Wearable systems, devices, and methods for measuring and analyzing body fluids

Abstract

Methods, systems, and devices are described herein in various embodiments that use a sample analysis system to analyze a bodily fluid sample from a user to determine parameters relevant to the user, including hydration, dehydration, rehydration, electrolyte loss, health status, recovery, and other conditions. In some embodiments, the disclosed methods can be performed using a device worn by a user and operably coupled to a sample analysis system configured to collect a bodily fluid sample, measure and analyze the bodily fluid to determine characteristics of the user's bodily fluids and / or physiological / health status parameters (e.g., hydration level, electrolyte loss, sweat rate, etc.).

Description

[Technical Field]

[0001] Cross-reference of related applications

[0001] This application claims priority and interest in U.S. Provisional Patent Application No. 16 / 827,349, filed on 23 March 2020, the contents of which are incorporated herein by reference. [Background technology]

[0002] background

[0002] The embodiments described herein relate to systems, apparatus, and methods used for near immediate and cumulative measurement and analysis of body fluids and specimens that may be contained in body fluids. The embodiments described herein also relate to embodiments of real-time hydration detection systems and hydration strategizing systems used in action. [Overview of the Initiative]

[0003] overview

[0003] This specification describes systems, apparatus, and methods for various embodiments of a sample analysis system that is attached to a user and configured to collect a body fluid sample, measure and analyze the body fluid to determine the characteristics of the user's body fluid and / or physiological / health status parameters (e.g., degree of hydration, electrolyte loss, sweating amount, etc.). [Brief explanation of the drawing]

[0004] Brief explanation of the drawing [Figure 1]

[0004] This is a schematic diagram illustrating an exemplary use of the sample handling device on the user's skin surface according to an embodiment. [Figure 2A]

[0005] This is a schematic diagram of a sample handling device according to an embodiment. The sample handling device can be used in conjunction with a sample analysis system ("SA system"). [Figure 2B]

[0005] This is a schematic diagram of a sample handling device according to an embodiment. [Figure 3]

[0006] This is a schematic diagram of an exemplary sample analysis system ("SA system"), including the sample handling apparatus shown in Figures 2A and 2B, according to an embodiment. [Figure 4]

[0007] This is a schematic diagram of exemplary data stored and / or used by a sample handling device according to one embodiment. [Figure 5A]

[0008] This is a schematic perspective view of an exemplary sample handling apparatus according to an embodiment. [Figure 5B]

[0009] Figure 3A is a schematic top view of an exemplary sample handling apparatus. [Figure 5C]

[0010] This is a schematic exploded view of an exemplary sample analysis system according to an embodiment. [Figure 6]

[0011] This flowchart schematically illustrates an exemplary method for measuring and analyzing a sample body fluid from a user using the SA system, according to an embodiment. [Figure 7]

[0012] This flowchart schematically illustrates an exemplary method for measuring a user's sweat volume using an SA system according to an embodiment. [Figure 8]

[0013] This flowchart schematically illustrates an exemplary method for measuring the user's hydration state using an SA system, according to an embodiment. [Figure 9]

[0014] This flowchart schematically illustrates an exemplary method, according to an embodiment, for measuring a user's cumulative electrolyte loss and associated physiological effects using an SA system. [Figure 10]

[0015] This flowchart schematically illustrates an exemplary method for measuring a user's core body temperature using an SA system, according to an embodiment. [Figure 11]

[0016] This is an exemplary plot showing measured impedance and flow rate values ​​of a sample body fluid over a period of time, measured and analyzed using an exemplary SA system according to the embodiment. [Figure 12]

[0017] An exemplary plot showing the verification of predicted body fluid loss levels in a subject using an exemplary SA system according to an embodiment. [Figure 13]

[0018] An exemplary plot showing the verification of impedance measurements related to body fluids measured using an exemplary SA system according to an embodiment. [Figure 14]

[0019] An exemplary plot showing the verification of the use of an exemplary SA system due to measurement errors related to impedance measurements of body fluids created using an exemplary SA system according to an embodiment. [Figure 15]

[0020] An exemplary plot showing impedance and temperature measurements related to an exemplary liquid measured using an exemplary SA system according to an embodiment. [Figure 16]

[0021] An exemplary plot showing data regarding the relationship between temperature measurements and impedance measurements created using an exemplary SA system according to an embodiment. [Figure 17]

[0022] An exemplary plot showing the relationship between impedance and temperature predicted based on data from mathematical models such as the data shown in FIG. 16 obtained from actual measurements. [Figure 18]

[0023] An exemplary plot showing the relationship between osmotic pressure and impedance measurements obtained from a plurality of sample liquids using an exemplary SA system of some embodiments. [Figure 19]

[0024] An exemplary plot showing osmotic pressure, temperature, and impedance measurements obtained over time from a sample liquid using an SA system according to an embodiment. [Figure 20]

[0025] An exemplary plot showing the mean absolute percentage error (MAPE) value for verifying the osmotic pressure values predicted by an SA system according to an embodiment using the osmotic pressure measured using an independent method. [Figure 21A]

[0026] This shows exemplary plots of ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities. [Figure 21B]

[0026] Exemplary plots of ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities are shown. [Figure 21C]

[0026] Exemplary plots of ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities are shown. [Figure 21D]

[0026] Exemplary plots of ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities are shown. [Figure 22]

[0027] This is an exemplary table showing changes in ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities. [Figure 23]

[0028] The following are illustrative diagrams of companion applications used with sample handling equipment according to several embodiments. [Modes for carrying out the invention]

[0005] Detailed explanation

[0029] Embodiments of the disclosure include a method comprising collecting a body fluid sample within a sampling area of ​​an apparatus, and guiding a portion of the body fluid sample from the sampling area to a first electrochemical interface, the first electrochemical interface comprising an excitation electrode and a sensing electrode. The method comprises applying an excitation signal to the portion of the body fluid sample at the first electrochemical interface through the excitation electrode, and sensing a response signal in response to the application of the excitation signal. The method further comprises measuring data relating to an instance of electrochemical properties of the portion of the body fluid sample based on the response signal.

[0006]

[0030] Embodiments of the disclosure include a system comprising a memory for storing a set of instructions, and a processor coupled to the memory, configured to execute the instructions stored in the memory. The processor is configured to receive, at a first time point, a first response signal obtained from a first portion of a sample fluid taken from a user, the first portion in contact with a first electrochemical interface of a device associated with the system. The processor is configured to receive, at a second time point, a second response signal obtained from a second portion of the sample fluid, the second portion in contact with a second electrochemical interface of a device associated with the system. The processor is further configured to receive information relating to the distance the sample fluid flows, which is the distance between the first and second electrochemical interfaces. The processor is further configured to calculate the flow rate of the sample fluid through a channel included in the device based on the first and second response signals and the distance.

[0007]

[0031] Embodiments of the disclosure include an apparatus comprising a sampling area having an inlet, an access port fluid-communicating with the sampling area, and a fluid-communicating channel with the access port. The sampling area is configured to receive an initial volume of fluid through the inlet. The channel is configured to guide a portion of the initial volume of fluid toward a pair of electrodes. The pair of electrodes comprises an excitation electrode and a sensing electrode. The excitation electrode is configured to apply an excitation signal to a portion of the initial volume of fluid, and the sensing electrode is configured to receive a response signal from the portion of the initial volume of fluid in response to the excitation signal. The sensing electrode is further configured to transmit the response signal to a processor for calculating the impedance associated with the portion of the initial volume of fluid.

[0008]

[0032] The embodiments described herein relate to systems, apparatus, and methods used for measuring and analyzing body fluids using wearable measurement and analysis systems. A sample analysis system can be configured to collect a body fluid sample and measure and analyze the body fluid to determine the characteristics of the user's body fluid (e.g., impedance, osmotic pressure) and / or physiological / health status parameters (e.g., hydration level, electrolyte loss, sweating rate, etc.). For example, the systems and apparatus described herein can collect a body fluid (e.g., sweat) sample and measure the impedance of the body fluid. The impedance measurement can then be used to determine and / or predict the characteristics of the sweat (e.g., osmotic pressure). In some examples, the body fluid sample can be collected as a continuous or semi-continuous flow, i.e., as generated by the body.

[0009]

[0033] In some embodiments, the collected bodily fluid can be guided to flow along a controlled channel, and the impedance of the bodily fluid can be measured at two or more test areas or locations associated with the controlled channel. The impedance measurements and known characteristics of the controlled channel (e.g., volume, length, distance between test areas) can be used to determine the linear velocity and / or volumetric flow rate associated with the bodily fluid. The volumetric flow rate can be a local or regional flow rate with respect to the part of the user's body to which the device for collecting the bodily fluid is attached. In some embodiments, the methods described herein can be used to predict whole-body flow rate and / or whole-body sweat volume from the regional flow rate in a region of the user's body.

[0010]

[0034] While we do not wish to be bound by any particular theory, it is believed that the electrolyte content of sweat is the main cause of its osmotic pressure. Therefore, the determined osmotic pressure can be used to estimate the electrolyte content of sweat. The sweat data can then be used to determine or predict the user's physiological parameters (e.g., hydration level, electrolyte loss, sweat volume, etc.).

[0011]

[0035] While this system is described above as being used to determine the electrolyte content of sweat based on impedance measurement, it can also be used to determine the osmotic pressure of other bodily fluids and / or secretions, including saliva, tears, urine, and breast milk, which can provide insights into the user's hydration state or other physiological parameters. In addition, although we do not wish to be bound by any particular theory, some scientific evidence suggests that the osmotic pressure of breast milk can be used to determine its nutritional content. Therefore, similar to the analysis described above, this system can be used to measure the impedance of breast milk, and this impedance can be correlated with the osmotic pressure of breast milk to provide insights into its nutritional content.

[0012]

[0036] As described herein, individuals such as athletes, military personnel, workers, children, the elderly, emergency patients, and the general population can greatly benefit from timely monitoring of their physiological status and health using suitable indicators of health, and from timely intervention or correction based on that monitoring. Some exemplary secondary indicators of physiological status and health include signs of hydration, body water loss, and electrolyte loss, which can affect physical and cognitive abilities.

[0013]

[0037] Studies have shown that up to 87% of endurance athletes experience physical impairments during training and competition due to dehydration, even when adequately hydrated. Dehydration can cause a drop in blood pressure, an increase in heart rate, an increase in respiratory rate, and decreased blood flow to the extremities. These physiological changes can lead to cardiopulmonary stress, impaired thermoregulation, and fatigue, all of which have a significant impact on the patient's health and / or athletic performance. Symptoms of mild dehydration are often subtle and imperceptible, so individuals may always suffer the consequences without realizing it.

[0014]

[0038] For example, under certain circumstances, if body fluids are lost and not adequately replenished, dehydration can occur, which can lower blood pressure and impair the circulation of blood and the components it carries (e.g., oxygen, nutrients, etc.). In some cases, a dehydrated body may compensate by initiating one or more physiological responses that can have undesirable effects. For example, to compensate for reduced circulation, the body may respond with an increased heart rate, causing cardiac stress and fatigue, or an increased respiratory rate, causing respiratory stress and fatigue. In some cases, the body may respond by reducing blood flow to the extremities (e.g., skin, appendages, muscles, etc.) to maintain blood flow to vital organs. This can lead to impaired thermoregulation, an increased risk of heatstroke, and / or muscle cramps and fatigue. In some situations, the body may respond to dehydration by constricting capillaries or otherwise altering the direction of circulation, reducing blood flow to the gastrointestinal tract to maintain blood flow to vital organs. This can lead to impaired water absorption and gastrointestinal problems (vomiting). In situations where dehydration continues to worsen, the body's condition can deteriorate further due to an increase in core body temperature, potentially leading to burns, further restricting blood flow to vital organs, and ultimately causing multiple organ failure and death.

[0015]

[0039] Dehydration impairs physical performance after just a 1% weight loss, and worsens exponentially with each additional percentage lost. Dehydration equivalent to 2% of body weight is widely recognized as the threshold at which statistically significant disability (approximately 29% impairment) is observed. Subsequently, performance declines rapidly, followed by increasing degrees of dehydration. Dehydration also causes cognitive impairment, manifesting as, for example, delayed reaction time, delayed and impaired decision-making, and decreased memory and judgment. These effects can directly lead to increased safety risks. If an individual's dehydration level reaches a critical level, medical intervention is required to prevent permanent side effects or failure of major vital organs. In extreme cases, it can even be fatal. Individuals often misunderstand how easily and quickly dehydration can occur because they do not know how to effectively monitor their hydration status during training. The effects of dehydration can be even more severe and / or harmful in children, the elderly, and emergency patients.

