Systems and methods for correcting sweat analyte measurement results

Abstract

A system for temperature-corrected sweat analyte measurement results is provided. The system includes a sweat collector (106) for collecting sweat from skin (102). The collected sweat is discharged from the sweat collector via a capillary tube (108) to an outlet (110). The sweat is discharged through the capillary tube by capillary action and evaporation from the outlet. Evaporation of the sweat from the outlet depends on the temperature. A flow sensor (112) measures the flow rate of the sweat discharged through the capillary tube. An analyte sensor (114) obtains the sweat analyte measurement result. The system also includes a controller configured to determine the temperature based on the measured flow rate. The sweat analyte measurement result is then corrected using the determined temperature. A method for correcting temperature-dependent sweat analyte measurement results is also provided.

Description

Technical Field

[0001] This invention relates to a system and method for correcting the measurement results of sweat analytes based on temperature. Background Technology

[0002] There is a need for non-invasive, semi-continuous, and long-term monitoring of biomarkers that indicate health and well-being, such as dehydration, stress, sleep, child health, and perioperative monitoring.

[0003] Sweat, tears, and saliva can all be obtained non-invasively. Sweat is a particularly readily available biofluid and a rich source of information related to the physiology and metabolism of the subject.

[0004] Some examples of clinically relevant components of sweat include monitoring sodium levels in dehydrated individuals. + Cl - and / or K + Lactic acid, which serves as an early warning sign of inflammation (and is associated with sepsis), glucose in diabetic patients and newborns, and cortisol, which is associated with sleep apnea and stress monitoring.

[0005] However, despite promising results from clinical practice as early as the 1940s and 1950s, the development of reliable sweat sensing has been hampered by several problems. To date, the effective application of sweat analysis has been primarily limited to the diagnosis of cystic fibrosis and drug and alcohol abuse testing.

[0006] As summarized by Mena Bravo and de Castro in “Sweat: A sample with limited present applications and promising future in metabolomics” J. Pharm. Biomed. Anal. 90, 90139–147 (2014), results from sweat sensing have been found to be highly variable, and the correlation between values ​​determined from blood and sweat samples exhibits a lack of various biomarkers. However, historical research in this field has involved relatively crude sampling techniques, such as collecting large amounts of sweat in bags or textiles. The limitations of such techniques may contribute to this apparent lack of correlation.

[0007] Access to sweat may be limited and uneven, especially for individuals resting in a non-thermoneutral state, which has a sweating rate as low as ~0.03–0.10 nl / min / gland. The term “non-thermoneutral state” in this context refers to an individual outside the thermoneutral zone, where the core body temperature remains very stable and there is no reason to induce sweat production for cooling the body: typically 25°C to 30°C for naked men at rest or 13°C to 22°C for men wearing clothes.

[0008] Efforts have been made to address these issues by bringing wearable sensors into near-direct contact with sweat as it seeps from the skin. A recent example is the wearable patch presented by Gao et al. in “Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis”, Nature 529, 509-514 (2016). The patch includes components for measuring Na+. + K + An array of sensors for glucose, lactic acid, and skin temperature was used. However, the focus of this study was on the development and integration of the sensors themselves, which, while clearly crucial, did not address the issues related to sweat sample collection. The latter primarily involves placing a few centimeters between the skin and the sensor. 2 The task is accomplished using a sized absorbent pad. The assumption is that a large amount of sweat is produced (hence always testing individuals who exercise extensively), the pad will absorb the sweat for analysis, and newly generated sweat will refill the pad and "wash away" the old sweat. However, it is likely that due to a cumulative effect, the sensor's time-correlated response will not directly reflect the actual level of the biomarker over time. Poor control over sample collection and presentation of the sensor may make sustained reliable sensing over long periods difficult. Such a patch may also not be designed to handle the small amounts of sweat produced under normal conditions, i.e., on the order of nanoliters per minute per sweat gland.

[0009] Continuous monitoring of high-risk patients (such as those with severe chronic diseases, those undergoing or following surgery, and the elderly) using sweat biomarker monitoring devices can provide higher quality diagnostic information than routine biomarker sampling, which is typically accomplished through repeated draws of multiple blood samples. Such continuous monitoring can be conducted in hospital settings or elsewhere. Human sweat, alone or as a mixture with sebum, is an readily available source for biomarker measurements in wearable skin devices. For example, cholesterol is an important biomarker associated with an increased risk of developing cardiovascular disease. Inflammatory markers or cytokines, such as interleukins (e.g., TNF-α, IL-6), play important roles in the detection or disease monitoring of immune responses and joint damage in rheumatoid arthritis and psoriatic arthritis, and enteropathy.

[0010] However, improvements are needed to existing devices for continuous or intermittent monitoring. In wearable or portable devices used for sweat monitoring, the detection of biomarkers or analytes in the biological fluid of interest tends to require the device to include an analyte sensor with a surface that immobilizes the captured substance; the captured substance binds to the biomarker. Typically, the captured substance is an antibody, and the analyte is a corresponding antigen. Alternatively, the detection principle may rely on a chemical reaction involving the analyte, such as an enzymatic reaction. In both cases, analyte detection / measurement can be temperature-dependent.

[0011] EP 3242112 A1 discloses a method and apparatus for measuring liquids, comprising: a sensor whose surface is arranged to receive a quantity of liquid; an electric heating element arranged to heat the surface to force the liquid to evaporate; and an arrangement for measuring the temperature of the surface. The temperature can be measured by measuring the resistance of the electric heating element.

