Sweat sensor

Abstract

The present invention relates to devices and methods for extracting and analyzing sweat from a user's skin. In particular, it is proposed to provide variability in the size of the sweat sensor inlet (102, 103, 104), which can be used to improve the determination of sweat parameters, such as the determination of the number of active sweat glands. The variability in the size of the inlet (102, 103, 104) of the sweat sensor (100) with which it extracts sweat from the user's skin (111) can be achieved by having multiple inlets, where at least some of the inlets have different opening sizes, and using different sizes of inlets depending on the different situations. Alternatively, one or more inlets can have an opening with a variable cross-sectional area, e.g. an adjustable diameter of the opening, of course a combination of both alternatives is also feasible. The processor of the sweat sensor can use information from all inlets or only the most suitable size of inlet to determine the sweat parameters. In another alternative, the processor can adjust the inlet to adjust the adjustable inlet opening to the most suitable size, and then determine the sweat parameters of interest.

Description

TECHNICAL FIELD

[0001] The present invention relates to sweat analysis by means of a wearable sensor. In particular, the present invention relates to a sweat sensor for analyzing a user's sweat that is drawn into the sweat sensor from the user's skin, to a method of analyzing a user's sweat drawn by the sensor from the user's skin, and to a computer program element. BACKGROUND

[0002] There is a demand for non-invasive, semi-continuous and long-term monitoring of biomarkers, i.e. biomolecules, that are indicative of disease / health conditions and good physical condition, in monitoring, for example, dehydration, stress, sleep, child health and perioperative monitoring.

[0003] Sweat, tears and saliva can all be obtained in a non-invasive way. Sweat is a particularly easy to obtain 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 are Na + , Cl - and / or K + , lactate as an early warning of inflammation, which is related to sepsis, glucose in diabetic patients and newborns and Cortisol related to sleep apnea and stress monitoring.

[0005] Continuous monitoring of high-risk patients, such as patients with severe chronic diseases, pre- or post-operative patients and the elderly, using a sweat biomarker monitoring device can provide a higher quality of diagnostic information than the usual spot checks of biomarkers, which are usually performed by repeated withdrawal of multiple blood samples. Such continuous monitoring can be performed in a hospital environment or elsewhere. Human sweat alone or in mixture with sebum can be an easily accessible source for biomarker measurements in a device that can be worn on the skin. Cholesterol, for example, is an important biomarker related to increased risk in the development of cardiovascular diseases. Inflammatory markers or cytokines, such as interleukins, like TNF-a, IL-6, play an important role in immune reactions and the detection or disease monitoring of joint damage in rheumatoid and psoriatic arthritis and in intestinal diseases.

[0006] Examples of biomarkers / biomolecules that can be detected in exo / cyrohormonal sweat using appropriate capture species (antibodies, inducers, molecularly imprinted polymers, etc.) are: small molecules, such as urea, creatinine, cholesterol, triglycerides, steroid hormones (cortisol), glucose, melatonin; peptides and proteins, including cytokines, such as IL-1a, IL-1b, IL-6, TNFa, IL-8 and TGF-b IL-6, cysteine proteases, DNAse I, lysozyme, Zn-a2-glycoprotein, cysteine-rich secretory protein-3 and dermcidin; and large biomarkers, such as hepatitis C virus.

[0007] As outlined by Mena-Bravo and de Castro in "Sweat: A sample with limited present applications and promising future in metabolomics (J. Pharm. Biomed. Anal. 90, 139-147 (2014))", it has been found that results from sweat sensing can be highly variable, and for various biomarkers there appears to be a lack of correlation between values determined from blood samples and sweat samples. In this regard, historical research in the field has involved relatively crude sampling techniques, such as collecting bulk sweat in a bag or textile. The deficiencies of such techniques can be a factor in contributing to this apparent lack of correlation. Thus, the review by Mena-Bravo and de Castro highlights further major setbacks for conventional sweat sensing techniques in terms of difficulties in producing sufficient sweat for analysis, sample evaporation problems, lack of appropriate sampling devices, need for trained staff and problems relating to standardisation of the amount of sample.

[0008] To address these problems, efforts have been made by making wearable sensors contact with sweat almost immediately as it emerges from the skin. A recent example is the wearable patch given by Gao et al. in "Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis (Nature 529, 509-514 (2016))". The patch includes an array of sensors for measuring Na + , K +glucose, lactate and skin temperature. However, the focus of this study was the development and integration of the sensor itself, which, while obviously crucial, did not address the issues related to sweat sample collection. The latter was accomplished primarily by placing a few square centimeter sized absorbent pad between the skin and the sensor. It was assumed that if there was sufficient sweat production (and thus, the test was performed on an individual who was exercising), the pad would absorb the sweat for analysis, while newly produced sweat would refill the pad and "wash away" the old sweat. However, due to the accumulation effect, the sensor's response over time is likely not to directly reflect the actual levels of biomarkers over time. The collection and submission of the sample to the published sensor can not be well controlled, making it difficult to perform continuous reliable sensing over a longer period of time. This patch also cannot be designed to handle the small amount of sweat that is normally produced, i.e., sub- to nano-liters per minute per sweat gland.

[0009] An adult human produces heat at rest of about 100 Joules per second (100 Watts). For a person wearing clothes at a temperature of about 22°C, this heat is removed by passive means, such as by conduction and convection. In this case, the core temperature remains constant. However, when i) a person engages in physical labor or exercise and / or ii) the ambient temperature increases, this conduction / convection process is not sufficient to maintain the core temperature. To maintain homeostasis, the body will cause the blood vessels in the skin to dilate to cool the blood, and it will begin to produce sweat, which cools the skin by evaporation.

[0010] At ambient temperature, people who are only slightly active or perform light work produce a relatively small amount of sweat, as discussed by Taylor in "Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans (Extrem Physiol Med 2013; 2: 4) and by Simmers in "Prolonged and localized sweat stimulation by iontophoretic delivery of the slowly metabolised cholinergic agent carbachol (Journal of Dermatological Science 89 (2018) 40-51). In the so-called thermoneutral zone, which is approximately in the range of 25°C to 30°C, the core temperature remains very stable and no sweat production is induced to cool the body. This zone is defined for naked people in a resting state. For people in a resting state wearing clothes, the thermoneutral zone is lower: approximately in the range of 13°C to 22°C. Therefore, when the temperature is in this zone and the person is in a resting state, the sweat production is very low.

[0011] According to Taylor, in a resting and thermoneutral situation, the sympathetic nerve firing (secretion by the coil of the sweat gland) can not cause measurable sweating, because the reabsorption of the sweat can match its formation rate. Simmers measured the sweat production rate of people wearing clothes, exposed to an air-conditioned environment, mainly performing non-physical work, and found typical values of the sweat rate of about 0.3 nl / min / gland (measured values between 0 and 0.7 nl / min / gland). When people are in a resting state but at an elevated temperature of 36°C, Taylor measured an average sweat production rate of 0.36 mg-cm -2 ·min -1 When assuming 2.03 million sweat glands per 1.8 m 2 (area of the skin of an average person) and a sweat density of 1 g / ml, the average sweat production is about 3.2 nl / min / gland. Since the elevated temperature is above the thermoneutral zone, the body needs to cool and in fact the sweat production rate increases.

[0012] Thus, a person in a resting state, such as a hospitalised patient, has a very low sweat rate, and thus a significant delay between sweat excretion and biomarker detection, which can hamper timely monitoring and early warning of any impending complications. The concentration of specific relevant biomarkers is related to the sweat rate, and thus the sweat rate of each gland should be assessed for clinically relevant interpretation. The application of conventional sweat sensing solutions is limited, as they require the person being monitored to engage in exercise, and tend to use rather complex microfluidic technology and sensors to determine the sweat rate.

[0013] For example, WO 2018 / 125695 Al discloses a wearable sweat biosensing device with active sweat sampling. An active method for delivering sweat is described, which exploits the electro-mechanical effect of electrophoresis. The electrophoresis plate comprises a hydrophobic dielectric layer (e.g. Teflon) covering the electrodes. A sweat coupling “wicking” component made of a hydrophilic material allows sweat from the skin surface to slowly diffuse onto the electrophoresis plate over time, and then the sweat is delivered by the electro-mechanical effect. This solution is very time consuming, and can be ineffective for small amounts of sweat due to evaporation. Furthermore, the technology requires mixing sweat received from the skin at different times, which is undesirable for reliable semi-continuous biomarker measurements.

[0014] Determining a user’s sweat rate with sensors is known in the art. For example, US 2015 / 0112165 Al discloses a method of determining the sweat rate of each gland. The method involves using a number of sweat rate sensors to monitor the cumulative change in the dielectric value of a porous material in a respective sweat collection chamber. Sodium sensors monitor the sodium concentration of the sweat in the respective chambers. By using a correlation curve derived from a volunteer test, the sodium ion concentration is related to the total sweat flow rate. This solution has two main disadvantages: (i) it assumes the number of sweat glands per surface area during the volunteer test, and (ii) it assumes that the correlation of sodium ion concentration and sweat rate determined from the volunteer test is applicable to any particular person / patient. The considerable variation observed between individuals makes the latter assumption unwise, and illness can make this variation even greater.

[0015] Heikenfeld et al. in "Digital nanoliter to milliliter flow rate sensor with in vivo demonstration for continuous sweat rate measurement (Lab Chip, 2019, 19, 178) and Yang et al. in "Wearable microfluidics: fabric-based digital droplet flowmetry for perspiration analysis" (Lab on a Chip. Accepted 4 January 2017. DOI: 10.1039 / c6lc01522k)" disclose a sweat rate sensor that collects sweat within a chamber positioned adjacent to the skin. A sweat droplet grows from the outlet of the chamber until it is released from the outlet by contact and is transferred to a wick opposite the outlet. Immediately prior to release, the sweat droplet comes into contact with one of a pair of electrodes that are mounted on the wick. The other electrode is mounted within the chamber. The electrodes are thus short-circuited by the connection provided by the sweat within the chamber and the sweat droplet that is still attached to it. This short-circuiting of the electrodes enables the device to count the sweat droplets prior to their release into the wick. However, this design requires one sweat rate sensor per chamber. This disadvantageously complicates the device. Furthermore, this design can not be compatible with providing an alternating sweat droplet sensing principle. SUMMARY

[0016] The inventors of the present invention have surprisingly found that for certain sweat rate ranges the accuracy of the prior art sensors and methods is low. The inventors of the present invention have found that this can limit the accuracy of sweat measurements, which will be explained in detail below.

[0017] It is therefore an object of the present invention, inter alia, to provide an improved sweat sensor and a method of analyzing sweat of a user.

[0018] The objects of the present invention are solved by the subject matter of the independent claims. Further embodiments and advantages of the present invention are incorporated in the dependent claims. Moreover, it is pointed out that all embodiments of the present invention with respect to the method can be carried out in the order of the steps as described, but this is not necessarily the only and essential order of the steps of the method presented herein. The methods disclosed herein can be carried out with another order of the steps disclosed, without departing from the respective method embodiments, unless explicitly referred to the contrary in the following.

[0019] Technical terms are used in their common sense. If certain terms are expressed with a specific meaning, the definition of the term will be given in the following in the context of the use of the term.

[0020] According to a first aspect of the present application, a sweat sensor for analyzing sweat of a user, which is drawn from the skin of the user to the sweat sensor, is proposed. The sensor comprises one or more inlets through which sweat of the user can be drawn into the sensor. Further, the sensor comprises an analyzer, which can comprise one or more analysis units, configured to analyze the sweat drawn by the sensor through the one or more inlets. The sensor is configured to control the size of the opening of the one or more inlets by a) changing the cross-sectional area of the opening of the one or more inlets and / or b) selecting an inlet having a specific size, e.g. for the next analysis cycle of the sensor.

[0021] The sensor, in particular the analyzer, can use or comprise e.g. a processor or microcontroller for such a control and / or selection, which will be explained in more detail in the following. In some embodiments, the microcontroller of the sensor comprises a processor.