[0016]

[0040] Hydration management is complicated by significant variations in sweating rates. Each individual can sweat at different rates based on personal factors such as age, sex, weight, body fat percentage, and health level, among many others. For any given individual, numerous additional variables influence sweating rates, including weather conditions, intensity of physical activity, and the amount and type of clothing or equipment worn. Even the same individual may have different sweating rates for the same activity on any given day.

[0017]

[0041] One method for measuring hydration is to record bare body weight before and after activity. The difference between the pre- and post-measurement values ​​is converted into a percentage of weight loss. However, since this method for measuring dehydration can only be performed through pre- and post-activity measurements, individuals cannot currently determine their hydration status during activity.

[0018]

[0042] Other methods used to measure hydration status include taking blood samples at regular intervals during activity and measuring the osmolality of plasma using an osmometer. Since current blood sampling methods cannot be performed during activity, this method presents some of the same problems as those described for the bare-body weight measurement method. This method provides information on hydration status before and after activity, although it is not performed during activity. This method is also highly invasive and inconvenient. Similar to blood sampling for plasma osmolality measurement, other available methods for collecting other body fluids for osmolality measurement are also used as a method to determine hydration status, but the results are not very good. Other fluids collected include saliva, urine, sweat, and tears. Each of these fluids presents challenges in both collection and osmolality measurement.

[0019]

[0043] Some devices collect sweat using patches that adhere to the skin. The sweat can be collected in an absorbent patch or absorbent reservoir. The patch is then removed from the individual, and the osmotic pressure of the sweat in the patch is measured using a benchtop device. This method requires a sufficient amount of sweat; that is, the individual must be drenched in sweat for 15-20 minutes to collect this minimum amount. This method cannot provide raw, immediate hydration monitoring for athletes. In addition, these patches need to be replaced every 15-20 minutes to collect accurate hydration levels throughout the entire duration of the activity being studied. Therefore, systems, devices, and methods are needed for the near-immediate measurement and analysis of body fluids.

[0020] Sample analysis system

[0044] Embodiments described herein relate to systems, apparatus, and methods used for near-immediate measurement and analysis of bodily fluids, such as sweat, and specimens that may be contained within them. Embodiments of the disclosed systems and apparatus are inherently lightweight and can therefore be worn by an individual during any activity. The systems, apparatus, and methods of the disclosure enable near-immediate measurement and analysis of bodily fluids by the independent, real-time nature of sample collection and analysis. Embodiments of the disclosed systems and methods also support repeated immediate measurements of bodily fluid samples performed over a period of time while an individual is engaged in activities.

[0021]

[0045] As used herein, the terms “sample” and / or “target sample” refer to any ion, molecule, or compound that can be detected and / or bound to the species to be detected (e.g., detection molecule or reagent), as described herein. Suitable samples include, but are not limited to, metal and nonmetal ions (e.g., Na + CT, Ca 2+ , K + , or Mg 2+This may include small chemical molecules such as ions, amino acids and nitrogen compounds such as urea, metabolites (e.g., lactates and pyruvates), xenobiotics such as drug molecules and enzymes, metabolic by-products, disease-related biomarkers, environmental molecules, clinical molecules, chemicals, pollutants, and / or biomolecules. More specifically, such chemical molecules may include, but are not limited to, pesticides, insecticides, toxins, therapeutic and / or abuse drugs, hormones, antibiotics, antibodies, organic materials, proteins (e.g., enzymes, immunoglobulins, and / or glycoproteins), nucleic acids (e.g., DNA and / or RNA), lipids, lectins, carbohydrates, whole cells (e.g., prokaryotic cells such as pathogenic bacteria and / or eukaryotic cells such as mammalian tumor cells), viruses, spores, polysaccharides, glycoproteins, metabolites, cofactors, nucleotides, polynucleotides, transition state analogs, inhibitors, nutrients, electrolytes, growth factors, and other biomolecules and / or non-biomolecules, as well as fragments and combinations thereof. Some of the specimens described herein may be proteins such as enzymes, drugs, cells, antibodies, antigens, cell membrane antigens, and / or receptors or their ligands (e.g., nerve receptors or their ligands, hormone receptors or their ligands, nutrient receptors or their ligands, and / or cell surface receptors or their ligands).

[0022]

[0046] As used herein, the term “sample” refers to a composition containing one or more specimens to be detected. A sample may be heterogeneous, containing various components (e.g., different proteins), or homogeneous, containing a single component. In some examples, a sample may be naturally occurring, a biomaterial, and / or an artificial material. Furthermore, a sample may be in its natural or denatured form. In some examples, the sample may be subjected to processing before detection. For example, the sample may be subjected to a dissolution step, a denaturation step, a heating step, a purification step, a precipitation step, an immunoprecipitation step, a column chromatography step, a centrifugation step, and so on. In some examples, separation (by electrophoresis) and / or immobilization of the sample may be performed on the natural substrate and / or the specimen of interest (e.g., a protein). In other examples, the sample may be denatured to expose its internal hydrophobic groups for immobilization in a flow channel.

[0023]

[0047] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural references unless otherwise explicitly indicated by the context. Therefore, for example, the term "component" is intended to mean a single component or combination of components, and "material" is intended to mean one or more materials or combinations thereof.

[0024]

[0048] As used herein, the term "and / or" is used in this disclosure to mean either "and" or "or" unless otherwise expressly stated.

[0025]

[0049] As used herein, “body fluids” may include any liquids obtained from the body of an individual (e.g., an athlete, worker, patient, etc.). For example, “body fluids” may include, but are not limited to, sweat, tears, blood, urine, breast milk, saliva, sebum, mucus, vitreous fluid, and others, or any combination thereof.

[0026]

[0050] Where used in this application, the terms “about” and “approximately” are used interchangeably. Any figures used in this application, with or without “about” or “approximately,” are intended to cover any normal variation recognized by a person skilled in the art. In certain embodiments, unless otherwise expressly stated or otherwise evident from the context, the terms “approximately” or “about” refer to a range of values ​​that are within 10% (greater than or less than) the given reference value in either direction (except where such a number is greater than 100% of the possible value or less than 0% of the possible value).

[0027]

[0051] As used herein, the term “rigidity” relates to an object’s resistance to deflection, deformation, and / or displacement caused by an applied force, and is generally understood to be the inverse of an object’s “flexibility.” For example, a wall with greater rigidity will be more resistant to deflection, deformation, and / or displacement when subjected to a force than a wall with less rigidity. Similarly, an object with greater rigidity can be characterized as more rigid than an object with less rigidity. Rigidity can be characterized in terms of the amount of force applied to an object and the distance resulting from the deflection, deformation, and / or displacement of a first part of the object relative to a second part of the object. When characterizing the rigidity of an object, the deflection distance may be measured as the deflection of a part of the object different from the part of the object to which the force is directly applied. In other words, in some objects, the point of deflection is different from the point to which the force is applied.

[0028]

[0052] As used herein, the terms “proximal” and “distal” refer to directions toward and away from the user, respectively, in which the device or system is positioned on the user’s body. For example, the end of the device that first touches the user’s body is the proximal end, while the opposite end of the device (e.g., the end of the device away from the user’s body) is the distal end.

[0029]

[0053] As will be described in more detail herein, any of the systems, apparatus, and methods can be used to repeatedly collect and analyze body fluid samples by, for example, taking a first body fluid sample or a first volume of body fluid, testing the first volume of body fluid or body fluid sample, draining the first volume of body fluid or body fluid sample, and taking a subsequent volume of body fluid or body fluid sample after a given time. Each of the terms “first,” “subsequent,” and / or “initial” can be used interchangeably to describe and / or refer to the amount, part, or volume of body fluid collected, transferred, deflected, guided, and / or drained during use of the sample analysis systems described herein. In some embodiments, the terms “first,” “subsequent,” and / or “initial” may refer to a predetermined, specified, desired, or given volume, part, or amount of body fluid, which may depend on several parameters, including the configuration of the apparatus, user requirements, etc.

[0030]

[0054] The embodiments and / or parts thereof described herein may be formed or constructed from one or more biocompatible materials. In some embodiments, the biocompatible material may be selected based on one or more properties of the constituent material, such as stiffness, toughness, durometer, and bioreactivity. Examples of suitable biocompatible materials include metals, glass, ceramics, or polymers. Examples of suitable metals include pharmaceutical-grade stainless steel, gold, titanium, nickel, iron, platinum, tin, chromium, copper, and / or alloys thereof.

[0031]

[0055] The embodiments and / or parts thereof described herein may include components formed by one or more parts, features, structures, etc. When referring to such components, it should be understood that the component may be formed by a single part having any number of sections, layers, regions, parts, and / or features, or by multiple parts or features. For example, when referring to a structure such as a wall or room, the structure may be considered as a single structure comprising multiple parts, or as multiple different substructures or other structures joined together to form a structure. Thus, a monolithic structure may, for example, include a set of substructures. Such a set of substructures may include multiple parts that are continuous or discontinuous with respect to each other. A set of substructures may also be assembled from multiple articles or components that are individually fabricated and then joined together (for example, by welding, adhesive, or any preferred method).

[0032]

[0056] In some embodiments, a sample analysis system (also referred to herein as a “SA system”) includes a single-use or disposable sample handling device and a durable sample processing device connected to the sample handling device. In some embodiments, the SA system may include a reusable sample handling device and a reusable, durable sample processing device coupled to the sample handling device. The sample handling device is configured to collect a bodily fluid sample, guide the sample to a test and measurement interface, and enable testing of the sample using a test stimulus and measurement of the response signal from the sample in response to the test stimulus. After testing the collected sample, the sample handling device is configured to guide the sample to be discharged. The response signal can then be analyzed to determine the quantitative properties of the sample, such as solute concentration, solvent content, and sample concentration.

[0033] Sample handling equipment

[0057] Figure 1 shows a schematic cross-section of the user's skin and illustrates an example of an exemplary sample handling device positioned on the user's skin. The schematic of the skin sample shows the density of secretory glands (e.g., sweat glands) leading to pores that release bodily fluids (e.g., sweat). The sample handling device (also referred to herein as the “SH device”) is represented by a disc and is shown to be positioned on the surface of the user's skin. As shown in the figure, the disc covers some of the pores that release bodily fluids and is configured to collect a sample of bodily fluid (e.g., sweat) from the user that can be measured and analyzed while the user is active (i.e., in near real time). Although the sample handling device is shown on the user's skin for collecting and analyzing sweat, it should be understood that the sample analysis system described herein, including the sample handling device, can be used without being attached to the user and can be used to analyze any number of other bodily fluids.

[0034]

[0058] Figures 2A and 2B are schematic diagrams of an exemplary sample handling device 110, showing some of the components included in the sample handling device 110 according to an embodiment. The schematic diagram of Figure 2B includes a diagram of exemplary configurations of various components of the sample handling device 110 and a flow path defined for the flow of a bodily fluid sample, indicated by dashed arrows. In some embodiments, the sample handling device 110 can be constructed monolithically. In some other embodiments, the sample handling device 110 can be constructed by assembling a set of parts or layers, as will be described in more detail herein. As shown in Figures 2A and 2B, the sample handling device 110 includes a sample collection area 112, an access port 114, a flow path 116, test areas 118A and 118B, a set of electrodes 120A and 120B, and optionally a temperature sensor 140.

[0035]

[0059] The sample collection area 112 is a part of the sample handling device 110 configured to receive and collect a bodily fluid sample, such as sweat, from the user's body when the sample handling device 110 is fitted to the user. The sample collection area 112 includes an opening 122, shown in Figure 2B, which allows access to the bodily fluid source when the sample handling device 110 is fitted to the user. The sample collection area 112 also defines a space or volume configured to be fluidly coupled to the opening 122, which is configured to hold or collect a bodily fluid sample when the sample handling device 110 is fitted to the user. Although not shown in Figures 2A and 2B, the sample handling device 110 may include one or more interface structures between the user's body and the sample collection area 112 of the sample handling device 110. Such interface structures may be configured to facilitate use or to enhance comfort while using the sample handling device 110. For example, one or more liners may be used to enhance comfort during use of the sample handling device 110 and to provide better contact with the user's body. In addition, the interface structure can be used to provide a seal between the sample handling device 110 and the user's body so that the pressure generated by the sweat glands pushes the sweat out through the channel 116.