[0012] WO 2017 / 058806 A1 discloses a wearable patch for measuring sweat biomarkers. Skin temperature measurements acquired by a resistive temperature sensor are used to correct for biomarker concentration measurements achieved using an electrochemical sensor. A drawback of the system disclosed in WO 2017 / 058806 A1 is that including an additional resistive temperature sensor increases the system's complexity and cost. Such an additional temperature sensor also requires continuous power consumption, which may make it unsuitable for sweat patches intended for wear over relatively long periods, such as 7 to 28 days.

[0013] Providing a simple and low-cost sweat sensing system that takes into account such temperature correlations while enabling relatively long-term monitoring, such as over a period of 7 to 28 days, remains a challenge. Summary of the Invention

[0014] This invention is defined by the independent claims. The dependent claims define advantageous embodiments.

[0015] According to one aspect, a system for correcting temperature-dependent sweat analyte measurements is provided, the system comprising: a sweat collector for collecting sweat from skin; an outlet from which the sweat may evaporate; a capillary for conveying the sweat from the sweat collector to the outlet; a flow sensor for measuring the flow rate of sweat through the capillary; an analyte sensor for obtaining the sweat analyte measurement from the sweat; and a controller configured to: determine a temperature based on the measured flow rate; and correct the sweat analyte measurement based on the determined temperature.

[0016] Analytical measurement results tend to be sensitive to the temperature at which the measurement is performed. This is because the measurement principle may rely on temperature-dependent processes, such as binding the analyte to a suitable functionalized surface, or involve chemical reactions of the analyte, such as enzymatic reactions. Temperature can affect the binding or chemical reaction of the analyte, which in turn affects the signal generated by the analyte sensor.

[0017] For example, a sweat monitoring system can utilize a patch worn on the skin, i.e., a patch around the body. The temperature to which the patch and the analyte sensor integrated therein are exposed can therefore vary, for example, between 20°C and 40°C. Therefore, it is desirable to be able to correct for the temperature dependence of such sweat analyte measurements.

[0018] A potential solution is to use conventional temperature sensors, such as resistive temperature sensors, as an additional component of the sweat monitoring system to monitor temperature. However, the continuous power consumption associated with the use of such an additional conventional temperature sensor may be incompatible with the requirements for operation of the sweat monitoring system over a relatively long period of time (such as 7 to 28 days). For such a system, ensuring minimal power consumption is crucial to ensuring reliable operation during the monitoring period.

[0019] This system uses a flow sensor to determine the temperature. Sweat evaporates from the outlet of a capillary tube, which is continuously supplied with sweat from a sweat collector that collects sweat from the skin. The sweat is driven by capillary action and the evaporation of sweat from the outlet through the capillary tube. The flow sensor enables the measurement of the flow rate of sweat through the capillary tube. Since the evaporation of sweat depends on the temperature, the flow rate serves as a proxy for the temperature. Therefore, the controller determines the temperature based on the measured flow rate, for example, based on a predetermined correlation between the flow rate and the temperature. The controller is also configured to correct the analyte measurement results based on the determined temperature.

[0020] Flow sensors are typically included in sweat sensing systems to correct for changes in sweat excretion rates in analyte measurements. For the purpose of correcting for temperature changes in analyte measurements, the requirement for additional sensing components, such as resistance temperature sensors, is eliminated. In other words, the number of components required to measure the temperature does not need to increase, minimizing the system's physical complexity and cost. Power consumption is also reduced compared to systems employing additional resistance temperature sensors.

[0021] The sweat collector, capillary, outlet, flow sensor, and analyte sensor can be at least partially housed within a patch for application to the skin. The patch provides a convenient method for mounting the components. Furthermore, by housing the capillary, outlet, and flow sensor within the same patch as the analyte sensor, the determined temperature can be close to the temperature at which the analyte measurement occurs. This facilitates temperature correction of the analyte measurement results.

[0022] The patch may include a thermally conductive layer disposed between the skin and the capillary, the outlet, the flow sensor, and the analyte sensor to conduct heat. In some embodiments, the system may be configured such that the difference between the skin temperature and the ambient temperature is negligible, for example, <1°C. In this case, the system can be considered to operate under “isothermal conditions.” For example, this operating mode may partially determine the derivation of the temperature-flow rate correlation. The thermally conductive layer can assist the system in operating under such isothermal conditions. The thermally conductive layer may be made, for example, of a metal or a metal alloy.

[0023] Alternatively, the patch may include a thermal insulating layer arranged to thermally insulate the capillary, the outlet, the flow sensor, and the analyte sensor from the skin. Temperature determination may be based on the flow rate of sweat under non-isothermal conditions, i.e., where the skin temperature differs from the ambient temperature. Therefore, the thermal insulating material can generate a stable and consistent temperature difference of a few degrees Celsius (e.g., 5°C) between the ambient air and the skin under controlled environmental conditions, such as the patient's expected environment in a hospital with a climate control system. The thermal insulating layer may be made, for example, of polymer foam.

[0024] The thickness of the patch on which the sweat collector, the capillary, the outlet, the flow sensor, and the analyte sensor are positioned can be less than 10 mm, preferably less than 5 mm. Limiting the thickness of the patch in this way can promote effective heat transfer between the skin and the patch, which may be advantageous when the system is operating at an isothermal temperature.

[0025] The system may include a steam receiving chamber for receiving evaporated sweat from the outlet, wherein the steam receiving chamber is arranged relative to the outlet, such as to protect the outlet from ambient airflow. In this way, the steam receiving chamber can help reduce the influence of such ambient airflow on the evaporation of sweat from the outlet, making the temperature rather than the velocity of the ambient airflow around the sensor decisive for the flow rate through the capillary.