[0022] Thus, a sweat sensor is proposed, which comprises inlets of various sizes and / or one or more inlets having an adjustable size. The respective method for selecting such inlets of various sizes and / or the method for controlling, i.e. adjusting, the size of the opening of such inlets having an adjustable cross-sectional area or diameter of the opening will be explained in more detail later on. In other words, the sweat sensor of the present application is able to provide at least two sizes of inlets, which can be selected / activated, in the sense that only the sweat drawn by the selected inlet or inlets is used for the sweat analysis in the next analysis cycle, by providing one or more inlets having an adjustable size of the opening and / or by providing at least two different inlets having different, predetermined / fixed sizes.

[0023] Thus, the sweat sensor of the present application can react to a determination / measurement of e.g. the sweat rate or the number of sweat glands per inlet by adjusting the size of the opening of the inlets to be used in the next analysis cycle of the sensor. For example, if the sensor has determined that the sweat rate of the user is higher than a predetermined threshold, the sensor can reduce the size of the opening of the inlets to be used in the next measurement. This reduction in size can then be achieved by selecting the inlets of the smaller size by means of a respective control signal and / or by adjusting the size of the cross-sectional area or diameter of the opening of one or more inlets having an adjustable size.

[0024] The sweat sensor presented herein has particular advantages in converting the concentration of a biomolecule in sweat, such as lactate or any of the previously mentioned biomolecules, to the concentration in blood. Such sweat monitoring provides an optimized approach for unobtrusive monitoring of a user, such as a patient or a healthy person or animal. It is well known that the correlation between the sweat concentration and the blood concentration depends on the sweat rate of each gland, which can be determined by the sensor of the present invention. In order to determine the sweat rate of each gland, the sensor determines the number of active sweat glands. This number not only depends on the person and the body position, but can also vary over time. The inventors of the present invention have found that sweat sensors of the prior art, which measure the sweat rate of each gland, only make accurate measurements for a certain range of active sweat glands per inlet, i.e. surface area. Based on this insight, the present invention increases this range by using various sizes of inlets. Furthermore, sensors and methods are presented and described, which are configured to preferably use the sweat rate of the user to trigger a respective control signal to perform an adaptive selection or dynamic adjustment of the various sizes of these inlets, i.e. the dynamic range of active sweat glands per inlet / surface area. Due to the proper sizing of the opening of the inlet used by the sensor, the measurements of the sensor, such as the biomolecule concentration in the blood of the user, are more accurate than the prior art.

[0025] In a preferred embodiment, the sweat rate is determined by measuring the fluid flow of the extracted sweat, the galvanic skin response (GSR) and / or the osmotic pressure, which will be explained in detail later.

[0026] In a preferred embodiment, as previously mentioned, the sensor controls the size to a proper inlet size. Then, one or more analysis units utilize the correctly sized inlet opening to measure the sweat rate, determine the number of glands and determine the sweat rate of each gland. For example, one or more discretization methods can be used for such measurements / determinations, which will be described in more detail later. The one or more analysis units also measure / determine the biomolecule concentration in the extracted sweat of the user. The sensor is configured to estimate the biomolecule concentration in the blood of the user based on the determined sweat rate of each gland and based on the measured biomolecule concentration in the extracted sweat. Due to the proper sizing of the opening of the inlet used by the sensor, the overall measurements of the sensor, in particular the final estimation of the biomolecule concentration in the blood of the user, are more accurate compared to the prior art.

[0027] Accordingly, the sweat sensor is able to determine the size of the openings of the inlets, which the sensor uses in the next analysis cycle to draw sweat and analyze the drawn sweat. As will become apparent from the detailed description below, the sensor can have one or more inlets, which can change their opening size by, for example, a mechanically controlled membrane or an aperture based on a (mechanically) reactive material. Such an embodiment of an aperture based on a reactive material can use, for example, an electroactive polymer, a magneto-rheological elastomer, or a shape memory polymer or any other suitable stimulus reactive material. Additionally or alternatively, the sensor can also have multiple inlets, which differ in size, and the sensor can control / select which of the inlets of different sizes will be used by the sensor for its next analysis cycle based on the expected target size of the openings of the inlets. In this next analysis cycle, the sensor will only draw and analyze sweat from those inlets which the sensor has selected accordingly. In other words, the sweat sensor has inlets of various sizes and performs a method to select the size of the opening of one or more inlets to be used. The sensor can use, for example, a processor or microcontroller to perform such control / selection, which will be explained in more detail in the context of the embodiments of, for example, the sweat sensor disclosed in Figure 5 It should be noted that in the context of the present application, the method steps described can be performed by, for example, a processor and / or microcontroller of the sweat sensor disclosed herein. In a specific embodiment, the microcontroller described herein comprises a processor.

[0028] The sensor can be configured to perform the control (i.e. selection and / or adjustment) of the size of the openings of the inlets based on, for example, a sweat parameter determined / measured by the sensor in the previous analysis cycle of the sensor, which the sensor will use in the next analysis cycle. For example, the sensor can determine the sweat rate of the user in the first analysis cycle and, depending on the determined value of the sweat rate of the user, the sensor can control (i.e. select and / or adjust) the size of the openings of one or more inlets, which the sensor will use in the next analysis cycle to draw sweat and analyze the drawn sweat. However, in other embodiments of the present application, other sweat parameters can also be determined by the sweat sensor, which will be described in more detail below.

[0029] The inventors of the present invention have found that it can be disadvantageous when the inlets used by prior art sweat sensors and methods all have the same size and also have a fixed size. The inventors of the present invention have found that prior art sensors, wherein all inlets have the same fixed size, can have a limited accuracy of the measurement. This is for example the case when the sensor uses a discretization method, which will be explained in more detail below. In particular, if there are more than a certain number of active sweat glands per inlet, the measurement of the relevant sweat can lose accuracy. Based on this insight, the present invention provides a sweat sensor, which can control, i.e. select and / or adjust, the size of the opening of at least one inlet of the sensor, for example by changing the cross-sectional area or diameter of the inlet, e.g. based on a diaphragm mechanism or a radially varying aperture, and / or by actively selecting an inlet with a desired size from a plurality of inlets with different sizes. Non-limiting examples of sensors with inlets of different sizes can be known from e.g. Figure 1 and Figure 2 The embodiments of Figs. 3 and Figure 4 show different embodiments of a sweat sensor, which use inlets with openings whose cross-sectional area or diameter can be adjusted by the sensor by control as described before.

[0030] It should be noted that a sweat sensor can have only one inlet, the opening size of which is adjustable, just as described before for the specific embodiments shown in Figs. 3 and Figure 4 The sensor can also have at least two inlets of different sizes, which have openings of different sizes, and these two embodiments can of course be combined, and can also be extended to more inlets, which have adjustable cross-sectional area / diameter or which have a large number of inlets openings of different sizes, as can be known from e.g. Figure 2

[0031] With the sweat sensor of the present invention, sweat can be transported from the skin up into the sensor through e.g. a cylindrical channel, so that the inlets can have a circular shape, as exemplarily shown in Figure 2 However, the present invention does not exclude other shapes / geometry, e.g. square inlets or inlets with a triangular cross-section. From Figure 2 It can be known from

[0032] ​It should be noted that in the context of the present application, the term "analysis unit" should be understood broadly. It should include any device capable of analyzing the sweat drawn by the sensor by performing measurements on the sweat. In particular, the analysis unit can be configured for determining a sweat parameter, such as the sweat rate or the number of active sweat glands per portal, which will be described in more detail below. For example, the analysis unit of the present application can comprise a fluid flow sensor, or a GSR sensor, or an electrochemical sensor. Of course, devices and methods of the prior art can be used to implement such an analysis unit, which will be clear to the skilled reader.

[0033] Furthermore, it should be noted that the term "user" as disclosed herein should be understood to include humans and animals. Thus, the sweat sensor and the method of the present application cannot only be applied to humans, but also to animals. In particular, livestock monitoring is a valuable application of the present application.

[0034] It should be noted that in the context of the present application, the term "size of the opening of the portal" describes the cross-sectional area of the opening of the portal. Thus, it is the cross-sectional area of the opening of the portal projected onto the skin, which can be clearly seen from the embodiments described in, for example, Figure 1 , Fig. 3 and Figure 4 Thus, the skilled reader will understand this feature as the skin contact area of the portal. We will also refer to it as the area in the following instead of the cross-sectional area of the opening.

[0035] The sweat sensor can comprise not only one analysis unit, but also a plurality of analysis units. In a preferred embodiment, for each different portal of the sensor, a separate analysis unit is provided, which can be known from, for example, Figure 1 and Figure 5 .

[0036] It will become apparent to the skilled reader from the present disclosure that the sweat sensor is a wearable sensor, which can be carried by the user in his / her daily life, since several ways are presented herein to provide the wearer with an unobtrusive sensor.

[0037] Thus, in a preferred embodiment, the sweat sensor of the present application comprises a processor or microcontroller, which is configured to control the size of the opening of one or more portals by varying the cross-sectional area of the opening of the one or more portals and / or by selecting portals having a specific size, which are used by the sensor to draw sweat and to analyze the drawn sweat, as described before and will be described below. Thus, in this embodiment, the control is performed by the processor or microcontroller of the sweat sensor.

[0038] In a preferred embodiment, the sensor checks regularly (e.g. every second, every minute or every half hour) whether the size of the inlet is still appropriate or should be changed because the number of active sweat glands, the sweat gland density or the sweat rate has changed significantly. Instead of using fixed time intervals for this, a trigger event such as an increase / decrease in heart rate or skin conductivity can be used.

[0039] According to another embodiment, the sweat sensor, preferably by means of a processor or microcontroller, is configured to:

[0040] determine the number of active sweat glands per inlet from which sweat is sucked by the sensor,

[0041] compare the determined number of active sweat glands per inlet with a reference setting regarding the number of active sweat glands per inlet,

[0042] wherein the sweat sensor is configured to control the size by:

[0043] A) increasing the size of the opening of at least one inlet compared to the size of the opening of the one or more inlets used in the previous analysis period and / or selecting for the next analysis period one or more inlets having a larger opening when the determined number of active sweat glands per inlet is below a predetermined minimum number of active sweat glands per inlet defined in the reference setting, and / or

[0044] B) decreasing the size of the opening of at least one inlet compared to the size of the opening of the one or more inlets used in the previous analysis period and / or selecting for the next analysis period one or more inlets having a smaller opening when the determined number of active sweat glands per inlet is above a predetermined maximum number of active sweat glands per inlet defined in the reference setting.

[0045] Further details regarding this embodiment will be set out in the following.

[0046] According to an exemplary embodiment, the one or more analysis units are configured to determine a sweat parameter of the user by analyzing the sucked sweat. Furthermore, the sensor is configured to control the size of the opening of the one or more inlets based on the sweat parameter determined by the one or more analysis units, using which the sensor sucks sweat and analyzes the sucked sweat.

[0047] Examples of sweat parameters determined by the analysis unit are the sweat rate of the user and the number of active sweat glands per inlet / region. Different embodiments of how the parameters are determined will be described in detail in the following.

[0048] In case the sweat sensor provides a plurality of analysis units, it is noted that each analysis unit, e.g. each analysis unit provided for each inlet of the sensor, respectively, is configured to determine a sweat parameter, e.g. the sweat rate or the number of active sweat glands per respective inlet. It refers, as a non-limiting example, to the sensor shown in Fig. 1 1 1, which comprises analysis units 108, 109 and 1 10, wherein each analysis unit is configured to measure the sweat rate of the user based on the sweat sucked by the respective inlet. Figure 1

[0049] In the following, an example is provided, wherein one or more analysis units of the sensor are configured for determining the number of active sweat glands per inlet, and the sensor is configured for controlling and thus selecting the size of one or more inlets, which the sensor uses for sucking sweat and analyzing the sucked sweat in the next analysis cycle of the sensor. Three sizes of inlets are a very practical implementation of the embodiments presented herein. For example, the three sizes can be 0.005 cm 2 , 0.02 cm 2 and 0.1 cm 2 , when using circular inlets, which correspond to a radius of 0.4 mm, 0.8 mm and 2 mm, respectively.