[0036]

[0060] In some embodiments, the sampling area 112 can be defined by one or more parts of the sample handling device 110. For example, in some embodiments, the sampling area 112 can be formed by assembling two or more parts or layers of a structure to define a specific volume for temporarily holding a collected bodily fluid sample, and including an opening 122 for collecting bodily fluids. At the time of assembly, two or more parts or layers can be selected or fabricated so that the sampling area 112 includes a suitable opening 122 and the main body of the assembled part of the sample handling device 110 defines a volume of the sampling area 112 that can hold a suitable amount of collected bodily fluids. For example, the thicknesses of two or more parts can be selected to determine the volume or liquid capacity of the sampling area 112. The two or more parts can be assembled using any preferred method, such as friction fitting, bonding with adhesive material (e.g., transfer adhesive), or using fasteners. In some other embodiments, the sampling area 112 may be formed monolithically by a single, integrated part or structure to include an opening 122 suitably configured for collecting a bodily fluid sample and to define a volume for holding the collected bodily fluid sample.

[0037]

[0061] The portion forming the sample handling device 110 and / or the sample collection area 112 may have a flexibility suitable for facilitating attachment by the user and facilitating access to a bodily fluid source. For example, in some embodiments, the portion or layer forming the sample handling device 110 and / or the sample collection area 112 may have a flexible property so that the sample handling device 110 can be attached to the user's skin surface and so that the proximal portion of the sample collection area 112 can optimally contact the user's skin and conform to the contours of the user's body, even when the user is active. In some embodiments, the sample handling device 110 and / or the sample collection area 112 may have a relatively rigid structure so that rigidity allows for better contact with the user's body surface and prevents the sample handling device 110 from shifting or detaching from the user during strenuous activity.

[0038]

[0062] As shown in Figure 2B, an opening 122 defined within the sample collection area 112 can be fluidly connected to a volume configured to provide access to a source of bodily fluid samples (e.g., skin including sweat pores) and to temporarily contain the bodily fluid samples collected from the source. The sample collection area 112 can be formed such that the volume and the opening 122 are defined within the body of the sample handling device 110 or within a portion of the body of the sample handling device 110. In some embodiments, for example, the sample collection area 112 can be configured so that, when the sample handling device 110 is positioned on the user's body, the sample collection area 112 is located proximal to the user's skin surface and covers a suitable area of ​​skin for collecting a suitable volume of bodily fluids, such as sweat, over a suitable period of time. For example, as shown in the schematic diagram of Figure 1, a piece of human skin of the user may have a specific density of sweat pores that release sweat, with each pore spaced apart from others at a specific distance. The sampling area 112 can be configured such that the opening 122, when placed on the user's skin, can cover a specific area of ​​skin containing a minimum number of sweat pores. Such positioning allows for the collection of an initial volume of sweat released from these pores over a desired period of time. In other words, the opening 122 can be large enough to collect sweat from enough sweat glands to substantially fill the sampling area 112 in a relatively short time, so that sweat can be analyzed immediately after the user begins to sweat.

[0039]

[0063] In some embodiments, the SA system may require a minimum amount of body fluid for accurate testing and analysis. The volume of the opening 122 and / or the sampling area 112 can be configured to determine the volume of body fluid collected in the initial sample and to ensure that the collected initial sample meets the minimum liquid requirement for accurate testing and analysis. In some embodiments, the sampling area 112 may include one or more structures (not shown in Figures 2A and 2B) configured to occupy and / or take up volume in the sampling area 112, so that the volume of the initial body fluid sample collected and guided through the access port 114 can be smaller than the total volume defined by the sampling area 112.

[0040]

[0064] The space-occupying structure can be defined within the sampling area 112 in any preferred manner. In some embodiments, the space-occupying structure can be solidly formed using one or more spacer portions of a spacer film assembled and / or deposited on the surface of the sampling area 112 as a material such as spacer ink (e.g., an ink cured by ultraviolet light) or other. For example, the space-occupying structure can be included (e.g., deposited) in a layer or portion used to form the wall of the sampling area 112. In some embodiments, the space-occupying structure can be implemented by one or more spacer layers or portions assembled together with one or more other parts to form the sampling area 112. In some embodiments, the space-occupying structure can include a covering material that defines a hollow inside the covering material and / or seals the volume defined inside the covering material. In some embodiments, the covering material of the space-occupying structure can be molded and / or formed to define a space that can be excluded or separated from the volume defined by the sampling area 112.

[0041]

[0065] In some embodiments, the volume of the initial sample can also determine the ease of sampling, the direction of the fluid flow being tested, and the discharge, thereby determining the rate at which the sample can be collected and tested or analyzed. In other words, in some embodiments of the sample handling device 110, an initial bodily fluid (e.g., sweat) sample can be collected, and the volume of the initial sample is determined by the volume of the sampling area 112. The collected initial sample can be guided into the flow path 116 through the access port 114 to be tested and discharged in a continuous flow of bodily fluid, making room for continuous sampling of bodily fluids subsequently secreted by the user during use. The processes of sampling, sample testing, and sample discharge can be carried out continuously at a suitable rate using the continuous flow of the collected bodily fluid sample through the sampling area 112, the access port 114, the flow path 116, and the testing area 118. In such embodiments, the volume of the sampling area 112 and the size of the opening 122 defined in the sampling area 112 can determine the rate at which the initial amount of sample is collected. The volume of the sample collection area 112 and the size of the opening 122 can partially determine the linear flow velocity (i.e., the volumetric flow rate divided by the cross-sectional area of ​​the flow path 116) of the sample as it is guided through the access port 114, the flow path 116, and the test area 118 before being discharged.

[0042]

[0066] In some embodiments, for example, the sampling area 112 may have a volume and / or liquid capacity of about 0.001 milliliters (mL) to about 25,000 mL. In some embodiments, the sampling area 112 may have a liquid capacity that includes all or part of the ranges between about 0.001 mL and about 0.01 mL, about 0.01 mL and about 0.50 mL, about 0.01 mL and about 1.00 mL, and about 1.00 mL and about 25,000 mL. In some embodiments, the sampling area 112 may have a volume sufficient to accommodate an initial amount of sample measured in a volume as small as a microliter (e.g., 20 drops of body fluid, 10 drops of body fluid, 5 drops of body fluid, 1 drop of body fluid, or any suitable volume in between) of body fluid. In other embodiments, the sampling area 112 may have a volume of, for example, about 5.0 mL, 10.0 mL, 15 mL, or more. In some embodiments, the sampling area 112 may have a volume of, for example, about 5.0 mL, 10.0 mL, 15 mL, or more.

[0043]

[0067] As shown in Figures 2A and 2B, the access port 114 of the sample handling device 110 is fluidically coupled to the sample collection area 112. The access port 114 can be an opening, through hole, conduit, fluid channel, or other defined within the body of the sample handling device 110 to fluidly connect the sample collection area 112 to the channel 116, which will be described in more detail below. In some embodiments, the sample collection area 112 can be formed by assembling two or more parts or structures as described herein. In some embodiments, one of those parts may be configured to include and / or define an opening 122, while another part may be configured to include and / or define the access port 114. One or more of the parts to be assembled may be configured to form one or more walls of the sample collection area 112 when assembled. In embodiments where the sample collection area 112 is defined within a monolithic structure, the access port 114 may be an orifice, conduit, and / or flow path defined within the body of the sample handling device 110 to fluidly connect the sample collection area 112 to the flow path 116.

[0044]

[0068] The access port 114 can be positioned at any suitable location relative to the sampling area 112 to mediate the fluid connection between the sampling area 112 and the flow path 116. For example, in some embodiments, the access port 112 can be an orifice defined on the inner surface of the sampling area 112. In some embodiments, the access port 114 can be defined in the distal portion of the sampling area 112 (i.e., the portion away from the user's body when the sample handling device 110 is in use). In some embodiments, for example, the access port 114 can be defined in the central portion relative to the opening 122 and / or volume defined by one or more walls of the sampling area 112 to hold the collected bodily fluid. In some other embodiments, for example, the access port 114 can be defined at an off-center position relative to the opening 122 and / or volume defined by the walls of the sampling area 112 to hold the collected bodily fluid. In some embodiments, the access port 114 can be positioned at any preferred location relative to the sampling area 112, the opening 122, and / or the flow path 116 in order to prevent the formation of bubbles in the collected bodily fluid sample and / or to allow bubbles to escape. In some embodiments, the access port 114 can be positioned such that the sampling area 112 is suitably formed to guide the flow of liquid toward the access port 114, for example, through a constriction, a conduit, the contour of one or more structures, and / or other means.

[0045]

[0069] The access port 114 can have any suitable size to allow the transfer of the collected bodily fluid sample from the sample collection area 112 to other parts of the sample handling device 110 (e.g., the test area 118). In some embodiments, the size of the access port 114 can range from several hundred microns to several millimeters. For example, the access port 114 can have an internal cross-sectional diameter of about 0.05 mm to about 5.0 mm. In some embodiments, the access port 114 can have a cross-sectional area sufficient to allow a continuous flow of the collected bodily fluid sample into the flow path 116.

[0046]

[0070] In some embodiments, the access port 114 can be configured to allow a continuous flow of the collected body fluid sample once the initial body fluid sample has reached a minimum volume. In some embodiments, the access port 114 can be configured to allow a continuous flow of the collected body fluid sample after the sampling area 112 has reached a minimum positive pressure due to the collection of a corresponding or minimum volume of body fluid (e.g., a volume as small as 20 drops, 10 drops, 5 drops, 1 drop, 0.001 mL, 0.0015 mL, 0.010 mL, 0.05 mL, 0.2 mL, 1.00 mL, or any suitable volume in between).

[0047]

[0071] The access port 114 can determine the flow rate of the collected bodily fluid to be tested using the SA system in conjunction with the sample handling device 110. In some embodiments, the access port 114 may have wicking properties to draw the collected liquid sample from the sampling area 112 into the flow path 116. In some embodiments, the collected sample in the sampling area 112 can be guided into and beyond the access port 114 by pressure differences. For example, the lower pressure in the access port 114 and flow path 116 compared to the sampling area 112 can draw the collected bodily fluid sample through the access port 114 and flow path 116. Similarly, as the sampling area 112 becomes increasingly filled with collected bodily fluid, the increase in pressure in the sampling area 112 (i.e., generated by the sweat glands) can push the collected bodily fluid sample through the access port 114 into the flow path 116. In other words, the seal between the sample handling device 110 and the user's body is sufficiently liquid-tight so that the pressure generated by the sweat glands pushes the sweat through the channel 116. In some other embodiments, the access port 114 may be configured so that the liquid in the sample collection area 112 is drawn out by capillary action.

[0048]

[0072] The channel 116 may have any suitable width, height, diameter, or cross-sectional area for receiving the collected bodily fluid sample from the sample collection area 112 through the access port 114, and for suitably transferring the liquid sample to other parts of the sample handling device 110, such as the test area 118. For example, the channel 116 may have a circular cross-section with a suitable diameter, or a rectangular cross-section with a suitable width and height. The width, height, or diameter of the channel 116 may range from several hundred microns to several millimeters. For example, the width, height, and / or diameter of one or more parts of the channel 116 may be approximately 0.05 millimeters (mm) to approximately 5.0 mm. The channel 116 may extend over any suitable length from several millimeters to several centimeters and be configured to take any suitable shape along its length. For example, the channel 116 may extend over a length of 5 millimeters (mm) to approximately 15.0 centimeters (cm). The flow path 116 can be configured to follow any suitable path, such as a linear path, a straight path, a curved path, or a meandering path.

[0049]

[0073] In some embodiments, the channel 116 may be formed to have a predetermined volume per unit length so that, given the length of the channel 116 between any two points, the volume of the portion of the channel 116 between those two points can be calculated. For example, as shown in Figure 2B, the channel 116 may include two test areas 118A and 118B with a gap DD between them. Given the length DD of the channel 116 between the two test areas 118, the volume of the portion of the channel 116 between the two test areas 118 can be calculated, and from this volume, the volume of the bodily fluid flowing between the two test areas 118 can be calculated. In some embodiments, the channel 116 may be formed such that its dimensions (e.g., height, width, diameter, length, etc.) are within specified tolerance limits so that the volume of the portion of the channel 116 can be estimated to be within a specified tolerance range (e.g., within ±1 pL, ±1 nL, ±1 μL, etc.).