[0026] The steam receiving chamber may include: a vent for allowing evaporated sweat to escape into the atmosphere; and a desiccant within the steam receiving chamber for maintaining a humidity level within the steam receiving chamber over a period of time. The steam receiving chamber is open to the atmosphere via the vent, but the effects of any changes in ambient humidity that might otherwise affect the rate of sweat evaporation from the outlet can be suppressed by the desiccant. The desiccant may alternatively be referred to as a "dehumidifier" due to its function of absorbing moisture from the air inside the steam receiving chamber.

[0027] The system may include a porous body, wherein the pores of the porous body define the outlet. The porous body may, for example, take the form of a porous membrane. The porous body can help ensure the flow of sweat, and therefore temperature determination is primarily governed by the evaporation of sweat from the porous body.

[0028] The controller can be configured to determine the temperature based on the measured flow rate using a predetermined correlation between the temperature and the flow rate. For ease of use of the correlation, a lookup table can be used, for example, to implement the temperature determination.

[0029] The controller can also be configured to: determine the perspiration rate based on the measured flow rate; and correct the sweat analyte measurement results based on the determined perspiration rate. By correcting the analyte measurement results for both temperature and perspiration rate, the analyte-related output ultimately provided by the system is more reliable and more directly comparable to measurements taken under different temperature and perspiration rate conditions.

[0030] The system may include an output device for transmitting calibrated sweat analyte measurements to a user. For example, the output device may include a user interface for displaying the calibrated analyte measurements.

[0031] According to another aspect, a method for correcting temperature-dependent sweat analyte measurement results is provided, the method comprising: collecting sweat and supplying the sweat to an outlet via a capillary tube, the sweat being discharged through the capillary tube by capillary action and evaporation of sweat from the outlet; measuring the flow rate of the sweat discharged through the capillary tube; determining a temperature based on the measured flow rate; obtaining the sweat analyte measurement results from the sweat; and correcting the sweat analyte measurement results based on the determined temperature.

[0032] For example, the method can be executed using a system as defined above.

[0033] Determining temperature based on a measured flow rate may include using a predetermined correlation between the temperature and the flow rate. For example, the predetermined correlation may take the form of a lookup table.

[0034] These and other aspects of the invention will become apparent from the embodiments described below and will be set forth with reference to the embodiments described below. Attached Figure Description

[0035] Referring to the accompanying drawings, embodiments of the invention will be described in more detail by way of non-limiting examples, wherein:

[0036] Figure 1 A cross-section of a patch disposed on the skin according to an embodiment is schematically depicted;

[0037] Figure 2 A graph showing skin temperature versus evaporative sweating rate is provided, assuming the skin temperature is the same as the ambient temperature.

[0038] Figure 3 A cross-section of a patch disposed on the skin according to another embodiment is schematically depicted;

[0039] Figure 4 It provides graphs of skin temperature versus evaporative sweating rate assuming different skin temperatures than ambient temperatures;

[0040] Figure 5 A block diagram of a system according to an embodiment is provided;

[0041] Figure 6 A flowchart of the method according to an embodiment is provided; and

[0042] Figure 7 A general computer architecture suitable for controllers used in the implementation system is shown. Detailed Implementation

[0043] It should be understood that the detailed descriptions and specific examples, when indicating exemplary embodiments of the apparatus, systems, and methods, are intended for illustrative purposes only and not to limit the scope of the invention. These and other features, aspects, and advantages of the apparatus, systems, and methods of the present invention will become better understood from the following description, claims, and drawings. It should be understood that the drawings are merely schematic and not drawn to scale. It should also be understood that the same reference numerals are used throughout the drawings to indicate the same or similar parts.

[0044] A system is provided for temperature-corrected sweat analyte measurement results. The system includes a sweat collector for collecting sweat from the skin. The collected sweat is discharged from the sweat collector to an outlet via a capillary. Sweat is discharged through the capillary due to capillary action and evaporation from the outlet. Evaporation of sweat from the outlet depends on temperature. A flow sensor measures the flow rate of sweat discharged through the capillary. An analyte sensor obtains the sweat analyte measurement results. The system also includes a controller configured to determine the temperature based on the measured flow rate. The sweat analyte measurement results are then corrected using the determined temperature.

[0045] The term “arrangement” can be considered an alternative to the term “system”.

[0046] Fluctuations in sweat temperature, as sampled by sweat patches, can occur because the patches are worn around the body (i.e., on the skin), where the skin is exposed to physiological skin temperatures ranging from 20°C to 40°C. Skin temperature changes during normal daily activities due to several factors, including anatomical location, feeding, sleep, physical exercise, health status, body composition, metabolic syndrome factors, outdoor exposure, seasonal weather changes, and circadian rhythms.

[0047] Analytical measurement results tend to be sensitive to the temperature at which the measurement is performed. This is because the measurement principle may rely on binding the analyte to a suitable functionalized surface or involve a chemical reaction of the analyte, such as an enzymatic reaction. Temperature can affect the binding of the analyte or the chemical reaction, which in turn affects the signal generated by the analyte sensor. Therefore, it is desirable to calibrate analyte measurements to account for temperature variations.

[0048] Measurements based on temperature-corrected analytes can be achieved using conventional temperature sensors, such as resistance temperature sensors. However, the continuous power consumption associated with the additional use of such conventional temperature sensors may be incompatible with the requirements for operation of sweat monitoring systems over relatively long periods (such as 7 to 28 days). For such systems, ensuring minimal power consumption is crucial for ensuring reliable operation during the monitoring period.