[0050] As the skilled person understands, the most appropriate size of the opening of the inlet to be used by the sensor can be based on the determined number of active sweat glands per inlet determined by the sensor previously with the respective measurement finger. If the majority of the smallest inlets provide 0 active sweat glands per inlet (e.g. 0.09 active sweat glands per inlet on average for the smallest inlets), the majority of the intermediate inlets provide 1 or 2 active sweat glands per inlet (e.g. 1.5 active sweat glands per inlet on average for the intermediate inlets), and the largest inlets provide 10 or more active sweat glands per inlet (which is a number that cannot be trusted anymore as it is so large), then the sensor selects the intermediate inlets to have the most appropriate size, as the reference settings stored e.g. within the sensor define that measurements realized with more than 5 active sweat glands are not accurate enough. Thus, the sensor sends a respective control signal to select only the inlets of the intermediate size or to activate only the analysis units of the inlets of the intermediate size for the next analysis cycle, in which next analysis cycle the next measurement of the sucked sweat will only use the sweat from the selected / activated inlets. The next measurement, i.e. the measurement in the subsequent analysis cycle, can again determine the number of active sweat glands per inlet, but this measurement can also determine another parameter of the sucked sweat.

[0051] ​Thus, the sensor is configured to select the intermediate sized aperture for the next analysis cycle based on the determined sweat parameters of the active sweat glands of each aperture. This means that the sensor will only analyze the imbibed sweat that is imbibed by the aperture having that intermediate size. Thus, the sensor, or a processor that can be comprised by the sensor, does not process data from apertures having another size than the determined suitable size. Thus, for the next analysis cycle only the apertures having the most suitable size are used, and the sensor can control this accordingly by adjusting the size of the cross-sectional area or diameter of the opening of the sensor and / or by not generating analysis data from the imbibed sweat by the apertures having the unsuitable size, or by disregarding data that can be generated by the analysis unit corresponding to the apertures having the unsuitable size.

[0052] Since the area of the three different sized apertures is generally known here, the density of active sweat glands can also be calculated by the sweat sensor, if desired. This density will be defined as the number of active sweat glands divided by the area.

[0053] As will be explained in the context of another embodiment below, one or more analysis units are configured for measuring the concentration of biomolecules in the imbibed sweat of the user, and in the example described before the sensor will determine the concentration of biomolecules based on the sweat only from the apertures having the appropriate intermediate size.

[0054] Another exemplary method of determining the most suitable size of the aperture to determine the number of active sweat glands is by using the measured sweat rate, since the sweat rate is related to the number of active sweat glands. For example, when the sweat rate is below 5 nl / min / cm 2 then the largest aperture is used; when the sweat rate is between 5 and 100 nl / min / cm 2 then the intermediate aperture is used; and when the sweat rate is above 100 nl / min / cm 3 then the smallest aperture is used. Thus, in this example the sweat sensor can determine the sweat rate by the provided analysis unit and control the opening size of the aperture used for imbibing the sweat and analyzing the imbibed sweat in the next analysis cycle accordingly.

[0055] In another example, the varying size of the aperture over time can be used as follows. Instead of having apertures of fixed size, apertures can be used that adjust their size in order to obtain the appropriate size for the determined number of active sweat glands of each aperture or the determined density of currently active sweat glands. Similar as explained before, the appropriate size can be based on the number of active sweat glands determined by the sensor in the previous analysis cycle. For example, when the measured number of active sweat glands per aperture exceeds 10, the size can be reduced. Alternatively, the sweat rate can be determined and the size of one or more apertures having an adjustable opening size can be reduced.

[0056] According to another exemplary embodiment of the present application, the sweat sensor comprises a plurality of inlets, wherein at least some of the plurality of inlets differ in their opening size / cross-sectional area projected onto the skin. The sensor is configured to select inlets having a specific size, which the sensor uses for the uptake of sweat and the analysis of the uptaken sweat.

[0057] It should be noted that the configuration of the sensor for selecting inlets having a specific size should imply that only the sweat uptaken by such selected inlets is used for processing in the next analysis cycle, such that the analysis unit analyzing the sweat uptaken by such selected inlets is activated. In case all analysis units are activated (e.g. as a standard procedure), the processor of the sensor only processes and considers data from the analysis unit of such selected inlets.

[0058] Exemplary embodiments of such selection of inlets having a specific size will be described in more detail below, e.g. in the context of the embodiments shown in Figure 1 , Figure 2 and Figure 5 .

[0059] According to another exemplary embodiment of the present application, the sweat sensor comprises a processor configured to compare the determined sweat parameter of the user with a reference setting of the sweat parameter. The processor is configured to determine a target size / area of the inlet opening, preferably based on the result of the comparison. The sensor is configured to only consider sweat uptaken by inlets having an opening size of the determined target size / area.

[0060] As the skilled reader will understand, the processor can also be configured for determining a range of target sizes, and can only consider sweat uptaken by inlets falling within the range of target sizes / areas.

[0061] As described before with non-limiting examples, the threshold value or reference setting can be stored within the sensor, and the sweat sensor can use it to compare the current measurement of the determined sweat parameter, and can accordingly adjust the size of the opening of the inlet or inlets used for the uptake of sweat and the analysis of the uptaken sweat in the next analysis cycle.

[0062] The inventors of the present invention have found that the accuracy of a sweat sensor can be improved if the size of the opening of the inlet (through which the sensor sucks the sweat that is subsequently analyzed) is controlled according to the current measurement of a sweat parameter (e.g. sweat rate or number of active sweat glands). In particular, the inventors have found that if the sweat sensor ensures a minimum number of active sweat glands per inlet, but even more importantly, that there are not too many active sweat glands per inlet for the sweat measurement, then the accuracy of the prior art sweat sensor can be improved. This embodiment is one way of ensuring that the proper size of the inlet is utilized by the sensor to correctly measure the sweat parameter.

[0063] According to another exemplary embodiment of the present invention, the sweat sensor has at least one inlet with an opening whose cross-sectional area is adjustable by the sensor.

[0064] As will be clear to the skilled reader, there are at least one inlet with an opening that is adjustable over its cross-sectional area projected onto the skin surface. In a preferred embodiment, the sweat sensor has at least one inlet with an opening whose diameter is adjustable by the sensor.

[0065] The variable size of the inlet opening can be realized, for example, using the same technology as the diaphragm, for example the well-known mechanical diaphragm, as described in the embodiments of Figure 4 Another alternative is more recent technology, for example the use of a hole diameter based on a soft super-elastic composite hydrogel in the shape of a donut, which is sensitive to heating or cooling, as described in Seo Gyun Kim et al. "Human-Iris-Like Aperture and Sphincter Muscle Comprising Hyperelastic composite Hydrogels Containing Graphene Oxide" (Macromol. Mater. Eng. 2019, 304, 1800560).

[0066] Figure 4 The diaphragm of always gives a very smooth circular hole. However, in alternative applications as shown in the embodiment of Fig. 3, also simpler forms are allowed, for example a square element that can be activated mechanically and / or electrically to provide a larger or smaller inlet opening depending on the determined sweat parameter value and the threshold or reference setting stored in the sensor.

[0067] Of course, other materials and mechanisms can also be used to provide an inlet with an opening whose cross-sectional area / diameter is adjustable by the sensor.

[0068] According to another exemplary embodiment of the present application, the sweat sensor comprises a processor configured to compare the determined sweat parameter of the user with a reference setting of the sweat parameter. The processor is configured for determining a target size / area of the inlet opening. Furthermore, the sensor is configured to adjust the cross-sectional area of the at least one inlet having an adjustable opening diameter based on or in accordance with the determined target size / area.

[0069] The sweat parameter determined by the one or more analysis units of the sensor is preferably the sweat rate of the user or the number of active glands per inlet. Based on the currently measured and thus determined value of this sweat parameter, the processor compares it with a reference setting and determines which size of inlet opening is appropriate for use for the next analysis cycle. Thus, the sensor is configured for controlling the cross-sectional area (e.g. diameter) of the at least one inlet having an adjustable opening cross-sectional area / diameter to the determined target size. It is possible that the target size / area is defined as a range of target sizes / areas and the sensor can accordingly control the adjustment of the cross-sectional area / diameter of the one or more size-adjustable openings.

[0070] According to another exemplary embodiment of the present application, the determined sweat parameter of the user determined by the one or more analysis units is at least one of the sweat rate of the user and the number of active sweat glands per inlet and / or per region.

[0071] The measurement and determination of the sweat rate of the user can be done in various different ways. For example, the sweat rate can be determined with advanced flow sensors, e.g. based on temperature differences. More details on such determination of the sweat rate of the user will be provided in more detail below. However, the sweat rate can also be determined by counting the number of droplets having a certain size. This is the method used, for example, in the sweat sensor of Eccrine Systems / University of Cincinnati, called “Digital Volumetric Dispensing System”, as proposed and described in patent application WO 2019 / 183529 A1.

[0072] Furthermore, the determination of the sweat rate can use a measurement of the osmotic pressure. In principle, the body of the user does not want to get rid of all ions, so when the sweat is transported from the sweat gland via the sweat duct to the skin surface, it tries to reabsorb in the sweat duct. However, if the sweat rate is high, this reabsorption does not occur completely. The ions are only reabsorbed to a small extent. Thus, the concentration of certain ions (in particular Na + and Cl - ) in the sweat is high in the case of a high sweat rate and low in the case of a low sweat rate. Thus, this concentration, i.e. the osmotic pressure, can be measured as a replacement for the sweat rate measurement. In this sense, it is a proxy measurement of the sweat and can be used in an exemplary embodiment of the present application.

[0073] Similarly, also the pH value can be used. Another alternative, proxy measurement for the sweat rate is the galvanic skin response (GSR), as described before and below. Thus, determining the sweat rate of the user can be a direct sweat rate measurement, e.g. by using a flow sensor, as described before and below. Alternatively or additionally, also such alternative measurements by this embodiment of the application can include the measurement of the concentration of certain ions, in particular Na + and Cl - ). More details on the physiological background can be found in the scientific article "The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications" by Z. Sonner et al., published in Biomicrofluidics 9, 031301.

[0074] According to an exemplary embodiment of the present application, the sweat sensor comprises a processor configured to compare a first value of a sweat parameter determined in a first analysis cycle of the sensor with a second value of the sweat parameter determined in a second analysis cycle of the sensor, the second analysis cycle following the first analysis cycle. Further, the sensor is configured to reduce the size / cross-sectional area of the opening of one or more inlets, which the sensor uses to draw sweat and analyze the drawn sweat in the next analysis cycle, if the second value exceeds the first value.

[0075] In one example thereof, the sweat parameter is e.g. the sweat rate of the user, and if the sweat sensor determines that the sweat rate of the user has increased to exceed a certain threshold value, the sensor reduces the size / area of the opening of one or more inlets, which the sensor uses to draw and analyze or to generate a corresponding control signal to select an appropriate inlet having a fixed opening size. In other words, the sensor can adjust one or more inlets, which each have an opening in their respective cross-sectional area (e.g. diameter) that can be adjusted by the sensor, and / or the sensor selects an inlet having a smaller size / area. This is also true for the number of active sweat glands for each inlet determined by the analysis unit(s), as described before. In this way, the sweat sensor ensures that no excessive number of active sweat glands for each inlet is used in the next analysis cycle of the processor. As described before, this improves the measurement accuracy of the sweat sensor.

[0076] According to a further exemplary embodiment of the present application, the one or more analysis units are configured to determine a sweat rate of each gland of the user, and the analysis units are configured to measure a concentration of the biomolecule in the drawn sweat of the user. The sensor is further configured to estimate the concentration of the biomolecule in the blood of the user based on the determined sweat rate of each gland and based on the measured concentration of the biomolecule in the drawn sweat.