[0050]

[0074] In some embodiments, based on the dimensional accuracy and / or tolerance of the flow path 116, the SH apparatus 110 can be configured to measure the time delay between a portion of the body fluid sample that has reached a first test area 118A and the same portion of the body fluid sample that has reached a second test area 118B. For example, a portion of the body fluid can be identified to first interact with electrode 120A in the first test area, a first excitation signal can be applied to the portion of the body fluid, and the response is recorded. The same portion of the body fluid can then pass through the flow path 116 and the second test area 118B at a distance DD, where a second excitation signal can be applied, and the induced response can be measured. Based on the responses measured in the first and second test areas 118, the portion of the body fluid identified in the first test area can be identified when it has passed through the second test area 118B after a measured period T, as will be described in more detail herein. Based on the known volume of the portion of the flow path 116 along the distance DD between test areas 118A and 118B, and the measurement period T, the volumetric flow rate associated with the flow of the body fluid sample can be calculated. In some examples, as described herein, the body fluid to be collected and analyzed may take the form of a continuous flow of body fluid to a specific area of ​​the user's body (e.g., an unobstructed flow of sweat from a skin patch on the user's arm / chest / abdomen / shoulder). Thus, the calculated volumetric flow rate of the body fluid sample can be used to generate an estimate of the secretion or expression rate of body fluids in the user's body in localized areas of the user's body and / or throughout the user's body. Although two test areas are described in the examples herein, in some embodiments, the SH apparatus 110 may preferably include any number of test areas, e.g., a third, fourth, and fifth test area, etc.

[0051]

[0075] In some embodiments, the channel 116 can be defined within a monolithically constructed, integral structure such that the diameter of the channel 116 is at least partially determined by the thickness of the monolithic structure defining the channel 116. In some other embodiments, the channel 116 can be constructed by assembling two or more parts or layers of a structure that define the channel 116 as a whole. In some embodiments, the channel 116 can be formed by several layers or parts assembled together to guide the flow of liquid through one or more passages, through holes, openings, and / or other means. The channel 116 can be configured so that external influences during use, such as forces caused by gravity, movements of the user's body, and others, do not interfere with the flow of liquid within the channel 116.

[0052]

[0076] In some embodiments, the flow path 116 may include various sections suitably configured to guide the flow of body fluid at a preferred flow rate or volumetric flow rate. For example, in some embodiments, the flow path 116 may include sections configured to have different cross-sectional shapes and / or sizes. For example, some sections of the flow path 116 may be circular or rectangular, while others are not. Similarly, some sections of the flow path 116 may have a narrower or wider cross-sectional area compared to other sections of the flow path 116. In some embodiments, the flow path 116 may include an inlet section and an outlet section. The inlet section of the flow path 116 may be configured to transfer body fluid collected in the sampling area 112 to the test area 118 described below via the access port 114. The outlet section of the flow path 116 may be configured to remove the body fluid sample after testing in the test area 118, for example, to be discharged into the environment from the sample handling device 110. For example, in some embodiments, the flow path 116 may be configured to be linear in some parts, defined by one or more test areas 118, and the outflow portion of the flow path 116 may include a winding ventilation path to reduce and / or avoid air ingress.

[0053]

[0077] The inlet and outlet portions of the channel 116 can be shaped to allow for optimal flow of the bodily fluid sample, optimal access to the bodily fluid sample for testing, and optimal discharge of the sample after testing. In some embodiments, portions of the channel 116 may also include structural and / or functional modifications to overcome or withstand physical forces such as stress and / or strain that may be experienced when the sample handling device 110 is used during strenuous activity. For example, in some embodiments, the channel 116 may be configured to include suitable linear, angular, and / or curved or meandering portions to better withstand different types of physical forces, including stress and / or strain, that a user may experience when wearing the sample handling device 110 during high-intensity or contact sports activities. In some embodiments, the channel 116 may be configured to include one or more curved or meandering portions that function as local traps to prevent air from outside the sample handling device 110 from flowing into the channel 116.

[0054]

[0078] As shown in the schematic diagram of Figure 2B, the flow path 116 may include an outlet 124 for discharging the collected and tested bodily fluid sample. In some embodiments, the bodily fluid sample can be guided through the outflow portion of the flow path 116 to the outlet 124 by a series of pressure differences. In some other embodiments, the bodily fluid sample can be guided toward the outlet 124 by one or more suitable physical forces after testing in the test area 118. For example, the bodily fluid sample can be discharged through the outlet 124 by gravity, capillary action, user movement and / or other means.

[0055]

[0079] As shown in Figures 2A and 2B, the sample handling device 110 includes test areas 118A and 118B. Although illustrated as having two test areas 118A and 118B, in some other embodiments, the sample handling device 110 may include any number of preferred test areas defined along the flow path 116. For example, in some embodiments, the sample handling device 110 may include one, two, three, or more test areas defined in a designated portion of the flow path 116 so that bodily fluids collected in the sample collection area 112 can be guided through one or more test areas for sequential or parallel processing via the access port 114, as described herein. In some embodiments, the test area 118 is separated from the flow path 116 but can be fluidically coupled to the flow path 116. In some embodiments, the test area 118 can be defined as part of the flow path 116. For example, the flow path 116 may include an inlet portion and an outlet portion separated by the test area 118, which is a third portion. The test area 118 can be configured to intersect with the flow of bodily fluids in the channel 116. In some embodiments, the test area 118 can be configured to define a volume sufficient to hold a portion of the bodily fluid sample during testing. As previously described, in some embodiments, the test areas 118A and 118B can be separated by only a known distance DD that can be implemented during the manufacture of the SH apparatus 110 to fit within specified tolerances.

[0056]

[0080] The test area 118 of the sample handling device 110 may include a pair of electrodes 120. In some embodiments, the electrodes 120 may include electrodes configured to supply power to one or more components included in the sample handling device 110 (e.g., one or more sensors such as a temperature sensor) and / or to carry signals (e.g., signals reporting temperature measurements from the temperature sensor) from one or more components to the sample handling device.

[0057]

[0081] A pair of electrodes 120 may include an excitation electrode and a sensing electrode. In some embodiments, each electrode of the pair of electrodes 120 may be configured to act as either an excitation electrode or a sensing electrode. In some embodiments, a pair of electrodes 120 may include an excitation electrode designed to deliver an excitation signal to a portion of a body fluid sample in a test area 118, and a sensing electrode designed to sense a response signal from the body fluid sample in response to the application of the excitation signal. A pair of electrodes may include a terminal portion (represented by circular portions of electrodes 120A and 120B in Figure 2B) configured to interact with a portion of the sample liquid described herein, and a sample end portion configured to interact with a portion of the sample liquid in one or more test areas 118.

[0058]

[0082] In some embodiments, for example, an excitation electrode may be configured to receive an excitation signal from a power source at its terminal end and to deliver the excitation signal at the sample end to a portion of the body fluid sample guided through a flow path to the test region 118. In another example, a sensing electrode may be configured to receive a response signal emitted from a portion of the body fluid sample in the test region 118 at the sample end that contacts the portion of the body fluid sample in the test region 118, and to deliver the received response signal to a terminal that contacts a portion of the sample processing apparatus so that the response signal can be suitably processed and / or analyzed by a processor and / or stored in memory associated with the sample processing apparatus. In some embodiments, the sample processing apparatus may be configured to receive response signals from electrodes 120 associated with two or more test regions 118A and 118B so that the characteristics of the sample body fluid can be determined by comparing the response signals from each of the two or more test regions 118.

[0059]

[0083] A pair of electrodes 120 may include a terminal that borders an electrical signal source and / or power source at an electrical interface with a connector 125 for electrical coupling with a sample processing apparatus 130, as described herein, for example. A pair of electrodes 120 may include a sample end that is formed to intersect a flow path 116 in one or more test areas 118 and is configured to border a bodily fluid sample flowing through the test area 118. A pair of electrodes 120 may include any preferred number of electrodes, the sample end of each electrode may be configured to deliver an excitation signal to the bodily fluid sample to be tested (e.g., as a current-delivering electrode) or to sense a response signal from the bodily fluid sample being tested using the excitation signal (e.g., as a voltage-sensing electrode).

[0060]

[0084] The number of electrodes can be suitably optimized in different embodiments of the sample handling device, taking into account parameters such as the number of electrodes required for effective delivery of the excitation signal, the number of electrodes required for a predetermined signal-to-noise ratio in the response signal obtained from the body fluid sample being tested, and the number of electrodes suitable for satisfying predetermined shape factors or structural and / or functional limitations, and / or others. For example, in some embodiments, a set of electrodes may include four electrodes, two of which are configured to deliver the excitation signal in the form of a test current signal, and two of which are assigned to record the response voltage from the body fluid sample after the test current signal has been applied. As an example, electrode 120 can be configured as a quad-pole impedance cell. In another example, in some other embodiments, a set of electrodes may include two electrodes, one of which is configured to deliver the excitation signal, and the other electrode is configured to read a voltage from the body fluid sample being tested, from which the impedance can be calculated. In some examples, the sensing electrode may be an impedance electrode configured to directly sense impedance in response to the application of an excitation signal, e.g., the application of a current. For example, electrode 120 can be configured as a bipolar impedance cell.

[0061]

[0085] In some embodiments, one or more electrodes can be shared among multiple test areas. For example, in some embodiments, an excitation electrode configured to deliver current can be shared among two or more test areas 118, and the shared excitation electrode may have a single terminal end that borders a connector 125 coupled to a sample processing device 130, and two or more sample ends (not shown in Figure 2B) located in the two or more test areas 118.

[0062]

[0086] In some examples, the distance between electrodes 118 associated with two or more test areas 118 can be used to determine the characteristics of a sample body fluid. For example, the impedance associated with the response signal from each test area 118 can be used to evaluate the flow rate and / or volumetric flow rate of the sample body fluid. In some examples, a pattern recognition method can be used to compare a first response (and / or impedance) from interaction with a portion of the body fluid, measured in a first test area 118A, with a response (and / or impedance) measured in a subsequent test area 118B to identify the same portion of the body fluid sample that elicits the first response. In some examples, the time delay between measuring the first response in the first test area 118A and measuring the subsequent response in a subsequent test area 118B located at a known distance DD along the flow path 116 can be used to determine the linear velocity and / or volumetric flow rate of the body fluid sample using a preferred method and / or algorithm. From the volumetric flow rate of the sample body fluid, the secretion or expression rate of the sample body fluid (e.g., the amount of sweat produced) can be estimated or predicted. In some embodiments, the excitation signal may be a test current signal used to test the electrode 120 or other components of the SH device 110 and / or a sample analysis system (e.g., connector, sample processing device, etc.) that includes the SH device 110.

[0063]

[0087] In some embodiments, electrode 120 is configured such that the test current signal is in the form of direct current. In some embodiments, the electrode is configured such that the applied test current signal is in the form of alternating current (AC). In embodiments using alternating current, electrode 120 can be configured such that the alternating polarity of the test current signal received by the electrode allows for a partial reversal of the effect of the salts of the body fluid sample on the electrode. Thus, the use of alternating current for excitation can assist in preventing rapid corrosion or ionization of the electrical interface of the electrode within the test region that would otherwise result from a direct current excitation signal. In some embodiments, one or more of electrodes 120 can have a carbon coating to reduce the corrosive action of the body fluid being tested. In some embodiments, the electrode can be capacitively or AC coupled to the electronics such that direct current cannot flow through the sample and the risk of corrosion or ionization is reduced.

[0064]

[0088] In some embodiments, electrode 120 can be configured to detect the presence of one or more ions in a body fluid sample. For example, in some embodiments, electrode 120 can be configured to detect and / or quantify the presence of one or more of Na + , Cl - , Ca 2+ , K + , or Mg 2+ ions in a portion of the initial volume of body fluid.

[0065]

[0089] In some embodiments, the composition of the conductive ink used to form the electrodes (e.g., by screen printing) may be optimized to perform specific detection and / or protective functions. In some embodiments, the electrodes may be coated with a material that can be used as a binder for specific samples that may be present in the sample fluid being analyzed. For example, the electrodes may be coated with a specific functionalizing material used to bind to and / or detect the presence of a specific sample so that the presence and / or concentration of that sample can be determined. As an example, the coating may be made using a conductive ink that can be a silver / silver chloride alloy that is optimal for ion detection. In some embodiments, conductive inks of different compositions may be used to facilitate the detection of specific target ions. In some embodiments, the functionalizing coating may be used for other samples (e.g., K + Cl - In addition to these, a specific sample (for example, Na + The electrodes can be optimized for ) . While the detection of the presence of ions has been described, the systems, apparatus, and methods described herein are equally suitable and / or can be used to detect and / or quantify the presence of a sample in a body fluid sample. For example, the presence of lactose, glucose, etc. can be detected and / or quantified.