[0049] Therefore, this system uses a flow sensor to determine the temperature. Sweat evaporates from the outlet of the capillary, and is continuously supplied to the capillary from a sweat collector that collects sweat from the skin. Sweat is driven by capillary action and evaporation. Since sweat evaporation depends on temperature, the sweat flow rate serves as a proxy for temperature. A controller included in the system determines the temperature based on the measured flow rate, for example, based on a predetermined correlation between flow rate and temperature. The controller then corrects the analyte measurement results based on the determined temperature.

[0050] The system can utilize a flow sensor for an additional purpose: correcting analyte measurements for changes in sweat excretion rate. Therefore, the flow sensor serves a dual purpose, eliminating the need for additional sensing components (such as resistance temperature sensors) for correcting analyte measurements for temperature variations. This simplifies the system's physical design and reduces its manufacturing costs due to the fewer components required. Furthermore, the system's power consumption can be reduced compared to systems employing additional resistance temperature sensors.

[0051] When using corresponding sensors for measuring flow rate and temperature (e.g., a flow rate sensor and a thermistor), both sensors require power (Pf for the flow rate sensor and Pt for the temperature sensor) to perform their respective functions. In the current case, only a single flow sensor requires power Pf (the opposite of Pf+Pt when using an additional temperature sensor). Although the flow sensor may need to operate over a longer time period to also perform temperature sensing, and therefore may consume slightly more energy, this will still be less than the energy consumed in the conventional scenario using a flow rate sensor and a thermistor.

[0052] Because variations in sweating rate can exist, it is expected that even at very low sweating rates (<~0.05 nl / min / gland), there will be some impact on temperature determinations, such as those using flow sensors. However, based on recent experiments, the inventors have found that, under ambient conditions, a sweating rate of 0.02–0.20 nl / min / gland can be readily obtained from sedentary individuals; this rate depends on the number of active glands, for example, the number of active glands in the forearm and palm areas can be as high as per cm. 2 Variations between 10 and 100 glands. Assuming there is a variation per cm when an individual is sedentary under environmental conditions. 2 Approximately 10-30 active glands are reasonable. This would imply a sweat rate of ~0.06-0.20 nl / min / gland, which is not considered to raise any significant issues regarding temperature determination via sweat flow rate measurement. Moreover, if a lower sweat rate is deemed more clinically appropriate, the patch geometry and size can, for example, be tailored to accommodate these low sweat rates to ensure reliable temperature determination. Another approach to reducing the correlation with sweat rate could be, for example, including additional small sweat reservoirs from which sweat is expelled via capillary channels due to evaporation.

[0053] Figure 1A patch 100, which may be included in a sweat sensing system, is schematically depicted. The patch 100 is shown near an area of ​​skin 102. For the purpose of sampling sweat generated in an area of ​​skin 102, the patch 100 may be applied to skin 102 in any suitable manner. For example, the patch 100 may be adhered to skin 102 using a suitable biocompatible adhesive or secured to skin by means of a strip, as is known per se.

[0054] Sweat is excreted by sweat glands 104 and collected by a sweat collector 106 included in the patch 100. Figure 1 As shown, the sweat collector 106 can take the form of a recessed portion of the patch 100, having an inner surface that, together with the skin 102, defines a container for collecting sweat. An outlet 107 may also be provided to allow evaporating sweat to escape from the sweat collector 106.

[0055] The sweat collector 106 is in fluid communication with the capillary 108. The capillary 108 extends to the outlet 110. Through a combination of capillary action and sweat evaporation from the outlet 110, sweat is discharged from the sweat collector 106 through the capillary 108.

[0056] After the capillary 108 (which may alternatively be referred to as a “microfluidic channel”) is filled, excess sweat can be removed due to the evaporation of sweat from the outlet 110, which promotes flow in the capillary 108.

[0057] The flow rate of sweat through capillary 108 is measured using flow sensor 112. Flow sensor 112 may include any suitable flow sensor, such as an optical flow sensor and / or a thermal flow sensor, such as a calorimetric flow sensor or a temperature gradient driven flow sensor. Such flow sensors are well known in themselves and will not be described further herein for the sake of brevity only.

[0058] It should be noted that the term "capillary" in this context is not limited to a single tube or channel. In this respect, Figure 1 The capillary 108 shown includes multiple paths 108A, 108B leading to outlet 110. Path 108A passes through flow sensor 112 and analyte sensor 114, while path 108B does not pass through any sensor. However, Figure 1 The arrangement shown should not be considered limiting, and any suitable arrangement of capillary 108, analyte sensor 114, and flow sensor 112 can be contemplated. For example, analyte sensor 114 may be arranged in a fluid path different from the fluid path of capillary 108 and flow sensor 112.

[0059] In one embodiment, a portion of the sweat collected by sweat collector 106 is transported to outlet 110, and the remainder is transported to analyte sensor 114 for analyte measurement, such as biomarker analysis.

[0060] The analyte sensor 114 can be considered as a component that collects analyte measurement data required for analyte measurement. The analyte sensor 114 can rely on any detection principle suitable for sensing sweat analytes. The analyte sensor 114 can, for example, include an electrochemical biosensor.

[0061] In a non-limiting example, the analyte sensor 114 includes a sensor surface on which a capture substance is immobilized. The capture substance can be selected to bind a specific analyte. For example, an antibody can be immobilized on the surface, capturing a specific antigen that is an analyte of interest. Thus, when a sample comes into contact with the surface, the capture substance can bind to the analyte present in the sample. As the analyte binds to the surface via the capture substance, various detectable properties of the surface, such as optical and mechanical properties, change relative to a surface without analyte.