[0077] The concentration of a biomolecule in sweat, e.g. lactate, can be converted to the concentration in blood, thus, sweat monitoring provides an ideal, unobtrusive way of monitoring a patient. A problem impeding this conversion is that the correlation between sweat concentration and blood concentration depends on the sweat rate of each gland. In order to determine the sweat rate of each gland, the number of active sweat glands needs to be determined. This number not only depends on the person and the body location, but can also vary over time. Prior art sweat sensors that measure the sweat rate of each gland can only do this within a certain range of active sweat glands per surface area. However, the sweat sensor of the present application increases this range by using various sizes of inlets. Thus, an improved estimation or determination of the biomolecule concentration in the blood of the user is proposed.

[0078] According to a further exemplary embodiment of the present application, the sweat sensor comprises a plurality of inlets having respective openings of a size that can be adjusted by the sensor. The sensor is configured to determine a sweat rate of the user and / or a number of active sweat glands of the user from the drawn sweat. The sensor is further configured to adjust all of the plurality of inlets to the same opening size based on the determined sweat rate and / or based on the determined number of active sweat glands.

[0079] According to an exemplary embodiment of the present application, a flow sensor is proposed that is arranged within or around a channel, e.g. a fluid channel, of the sensor, wherein the channel connects the at least one inlet with the analysis unit. The flow sensor is configured to measure the sweat rate of the sweat.

[0080] It should be noted that the term "sweat rate" is synonymous to the term "discharge rate" in this context, and "sweat" or "drawn sweat" is to be understood as "discharged sweat".

[0081] According to a preferred embodiment, one or more of the plurality of sample areas in which an inlet is arranged can comprise a channel connected to a cavity. The sensor can be a flow sensor arranged in the channel and can measure the discharge rate of the sweat discharged at the sample area. The channel and the sample area can be arranged such that the sweat discharged at the sample area at least partially fills the cavity, flows into the channel and along the channel and interacts with the flow sensor.

[0082] Accordingly, the channel can effectively provide an outlet for the cavity, such that sweat collected in the cavity can flow out of the cavity through the channel. A sensor can be disposed in the channel. The channel can be centrally disposed at the top of the cavity, i.e. the top surface of the cavity facing the skin surface. The channel can comprise a cylindrical channel attached to the main cavity and a rectangular channel attached to the cylindrical channel. One or more biomolecule concentration sensors can be disposed in the channel.

[0083] The flow sensor can comprise an upstream temperature sensor; a downstream temperature sensor; and a pulsed heating element. The discharge rate can be measured by calculating a difference between a temperature measured by the upstream temperature sensor and a temperature measured by the downstream temperature sensor relative to the pulsed heating element to derive a flow rate measurement; and integrating the flow rate measurement as a function of time to obtain the discharge rate. The pulsed heating element can be disposed between the upstream temperature sensor and the downstream temperature sensor. The sensor can be pre-calibrated in a factory test using different fluids.

[0084] According to another aspect of the present invention, a method of analyzing sweat of a user drawn by a sensor from the skin of the user is presented. The method comprises the steps of drawing sweat from the skin of the user through one or more inlets of the sensor and analyzing at least some of the drawn sweat by an analysis unit of the sensor. Further, the method comprises the step of controlling a size of an opening of the one or more inlets based on the analysis result of the drawn sweat, which the sensor uses for drawing sweat and analyzing the drawn sweat in a subsequent analysis cycle of the sensor. The control of the size is done by increasing or decreasing the size of the adjustable opening of at least one inlet compared to the size of the opening of the inlet used in the previous analysis cycle and / or by selecting one or more inlets with a larger opening or with a smaller opening for the next analysis cycle.

[0085] As explained in detail before, the control of the size is to be understood as adjusting the cross-sectional area of the opening of the one or more respective inlets.

[0086] The sensor, which can be used to perform this method, can have fixed size inlets with different opening sizes / cross-sectional areas of the openings, can have time-varying and adjustable inlet sizes / areas, and also a combination of both can be used, as explained in detail before. In other words, this control encompasses both embodiments described herein, i.e. the use of fixed size inlets which are selectively chosen by the sensor for the next analysis cycle to draw and analyze sweat, as explained for example in the case of the embodiments shown in Figure 1 、 Figure 2 and Figure 5 . However, this control also applies to another embodiment, in which a time-varying inlet area size is used, for example by using a time-varying inlet area size as shown in Fig. 3 andFigure 4 the entrance of the opening.

[0087] The inventors of the present invention have found in their research that if the size / area of the entrance is adjusted based on the currently measured sweat parameters of the user, the accuracy of the measurement and analysis of the user's sweat can be improved. Specifically, with the method of the present invention, it can be ensured, for example, that too few active sweat glands per entrance are not used for the measurement and too many active sweat glands per entrance are not used for the measurement in case of a measurement with such a sweat sensor. In other words, the method presented herein can ensure that the optimal size / area of the opening of the entrance or entrances used for the absorption of sweat and the subsequent analysis of the sweat is achieved.

[0088] As mentioned before, in a preferred embodiment, the step of controlling the size of the opening of the entrance or entrances by changing the cross-sectional area of the opening of the entrance or entrances and / or by selecting an entrance with a specific size is performed by a processor or microcontroller of the sensor, wherein the sensor uses the entrance or entrances for the absorption of sweat and the analysis of the absorbed sweat.

[0089] In the following, a processing method for a fixed size of the entrance area will be explained.

[0090] There are various options for the processor to process the data. The following are the most obvious methods.

[0091] A. The processor uses only the information from the entrance with the most suitable size / area to determine the number of active sweat glands / density of sweat glands.

[0092] B. The processor uses the information from all entrances to count the number of active sweat glands in the probed area.

[0093] C. The processor uses method A for cases where the number of active sweat glands is large and method B for cases where the number of active sweat glands is small.

[0094] Case A - only the entrance with the most suitable size / area.

[0095] Determining the most appropriate size / area can be based on how many active sweat glands are measured at each particular size of the portal. For example, there are three sizes of portals, and most of the smallest portals provide 0 active sweat glands (e.g., for the smallest portals, on average 0.09 active sweat glands per portal), most of the intermediate portals provide 1 or 2 active sweat glands per portal (e.g., for the intermediate portals, on average 1.5 active sweat glands per portal), and the largest portals provide 10 or more active sweat glands (which is a number that is no longer trusted because it is so large), then the conclusion is that the intermediate portals have the most appropriate size / area. In case A, then only these portals will be used to determine the number of active sweat glands. Since the area of the intermediate size portals is known, the density of active sweat glands (i.e., density = number / area) can also be determined if desired. There is still the choice of determining the concentration of the biomarker from only the sweat from the intermediate size portals or from all of the sweat from the system (i.e., from all of the portals). Another method for determining the most appropriate size of the portals to determine the number of active sweat glands is by using the measured sweat rate, since the sweat rate is correlated to the number of active sweat glands. For example, when the sweat rate is below 5 nl / min / cm 2 , then the largest portals are used, when the sweat rate is between 5 and 100 nl / min / cm 2 , then the intermediate portals are used, and when the sweat rate is above 100 nl / min / cm 2 , then the smallest portals are used.

[0096] Case B - All portals

[0097] Using all of the portals to determine the number of active sweat glands is feasible when the density of active sweat glands is low. However, as the density of active sweat glands increases, it becomes less accurate because then the larger portals will be delivered by many active sweat glands. To address this issue, there is option C.

[0098] Case C - Use method A for high sweat rates and method B for low sweat rates

[0099] This case is to address the issue mentioned under case B. Determining which method (A or B) to use can be based on the sweat rate or the determined number of active sweat glands (similar to the explanation in case A).

[0100] Intermediate case - use several, but not all sizes of portals

[0101] One example of an intermediate case is when the smallest and intermediate sized entrances are used to determine the number of active sweat glands, while the largest sized entrance is not used for this purpose. (Note: The largest entrance can still be used to determine the concentration of biomarkers, or can even not be used for this, and thus be completely ignored).

[0102] In the following, adjustment and processing methods for varying entrance sizes over time will be explained.

[0103] Instead of having entrances with fixed sizes, entrances can be used whose size is adjusted in order to obtain a suitable size for the current active sweat gland density. Similar to the explanation of case A in the previous section, the suitable size / area can be based on the currently measured number of active sweat glands (e.g. the size should be decreased when the number of active sweat glands measured at each entrance exceeds 10) or the sweat rate (e.g. for < 5 nl / min / cm 2 , the size is increased to a larger cross-sectional area of the entrance opening).

[0104] The size of the entrances can be adjusted individually (i.e. each entrance can take its own optimal size based on the number of active sweat glands or the sweat rate determined for that particular entrance). However, since we expect the most direct application to be a wearable sensor, which is small and thus only covers a small area of the skin (most likely around 1 cm 2 ), we expect that the density of active sweat glands over this area does not vary greatly, so it would be appropriate to adjust all entrances to the same size.

[0105] It can be checked periodically (e.g. every second, every minute or every half hour) whether the size of the entrances is still appropriate, or should be changed because the density of active sweat glands has changed greatly. Instead of using a fixed time lapse for this, a triggering event like an increase / decrease in heart rate or skin conductivity can be used.

[0106] Since at every point in time, all entrances will have a size that is appropriate for the density of active sweat glands, the sweat collected from all entrances can be used for further analysis, e.g. of the concentration of biomarkers.

[0107] In particular, the method can be used to determine the number of active sweat glands with one or more analysis units of the sensor and after the sensor has adjusted the opening size / area of the entrance used for this based on a first analysis cycle of the sensor. Thus, in the first analysis cycle, the sweat parameters of the user can be determined and the size of the opening of one or more entrances is controlled accordingly, and then another analysis cycle determines the sweat parameters and / or biomolecule concentrations in a second analysis cycle.

[0108] According to another exemplary embodiment of the present application, the method comprises the step of determining the number of active sweat glands per portal from which sweat is picked up by the sensor. Furthermore, the determined number of active sweat glands is compared to a reference setting of this parameter regarding the number of active sweat glands. When the determined number of active sweat glands is lower than a predetermined minimum number of active sweat glands defined in the reference setting, the method comprises the step of increasing the size of the opening of the at least one portal compared to the size of the opening of the one or more portals used in the previous analysis period and / or selecting one or more portals with a larger opening for the next analysis period. In other words, when it is determined in the method that there is an excessively low number of active sweat glands, the method ensures that the size of the opening of the portals used is increased in the next analysis period.

[0109] Furthermore, when the determined number of active sweat glands per portal is higher than a predetermined maximum number of active sweat glands defined in the reference setting, the method comprises the step of decreasing the size / area of the opening of the at least one portal compared to the size of the opening of the one or more portals used in the previous analysis period and / or selecting one or more portals with a smaller opening for the next analysis period.

[0110] In other words, in the case where it is detected with the method that the currently measured number of active sweat glands is higher than a predetermined maximum threshold, then the size of the opening of the portals used is decreased.

[0111] According to another exemplary embodiment of the present application, the method comprises the step of determining the sweat rate of the user and using the determined sweat rate to determine the number of active sweat glands per portal from which sweat is picked up by the sensor.

[0112] In other words, in this embodiment, the skilled reader is taught that the size / area of the portal should be large when the number of active sweat glands is low and small when the number of active sweat glands is high. Furthermore, the size / area of the portal should be small when the sweat rate is high and large when the sweat rate is low. Furthermore, the sweat rate can be used to obtain a rough estimate of the number of active sweat glands. This can also be understood as targeting a certain number, in particular a maximum number, of active sweat glands per portal.