[0066]

[0090] In some embodiments, the sample handling device 110 may optionally include one or more temperature sensors 140. The temperature sensors 140 can be suitably positioned in or near one or more test areas 118 and can be configured to record the temperature of the body fluid sample being tested in one or more test areas 118. In some embodiments, the temperature sensors 140 can be positioned to monitor and measure the temperature of the body fluid sample during testing in one or more test areas 118. The temperature sensors 140 can be any suitable temperature sensing device that can be suitably positioned adjacent to and near the test areas 118 to measure the temperature of the body fluid sample. For example, the temperature sensors 140 can be a thermistor or a thermistor assembly. In some embodiments, the sample handling device 110 may include additional sensors (not shown) for recording ambient conditions. For example, the sample handling device 110 may include temperature sensors for measuring the user's skin temperature and / or ambient temperature. In some embodiments, the sample handling device 110 and / or a sample processing device coupled to the sample handling device 110 may include any number of additional sensors for sensing pressure, humidity, etc.

[0067]

[0091] When in use, the sample handling device 110 is positioned on the surface of the user's body to collect and guide bodily fluids for testing and analysis in order to determine the user's physical and / or health condition. For example, the sample handling device 110 can be positioned on the arm of an athlete participating in a sporting event to collect and test the user's sweat and analyze the salt concentration of the collected sweat, from which the user's hydration state, electrolyte loss, and sweating volume can be determined. The sweat is collected in the sample collection area 112 of the sample handling device 110 and guided continuously through the access port 114 to the channel 116. In some examples, a spacer portion included in the sample collection area 112 can occupy space within the sample collection area 112 and reduce the amount of bodily fluid sample that needs to be collected to facilitate or initiate the flow of bodily fluids through the channel 116. The portion of the channel 116 is configured to guide the collected sweat in a continuous flow to a test area 118 where the sweat interacts with a set of electrodes 120. An excitation signal or test current signal is delivered to a sample sweat in the test area 118 via one or more electrodes (current-delivering electrodes) from a set of electrodes 120. The response voltage generated by the sweat sample in response to the excitation signal or test current signal is read by one or more electrodes (voltage-sensing electrodes, distinct from the current-delivering electrodes) from the set of electrodes 120. In some examples, an excitation signal or test current signal can be delivered, and the response voltage can be read continuously. The voltage read from the sweat sample is used to calculate the impedance associated with the sweat sample, and the impedance can be correlated with the quantification or measurement of the salt concentration of the sweat and other physiological information of the user. Thus, the user's sweat can be continuously tested over a period of time, and the measurement of the salt concentration of the user's sweat can be correlated with continuous measurements of the user's hydration, electrolyte loss, and sweat volume over a period of time while the user is active.

[0068] Exemplary sample analysis system

[0092] Figure 3 is a schematic diagram of a sample analysis system 100 according to an embodiment. The SA system includes a sample handling device 110 (also referred to herein as the SH device) and a sample processing device 130 (also referred to herein as the SP device), which are coupled to each other via a connector 125. In some embodiments, the connector 125 can be permanently connected to the sample handling device 110 and / or the sample processing device 130, or it can be detached from them. In some examples, the sample analysis system 100 can be configured to incorporate a wearable device 145 (e.g., a smartwatch, wristband odometer, activity tracker, heart rate monitor, and / or other devices that may be commercially available (e.g., devices available from Garmin®, Fitbit®, Apple Watch®)). The SA system 100 includes a sample processing device 130, which is illustrated in Figure 3 to be coupled to a wearable device 145. However, in some embodiments, the sample handling device 110 can be directly coupled to or connected to the wearable device 145 without requiring the sample processing device 130.

[0069]

[0093] In some embodiments, the SA system 100 may optionally include and / or be configured to work with a companion application 147, which can be instructions stored in memory and executed by a processor. In some examples, the companion application 147 may be run on a remote device (e.g., a smartphone, tablet, or computer). The companion application 147 may be configured to receive data from the SH device 110 and / or the sample processing device 130 and / or an optional wearable device 145, perform additional analysis, and / or generate a data report for the user. An exemplary embodiment of the companion application 147 is shown in Figure 23.

[0070]

[0094] The connector 125 may be a mechanical connector configured to engage, couple, and / or connect the sample handling device 110 to the sample processing device 130. In some examples, the connector 125 may be configured to engage with a portion of the sample handling device 110 so that the sample handling device 110 can be mounted onto the sample processing device 130 before being mounted to a user. In some embodiments, the sample processing device 130 may be configured as a durable, multi-use device, and the sample handling device 110 may be configured as a single-use device that can be mounted and / or connected to the sample processing device over a period of use (e.g., an active period) and then discarded and replaced with another sample handling device 110. The connector 125 may be configured to allow for easy removal and replacement of the sample handling device 110. In addition to physical connections, the connector 125 may include a set of suitable electrical connections for electrically coupling the sample handling device 110 to the sample processing device 130. For example, the connector may be in the form of a pogo pin or a flexible contact that can be engaged to provide an electrical connection when the sample handling device 110 is mechanically coupled to the sample processing device 130, for example, using a snap ring interface. Although the sample handling device 110 is described as being configured to connect to the sample processing device 130, in some embodiments in which the sample handling device 110 can be directly attached to the wearable device 145, the connector 125 may be configured to engage, couple, and / or connect the sample handling device 110 to the wearable device 145.

[0071]

[0095] The sample processing device 130 may have a shape factor suitable for easy attachment by the user during a series of strenuous activities, so that the sample handling device 110 can be properly brought into contact with the user's body (e.g., a part of the user's skin). The sample processing device 130 may include a processor 132, a memory 136, a communication device 138, and a display 142.

[0072]

[0096] The processor 132 can be, for example, a hardware-based integrated circuit (IC) or any other suitable processing unit configured to run and / or execute a set of instructions or code. For example, the processor 132 can be a general-purpose processor, a microprocessor, a central processing unit (CPU), a microcontroller, an accelerator processing unit (APU), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), a programmable logic array (PLA), a composite programmable logic device (CPLD), a programmable logic controller (PLC), and / or others. The processor 132 is operably coupled to the memory 136 via a system bus (e.g., an address bus, a data bus, and / or a control bus). The processor 132 can be configured to perform a set of functions for testing, measuring, and analyzing the properties of a sample fluid collected by a sample handling device, either in real time or near immediate. For example, the processor 132 may be configured to generate a set of excitation signals to examine a bodily fluid sample, provide instructions for the delivery of the excitation signals via electrodes in the sample handling device 110, receive response signals obtained from the bodily fluid sample read by electrodes in the sample handling device 110, interpret the response signals to determine the characteristics of the sample bodily fluid, and consequently display the user's physical condition. In some embodiments, the processor 132 may also be configured to perform additional functions, such as displaying relevant information regarding the characteristics of the analyzed sample bodily fluid and / or the user's condition at the time of testing to the user via the display 142. In some embodiments, the processor 132 may also be configured to transmit a set of signals, interpretations, and / or analysis results to a remote computer device for further processing, as described herein.

[0073]

[0097] The memory 136 of the sample processing device 130 may be, for example, random access memory (RAM), a memory buffer, a portable hard drive, read-only memory (ROM), erasable programmable read-only memory (EPROM), and / or other. The memory 136 may store one or more software modules and / or code that may include, for example, user dates relating to future use / analysis, and / or instructions for causing the processor 132 to perform one or more processes, functions, and / or other actions described herein (e.g., generation of excitation signals, delivery of test signals, reading and analysis of response signals). In some embodiments, the memory 136 may be portable memory (e.g., a flash drive, a portable hard disk, and / or other) that can be operably coupled to the processor 132. In other examples, at least a portion of the memory may be operably coupled remotely to the sample processing device 130. For example, a remote database server may be operably coupled to the sample analysis system 100 via the sample processing device 130.

[0074]

[0098] The communicator 138 can be a hardware device operably coupled to the processor 132 and memory 136, and / or software stored in memory 136 executed by the processor 132. The communicator 138 can be, for example, a small network interface card (NIC), a Wi-Fi module, a Bluetooth® module, a radio frequency communication module, and / or any other suitable wired and / or wireless communication device. Furthermore, the communicator can include a switch, router, hub, and / or any other network device. The communicator 138 can be configured to connect the sample processing device 130 to a communication network or one or more computer devices. In some examples, the communicator 138 can facilitate the reception and / or transmission of files and / or sets of files to and from one or more computer devices (e.g., computers, smartphones, remote databases, servers, etc.) over the communication network.

[0075]

[0099] The display 142 may be a low-power module configured to display one or more results from the analysis of a body fluid sample collected and tested by the sample analysis system 100. For example, the display 142 may be configured to have a set of backlit icons indicating the user's hydration status, or an indication of an increase in the user's hydration, or the like. In some embodiments, the display 142 may also be configured to include a status indicator related to the sample processing device 130 or the sample handling device 110. For example, the display 142 may be configured to warn the user that the sample handling device 110 needs to be charged or that the sample processing device 130 needs to be charged with power. For example, the sample processing device 130 may be configured to be powered by a disposable or rechargeable battery power unit. In embodiments including a rechargeable power supply, the sample processing device 130 may include a configuration for recharging the power unit when plugged into a power outlet. In some embodiments, the sample processing device 130 may include a device for indicating the charge status.

[0076]

[0100] Figure 4 is a schematic diagram of different types of data handled by the sample analysis system 200 according to an embodiment. The sample analysis system 200 can be substantially similar in shape and / or function to the sample analysis system 100 described above with respect to Figure 3. For example, the sample analysis system 200 may include a sample handling device 210 which is substantially similar in shape and / or function to the sample handling device 110 described with respect to Figures 2A and 2B. For example, the sample handling device 210 may include a sample collection area, an access port, a flow path, a test area, and a set of electrodes, as described with respect to the sample handling device 110. The sample handling device 210 can be used to collect and analyze sample fluids, as described above with respect to the sample handling device 110. The sample analysis system 200 may optionally include a sample processing device 230 which is substantially similar in shape and / or function to the sample processing device 130 described above. For example, the sample processing device 230 may include, among other things, a processor, memory, a communication device, and a display. In some embodiments, as described herein, the sample analysis system 200 may include a wearable device (not shown) or a remote device (not shown) operably coupled to the sample processing system 210.

[0077]

[0101] Figure 4 illustrates the types of data used and / or stored by an exemplary sample analysis system 200. Some of the data described herein can be handled partially and / or completely by the sample handling device 210 and / or the sample processing device 230. For example, some of the data described herein can be stored, used, and / or transmitted and received in any preferred manner in the sample handling device 210 and / or the sample processing device 230. In some embodiments, the data can be handled by one or more remote devices and / or wearable devices operably coupled to the sample handling device 210 and / or the sample processing device 230. The data may include data collected, measured, and / or calculated by the sample handling device 210. The data may also include data acquired and / or calculated by the sample processing device 230. In some examples, the data may also include data received by the sample analysis system 200 (e.g., data received from a remote source or external device). In some embodiments, the data may include data collected, measured, and / or calculated by a companion application (not shown in Figure 4) operably connected to the SA system 200. A companion application (for example, companion application 147 described with respect to Figure 3) can be configured to receive data from the SH device 210 and / or the SP device 230 and / or any remote / wearable device coupled to or used with the SH device 210 / SP device 230. The companion application can be configured, for example, to receive data, perform calculations, generate and / or report additional downstream metrics (e.g., convert sweat loss to sweat rate, correlate the sweat rate with weather and / or user biometric information, and / or other).

[0078]

[0102] The impedance data 221 may include impedance measurements from a portion of the sample liquid taken by the sample handling device 210 for analysis. In embodiments including two or more test regions, the impedance data may include impedance measurements in each test region.

[0079]

[0103] In some examples, impedance measurements can be measured as a function of time. Flow rate data 223 includes data related to the calculation of the flow rate of the sample fluid being analyzed by the sample handling device 210. In some embodiments, the sample handling device 210 is configured to use impedance measurements from two or more test areas to estimate the flow rate associated with the sample fluid being analyzed, as described herein. Temperature data 225 includes temperature measurements of the sample fluid during testing by the temperature sensor 140. In some examples, temperature data 225 may include temperature measurements from other temperature sensors associated with the sample analysis system 200. For example, in some examples, temperature data 225 may include ambient temperature and / or the user's body temperature. In some examples, temperature data may include weather information received from an external source.

[0080]

[0104] User data 227 includes any data relating to a specific user and / or subgroup or user. For example, in some embodiments, the sample analysis system 200 may be configured to collect and analyze bodily fluids from a user over a period defined in a use example. The sample analysis system 200 may then be reused by the same user for a second use example (e.g., using different single-use sample handling devices or the same reusable sample handling device). The sample analysis system 200 may then be configured to track each use of the system by the same user. In some embodiments, the SA system 200 may store user history relating to the user included in the user data 227. User data 227 may also include information about one or more users, including demographic information, personal information, identification information, information representing the user's priority of use of the SA system 200, user activity profiles, and / or others.