[0062] Alternatively or additionally, the analyte sensor 114 may include a sensor surface in which a reaction involving the analyte, such as an enzymatic reaction, can occur. For example, the reaction can be detected by electrochemical means. Such analyte sensing methods are well known to those skilled in the art and will not be described further herein for the sake of brevity only.

[0063] A porous body 116, such as a porous membrane, may be disposed at the end of the capillary 108. The pores of the porous body 116 may define an outlet 110. The porous body 116 may help ensure a relatively strong capillary pull, and the flow of sweat and therefore the temperature determination are primarily controlled by the evaporation of sweat from the porous body 116.

[0064] The porous body 116 can be made of any suitable material, such as polymers, for example, polyethylene terephthalate. Microporous structures can be provided in the polymer, for example, using an excimer laser. For example, the pores of the porous body 116 can have diameters ranging from 50 μm to 250 μm.

[0065] By selecting the evaporation zone provided by the porous body 116, the flow rate through the capillary 108 can be tuned, for example, so as not to exceed the expected perspiration rate. By avoiding a flow rate exceeding the expected flow rate, for example, about 0.2 nl / min / gland, a constant filling of the capillary 108 with sweat can be advantageously maintained.

[0066] Generally, the rate of sweat evaporation depends on ambient humidity, ambient temperature, skin temperature, and ambient airflow velocity. Physiologically, humans can lose excess metabolic heat through radiation, convection, and sweat evaporation. Heat loss through convection and radiation can be very effective at low air temperatures; however, as ambient temperatures rise, the evaporative cooling effect of sweat becomes increasingly important for temperature regulation. Based on Dalton's law of partial pressures, sweat droplets excreted on the skin surface exist in equilibrium between liquid and gas phases, depending on ambient temperature and humidity. The more sweat in the gas phase, the greater the heat loss (i.e., the cooling effect), due to the latent heat of vaporization required for the phase change from liquid to gas.

[0067] like Figure 1 As shown, patch 100 includes a steam receiving cavity 119 for receiving evaporated sweat from outlet 110. The steam receiving cavity 119 surrounds outlet 110 and protects outlet 110 from ambient airflow. In this way, the steam receiving cavity 119 helps reduce the impact of such ambient airflow on the evaporation of sweat from outlet 110, making the temperature rather than the velocity of the ambient airflow around the sensor decisive for the flow rate through capillary 108.

[0068] While enclosing the outlet 110 within the patch 100 may be preferred for the purpose of reducing the effects of ambient airflow, compensation for changes in ambient airflow can be achieved in other ways. For example, other forms of shielding are contemplated, such as positioning the patch 100 under clothing.

[0069] Humidity can also be an important factor in determining the rate of sweat evaporation, because if the amount of water vapor already present in the air near the sweat droplet is such that the gaseous portion is filled (i.e., relative humidity (RH) = 100%), evaporation will not occur, and no cooling will take place. The highest sweat evaporation likely occurs at higher skin temperatures and lower relative humidity levels. However, under constant relative humidity, the rate of sweat evaporation will depend only on the ambient (≈skin / sweat) temperature, thus achieving a direct linear correlation between the rate of sweat evaporation and skin temperature.

[0070] exist Figure 1 In the illustrated embodiment, the steam receiving chamber 119 contains a desiccant 122. The humidity capacity and amount of the desiccant 122 can be selected such that the humidity in the steam receiving chamber 119 is maintained at a predetermined level. By selecting a suitable amount and type of desiccant 122, the system can be allowed to operate over a wider dynamic range of perspiration rates. The desiccant 122 may include one or more of, for example, silica gel, calcium oxide, and calcium sulfate. The steam receiving chamber 119 is open to the atmosphere via a vent 120, but the effects of any changes in ambient humidity that might otherwise affect the rate of sweat evaporation from the outlet 110 can be suppressed by the desiccant 122.

[0071] Therefore, the constant relative humidity provided in the steam receiving chamber 119 by the desiccant 122 can establish a direct and reliable correlation between sweat flow rate and temperature. However, the desiccant 122 can be excluded, for example, in situations where ambient humidity is well controlled, such as in hospital settings, and / or in cases where the system includes additional sensing modules for compensating for humidity variations.

[0072] The following non-limiting examples are provided to illustrate the effectiveness of desiccant 122 in maintaining humidity levels.

[0073] As can be seen from Equation 1, the amount of desiccant 122 required to control the humidity in the closed sweat patch 100 can depend on several variables.

[0074]

[0075] Where Q = amount of desiccant (kg), C eq =Concentration of water vapor at equilibrium (g / m³) 3 D = Decimal difference (unitless) between the relative humidity (RH) outside the casing and the target RH inside; V = Net air volume inside the casing (m³). 3 N = air exchange rate (1 / day), t = minimum number of days (days) to maintain the target RH range, M H = Specific moisture storage of the adsorbent, including hysteresis effect (g / kg for 1% RH change), F = Target range of RH fluctuation (%).

[0076] The equilibrium concentration of water vapor (absolute humidity at saturation; 100% RH) can vary with temperature (T in °C), for example, 17.3 g / m³ at 20 °C. 3 ; 18.3 g / m at 21℃ 3 ; 20.0 g / m at 22.5℃ 3 The concentrations at other temperatures can be obtained using Equation 2.