[0113] According to another aspect of the application, a program element for analyzing sweat of a user is presented, the sweat being drawn by a sensor from the skin of the user. The program element, when executed by a processor, is adapted to analyze at least some of the drawn sweat by an analysis unit of the sensor, to control a size of an opening of one or more inlets of the sweat sensor based on a result of the analysis of the drawn sweat, the sensor using the one or more inlets to draw the sweat and to analyze the drawn sweat in a subsequent analysis cycle, and wherein the control of the size is performed by increasing or decreasing the size of the adjustable opening of the at least one inlet compared to the size of the opening of the inlet used in a previous analysis cycle and / or by selecting one or more inlets with a larger opening or with a smaller opening for the next analysis cycle.

[0114] The program element can be part of a computer program, but it can also be the entire program itself. For example, the program element can be used to update an already existing computer program to achieve the present application.

[0115] The program element can be stored on a computer readable medium, such as a storage medium, e.g. a USB stick, a CD, a DVD, a data storage device, a hard disk or any other medium on which the above program element can be stored.

[0116] Different embodiments of the sweat sensor and related methods of the present application are described in the following, which have been mentioned before and will be referred to as "discretization sensor / method" in the following. It is to be understood that the respective sensor is configured to perform such a method. These discretization methods are examples of methods and sensors for determining the number of active glands per inlet or area and / or for determining the sweat rate or the sweat rate per gland, as described herein. As will be clear to the skilled reader, other methods / sensors can also be used to determine these parameters. These sensors and methods can be combined with the idea of the present application to provide sweat sensors with inlets of various sizes and / or with size adjustable inlets and methods for their selection and / or adjustment.

[0117] The first discretization method classifies different inlets / sample areas, the sensor drawing discrete sweat volume levels x, 2x, 3x, 4x, etc. out of the volume of sweat, wherein x is the assumed volume of sweat being excreted by a single gland, i.e. the basal excretion rate. The sample area is to be understood as the area from which sweat is drawn from the skin and is defined by the inlet.

[0118] When using this discretization approach, the sweat sensor of the present embodiment is configured to determine a sweat excretion rate of each sweat gland of a user, and the sensor comprises a fluidic structure configured to be brought into contact with the skin of the user to collect sweat excreted from sweat glands at the skin surface of the user, the fluidic structure comprising a plurality of sample areas, each sample area comprising a cavity configured to collect the excreted sweat, and two or more of the plurality of sample areas comprising an analysis unit configured to acquire sensor data relating to an excretion rate of the sweat excreted at the sample area. A processor is also provided, the processor being configured to receive sensor data from two or more sensors of the fluidic structure, determine from the received sensor data a number of sweat glands at each sample area and a total sweat excretion rate of the sample areas; determine from the number of sweat glands at each sample area a total number of sweat glands; and determine a sweat excretion rate of each sweat gland using the total sweat excretion rate and the total number of sweat glands.

[0119] According to an embodiment, the number of sweat glands at each sample area is determined by determining from the received sensor data a zero excretion rate corresponding to zero sweat glands at the sample area, such that sensor data below a predetermined threshold is classified as the zero excretion rate; determining from the received sensor data a base excretion rate corresponding to one sweat gland at the sample area, such that multiples of the base excretion rate correspond to multiples of one sweat gland; and classifying the sensor data from each sample area according to the zero excretion rate, the base excretion rate, and multiples of the base excretion rate to determine the number of glands at each sample area.

[0120] According to an embodiment, the processor is configured to determine the total sweat excretion rate of the sample areas by summing the sensor data from all sample areas except those classified as the zero excretion rate; determine the total number of sweat glands by summing the determined number of glands at each sample area; and determine the sweat excretion rate of each sweat gland by dividing the total sweat excretion rate by the total number of sweat glands.

[0121] According to an embodiment, one or more of the plurality of cavities are isolated into a plurality of conical structures; and a center of each conical structure is in contact with the skin when the skin is in a first position, and the center of each conical structure is not in contact with the skin when the skin is in a second position, such that the excreted sweat flows between the conical structures.

[0122] According to an embodiment, the sweat sensor comprises a concentration sensor configured to determine a concentration of a compound in the excreted sweat.

[0123] According to an embodiment, the sweat sensor comprises three or more sample areas arranged in a triangular pattern, wherein the processor is configured to determine from the received sensor data a rate of excretion of each of the three sample areas at a first point in time; determine from the received sensor data a rate of excretion of each of the three sample areas at a second point in time occurring after the first point in time; calculate a first point in time ratio indicative of a ratio of the rates of excretion at the three sample areas at the first point in time; calculate a second point in time ratio indicative of a ratio of the rates of excretion at the three sample areas at the second point in time; calculate a difference between the first point in time ratio and the second point in time ratio; and determine a degradation of the fluidic structure in response to the difference between the first point in time ratio and the second point in time ratio exceeding a predetermined threshold.

[0124] According to an embodiment, the sweat sensor comprises a supplemental fluidic structure configured to be in contact with the skin of the user to collect sweat excreted from sweat glands at the skin surface of the user, the supplemental fluidic structure comprising a supplemental sample area comprising: a supplemental cavity configured to collect the excreted sweat; a supplemental channel connected to the supplemental cavity; and a concentration sensor disposed in the supplemental channel and configured to determine a concentration of a compound in the excreted sweat, wherein the supplemental sample area is arranged such that the excreted sweat at the supplemental sample area at least partially fills the supplemental cavity, flows into the supplemental channel and along the supplemental channel and interacts with the concentration sensor; and a size of the supplemental cavity of the supplemental fluidic structure is at least one hundred times larger than one of the cavities of the fluidic structure.

[0125] According to an embodiment, one or more of the plurality of sample areas further comprises a channel connected to the cavity; the sensor is a flow sensor disposed in the channel and configured to measure a rate of excretion of the sweat excreted at the sample area; and

[0126] the channel and the sample area are arranged such that the excreted sweat at the sample area at least partially fills the cavity, flows into the channel and along the channel and interacts with the flow sensor.

[0127] According to an embodiment, the flow sensor comprises an upstream temperature sensor; a downstream temperature sensor; and a pulsed heating element, wherein the rate of excretion is measured by: calculating a difference between a temperature measured by the upstream temperature sensor relative to the pulsed heating element and a temperature measured by the downstream temperature sensor to arrive at a flow rate measurement; and integrating the flow rate measurement as a function of time to obtain the rate of excretion.

[0128] According to an embodiment, the fluidic structure of the sweat sensor comprises a main intersection and an outlet channel connected to the main intersection and configured to remove the excreted sweat from the fluidic structure; and one or more of the plurality of channels is connected to the main intersection such that the excreted sweat flows through the channel, into the main intersection and then into the outlet channel.

[0129] According to an embodiment, the sweat sensor comprises a fluid leveler disposed in one or more of the plurality of cavities and composed of a hydrophilic material, wherein the fluid leveler is configured to direct the expelled sweat to the channel.

[0130] According to an embodiment, the sweat sensor comprises a bubble eliminator configured to eliminate bubbles formed in the expelled sweat, the bubble eliminator comprising: a first portion comprising a plurality of hydrophilic protrusions arranged in sequence to define a plurality of channels between the hydrophilic protrusions; and a second portion comprising a hydrophobic material and a vent, wherein the first portion is disposed opposite the second portion; and the bubble eliminator is disposed in one or more of: the channel and the outlet channel.

[0131] According to an embodiment, the sweat sensor comprises wherein the plurality of sample regions are arranged adjacent to each other such that expelled sweat collected in a first cavity can overflow into an adjacent cavity; the sensor is a colorimetric sensor disposed within one of the plurality of cavities and configured to activate a color change of a sample region in response to interaction with the expelled sweat; the sensor data is data indicative of the coloration of the sample regions; and the processor is configured to determine the number of sweat glands by determining a zero expulsion rate from the received sensor data, which corresponds to a zero sweat gland at a sample region without coloration; determining a base expulsion rate from the received sensor data, which corresponds to one sweat gland at a sample region with coloration at a single sample region; determining a multiple of the base expulsion rate from the received sensor data, which corresponds to a multiple of one sweat gland at a sample region with coloration at a plurality of adjacent sample regions; and classifying the sensor data from each sample region according to the zero expulsion rate, the base expulsion rate, and the multiple of the base expulsion rate to determine the number of glands at each sample region.

[0132] According to an embodiment, the processor is configured to determine a sweat expulsion rate at each sample region except for the sample region classified as the zero expulsion rate by dividing the volume of the cavity by the time taken for coloration to occur at the sample region; determine a total sweat gland expulsion rate for the sample regions by summing the determined sweat expulsion rates at all sample regions except for the sample region classified as the zero expulsion rate; determine a total number of sweat glands by summing the determined number of sweat glands at each sample region; and determine a sweat expulsion rate per sweat gland by dividing the total sweat gland expulsion rate by the total number of sweat glands.

[0133] The above sensor embodiments relate to a first discretization method, which is now described as a method embodiment.

[0134] According to an embodiment, a method for determining sweat excretion rate of each sweat gland of a user is presented, the method comprising: collecting, by a fluidic structure, sweat excreted from sweat glands at a skin surface of the user by collecting the excreted sweat within cavities at a plurality of sample regions of the fluidic structure, each sample region comprising a cavity; obtaining, as sensor data from two or more sensors at one or more of the plurality of sample regions, an excretion rate of the excreted sweat measured at the sample region; receiving, by a processor, the sensor data from the two or more sensors of the fluidic structure; determining, from the received sensor data, a number of sweat glands at each sample region and a total sweat excretion rate of the sample region; determining, from the number of sweat glands at each sample region, a total number of sweat glands; and determining, using the total sweat excretion rate and the total number of sweat glands, a sweat excretion rate of each sweat gland.

[0135] In a preferred embodiment, the sensor data is an excretion rate / sweating rate measured at the inlet / sample region; and the number of sweat glands at each sample region is determined by: determining, from the received sensor data, a zero excretion rate corresponding to zero sweat glands at the sample region, such that sensor data below a predetermined threshold is classified as the zero excretion rate; determining, from the received sensor data, a base excretion rate corresponding to one sweat gland at the sample region, such that multiples of the base excretion rate correspond to multiples of one sweat gland; and classifying the sensor data from each sample region according to the zero excretion rate, the base excretion rate, and the multiples of the base excretion rate to determine the number of glands at each sample region.

[0136] This first discretization method and the corresponding sensor embodiment of the present invention has been used Figure 10 in the embodiment shown.

[0137] A second discretization method and corresponding sensor configuration will be described below. The essence of the second discretization method is that, inside the sensor, the number of active sweat glands can be determined, as described below. It takes advantage of the fact that each eccrine sweat gland produces its sweat in bursts; it produces sweat for a relatively short period, and then does not produce sweat for a longer period (e.g., 30 seconds of sweat production, 90 seconds of no sweat production).

[0138] According to an embodiment of the present application, therefore, a sweat sensor, in particular one or more analysis units, are configured to sense sweat droplets. Furthermore, the sweat sensor is configured to receive sweat from one or more sweat glands and to transport the sweat as discrete sweat droplets to the one or more analysis units. Furthermore, a processor is included which is configured to record sweat droplets sensed by the one or more analysis units over a time period. The processor is further configured to determine time intervals between consecutively sensed sweat droplets over the time period; and to use the time intervals to identify at least one active period of each of the one or more sweat glands during which the respective sweat gland excretes sweat, and to identify at least one rest period of each of the one or more sweat glands during which the respective sweat gland does not excrete sweat, the active and rest periods being assigned to the one or more sweat glands.

[0139] In a preferred embodiment, the processor is further configured to determine a number of sweat glands to which active and rest periods are assigned.

[0140] In another embodiment, the processor is further configured to receive a measure of a volume of each recorded sweat droplet; and to determine a sweat rate of each sweat gland from the number of recorded sweat droplets, the measure of the volume of each recorded sweat droplet, and the determined number of sweat glands; optionally, wherein the processor is configured to identify the at least one active period and the at least one rest period based on the measure of the volume of each recorded sweat droplet and the time intervals.

[0141] In another embodiment, the one or more analysis units / sensors are configured to sense an indicator of a volume of a sweat droplet, and the processor is configured to receive the sensed indicator.

