and other necessary components. In some embodiments, the disclosed invention will be combined with additional sweat sensing device components and capabilities.

[0040] This has been a description of the disclosed invention along with a preferred method of practicing the invention, however the invention itself should only be defined by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A wearable sweat sensing device, comprising:

an adhesive layer configured to removably secure the device to a skin surface of an individual; a flexible substrate, comprising an inlet, one or more sample transport channels, and one or more sensing areas;

a seal configured to define a collection region on the skin surface, wherein the collection region has a collection surface area; and

one or more sensors for measuring a characteristic of an analyte in a sweat sample.

2. The device of claim 1, wherein the seal comprises one of the following: a flexible o-ring, and a rigid o-ring.

3. The device of claim 2, wherein the adhesive layer has one of the following configurations:

circumscribing the seal, or located between the seal and the skin surface.

4. The device of claim 1, wherein the adhesive layer comprises the seal.

5. The device of claim 4, wherein the adhesive layer comprises a perimeter region having a perimeter surface area that is a total surface area of the device minus the collection surface area, and wherein the collection region further comprises a pattern of an adhesive.

6. The device of claim 4, wherein the collection surface area is maximized with respect to the perimeter surface area.

7. The device of claim 4, wherein the ratio of the collection surface area to the perimeter surface area is one of the following: greater than (>)l, >1.5, >2, >5, and >10.

8. The device of claim 1, wherein the one or more sensors is one of the following: an optical sensor, an electrochemical sensor, a colorimetric sensor, an enzymatic sensor, and an ion-selective electrode sensor

9. The device of claim 1, wherein the device is configured to measure a volumetric sweat rate.

10. The device of claim 1, further comprising an output reader.

11. The device of claim 10, wherein the output reader comprises one or more light sources, and one or more photodetectors configured to detect light from the one or more light sources.

12. The device of claim 11, wherein the one or more light sources comprise one of the following: one or more light-emitting diodes (LED) having a single color, one or more LEDs having a plurality of colors, and an array of LEDs.

13. The device of claim 10, wherein the one or more photodetectors are one of the following: a camera, a photodiode, a photovoltaic sensor, a photoelectric sensor, a thermal sensor, a photochemical sensor, and a polarization sensor.

14. The device of claim 10, further comprising one or more filters configured to change a wavelength of light emitted by the one or more light sources.

15. The device of claim 10, further comprising one of the following: a processor, an RFID antenna, and a Bluetooth antenna.