[0081]

[0105] The SA system 200 is configured to handle additional data 229, which may include data to be calculated and data used to perform the calculations. For example, additional data 229 may include data associated with the calculation of impedance, osmotic pressure, hydration, fluid loss, electrolyte loss, sweat rate, core body temperature, etc. Additional data 229 may include data used to perform corrections to the measured values ​​based on other variables. For example, additional data 229 may include data used for temperature-based correction of impedance measurements. Additional data 229 may include predictions made based on the analysis of the sample body fluid, including predictions of fluid loss over a long period, predictions of effects on the body, predictions or suggestions for hydration strategies, and others. Additional data 229 may include data collected immediately or nearly immediately during the user's use of the sample handling device 210 (e.g., immediate flow rate, immediate hydration status, etc.). Additional data 229 may also include cumulative data collected over a period of time (e.g., cumulative fluid loss, cumulative electrolyte loss, cumulative fluid and / or electrolyte loss rate, etc.).

[0082]

[0106] The additional data 229 may also include analytical reports or summaries (e.g., post-activity summaries). In some embodiments, the additional data 229 may include historical data relating to one or more users, geographical usage areas, etc. The additional data 229 may also include population data, such as statistical data, data relating to the social networks of users of the SA system, and data used or acquired by companion applications used with the SA system. In some embodiments, the additional data 229 may include product recommendations, competency indicators, measures of competency impairment, proposed recovery plans, etc.

[0083]

[0107] Figures 5A and 5B illustrate an exemplary sample handling device 310 according to an embodiment. The sample handling device 310 can be substantially similar in shape and / or function to the sample handling devices 110 and 210 described above with respect to Figures 2A-2B and 4, respectively. For example, the sample handling device 310 may include a sample collection area, an access port, a flow path, a test area, and a set of electrodes, as described with respect to the sample handling device 110. The sample handling device 310 can be constructed in substantially the same manner as the embodiments of the sample handling device described in international application PCT / US2019 / 061301 ('301 application) entitled "Wearable systems, devices, and methods for measurement and analysis of body fluids," filed November 13, 2019, the entire disclosure of which is expressly incorporated herein by reference for all purposes.

[0084]

[0108] In some embodiments, the sample handling device 310 can be configured to include a series of test areas, each containing a set of electrodes for testing and evaluating the optimal arrangement of the test areas, as shown in Figures 5A and 5B. Such embodiments can be used to test various distances to find the optimal distance between the test areas, given specific arrangements of the test areas 318A, 318B, and 318C and known distance intervals between these test areas.

[0085]

[0109] Figure 5C shows an exploded view of an exemplary sample analysis system 300, including a sample handling device 310' which can be substantially similar in structure and / or function to the sample handling device 310 described and shown in Figures 5A and 5B. The sample analysis system 300 also includes a sample processing device 330, according to the embodiment. As shown, the sample processing device 330 includes a housing cover 331, a transparent lens 333, a display mask 335, a display 342, a PCB substrate 341, a housing bottom 337, a physical connector 325, and an electrical connector (not shown in Figure 5C) for connection to the sample handling device 310. The upper or distal side of the PCB substrate 341 (the side away from the sample handling device 310 and / or away from the user's body when the system 300 is in use) can be configured to hold a power supply (e.g., a battery) and a display connector. The proximal side (the side closer to the sample handling device 310 and / or closer to the user's body when using the system 300) may include a pogo pin that serves as an electrical connector 325 between the sample processing device 330 and the sample handling device 310. The pogo pin (not shown) can be bounded to a corresponding pin pad on the sample handling device 310 to provide the necessary electrical connection to operably couple the sample processing device 330 and the sample handling device 310, as described above with respect to the sample analysis systems 100 and / or 200. In some embodiments, the system 300 may include a thermoplastic adapter ring 339, as shown in Figure 5C, which is configured to attach the housing of the sample processing device 330 to the sample handling device 310.

[0086]

[0110] Figure 6 shows a flowchart illustrating a method 450 of using a sample analysis system including a sample handling device and a sample processing device, such as those described herein. The sample analysis system can be used to collect, test, and analyze bodily fluid (e.g., sweat) samples at near-immediate, real-time speeds and / or cumulatively over long periods of time. In some embodiments, the sample analysis system may be similar to and / or substantially identical to any of the sample analysis systems 100, 200, and / or 300, which are linked to any of the sample handling devices 110, 210, and / or 310 described herein.

[0087]

[0111] Method 450 includes, in 451, taking a bodily fluid sample via a sample handling device of a sample analysis system. In some examples, the bodily fluid source may be sweat, for example. When the sample collection area of ​​the sample handling device is filled to capacity, or when a substantial amount of sample bodily fluid has been collected, the method includes, in 452, guiding the sample liquid to contact a first electrochemical interface. In some examples, the collected sample is continuously guided toward the electrochemical interface, tested, and discharged when a new sample is continuously collected. For example, the sample liquid is guided through a channel via an access port to a test area that brings the sample bodily fluid into contact with the test ends of a pair of electrodes.

[0088]

[0112] Method 450 includes, in 453, applying an excitation signal to the sample fluid in contact with the first electrochemical interface via a first excitation electrode. The excitation signal can be any suitable signal (e.g., a DC and / or AC pulse) having any suitable set of parameters that define the excitation signal (e.g., magnitude, polarity, duration, etc.). In some embodiments, the excitation signal is delivered via test ends of a pair of current-delivering electrodes included in the sample handling device of the sample analysis system in use. Method 450 further includes, in 454, receiving a first response signal via a first sensing electrode in response to the application of the first excitation signal. The sample analysis system may be configured to receive a response signal (e.g., a nearly immediate response signal) from the sample fluid after the application of the excitation signal. For example, a response voltage can be read via test ends of a pair of voltage-sensing electrodes included in the sample handling device in use.

[0089]

[0113] In some embodiments, as previously described, two or more test areas can be included at known distance intervals along the flow path in the sample handling device. Two or more electrochemical interfaces in the two or more test areas can be used to obtain a response from a portion of the body fluid sample as a portion of the sample body fluid is guided to flow along the flow path, based on which flow rate estimation is performed. Thus, in some examples, method 450 includes a set of optional steps 455-457 (shown by dotted lines) to guide and use an exemplary second test area including a second excitation electrode and a second sensing electrode to obtain a second response signal from a portion of the sample liquid tested at a first electrochemical interface in the first test area.

[0090]

[0114] In 455, Method 450 includes guiding the sample body fluid to contact a second electrochemical interface in a second test area, for example. In 456, Method 450 includes applying a second excitation signal to the sample body fluid in contact with the second electrochemical interface via a second excitation electrode. As described with respect to the first excitation signal, the second excitation signal can be any suitable signal (e.g., a DC and / or AC pulse) having any suitable set of parameters that define the excitation signal (e.g., magnitude, polarity, duration, etc.). In some examples, the second excitation signal can be substantially the same as the first excitation signal (e.g., similar or identical in magnitude, polarity, duration, etc.). In some embodiments, the excitation signal is delivered via the test ends of a second set of current-delivering electrodes included in the sample handling device of the sample analysis system in use.

[0091]

[0115] In 457, the method includes receiving a second response signal via a second sensing electrode in response to the application of a second excitation signal at a second electrochemical interface.

[0092]

[0116] In some embodiments, one or more current-delivering electrodes can be shared between two or more electrochemical interfaces in two or more test areas. For example, an excitation electrode having a single termination connected to an excitation signal source (e.g., a termination that telecommunicates with a part of a sample processing device via an electrical connector) may have two sample or test ends located at two electrochemical interfaces in two test areas. Thus, the shared excitation electrode can, for example, receive a single excitation signal from a sample processing device and simultaneously apply a first excitation signal and a second excitation signal (which may be the same as the first excitation signal) to parts of the sample fluid in the first and second test areas.

[0093]

[0117] A first excitation signal and / or a second excitation signal can be continuously applied while the sample fluid is guided to flow through the flow path of the sample handling device, such that a given portion of the sample fluid is expected to pass through a first electrochemical interface in a first test area at a first time point and through a second electrochemical interface in a second test area at a second time point occurring only a specified duration or time delay after the first time point.

[0094]

[0118] The first and second response signals can be received and analyzed as a function of time. In some embodiments, the first and second response signals can be analyzed in the time domain. In some examples, one or more algorithms (e.g., pattern recognition algorithms, template matching algorithms, and / or others) can be used to identify features in the first and second responses as a function of time that can be used to determine a first time point in time when a first response is obtained from a portion of the sample fluid at a first electrochemical interface (e.g., a first test area) and a second time point in time when a second response is obtained from the same portion of the sample fluid at a second electrochemical interface (e.g., a second test area).

[0095]

[0119] In some embodiments, one or more statistical and / or analytical procedures may be performed to identify a first response and / or a second response associated with a portion of the sample fluid. In some examples, one or more procedures may be performed using statistical and / or machine learning tools, including a neural network (e.g., a deep network) that can be constructed in conjunction with a sample handling or sample processing device. For example, the procedure may include examining separate time windows of the first and second response signals as a function of time. In some examples, the procedure may include calculating the cross-correlation between a identified time window of the first response signal and a identified time window of the second response signal. In some examples, the relative maximum point of the correlation value (e.g., the maximum value of the correlation value) may be used to determine the relative shift between the first and second response signals, and based on this relative shift, the duration or time delay between the first and second time points can be calculated.

[0096]

[0120] In some embodiments, the first and second response signals may be transformed into phase space and analyzed for maximum phase correspondence to identify the first and / or second response associated with a specified portion of the sample fluid. In some embodiments, the transformation into phase space may be computational and / or time-intensive. Thus, the sample analysis system may be configured to detect the state of use and select an appropriate calculation method based on the detected state of use. For example, if a real-time state of use is detected with limited time and / or processing capacity, a method may be used to determine the time delay identified using maximum correlation. If a post-activity state is detected and / or time and / or processing capacity are not limited, a calculation based on phase space may be employed.

[0097]

[0121] In some embodiments, the volumetric flow rate associated with the sample fluid being analyzed can be estimated based on the calculation of a volume related to a known distance interval between a first electrochemical interface and a second electrochemical interface, and based on the calculated duration or time delay between a portion of the sample fluid that has passed through the first electrochemical interface and a portion of the sample fluid that has passed through the second electrochemical interface.

[0098]

[0122] In 458, method 450 includes directing the sample fluid to an outlet port so that it is discharged into the environment. In some embodiments, the discharge of the sample fluid can impart momentum to the remaining fluid flow in the channel (for example, by generating a pressure difference configured to draw more fluid towards the outlet port).

[0099]

[0123] In some embodiments, as previously described, the sample handling device of the sample analysis system may be configured to continuously collect a body fluid sample or a certain volume of body fluid and guide it to one or more test areas, test a portion of the sample, and discharge the sample to make room for the next sample. Thus, Method 450 can be repeatedly performed on multiple samples yielding intermittent or continuous results from testing and analysis, as represented by the loop between steps 458 and 451 in Method 450. The sample analysis system may be configured to reduce, as necessary to meet the user's requirements, the time required to collect a sufficient body fluid sample for testing, the time required to guide the liquid to the test areas and test the sample, and the time required to analyze the test results and discharge the sample. In some examples, the adaptation of one or more parts of the sample handling device may be made to form a series of sample handling devices with varying response speeds, so that different users can obtain a custom or personalized sample analysis system with a personalized sample handling device and / or a personalized sample processing device. In some embodiments, data from different users (e.g., a team) can be stored, retained, and / or displayed to monitor the hydration levels, electrolyte loss, and / or sweating of multiple users. In some examples, a user can select a suitable sample analysis system based on the type of activity they can perform and / or the sample analysis volume or rate they desire.

[0100]

[0124] For example, a user with a history of excessive sweating may use a sample handling device that includes a sample collection area with openings that are more suitable for covering only a small number of sweat glands, compared to a sample handling device used by a user with very little sweating. In some cases, athletes who engage in strenuous exercise requiring faster sample analysis may use a sample handling device with a sample collection area with a smaller liquid capacity, so that smaller amounts of sweat are tested more frequently when the user, an athlete engaging in strenuous exercise, uses the sample analysis system during activity.