[0142] In another embodiment, the processor is configured to fit data received from the sensor to a first template model, the data comprising at least the time intervals, and a measure of a volume of each recorded sweat droplet, thereby identifying the active and rest periods of each of the one or more sweat glands.

[0143] In another embodiment, the fitting to the first template model additionally uses: a number of sweat droplets within the at least one active period, a duration of the at least one active period, and / or a duration of the at least one rest period.

[0144] In another embodiment, wherein the processor is configured to assess a degree of fit of the data to the first template model, and, optionally, based on the degree of fit, to fit at least a portion of the data to a further first template model.

[0145] In another embodiment, the processor is configured to, after fitting the data to the first template model, fit at least a portion of the data to a second template model, wherein the first template model is based on at least some of sweat droplets obtained from a sweat sample composed of sweat excreted by a single sweat gland, and the second template model is based on at least some of sweat droplets obtained from another sweat sample composed of sweat excreted by two or more sweat glands.

[0146] In another embodiment, the sensor is arranged to deliver a sweat droplet having a predetermined volume to the one or more analysis units.

[0147] In another embodiment, the sensor comprises a sensing device for detecting a parameter related to a concentration of an analyte, the concentration of the analyte varying as a function of the rate of sweating, wherein the processor is configured to use the parameter in allocating the active periods and the rest periods to the one or more sweat glands.

[0148] In another embodiment, the sensing device is an electrical conductivity sensor, and the parameter is electrical conductivity.

[0149] In another embodiment, the sensor comprises a biomarker sensor; optionally, wherein the processor is configured to receive a plurality of biomarker concentrations from the biomarker sensor over at least one active period of a respective sweat gland and determine a change in the biomarker concentration over time during the at least one active period.

[0150] The above sensor embodiments relate to a second discretization method, which will now be described as a method embodiment.

[0151] The method comprises the steps of: receiving sweat from one or more sweat glands; delivering the sweat as discrete sweat droplets to an analysis unit; sensing the sweat droplets using a sensor over a period of time; recording the sensed sweat droplets over the period of time; determining time intervals between consecutively sensed sweat droplets over the period of time; and using the time intervals, identifying at least one active period of each of the one or more sweat glands during which the respective sweat gland excretes sweat, and identifying at least one rest period of each of the one or more sweat glands during which the respective sweat gland does not excrete sweat, the active periods and the rest periods being allocated to the one or more sweat glands.

[0152] In another embodiment, the method further comprises determining a number of sweat glands to which the active periods and the rest periods are allocated.

[0153] In another embodiment, the method further comprises receiving a measure of the volume of each recorded sweat droplet, and determining a sweat rate for each sweat gland from the number of recorded sweat droplets, the measure of the volume of each recorded sweat droplet, and the determined number of sweat glands; optionally, wherein identifying the at least one active period and the at least one rest period is based on the measure of the volume of each recorded sweat droplet and the time interval.

[0154] Particular, non-limiting examples of sensors and methods using the second discretization method are directed to Figure 11 are described and shown in Figure 11 .

[0155] In the following, the second discretization method and sensor are described, and focus is on the processing aspect.

[0156] According to an embodiment of the invention, a sweat sensor, in particular one or more analysis units, is configured to sense sweat droplets and receive sweat from one or more sweat glands and transport the sweat as discrete sweat droplets to the sensor. It comprises a processor configured to record sweat droplets sensed by the one or more analysis units over a time period, determine a time interval between successively sensed sweat droplets over the time period; and using the time interval, identify at least one active period for each of the one or more sweat glands, in which active period the respective sweat gland excretes sweat, and identify at least one rest period for each of the one or more sweat glands, in which rest period the respective sweat gland does not excrete sweat, the active periods and the rest periods being assigned to the one or more sweat glands.

[0157] According to another embodiment, the processor is further configured to determine a number of sweat glands to which active periods and rest periods are assigned.

[0158] According to another embodiment, the processor is further configured to receive a measure of the volume of each recorded sweat droplet; and determine a sweat rate for each sweat gland from the number of recorded sweat droplets, the measure of the volume of each recorded sweat droplet, and the determined number of sweat glands; optionally, wherein the processor is configured to identify the at least one active period and the at least one rest period based on the measure of the volume of each recorded sweat droplet and the time interval.

[0159] According to another embodiment, the sensor / one or more analysis units are configured to sense an indicator of the volume of a sweat droplet, and the processor is configured to receive the sensed indicator.

[0160] According to another embodiment, the processor is configured to fit data received from the sensor to a first template model, the data comprising at least the time interval and a measure of the volume of each recorded sweat droplet, thereby identifying active periods and rest periods for each of the one or more sweat glands.

[0161] According to another embodiment, the fitting of the first template model additionally uses: a number of sweat droplets in the at least one active period, a duration of the at least one active period, and / or a duration of the at least one rest period.

[0162] According to another embodiment, the processor is configured to evaluate a degree of fit of the data to the first template model, and optionally, based on the degree of fit, fit at least a portion of the data to another first template model.

[0163] According to another embodiment, the processor is configured to, after fitting the data to the first template model, fit at least a portion of the data to a second template model, wherein the first template model is based on at least some of the sweat droplets from a sweat sample composed of sweat excreted by a single sweat gland, and the second template model is based on at least some of the sweat droplets from another sweat sample composed of sweat excreted by two or more sweat glands.

[0164] According to another embodiment, the sensor is arranged to deliver a sweat droplet having a predetermined volume to the sensor.

[0165] According to another embodiment, the one or more analysis units comprise a sensing device for detecting a parameter related to a concentration of an analyte, the concentration of the analyte varying as a function of the rate of sweating, wherein the processor is configured to use the parameter in assigning active periods and rest periods to the one or more sweat glands.

[0166] According to another embodiment, the sensing device is an electrical conductivity sensor, and the parameter is electrical conductivity.

[0167] According to another embodiment, the sensor comprises a biomarker sensor; optionally, wherein the processor is configured to receive a plurality of biomarker concentrations from the biomarker sensor over at least one active period of the respective sweat gland, and determine a change in the biomarker concentration over time during the at least one active period.

[0168] The above sensor embodiments relate to processing aspects of the second discretization method, which will now be described as method embodiments.

[0169] A method is presented having the steps of receiving sweat from one or more sweat glands; delivering the sweat as discrete sweat droplets to one or more analysis units of a sweat sensor; sensing the sweat droplets using the one or more analysis units over a time period; recording the sensed sweat droplets over the time period; determining time intervals between successively sensed sweat droplets over the time period; and using the time intervals, identifying at least one active period for each of the one or more sweat glands during which the respective sweat gland excretes sweat, and identifying at least one rest period for each of the one or more sweat glands during which the respective sweat gland does not excrete sweat, the active periods and the rest periods being assigned to the one or more sweat glands.

[0170] According to an embodiment, the method comprises determining a number of sweat glands to which active periods and rest periods are assigned.

[0171] According to an embodiment, the method comprises receiving a measure of the volume of each recorded sweat droplet; and determining a sweat rate for each sweat gland from the number of recorded sweat droplets, the measure of the volume of each recorded sweat droplet, and the determined number of sweat glands; optionally, wherein identifying the at least one active period and the at least one rest period is based on the measure of the volume of each recorded sweat droplet and the time intervals.

[0172] As already explained in the foregoing, methods and sensors using the first and / or the second discretization method can be used with the sensor and method of the present invention. Thus, the methods and sensors of the discretization method are disclosed as embodiments of the present invention. This will be highlighted by Figure 10 and Figure 11 embodiments.

[0173] These and other features of the present invention will become apparent and elucidated with reference to the embodiments described hereinafter. BRIEF DESCRIPTION OF DRAWINGS

[0174] Exemplary embodiments of the present invention will be described in the following drawings.

[0175] Figure 1 A sweat sensor for analyzing sweat of a user drawn from the skin of the user into the sweat sensor according to an exemplary embodiment of the present invention is schematically shown.

[0176] Figure 2 A sweat sensor having a plurality of differently sized inlet openings according to an exemplary embodiment of the present invention is schematically shown.

[0177] Fig. 3 schematically shows an inlet having an opening whose diameter is adjustable by the sweat sensor according to an exemplary embodiment of the present invention.

[0178] Figure 4A diaphragm mechanism used as an inlet with its diameter adjustable by a sensor is schematically illustrated in accordance with an example embodiment of the present application.

[0179] Figure 5 A sweat sensor with adaptively selected inlet size / area is schematically illustrated in accordance with an example embodiment of the present application.

[0180] Figure 6 A sweat sensor with adaptive cross-sectional area or diameter of the inlet size is schematically illustrated in accordance with an example embodiment of the present application.

[0181] Figure 7 A flowchart of a method of analyzing the user's sweat drawn by the sensor from the user's skin is schematically illustrated in accordance with an example embodiment of the present application.

[0182] Figure 8 A flowchart of a method of adaptively selecting the size of one or more openings of the sensor is schematically illustrated in accordance with an example embodiment of the present application.

[0183] Figure 9 A flowchart of a method of dynamically adjusting the size of one or more inlets of the sensor is schematically illustrated in accordance with an example embodiment of the present application.

[0184] Figure 10 A sweat sensor using a first discretization method to determine the number of active glands per inlet is schematically illustrated in accordance with an example embodiment of the present application.

[0185] Figure 11 A sweat sensor utilizing a second discretization method disclosed herein to determine the sweat rate / swat rate per gland is schematically illustrated in accordance with an example embodiment of the present application. DETAILED DESCRIPTION

[0186] Figure 1A sweat sensor 100 is shown for analyzing sweat drawn from a user's skin 111 into the sensor 100. The sensor 100 includes three inlets 102, 103, and 104 through which the user's sweat can be drawn into the sensor 100. Each inlet 102, 103, and 104 is connected to analysis units 108, 109, and 110 via corresponding fluid channels 105, 106, and 107. In this way, sweat drawn by the inlet 102 with the smallest opening is analyzed independently of other sweat drawn by the remaining inlets 103 and 104 by the analysis unit 108. The same applies to inlets 103 and 104 and their respective analysis units 109 and 110. The sweat sensor 100 may, of course, include additional components, such as a processor for further processing of the analyzed data, but these are not shown for illustrative purposes. Within a housing 101, three different sample areas are provided through inlets 102, 103, and 104 of different sizes. Analysis units 108, 109, and 110 can be configured to determine, for example, the user's sweating rate and / or the number of active sweat glands at each inlet, based on the sweat drawn accordingly, as described previously and below. Furthermore, the sweat sensor 100 is configured to control (i.e., select) the size of the opening of the inlet (which the sensor uses to draw sweat) and to analyze the drawn sweat. For example, sensor 100 determines the number of active glands at each inlet 102, 103, and 104 within a first analysis cycle by analyzing the sweat drawn at each inlet. This determination is performed by analysis units 108, 109, and 110. Figure 1As can be seen, the inlet 102 with the smallest size opening receives sweat from only one gland 112 of the user's skin 111. The medium size inlet 103 receives sweat from three glands 113 and the large size inlet 104 receives sweat from five sweat glands 114 of the user's skin. The processor (not shown here) of the sweat sensor 100 is configured to compare the determined number of glands per inlet to a previously defined reference setting. This predetermined reference setting can be stored in a storage medium internal or external to the sensor. For example, the reference setting can define that if at least two active sweat glands drain sweat into an inlet and at most four active sweat glands drain sweat into an inlet, only the inlet should be used in the sense that the sweat drawn by these inlets is analyzed and the data of this analysis is further processed by the sensor. Thus, the processor of the sweat sensor 100 determines that only the inlet 103 should be used for the next analysis cycle of the sensor, so that the further measurements and analysis of the sensor are conducted in the future only with the inlet 103 and the analysis unit 109. In this way, the sensor controls the size, i.e. selects the size of the inlet to be actively used. This can improve the accuracy of the measurements made by the sweat sensor, e.g. the determination of the number of active sweat glands in the subsequent analysis cycle, and thus also the determination of the concentration of biomolecules in the user's sweat and blood.