[0077] C eq =7.36e (T / 19.96) -2.75 Equation 2

[0078] Substituting equation 2 into equation 1, we get:

[0079]

[0080] Assume the following: C eq = 20.0 g / m³ at equilibrium at 22.5℃ 3Water vapor; ambient RH = 80%; target RH in the casing = 50%; D = 0.30 (i.e., the difference between ambient RH and target RH); steam receiving chamber dimensions of 5mm x 5mm x 1mm; V = 2.5 x 10 -8 m 3 (Net air volume enclosed within the casing); N = 1 air exchange rate (1 / day); t = 7 days (minimum number of days required to maintain the target RH range); M H =3g / kg, for a 1% RH change; for a target range of ±5% RH fluctuation, F = 10%.

[0081]

[0082] The required small amount of desiccant 122 (0.035 mg) confirmed the feasibility of the proposed method for controlling the humidity of the enclosed air in patch 100.

[0083] To illustrate how temperature can be determined based on the evaporation rate, the following exemplary scenario is presented, in which the RH in patch 100 is constant at 50%, and the difference between skin temperature and ambient temperature can be negligible (<1°C, i.e., isothermal conditions). In this example, it is assumed that the air velocity on patch 100 is very low (≈0.001 m / s), and both skin and ambient temperatures are 35°C. It is possible to determine the evaporative sweat rate (ESR) using the following Equation 4 (proposed by Nielsen B. Olympics in Atlanta: a fight against physics. Medicine & Science in Sports & Exercise. 1996; 28(6):665-8).

[0084]

[0085] Where A = total skin surface area, E sw = Heat loss rate of sweat (≈675WL) -1 h), P sk =Mean skin water vapor pressure, P a = Ambient water vapor pressure, and v = air velocity.

[0086] In addition, P sk and P a It can be determined based on the water vapor saturation pressure of the air (i.e., at 100% humidity), which can be approximated using the following Equation 5.

[0087] P ws =e (77.3450+0.0057T-7235 / T) / T 8.2 [kPa] Equation 5

[0088] Where T = temperature in [K], which in the current example is: T sk =T a =35℃ + 273.15K = 308.15K. Importantly, note the water vapor pressure P of sweat when it is excreted from the sweat glands. sk At 100% humidity, and with an ambient water vapor pressure P a The humidity is 30% (due to the presence of desiccant 122 in the sealed patch 100).

[0089] Therefore, this implies:

[0090] P sk =e (77.3450+0.0057*308.15-7235 / 308.15) / (308.15) 8.2 =5.607 kPa

[0091]

[0092] Furthermore, assuming the skin area covered by the steam receiving chamber is 5mm x 5mm, Equation 4 is used:

[0093]

[0094] The above analysis can be repeated within the physiological skin temperature range (i.e., 20°C to 40°C) to obtain the correlation between sweat evaporation rate and skin temperature, such as... Figure 2 As shown. Figure 2 The drawing shown is based on the above assumptions (for a 5mm x 5mm skin area covered by patch 100, RH = 30%, isothermal (T) sk =T a (v = 0.001 m / s).

[0095] With isothermal boundary conditions (i.e., T) sk ≈T a Small deviations (<0.5℃) can lead to small but acceptable errors in temperature estimation, approximately ≤0.5℃, in the temperature range of 20℃ to 40℃.

[0096] The body 124 of patch 100 can be made of any suitable material, such as polymers, for example, elastomers. For example, the material can be selected based on its thermal conductivity and whether the skin temperature and the temperature of the vapor receiving cavity 119 are intended to be the same (isothermal) or different (non-isothermal).

[0097] Similar considerations can be applied to the thickness of patch 100. To facilitate isothermal operation, the thickness of patch 100 can be less than 10 mm. Preferably, the thickness is less than 5 mm to facilitate efficient heat transfer from skin 102 to patch 100.

[0098] like Figure 3 As schematically depicted, when the system is intended to operate under the isothermal conditions described above, patch 100 may include a thermally conductive layer 126 for conducting heat between skin 102 and capillary 108, outlet 110, flow sensor 112, and analyte sensor 114. The thermally conductive layer 126 may be made, for example, of a metal or metal alloy.

[0099] In an alternative embodiment, temperature is determined based on the evaporation flow rate of sweating under non-isothermal conditions, i.e., where skin temperature differs from ambient temperature (T0). sk ≠T a ).

[0100] Although not shown in the figure, this can be achieved by using a patch 100 made of a relatively thick (e.g., 2-3 cm thick) thermal insulation material, such as polymer foam. The thermal insulation material can generate a stable and consistent temperature difference of a few degrees Celsius (e.g., 5°C) between the ambient air and the skin under controlled environmental conditions, such as the patient's expected environment in a hospital with a climate control system.

[0101] The following is an explanation of the operation of the system under non-isothermal conditions. In this example, the room temperature is maintained at 25°C, while the skin temperature is maintained at 35°C. By using Equation 5, and assuming that for P... a At 30% humidity, we obtain:

[0102] P sk,35 =e (77.3450+0.0057*308.15-7235 / 308.15) / (308.15) 8.2 =5.607 kPa

[0103]

[0104] Assuming the skin area covered by the steam receiving chamber is 5mm x 5mm, using Equation 4:

[0105]

[0106] The above analysis can be repeated within the physiological skin temperature range (i.e., 20°C to 40°C) to obtain the non-isothermal correlation between sweat evaporation rate and skin temperature, such as... Figure 4 As shown. Figure 4 The drawing shown is based on the above assumptions (at a fixed ambient temperature of 25°C, for a 5mm x 5mm skin area covered by patch 100, RH = 30%, non-isothermal (T) sk ≠T a (v = 0.001 m / s).

[0107] Therefore, the correlation between flow rate and sweat temperature can be easily established and used, for example, to create a lookup table. Once the sweat temperature is determined by measuring the evaporative flow rate, this can then be used to correct analyte measurements, such as the concentration of biomarkers measured in sweat.