[0101]

[0125] In some embodiments, the sample processing device can be personalized to store and retain a history of results from the analysis of the user's physical or health condition for future use of the sample analysis system. In some embodiments, the sample analysis system can be configured to export a set of collected data and / or analysis from the memory of the sample processing device to a remote device at a predetermined intermittent interval. For example, in some embodiments, the sample analysis system can export analysis data and / or analysis results to a wearable device or smartphone each time the sample handling device is changed or replaced. In some embodiments, the exported data can be retained and recorded and associated with a suitable identifier tagged to the user. The data associated with the user can then be used to graphically display the user's physical condition, health condition, performance or other progress, and in some embodiments, the physical / health condition of an individual user can be predicted before performing a planned activity. In some embodiments, the sample analysis system may include a remote application running on a remote server or computer device to provide the user with a plan (e.g., a hydration strategy that may be optimal for a user such as an athlete when planning to perform in a critical sporting event). Remote applications may include predictive algorithms that can be used to devise strategic plans for hydration, electrolyte balance maintenance, and other purposes.

[0102]

[0126] As previously described, the sample analysis systems and / or sample handling devices described herein can be integrated with wearable devices such as smartwatches, odometers, and GPS systems. In some examples, when a sample analysis system including a sample handling device is integrated with a wearable device, the sample handling device may include interface elements for physical and electrical connection with the sample handling device. The sample handling device may perform functions such as providing commands for the delivery of excitation signals, providing excitation signals in the form of test currents to the ends of electrodes, and receiving response signals obtained from the sample under test via electrodes. The sample handling device may include electronic equipment necessary for analyzing the response signals and / or communicating data to a remote computer device or the like. For example, the electronic equipment may be programmed with a unique analysis code for interpreting the collected readings. Interpreted readings may be output to the display of the sample handling device to provide the wearer with information on sweat volume and overall hydration status. In examples where the sample handling device can directly interface with a wearable device, the wearable device may be configured to directly engage with the sample handling device physically and electrically and to perform functions such as providing commands, providing excitation signals, and receiving and analyzing response signals. Electronic devices included in the wearable device can be used to run a program using a unique analysis code for interpreting the collected readings. The interpreted readings can be output to the wearable device's display or a display associated with a remote computer device (e.g., a smartphone) to provide the wearer with information about sweat volume and overall hydration status.

[0103]

[0127] Figure 7 is a flowchart illustrating an exemplary method 550 for calculating the amount of sweat produced by a user using a sample handling device, according to an embodiment. In 551, method 550 includes receiving a first response signal at a first time point from a sample body fluid taken from the user, which is in contact with a first electrochemical interface of the device (e.g., sample handling devices 110, 210, and / or 310). In 552, method 550 includes receiving a second response signal at a second time point from a sample body fluid in contact with a second electrochemical interface located at a known distance from the first electrochemical interface of the device. The second time point may be after the first time point. As previously described with respect to method 450 above, the first and second response signals can be obtained in response to the application of a first excitation signal at the first electrochemical interface and the application of a second excitation signal at the second electrochemical interface, respectively.

[0104]

[0128] In 553, method 550 includes calculating the flow rate of a sample fluid through a sample handling device based on a first response signal, a second response signal, and a known distance. For example, the linear flow velocity can be calculated by estimating the time delay between a portion of the sample fluid that has passed through a first electrochemical interface in a first test area and the same portion of the sample fluid determined by pattern recognition, template matching, determination of the maximum cross-correlation in a time-domain signal, determination of the maximum phase correlation in phase space, and / or otherwise, as described above. The volumetric flow rate can be calculated by applying the known volume of the portion of the flow path through which the fluid sample is thought to be passing to the calculated duration or time delay between the response from the first test area received at the first electrochemical interface and the corresponding second response signal received at the second electrochemical interface in the second test area. In some examples, the measured flow rate can be verified against a known volumetric flow rate by using a calibrated syringe pump. In some embodiments, the calculated flow rate of a portion of the sample fluid can be used to determine the local expression or secretion rate of the fluid in a part of the user's body. For example, in some cases, the calculated flow rate of a portion of the sample fluid can be used to determine the amount of localized sweating on the user's body in the area where the device is attached to the user (e.g., arms, chest, abdomen, and / or other areas). For example, known values ​​of the size of the opening (e.g., opening 122), the size of the access port (e.g., access port 114), the size of the sample collection area (e.g., sample collection area 112), and / or the size of the flow path of the SH device in use (e.g., flow path 116) can be used to predict the amount of localized sweating on the user's body in the area where the device is attached to the user, based on the calculated flow rate of a portion of the sample fluid.

[0105]

[0129] In some examples, method 550 includes receiving user information and / or device information in 554. User information may include, for example, biometric data relating to the user (e.g., height, weight, BMI, sex, age, race, etc.). In some examples, user information may include, for example, physiological data including heart rate, respiratory rate, body temperature, etc. In some examples, user information may include the geographical location of the user's activity, altitude, atmospheric pressure, ambient weather conditions, seasonal variations, etc. Device information may include information relating to the SH device in use, such as sampling parameters (e.g., dimensions relating to the sampling area, dimensions relating to the access port, manufacturing information relating to the device (e.g., device type (e.g., disposable / reusable) model, batch, identification marker, and / or others)), and device usage (e.g., usage time, usage period, and / or others).

[0106]

[0130] In 555, method 550 includes calculating the amount of sweating of the user based on the flow rate and information through the device. For example, the local secretion or expression rate of body fluid can be calculated based on information about the device (e.g., the amount to be collected, the area from which the body fluid is collected, the area of ​​the body on which the sample handling device is placed to collect the body fluid, etc.) and based on the calculated flow rate of body fluid through the sample handling device. The local secretion rate can be associated with the part of the body to which the device is attached (e.g., the forearm, upper arm, back of the hand, chest, back, abdomen, etc.).

[0107]

[0131] For example, based on the flow rate of sweat collected in the sample handling device, and based on the area defined by the inlet port and / or size (e.g., 12 mm in diameter) and / or volume of the sampling area of ​​the sample handling device, the local sweat rate, also referred to herein as local sweating, can be calculated for the part of the user's body from which sweat is collected during use. In some embodiments, local fluid loss information can be used to predict the user's total body sweating. Based on information about the user (e.g., the user's body surface, height, weight, race, ethnicity, diet, health, and / or other), the local sweat rate can be predicted to obtain the total body sweating rate. In some examples, the measured total body sweating can be validated against known methods for estimating sweating by using a calibrated syringe pump (e.g., by using Macroduct® Technology).

[0108]

[0132] In some embodiments, user behavioral information (e.g., activity, pace of activity, activity intensity, percentage of effort involved, VO2max, etc.) can be used to calculate changes related to whole-body sweating during activity (e.g., fluctuations in sweat rate with changes in intensity, effort, etc.). In some embodiments, further calculations can be performed using whole-body sweating and other relevant data obtained from additional sources. For example, environmental information (e.g., heat, humidity, cloud cover, wind, altitude, etc.) can be obtained from one or more sources (e.g., remote devices, wearable devices, etc.), and based on whole-body sweating and environmental information, the SA system can be used to calculate changes in whole-body sweating rate due to environmental factors and fluctuations in environmental factors. In some embodiments, the methods and / or systems described herein can be used to generate predictive models that can be used to provide the user with predictions and / or advance guidance. For example, in some embodiments, whole-body sweating rate, core body temperature, behavioral information, and environmental information can be used to calculate the user's sensitivity to these factors and to create a sensitivity model of the user's sweating rate based on these variables. The information and calculated values ​​can be used to generate a predictive model of whole-body sweat volume for each individual user at a predicted future location, based on predicted environmental information (e.g., temperature, humidity, altitude, wind, cloud cover, etc.) in relation to the predicted duration and intensity of the user's activity.

[0109]

[0133] Figure 8 is a flowchart illustrating an exemplary method 650 for estimating a user's hydration state using a sample handling device, according to an embodiment. Method 650 includes, in 651, receiving the user's total body sweat volume measured at multiple points in time over a period of time. The sweat volume may be total body sweat volume measured using methods 450 and / or 550, respectively, as described in Figures 6 and 7. Method 650 further includes, in 652, receiving information about the user and / or the user's behavior. For example, information about the user may include biological, biological, and / or physiological information. Examples of behavioral information may include information about the user's initial body weight and / or the user's fluid intake over the period of total body sweat volume measurement. In 653, the method includes calculating the user's hydration state over a period of time based on the total body sweat volume and the information about the user's physiological function and / or behavior over that period. For example, based on the measured total body sweat volume over a specified period of time, the sample analysis system can calculate the cumulative fluid loss suffered by the user. In some embodiments, cumulative fluid loss can be estimated from the calculation of the time integral of whole-body sweating, which is considered a function of time over a specified period. In some examples, the calculation of cumulative fluid loss suffered by the user can be verified by other independent methods, for example, by measuring the change in body weight from the beginning to the end of a specified period. The cumulative fluid loss measured over that period can be measured together with the user's initial body weight, and by taking into account fluid intake during the specified period, the user's net hydration state can be estimated as a percentage change in body weight.

[0110]

[0134] In some embodiments, impedance measurements may be affected by temperature. It may be desirable to correct or adjust impedance measurements obtained from bodily fluids using the sample handling apparatus described herein. Figure 9 is a flowchart illustrating an exemplary method 750 for estimating temperature-adjusted impedance measurements using a sample handling apparatus according to an embodiment.

[0111]

[0135] In 751, method 750 includes receiving a temperature associated with a sample body fluid taken from a user. In 752, method includes receiving a first response signal obtained from the sample body fluid in contact with a first electrochemical interface of the apparatus at a first time point. The temperature may be a user-related temperature measurement (e.g., skin temperature) made using a temperature sensor associated with the sample handling apparatus (e.g., temperature sensor 140 of sample handling apparatus 110) during measurement of the impedance associated with the sample body fluid at the electrochemical interface of the sample handling apparatus, as described herein.

[0112]

[0136] In 753, method 750 includes calculating a first impedance measurement based on a first response signal and temperature. The first impedance measurement can be corrected for temperature using a suitable temperature-based correction algorithm adapted to determine the correction amount. In some examples, the impedance measurement and / or temperature-corrected impedance measurement can be verified using independent methods, for example, by commissioning with a blind temperature sweep study along with impedance measurements made using a fixed resistor.

[0113]

[0137] In 754, method 750 includes receiving a second response signal at a second time point from a sample fluid in contact with a second electrochemical interface located at a known distance from a first electrochemical interface of the apparatus. In 755, as previously described with respect to the first response signal, the method involves calculating a second impedance measurement based on the second response signal and temperature. The second impedance measurement may be a temperature-corrected measurement using the temperature-based correction algorithm described above.

[0114]

[0138] In 756, method 750 includes calculating a first osmotic pressure and a second osmotic pressure based on a first impedance measurement and a second impedance measurement corrected for temperature. In some embodiments, the sample analysis system may be configured to generate a correlation curve that can be used to create an algorithmic formula for converting temperature-corrected impedance measurements to osmotic pressure.

[0115]

[0139] In 757, method 750 includes calculating the flow rate of the sample body fluid through the apparatus based on a first response signal, a second response signal, and a known distance. The calculation of the flow rate may be the same as in methods 450 and / or 550 described above. In 758, the method involves calculating the cumulative electrolyte loss based on a first osmotic pressure, a second osmotic pressure, and the flow rate. The measurement of the cumulative electrolyte loss may be based on the method for measuring cumulative fluid loss described in methods 550 and / or 650. For example, the flow rate of the sample body fluid and the immediate electrolyte loss over a period of time can be used to calculate the cumulative electrolyte loss, which can be defined by the time integral of the immediate electrolyte loss.

[0116]

[0140] As previously explained, in 759, the sample analysis system may receive information on the user's physiological functions and / or behavior, and in 760, the method includes calculating the user's physical condition / health status based on cumulative electrolyte loss and information. In some examples, method 750 includes calculating the user's health status based on cumulative electrolyte loss and information.

[0117]

[0141] In some examples, the sample handling devices and / or sample analysis systems described herein can be used to determine a user's core body temperature based on one or more temperature measurements taken using the sample handling device. Figure 10 is a flowchart illustrating an exemplary method 850 for calculating a user's core body temperature using a sample handling device, according to an embodiment. In 851, method 850 includes receiving the temperature associated with a sample body fluid taken from the user. In 852, method 850 includes receiving the user's sweat volume measured at multiple points in time over a period of time. In 853, method 850 includes receiving information about the user and / or information about the user's behavior. For example, information about the user may include biological, biological, and / or physiological information. Examples of behavioral information may include information about activities performed by the user over the measurement period (e.g., measurements obtained from an accelerometer worn by the user), energy consumed by the user over the measurement period, and / or other information. Another example of behavioral information may include the user's water intake over the measurement period of total body sweat volume. However, in some embodiments, method 850 can use the amount of sweat obtained in 852 as a substitute for information about the user's activity, and does not require additional information about the user's activity in 853.