[0187] In other words, Figure 1 The sweat sensor 100 shown in Fig. 1 ignores the sweat drawn by the inlets 102 and 104 in the future analysis cycle. Based on the determined sweat rate Figure 1 In another exemplary embodiment of the embodiment shown in Fig. 1, the sensor can be configured to determine the sweat rate with the analysis units 108, 109 and 110 and can store a respective reference setting with respect to the expected target size of the inlet openings, which depends on the determined sweat rate.

[0188] Furthermore, after the sensor has controlled the size to the appropriate inlet size as described before, the analysis units 108, 109 and 110 measure the sweat rate with the correctly sized inlet openings, determine the number of glands and determine the sweat rate of each gland. For example, one or more of the discretization methods described herein before can be used for such measurements / determinations. The analysis units 108, 109 and 110 also measure / determine the concentration of biomolecules in the drawn sweat of the user. The sensor 100 is configured to estimate the concentration of the biomolecule (e.g. lactate) in the blood of the user based on the determined sweat rate of each gland and based on the measured concentration of biomolecules in the drawn sweat. Due to the appropriate sizing of the openings of the inlets used by the sensor, the overall measurement of the sensor, in particular the final estimation of the concentration of the biomolecule in the blood of the user, is more accurate compared to the prior art.

[0189] Figure 2 A bottom view of a sweat sensor 200 according to an exemplary embodiment of the present invention is schematically shown. In this bottom view, it can be seen that the sensor 200 has a plurality of inlets that differ in their opening size. The sensor 200 is configured to select an inlet of a specific size, which the sensor uses to draw sweat and analyze the drawn sweat for use in the next analysis cycle of the sensor. The selection of an inlet with such a specific size can be based on determined sweat parameters of the user and can be based on comparison with reference settings or thresholds, as described previously and will be described below. The sensor 200 includes a first set of inlets 201a, 201b, and 201c, which have the same size and... Figure 2 The opening shown has the largest size. Furthermore, the sensor 200 includes three inlets with openings 202a, 202b, and 202c, each with a slightly smaller opening diameter. Additionally, there is a third group of multiple inlets of the same size, indicated by reference numerals 203a to 203f. This non-limiting example of the combination of openings in the sweat sensor 200 is merely one possible configuration of multiple sized inlets packaged together.

[0190] Since sweat is typically guided upwards from the skin into the sensor through cylindrical channels, therefore... Figure 2 As shown, the entrance is generally circular. However, this invention does not exclude other shapes, such as a square opening. From Figure 2 As can be seen, there is very little space between the inlets, which is desirable to keep the sensor small and thus less obtrusive to the wearer. Of course, the sensor 200 can be configured to select inlets of a specific size based on sweat parameters determined from sweat already absorbed from the user, and based on a comparison of the sensor with, for example, a reference setting. The corresponding control signals used to activate, for example, the analysis units associated only with openings 201a to 201c are non-limiting options.

[0191] Figure 3 schematically illustrates an inlet 300 with an opening 303, the cross-sectional area of ​​which can be adjusted by a sensor according to an exemplary embodiment of the invention on its projection onto the skin. From the left side... Figure 3A As can be seen, the entrance 300 includes a frame 301, within which four movable mechanical components 302 are positioned. Figure 3A In this configuration, four movable mechanical elements 302 are positioned such that they define the minimum possible inlet opening 303. However, in Figure 3B In this configuration, the mechanical component 302 is adjusted slightly by corresponding sensors to ensure that the opening 303 provided by the inlet 300 is of medium size. Figure 3CIn this embodiment, the sensor 300 has adjusted the mechanical element 302 such that the opening of the inlet 300 has a maximum size. The adjustment of the mechanical element 302 can be based on a control signal issued by a microcontroller or processor of the sweat sensor. The sweat sensor can generate such a control signal based on, for example, the sweat rate of the user that has been measured in a previous analysis cycle or based on the number of active sweat glands determined for this inlet 300 in a previous analysis cycle.

[0192] To ensure that only sweat is captured from the open inlet and not from underneath the material surrounding it, i.e. the part that is opened or closed to change the size, this material can be covered by a sponge or wick that is in contact with the skin to absorb sweat in this area.

[0193] Figure 4 Another embodiment of an inlet with an opening that can be adjusted in its diameter by the sensor is schematically shown according to an exemplary embodiment of the present application. Figure 4 A diaphragm mechanism 400 is schematically shown that uses a plurality of movable flaps 401 to define and adjust the diameter of an opening 402. Such a mechanical mechanism can also be used not only in one inlet of the sensor but also in a plurality of inlets. In an alternative or in combination, a super-elastic composite hydrogel can also be used that reacts upon heating and cooling in order to adjust the diameter of the opening. Such an inlet 400 can thus be implemented in a sweat sensor according to an exemplary embodiment of the present application to control the size of the opening.

[0194] Figure 5 Another sweat sensor 500 according to an exemplary embodiment of the present application is schematically shown. The sensor 500 comprises a housing 501 in which three inlets 502, 503 and 504 of different sizes are arranged in the housing. In each fluid / liquid channel connecting the inlets and the respective analysis unit 512 in which the fluid flow rate / pressure is measured, at least one valve 506 for closing or opening the fluid channel is included. In Figure 5 In this embodiment, the sensor 500 comprises a separate analysis unit 511 for analyzing the sweat, e.g. biological molecules in the sweat can be measured. In a particular embodiment, the analysis unit 511 is configured to measure the concentration of biological molecules in the drawn sweat of the user and the sensor is configured to estimate the concentration of the biological molecules in the blood of the user based on the determined sweat rate of each gland and the measured concentration of biological molecules in the drawn sweat.

[0195] In Figure 5 In this embodiment, the sweat sensor 500 comprises an array of valves 506 and a microfluidic system 507 for transporting the sweat of the skin 505 from each inlet to the associated analysis unit 512. In Figure 5In the embodiment of the sweat rate control selection for inlets with appropriate dimensions / cross-sectional area, this will now be explained in detail. The fluid flow (rate) / pressure measurement analysis unit 512 can be implemented as a flow sensor, or a GSR sensor or a sweat detector such as an electrochemical sensor. The reference setting stored in element 510 can thus be a reference value for e.g. fluid flow, sweat rate or osmotic pressure. The sweat rate signal of each inlet is collected in element 508 and transmitted to the microcontroller 509 via an electrical connection. As the skilled reader will understand, the microcontroller comprises a processor as described before. The microcontroller 509 can read the reference setting stored in element 510. Based on the received sweat rate signal of each inlet and the reference setting, the microcontroller can send an electrical signal to the microfluidic system 507 such that for the next analysis cycle of the sensor 500 the inlet with the most appropriate dimensions is used, i.e. all inappropriate valves 506 are closed. After this adaptive selection of the most appropriate inlet, the sweat sensor 500 can transmit the sweat drawn in the next analysis cycle by the microfluidic system 507 to the actual sweat analysis unit 511 of the sensor 500 which now measures the intended parameter, e.g. the concentration of biomolecules in the drawn sweat, with the correctly selected inlet. It should be noted that the method associated with the sensor 500 will be described later on in the context of Figure 8 .

[0196] Figure 6 A sweat sensor 600 is schematically shown which has an inlet which can change its dimensions / area, e.g. by a diaphragm mechanism. The sensor 600 comprises an adaptive inlet geometry 601 which can adjust the dimensions of its opening by a mechanical actuator 602. The sweat drawn in by the inlet 601 in a first analysis cycle is analyzed by an analysis unit 604. This analysis unit can be e.g. a fluid flow sensor, a GSR sensor or an electrochemical sensor. A reference setting is stored in element 605 such that the microcontroller 603 can compare the result of the analysis unit 604 with the reference setting. Also, this microcontroller 603 can comprise a processor for its purposes described herein. The analysis unit 604 has determined an intended parameter of the sweat, e.g. the sweat rate. The reference setting can then define what opening area (i.e. cross-sectional area, e.g. diameter of the adjustable inlet) is preferred for the currently measured sweat rate. A corresponding electrical signal can be sent by the microcontroller 603 to the mechanical actuator. Thus, the cross-sectional area or diameter of the adaptive inlet 601 is adjusted accordingly. In the next analysis cycle, the sweat drawn in by the inlet 601 can then be transmitted to a measurement unit 606, i.e. an actual biomarker measurement unit, which determines and measures the sweat parameter of the sweat drawn at that time with the correctly dimensioned inlet. It should be noted that the method associated with the sensor 600 will be described later on in the context ofFigure 9 are described.

[0197] Figure 7 A method of analyzing sweat of a user drawn by a sensor from the skin of the user is schematically illustrated. Figure 7 The method of Fig. 1 comprises the step of drawing sweat from the skin of a user through one or more inlets of a sensor, which step is illustrated as step S1. Further, the step of analyzing at least some of the drawn sweat with an analysis unit of the sensor is illustrated as step S2. Further, step S3 defines controlling the size of the opening of the one or more inlets through which the user will draw sweat and analyze the drawn sweat in a subsequent analysis cycle based on the analysis result of the drawn sweat.

[0198] If the concentration of biomolecules in sweat is translated into a concentration in blood, such sweat monitoring provides an ideal, unobtrusive way of monitoring a patient. The problem that hinders this translation is that the correlation between sweat concentration and blood concentration depends on the sweat rate of each gland. Therefore, in order to determine the sweat rate of each gland, the number of active sweat glands is more reliably determined over a larger range of active sweat glands. Prior art sweat sensors that measure the sweat rate of each gland can only do this over a certain range of active sweat glands per inlet / surface area. Figure 7 The method described in Fig. 1 increases this range by selectively using inlets of various sizes. Further, the method that is adapted to perform an adaptive selection or dynamic adjustment of these inlets of various sizes, i.e. the dynamic range of active sweat glands per surface area, uses the sweat rate, such as fluid flow, GSR, osmotic pressure, as a trigger / control signal. Also, in an embodiment, a combination of adaptive selection and dynamic adjustment is of course feasible. Figure 7

[0199] Figure 8 A flowchart of a method of analyzing sweat of a user drawn by a sensor and controlling the respective sweat sensor is schematically illustrated. Figure 8 The method shown in Fig. 1 can for example be used to control the sweat sensor 500 shown in Fig. 2. Figure 5 The sweat sensor 500 shown in Fig. 2. Figure 8 ​The illustrated method comprises using the default size or area of the inlet for the absorption of sweat and the analysis of the absorbed sweat when a low sweat rate is measured. However, when a critical sweat rate is reached due to excessive sweating, an inlet with an optimal inlet size or inlet area can be selected for such a high sweat rate using a control signal. As already explained before, the inventors of the present application have found that the sweat measurement is not accurate if more than a certain number of active sweat glands per inlet are used, and thus for a too high sweat rate, a smaller sized inlet or multiple smaller sized inlets should be selected for the sweat measurement. If at a later point in time, the sensor determines that the sweat rate has decreased and reached a reference sweat rate (e.g. corresponding to the sweat in a low sweat or resting state), the sensor can be controlled again such that the inlet with the default size is used again for future analysis cycles of the sensor. This logic and control method is illustrated in Figure 8

[0200] Figure 9 A flow chart of a method of a sweat sensor with dynamic adjustment of the inlet size is illustrated. If the sensor determines a low sweat rate, the sensor uses the default inlet size. However, if it is determined that a critical sweat rate is reached, e.g. a predetermined threshold is exceeded, the sensor is controlled such that it adjusts the inlet size such that the size is reduced.