[0108] Figure 5 A block diagram of a system 200 for correcting temperature-related sweat analyte measurements is shown. The arrow between the block representing flow sensor 112 and controller 202 indicates data related to the flow of sweat in capillary 108 received by controller 202. Similarly, the arrow between the block representing analyte sensor 114 and controller 202 indicates data related to analyte measurements received by controller 202.

[0109] Controller 202 uses data relating to the flow of sweat in capillary 108 to determine the temperature. As previously described, this process can utilize the correlation between flow rate and temperature. For example, a lookup table can be used by controller 202 in this process, although other means of determining temperature based on the relationship with flow rate would be readily apparent to a technician.

[0110] The controller 202 then uses the determined temperature to correct the analyte measurement results. For example, using a known relationship between temperature and analyte measurement results, the analyte measurement results can be corrected to a predicted measurement result at a specific temperature. In this way, the corrected analyte measurement results can be compared with each other, even though the corresponding temperatures at which the actual measurements occurred are different.

[0111] The calibrated analyte measurement results can then be transmitted from controller 202 to output device 204, which transmits the calibrated analyte measurement results to a user, such as a patient and / or healthcare provider. For example, output device 204 may include a user interface for displaying the calibrated analyte measurement results. Alternatively or additionally, output device 204 may include a suitable transmitter for sending the calibrated measurement results to an external device, such as a smartphone.

[0112] Although not shown in the figures, it should be noted that controller 202 and / or output device 204 may be included in patch 100. Alternatively, some of the data processing performed by controller 202 may occur in a suitable module within patch 100, and the remainder may be performed on a separate data processing device. In this case, patch 100 may include a suitable transmitter for sending partially processed data to the separate data processing device. Sharing data processing with such a separate device to reduce the power consumption of patch 100 can be advantageous.

[0113] Figure 6A flowchart of method 300 according to an embodiment is provided. For example, method 300 can be implemented using system 200 described above.

[0114] Method 300 includes collecting sweat in the first step 302 and supplying the sweat to an outlet via a capillary. As previously described, the sweat is discharged through the capillary by capillary action and evaporation from the outlet.

[0115] In step 304, the flow rate of sweat expelled through the capillaries is measured. The flow rate measured in step 306 is then used to determine the temperature. For example, step 306 may include using a predetermined correlation between temperature and flow rate, as previously described.

[0116] In step 308, a sweat analyte measurement is obtained from the sweat. Then, in step 310, the sweat analyte measurement is corrected based on a determined temperature. This temperature-based correction ensures that meaningful (corrected) analyte measurements are provided that can be compared with other measurements, regardless of the temperature conditions under which the measurement was performed.

[0117] Figure 7 An example of a computer 400 for implementing the controller 202 described above is shown. The computer 400 includes, but is not limited to, a PC, workstation, laptop computer, PDA, handheld device, server, storage device, etc. Typically, in terms of hardware architecture, the computer 400 may include one or more processors 401, memory 402, and one or more I / O devices 403 communicatively coupled via a local interface (not shown). The local interface may be, for example, but not limited to, one or more buses or other wired or wireless connections, as known in the art. The local interface may have additional elements, such as controllers, buffers (caches), drivers, repeaters, and receivers, to enable communication. Furthermore, the local interface may include address, control, and / or data connections to enable appropriate communication between the aforementioned components.

[0118] Processor 401 is a hardware device for executing software that can be stored in memory 402. Processor 401 can actually be any custom or commercially available processor, central processing unit (CPU), digital signal processor (DSP), or auxiliary processor among several processors associated with computer 400, and processor 401 can be a semiconductor-based microprocessor (in the form of a microchip) or microprocessor.

[0119] Memory 402 may include any one or a combination of volatile memory elements (e.g., random access memory (RAM), such as dynamic random access memory (DRAM), static random access memory (SRAM), etc.) and non-volatile memory elements (e.g., ROM, erasable programmable read-only memory (EPROM), electronically erasable programmable read-only memory (EEPROM), programmable read-only memory (PROM), magnetic tape, optical disc read-only memory (CD-ROM), magnetic disk, floppy disk, cassette tape, tape cartridge, etc.). Furthermore, memory 402 may contain electronic, magnetic, optical, and / or other types of storage media. Note that memory 402 may have a distributed architecture, in which various components are located remotely from each other but are accessible by processor 401.

[0120] The software in memory 402 may include one or more individual programs, each including an ordered list of executable instructions for implementing logical functions. According to an exemplary embodiment, the software in memory 402 includes: a suitable operating system (O / S) 404, a compiler 4040, source code 406, and one or more applications 407.

[0121] Application 407 includes many functional components, such as computing units, logic, functional units, processes, operations, virtual entities and / or modules.

[0122] The operating system 404 controls the execution of computer programs and provides scheduling, input-output control, file and data management, memory management, communication control, and related services.

[0123] Application 407 can be a source program, an executable program (object code), a script, or any other entity that includes a set of instructions to be executed. When it is a source program, the program is typically translated by a compiler (such as compiler 405), assembler, interpreter, etc., and may or may not be included in memory 402 to operate correctly in conjunction with operating system 404. Furthermore, application 407 can be written in an object-oriented programming language (which has classes of data and methods) or a procedural programming language (which has routines, subroutines, and / or functions), such as, but not limited to, C, C++, C#, Pascal, BASIC, API calls, HTML, XHTML, XML, ASP scripts, JavaScript, FORTRAN, COBOL, Perl, Java, ADA, .NET, etc.