[0118]

[0142] In 854, method 850 includes calculating the core body temperature over a period of use based on temperature and sweat rate. In some embodiments, the sample analysis system can determine blood flow using validated sweat rate data and / or an indicator of the activity level to which the use is relevant. The temperature measurement performed may be the user's skin temperature. In some embodiments, the determination of core body temperature may be based on considering the temperature change from the core to the extremities (skin, etc.) as a function of blood flow. In some examples, the calculated core body temperature may be validated by an independent method, such as using a chronometer.

[0119]

[0143] Figure 11 is an exemplary plot showing measured impedance and flow rate values ​​of a sample fluid over a period of time, measured and analyzed using an exemplary SA system according to an embodiment. The curve represents the impedance values ​​measured at two electrochemical interfaces (e.g., test areas) over 20 minutes. The step plot represents the total flow rate of the fluid through the sample handling device. In some examples, as shown, the phase shift measured between the two impedance plots is inversely proportional to the flow rate through the SA system.

[0120]

[0144] Figure 12 is an exemplary plot showing the validation of predicted fluid loss levels in a subject using an exemplary SA system according to an embodiment. Dark bars represent estimated actual total fluid loss, and light bars represent the quality of prediction compared to actual values.

[0121]

[0145] Figure 13 is an exemplary plot showing the verification of impedance measurements related to body fluids measured using an exemplary SA system according to an embodiment. The plot shows impedance measurements on the x-axis made using a fixed resistor, plotted against impedance measurements on the y-axis made using predictions by using the sample handling apparatus described herein, and fitted with a straight line, representing the close similarity and / or linear relationship between the predicted impedance measurements and the actual impedance measurements.

[0122]

[0146] Figure 14 further shows a plot of measurement error estimated by comparing predicted values ​​with actual measured values ​​using independent means. Figure 14 is an exemplary plot showing the measurement error as a function of actual impedance measurements to verify the use of the exemplary SA system. The measurement error can be related to impedance measurements of body fluids performed using the exemplary SA system according to the embodiment.

[0123]

[0147] Figure 15 is an exemplary plot showing test impedance and temperature measurements associated with a test liquid (having a constant osmotic pressure) measured under controlled temperature fluctuations by performing a temperature sweep using an exemplary SA system according to an embodiment. The plot shows the temperature sweep 1561 and the change in the measured impedance 1562 with respect to the temperature change represented by the temperature sweep 1561.

[0124]

[0148] Figure 16 is an exemplary plot showing data relating to the relationship between temperature measurements and the measured impedance of a test liquid with a known osmotic pressure, calculated using an exemplary SA system according to an embodiment. For example, in some embodiments, a mathematical model can be constructed using data collected using other independent methods that measure properties such as impedance from the sample handling device and / or sample body fluid. In some embodiments, the mathematical model can be represented by an expression (e.g., an equation) related to a fitted curve used to fit the model to the data. In some examples, the data can be collected during the execution of the test under controlled conditions, for example, in a temperature sweep as described with respect to Figure 15.

[0125]

[0149] Figure 17 is an exemplary precision analysis plot showing the relationship between impedance measured from a sample fluid and temperature obtained from actual measurements. The plot also shows predicted impedance values ​​represented by a horizontal line, which are based on measured values ​​and / or data from mathematical models, such as the data shown in Figure 16, created using a sample handling apparatus as described herein. More specifically, this plot shows that, according to the embodiment, the error rate that occurs while performing temperature correction using the SA system is only 0.1775%.

[0126]

[0150] Figure 18 is an exemplary plot used to validate the conversion method used to convert impedance measurements to osmotic pressure. The plot in Figure 18 shows the relationship between the osmotic pressures of several known control solutions (of known osmotic pressure and / or electrolyte content) and impedance measurements obtained from several control solutions used as sample liquids tested by exemplary SA systems of several embodiments. Specifically, the plot in Figure 18 shows that an accuracy of 97.29% was obtained in the calculation of osmotic pressure based on impedance measurements obtained using the SA system, as described herein. In some examples, the plots shown can be used as calibration curves to calibrate the SA analysis system according to some embodiments. Some such relationships can be used to develop a suitable mathematical model using appropriate equations and / or formulas for calibration curves that can be used to generate a model of the relationship between osmotic pressure and impedance. In the exemplary curves shown in Figure 18, control solutions of known osmotic pressure (i.e., electrolyte content) were delivered through a set of test sample analysis systems using an injection pump in a benchtop setting with several different sample processing devices and several different sample handling devices. As described above, the best-fit curve shows an accuracy of 97.3%. The equation used to obtain the curve acts as an algorithm that converts temperature-controlled impedance into osmotic pressure.

[0127]

[0151] Figure 19 is an exemplary plot showing osmotic pressure, temperature, and impedance measurements obtained over time from a sample liquid during a blind osmotic pressure test using the SA system according to an embodiment. The plot shows raw impedance measurements and predicted osmotic pressure data measured and calculated by the exemplary sample analysis system, compared to the actual osmotic pressure from a control solution with a known osmotic pressure. A blind osmotic pressure test was performed in a benchtop setting using a control solution with a known osmotic pressure, and raw impedance values ​​were recorded using a set of sample processing devices. The collected data and the developed algorithm were used to convert the raw data into temperature-corrected osmotic pressures relative to the measurements. The plot in Figure 19 shows the actual osmotic pressure of the control solution delivered by the test setup and the predicted / calculated osmotic pressure values ​​using the SA system according to an embodiment. Figure 20 below shows that the accuracy of the above test is 98.3%.

[0128]

[0152] Figure 20 is an exemplary plot showing the mean absolute error rate (MAPE) values ​​associated with measurement data (e.g., the data shown in Figure 19) to validate the osmotic pressure values ​​predicted by the SA system according to the embodiment, using osmotic pressure measured using an independent method. The actual and predicted values ​​yielded a mean absolute error rate (MAPE) of 1.7%(B) or an accuracy of 98.3%, as shown in Figure 20.

[0129]

[0153] Figures 21A–21D show exemplary plots of ion concentrations (e.g., [Na+], [K+], [Cl-]) and sweating rates in sweat samples obtained from multiple locations on the body of users performing low and moderate levels of activity. Specific levels or thresholds of ion concentration that can be used to determine the optimal positioning of the sample handling device for use and obtain desired results are also shown (dotted horizontal lines).

[0130]

[0154] Figure 22 is an illustrative table showing changes in ion concentrations in sweat samples obtained from multiple locations on the body of users performing low- and moderate-level activities. It also shows indicators (boxes) for specific locations that can be used to determine the optimal positioning of the sample handling device for use and to obtain the desired results.

[0131]

[0155] Figure 23 shows an illustrative diagram of a companion application described herein, used with a sample handling device, according to several embodiments.

[0132] conclusion

[0156] In summary, this specification describes systems and methods used for the immediate measurement and analysis of body fluid samples to evaluate the characteristics and / or physiological / health status parameters of a user's body fluids (e.g., hydration level, electrolyte loss, sweating rate, etc.).

[0133]

[0157] While various embodiments have been described above, it should be understood that these embodiments are presented merely as examples and not limiting. Where the schematic diagrams and / or embodiments described above represent specific components arranged in a particular orientation or position, the arrangement of components may be modified. While embodiments have been described in particular, it should be understood that various changes in shape and detail are possible. While various embodiments have been described as having specific features and / or combinations of components, other embodiments having any combination of features and / or components from any of the embodiments described above are also possible. Any part of the apparatus and / or method described herein may be combined in any combination, except for mutually exclusive combinations. The embodiments described herein may include various combinations and / or partial combinations of the functions, components, and / or features of the different embodiments described.

[0134]

[0158] If the methods described above represent specific events occurring in a particular order, the order of those events may be modified. Additionally, some events may not only occur sequentially as described above, but also simultaneously in parallel processes, if possible.

Claims

1. The process involves collecting a bodily fluid sample within the sample collection area of ​​the device, The body fluid sample is guided from the sample collection area to a first electrochemical interface including a first excitation electrode and a first sensing electrode, Applying a first excitation signal from the first excitation electrode to the portion of the body fluid sample at the first electrochemical interface, To sense a first response signal in response to the application of the first excitation signal, The first impedance data relating to the portion of the bodily fluid sample is measured at a first time point based on the first response signal. The bodily fluid sample is guided from the first electrochemical interface through a channel to a second electrochemical interface including a second excitation electrode and a second sensing electrode, The second excitation signal is continuously applied from the second excitation electrode to the bodily fluid sample at the second electrochemical interface, To sense a second response signal in response to the application of the second excitation signal, The second impedance data relating to the bodily fluid sample is measured based on the second response signal, The first feature associated with the first impedance data is compared with the second feature associated with the second impedance data, and based on the similarity between the first feature and the second feature, the second time point in time when the portion of the bodily fluid sample passed the second electrochemical interface is identified. Based on the similarity between the first feature and the second feature, and the difference between the second time point and the first time point, the flow rate of the bodily fluid sample passing through the flow path is determined. Methods that include...

2. To obtain information related to the user's physiological functions, Based on the information relating to the physiological functions of the user and the flow rate of the body fluid sample, the characteristics of the body fluid source from which the body fluid sample was collected are determined. The method according to claim 1, further comprising:

3. The method according to claim 2, wherein the source of the body fluid is sweat, and the characteristic of the source of the body fluid is the amount of sweat.

4. The osmotic pressure related to the portion of the body fluid sample is determined based on the first impedance data or the second impedance data relating to the portion of the body fluid sample. To obtain information related to the user's physiological functions, Based on the osmotic pressure and the information relating to the user's physiological function, the electrolyte content related to the body fluid source from which the body fluid sample was collected is calculated. The method according to claim 1, further comprising:

5. To obtain information related to the user's physiological functions, To obtain information related to the user's actions, wherein the actions relate to water intake or water loss, The rate of change in the user's hydration is determined based on at least one of the following: the information relating to the user's physiological functions, the information relating to the user's behavior, or the flow rate of the bodily fluid sample. The method according to claim 1, further comprising:

6. To receive the temperature related to the aforementioned body fluid sample, The first and second impedance data, which are temperature-corrected, are calculated based on the temperature for the portion of the bodily fluid sample. The method according to claim 1, further comprising:

7. Receiving temperature related to the user's body, To obtain information related to the physiological functions of the user, The core body temperature of the user is determined based on the temperature, the information related to the user's physiological functions, and the flow rate of the body fluid sample. The method according to claim 1, further comprising:

8. The method according to claim 1, wherein the second excitation electrode and the first excitation electrode are shared excitation electrodes having two sample ends.

9. A memory that stores one set of instructions, A processor coupled to the memory, configured to execute the instructions stored in the memory. A system that includes, The aforementioned processor, A first response signal is received at a first time point from a first portion of a sample body fluid taken from the user, which is in contact with the first electrochemical interface of the device related to the system. The first impedance associated with the first response signal is calculated, Identify the first feature related to the first impedance, A second response signal obtained from a second portion of the sample fluid that is in contact with the second electrochemical interface of the apparatus related to the system is continuously received. The second impedance related to the second response signal is calculated, Identify the second characteristic related to the second impedance, The first feature is compared with the second feature, and based on the similarity between the first and second features, a second point in time is identified when the first portion of the sample fluid passes through the second electrochemical interface. The distance between the first electrochemical interface and the second electrochemical interface, and information regarding the distance over which the flow of the sample fluid moves, is received. Based on the first impedance, the second impedance, and the distance, the flow rate of the sample fluid through the flow path included in the apparatus is calculated. It is configured in such a way. system.

10. The system according to claim 9, wherein the aforementioned features include phase.

11. The aforementioned sample bodily fluid contains sweat, and the processor is Based on the first impedance, the second impedance, and the flow rate, the amount of sweat produced by the user is calculated. The system according to claim 9, configured as described above.

12. The aforementioned processor further, The temperature related to the sample body fluid is received, The system according to claim 11, wherein the amount of sweat calculated based on a temperature-corrected first impedance and a temperature-corrected second impedance is configured to calculate based on the temperature, the temperature-corrected first impedance, and the temperature-corrected second impedance.

13. The aforementioned processor further, The temperature related to the user's skin is received, The system receives information related to the physiological functions of the user. Based on the temperature, the information related to the user's physiological functions, and the amount of sweat, the user's core body temperature is determined. The system according to claim 11, configured as follows.

14. The aforementioned processor further, The system receives information related to the physiological functions of the user. Based on the information relating to the user's physiological functions and the amount of sweat, the user's hydration state is determined. The system according to claim 11, configured as follows.

15. The aforementioned processor further, The system receives information related to the physiological functions of the user. Based on the information relating to the user's physiological functions and the amount of sweat, the electrolyte loss suffered by the user is determined. The system according to claim 11, configured as follows.

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