[0201] In Figure 10 The sensor embodiment of the present application illustrated uses a first discretization method. Here, the present application is used in the sense that the largest and the smallest inlet are excluded, i.e. by a respective control signal of the sensor, and only the inlets of the intermediate sizes are considered for the measurement of the next or even more analysis cycles of the sensor. In other words, Figure 10 The sensor of the present application is configured to select the inlets of the intermediate sizes for the next analysis cycle based on the number of active sweat glands previously determined by the sensor from the measurement of the first analysis cycle. In Figure 10 In the sweat sensor of the present application, the measured amount of sweat from each inlet is x, 1, 2 or 3 times x, where x is e.g. 2 nl / min, thus the actual values measured from left to right are e.g. 4.1 nl / min, 0.01 nl / min, 3.9 nl / min, 6.2 nl / min, 1.9 nl / min, 0.02 nl / min, 5.8 nl / min, 2.0 nl / min, 4.1 nl / min. The number of active glands is then determined by the sensor to be 2, 0, 2, 3, 1, 0, 3, 1, 2, respectively.

[0202] Figure 11 ​A sensor 1100 according to an exemplary embodiment of the application is shown, which uses the second discretization method as described in detail before. The inlet 1104 of the sensor 1100 is shown in close proximity to a sweat gland 1108. The sensor 1100 comprises one or more inlets of adjustable size, as for example shown in Figs. 3 and Figure 4 , and the sensor adjusts this size based on the measured sweat parameters. Alternatively or additionally, it comprises a plurality of inlets 1104, and at least some of the plurality of inlets differ in their opening size, and the sensor is configured to select an inlet having a particular size, which the sensor uses to suck up sweat and analyze the sucked-up sweat in the next analysis cycle.

[0203] The sweat expelled by the sweat gland 1108 enters through the inlet 1104 and fills the chamber. As shown in Figure 11 , the sensor 1100 can comprise a plate 1110, which is attached to the surface of the skin 1106. In order to compensate for the limited amount of sweat received into a single chamber, the sensor 1100 can for example comprise a plurality of such chambers, for example 2 to 50 chambers, such as 10 to 40 chambers, for example about 25 chambers, defined by such inlets 1104.

[0204] Once the inlet 1104 has been filled with sweat, a sweat droplet 1112 protrudes from the outlet 1114 of the chamber. In the example shown, the outlet 1114 is delimited by the upper surface of the plate 1110, and once the chamber has been filled with sweat, a hemispherical sweat droplet 1112 is formed on top of the outlet 1114. More generally, the sweat sensor 1100 can be configured such that the formation speed of the sweat droplet 1112 is determined by the sweat rate, while the volume of the sweat droplet 1112 can be determined by the fluid transport assembly of the sensor. Figure 11

[0205] The sensor 1100 can enable the formation of sweat droplets 1112 of relatively uniform size, and in addition can also handle variable sweat droplet 1112 volumes. With respect to the latter, one or more analysis units to which the sensor 1100 transports the sweat droplets 1112 can be configured to both count the sweat droplets 1112 and determine the time each sweat droplet 1112 spends by the analysis unit. Figure 11 An example is shown in which the detachment of the sweat droplet 1112 is achieved by a fluid transport assembly in which the upper surface of the plate 1110 and the lower surface of a further plate 1128 are provided with passive gradients, for example chemical and / or topological gradients. In this respect, the arrows 1126A and 1126B denote the direction of the gradients provided on the upper surface of the plate 1110 and the lower surface of the further plate 1128, respectively, for transporting the sweat droplet 1112 towards the analysis unit.

[0206] ​The detachment of defined sweat droplets 1112 can alternatively or additionally be achieved by the fluid delivery assembly applying a pressure gradient to the sweat droplets 1112 protruding from the outlet 1114. This can be seen as an example of providing an active gradient in order to overcome the contact angle hysteresis of the sweat droplets 1112, as the fluid delivery assembly actively applies pressure / force to the sweat droplets 1112 in order to overcome the contact angle hysteresis of the sweat droplets 1112.

[0207] For example, the pressure gradient can be applied by contacting the protruding sweat droplets 1112 with a carrier fluid stream. The carrier fluid is preferably a fluid that does not mix with the sweat droplets 1112. As the sweat droplets 1112 are substantially prevented from mixing with the carrier fluid, the analysis unit is able to detect each discrete sweat droplet 1112 that is carried by the carrier fluid. Suitable examples of such carrier fluids include oils that do not absorb moisture, i.e. have a relatively low or negligible hygroscopicity, such as oxycyte. Oxycyte is a perfluorocarbon compound that is commonly used as a blood substitute.

[0208] In such examples where the carrier fluid stream separates the sweat droplets 1112, a further plate 1128 can be provided opposite the plate 1110 defining the chamber 1102, as previously described. The sweat droplets 1112 can form and grow until the sweat droplets 1112 contact the further plate 1128, at which point the sweat droplets 1112 can block the channels defined by the space between the respective plates 1110, 1128. The sweat droplets 1112 can then be transferred by the carrier fluid stream. In this way, relatively uniform sized sweat droplets 112 can be provided; the size of which is determined by the distance 1130 between the plates 1110, 1128. The carrier fluid stream can further assist in transporting the sweat droplets 112 to the one or more analysis units.

[0209] In the event that, for example, such a carrier fluid stream is insufficient to separate the sweat droplets 1112, the fluid delivery assembly can be configured to induce a pulse or peak in the flow rate, which can provide sufficient pressure to release the sweat droplets 1112 from the outlet 1114. For example, a piezoelectric pump can be used to induce such a peak in the flow rate of the carrier fluid. This can be achieved directly by varying the pulse frequency of the pump.

[0210] Accordingly, such a sensor 1100 is configured to receive sweat from one or more sweat glands and transport the sweat as discrete droplets to one or more analysis units, which can then be advantageously used to determine the sweat rate or swat rate of each gland using the second discretization method as disclosed herein.

[0211] The sensor 1100 can also use the processing aspect of the second discretization method, as described in detail herein. To this end, the sensor 1100 comprises a processor configured to count the number of sweat droplets 1112 sensed by the analysis unit over a time period and determine the time interval between consecutively sensed sweat droplets 1112 over the time period. The processor also receives a measured value of the volume of each counted sweat droplet 1112. The processor is further configured to utilize the time interval and the measured value of the volume of each counted sweat droplet 1112 to identify an active period (i.e. a sweat burst period) of the one or more sweat glands 1108 during which the one or more sweat glands 1108 are actively sweating, and to identify a resting period of the one or more sweat glands 1108 during which the one or more sweat glands 1108 are not actively sweating. This process of identifying the sweat burst period and the resting period of the one or more sweat glands 1108 simultaneously involves assigning the active period and the resting period to the one or more sweat glands 1108.

[0212] The processor then determines the number of sweat glands 1108 to which the active period and the resting period are assigned, and subsequently determines the sweat rate of each sweat gland from the number of sweat droplets 1112, the measured value of the volume of each counted sweat droplet 1112, and the determined number of sweat glands 1108.

[0213] The sensor 1100 thus determines the sweat rate of each sweat gland by assigning the sweat droplets 1112 to specific sweat glands 1108 based on the intermittent sweat ejection behavior of the sweat glands 1108. The sensor can also be physically simpler than conventional sweat sensing systems, as the sensor 1100 can transport the sweat droplets 1112 from several inlets / chambers to a common analysis unit.

[0214] The above-described embodiments are merely representative and not limiting of the present application, and one of ordinary skill in the art will be able to devise numerous alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word "comprising" does not exclude the presence of elements or steps other than those listed in a claim. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. The application can be implemented by means of hardware comprising several distinct elements, and / or by means of a programmed processor. In the device claim enumerating several means, several of these means can be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

Claims

1. A sweat sensor (100, 500, 600) for analyzing sweat absorbed from a user's skin (111, 505), said sweat sensor comprising: One or more inlets (102, 103, 104, 303, 402) through which the user's sweat can be drawn into the sweat sensor. Analyzers (108, 109, 110, 511, 512, 606) are configured to analyze the sweat captured by the sweat sensor to determine sweat parameters, and The sweat sensor is configured to control the size of the opening of the one or more inlets by changing the cross-sectional area of ​​the opening of the one or more inlets and / or selecting an inlet with a specific size, based on a comparison result between the sweat parameters determined by the analyzer and a reference setting of the sweat parameters.

2. The sweat sensor according to claim 1, wherein, The sweat sensor includes: Multiple inlets for absorbing sweat. Wherein, at least some of the plurality of inlets differ in their opening size, and The sweat sensor is configured to select an inlet of a specific size.

3. The sweat sensor according to claim 1 or 2, wherein, The determined sweat parameters of the user are at least one of the user's sweating rate and the number of active sweat glands at each inlet.

4. The sweat sensor according to claim 1 or 2, wherein, The analyzer is configured to compare a first value of the sweat parameter determined in a first analysis cycle of the sweat sensor with a second value of the sweat parameter determined in a second analysis cycle of the sweat sensor, the second analysis cycle being after the first analysis cycle. The sweat sensor is configured to reduce the size of the opening of the one or more inlets when the second value exceeds the first value. The sweat sensor uses the one or more inlets to draw in the sweat and analyze the drawn sweat in the next analysis cycle.

5. The sweat sensor according to claim 1 or 2, in, The analyzer is configured to determine the sweating rate of each gland in the user. The analyzer is configured to measure the concentration of biomolecules in the sweat inhaled by the user, and The sweat sensor is configured to estimate the concentration of the biomolecules in the user's blood based on the determined sweating rate of each gland and the measured concentration of the biomolecules in the absorbed sweat.

6. The sweat sensor according to claim 1 or 2, wherein, The sweat sensor also includes: Multiple inlets, each having a corresponding opening whose size can be adjusted by the sweat sensor. The sweat sensor is configured to determine the user's sweating rate and / or the number of the user's active sweat glands from the absorbed sweat. The sweat sensor is configured to adjust all of the plurality of inlets to the same opening size based on the determined sweating rate and / or the determined number of active sweat glands.

7. The sweat sensor according to claim 1 or 2, wherein, The sweat sensor also includes: A flow sensor is disposed in the channel of the sweat sensor, the channel connecting at least one inlet to the analyzer, and The flow sensor is configured to measure the rate of excretion of sweat.

8. A method for analyzing a user's sweat, the sweat being drawn from the user's skin by the sweat sensor through one or more inlets, the method comprising the steps of: Analysis of at least some of the sweat sampled, Based on the analysis results of the absorbed sweat, the size of the openings of the one or more inlets is controlled in subsequent analysis cycles, and The size control is achieved by increasing or decreasing the size of the adjustable opening of the at least one inlet compared to the size of the opening of the inlet used in the previous analysis cycle and / or by selecting one or more inlets with larger or smaller openings for the next analysis cycle.

9. The method according to claim 8, wherein the method comprises: The number of active sweat glands at each inlet is determined, and the sweat is drawn from the inlet by the sweat sensor. The number of active sweat glands at each entrance was determined and compared with a reference setting for the number of active sweat glands at each entrance. The size control is achieved through the following methods: A) When the number of active sweat glands at each determined inlet is less than a predetermined minimum number of active sweat glands at each inlet as defined in the reference setup, increase the size of the opening of the at least one inlet compared to the size of the opening of the one or more inlets used in the previous analysis cycle and / or select one or more inlets with a larger opening for the next analysis cycle, and / or B) When the number of active sweat glands in each determined inlet is higher than the predetermined maximum number of active sweat glands in each inlet as defined in the reference setting, the size of the opening of the at least one inlet is reduced compared to the size of the opening of the one or more inlets used in the previous analysis cycle, and / or one or more inlets with smaller openings are selected for the next analysis cycle.

10. The method according to claim 9, wherein, The method includes: Determine the user's sweating rate, and The determined perspiration rate is used to determine the number of active sweat glands at each inlet, from which sweat is drawn by the sweat sensor.

11. A computer program product comprising a computer program for analyzing a user's sweat, the sweat being absorbed from the user's skin by a sweat sensor, the computer program, when executed by a processor of a sweat sensor according to any one of claims 1 to 7, being adapted to cause the sweat sensor to perform the method according to any one of claims 8 to 10.

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