[0124] I / O device 403 may include input devices, such as, but not limited to, a mouse, keyboard, scanner, microphone, camera, etc. Furthermore, I / O device 403 may also include output devices, such as, but not limited to, a printer, monitor, etc. Finally, I / O device 403 may also include devices that communicate with both inputs and outputs, such as, but not limited to, a network interface controller (NIC) or modulator / demodulator (for accessing remote devices, other files, devices, systems, or networks), radio frequency (RF) or other transceivers, telephone interfaces, bridges, routers, etc. I / O device 403 also includes components for communication over various networks, such as the Internet or intranets.

[0125] When the computer 400 is in operation, the processor 401 is configured to execute software stored in the memory 402 to transfer data to and from the memory 402, and typically controls the operation of the computer 400 according to the software. Applications 407 and the operating system 404 are read, possibly buffered within the processor 401, and then executed.

[0126] When application 407 is implemented as software, it should be noted that application 407 can actually be stored on any computer-readable medium for use by or in connection with any computer-related system or method. In the context of this document, a computer-readable medium can be an electronic, magnetic, optical, or other physical device or module that can contain or store computer programs for use by or in connection with a computer-related system or method.

[0127] There is a need for non-invasive, semi-continuous, and long-term monitoring of biomarkers indicating health and well-being, for example, to monitor dehydration, stress, sleep, child health, and perioperative care, but it can also be used for random sampling measurements. For example, this disclosure can be applied to the field of patient monitoring as an early warning of sudden deterioration in patients in general wards and for investigations of sleep disorders. This represents an improvement because measurements are currently only taken on a random basis when patients visit their physicians.

[0128] By studying the accompanying drawings, description, and claims, those skilled in the art can understand and implement other variations of the disclosed embodiments in practicing the claimed invention. In the claims, the word "comprising" does not exclude other elements or steps, and the words "a" or "an" do not exclude a plurality. Measures recited in dissimilar dependent claims may be advantageously combined. Any reference numerals in the claims should not be construed as limiting the scope.

Claims

1. A system (200) for correcting temperature-related sweat analyte measurement results, the system comprising: A sweat collector (106) for collecting sweat from the skin; Outlet (110), from which the sweat can evaporate; A capillary tube (108) is used to transport the sweat from the sweat collector to the outlet; A flow sensor (112) is used to measure the flow rate of the sweat through the capillary; An analyte sensor (114) for obtaining a measurement result of the sweat analyte from the sweat; and The controller (202) is configured as follows: Temperature is determined based on the measured flow rate using a predetermined correlation between flow rate and temperature, which maps the measured flow rate to a unique temperature within a predefined temperature range; and The sweat analyte measurement results are corrected based on the determined temperature.

2. The system (200) according to claim 1, wherein, The sweat collector (106), the capillary (108), the outlet (110), the flow sensor (112), and the analyte sensor (114) are at least partially housed within a patch (100) for application to the skin.

3. The system (200) according to claim 2, wherein, The patch (100) includes a thermally conductive layer (126) arranged to conduct heat between the skin and the capillary (108), the outlet (110), the flow sensor (112), and the analyte sensor (114).

4. The system (200) according to claim 2, wherein, The patch (100) includes a thermal insulation layer arranged to thermally insulate the capillary (108), the outlet (110), the flow sensor (112), and the analyte sensor (114) from the skin.

5. The system (200) according to any one of claims 2 to 4, wherein, The thickness of the patch (100) in which the sweat collector (106), the capillary (108), the outlet (110), the flow sensor (112), and the analyte sensor (114) are located is less than 10 mm, preferably less than 5 mm.

6. The system (200) according to any one of the preceding claims, comprising a steam receiving chamber (119) for receiving evaporated sweat from the outlet (110), wherein, The steam receiving chamber is arranged relative to the outlet to protect the outlet from ambient airflow.

7. The system (200) according to claim 6, wherein, The steam receiving chamber (119) includes: Vent (120) for allowing evaporated sweat to escape into the atmosphere; and The desiccant (122) in the steam receiving chamber is used to maintain the humidity level in the steam receiving chamber for a period of time.

8. The system (200) according to any one of the preceding claims, comprising a porous body (116), wherein, The pores of the porous body define the outlet (110).

9. The system (200) according to claim 8, wherein, The porous body (116) takes the form of a porous membrane.

10. The system (200) according to any one of the preceding claims, wherein, The controller (202) is configured to determine the temperature based on the measured flow rate using a predetermined correlation between the temperature and the flow rate.

11. The system (200) according to claim 10, wherein, The predetermined relevance is implemented in the form of a lookup table.

12. The system (200) according to any one of the preceding claims, wherein, The controller (202) is also configured to: The sweating rate is determined based on the measured flow rate; and The sweat analyte measurement results are corrected based on the determined sweating rate.

13. The system (200) according to any one of the preceding claims, comprising an output device (204) for transmitting calibrated sweat analyte measurement results to a user.

14. A method (300) for correcting temperature-related sweat analyte measurement results, the method comprising: (302) Collect sweat and supply the sweat to an outlet through a capillary tube, the sweat being discharged through the capillary tube by capillary action and evaporation of the sweat from the outlet; Measure (304) the flow rate of the sweat through the capillary; (306) Temperature is determined based on the measured flow rate by a predetermined correlation between flow rate and temperature, the predetermined correlation mapping the measured flow rate to a unique temperature within a predefined temperature range; The measurement results of the sweat analyte (308) are obtained from the sweat; and The sweat analyte measurement results are corrected based on the determined temperature (310).

15. The method (300) according to claim 14, wherein, Determining the temperature (306) based on the measured flow rate includes using a predetermined correlation between the temperature and the flow rate.

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