Wearable system, device and method for measuring and analyzing bodily fluids

Abstract

The present disclosure relates to wearable systems, devices and methods for measuring and analyzing bodily fluids. Systems, devices, and methods are described herein for various embodiments of a sample analysis system worn by a user configured to collect a sample of bodily fluid, and to measure and analyze the bodily fluid to determine characteristics and / or health parameters of the bodily fluid of the user (e.g., degree of hydration, electrolyte loss, rate of perspiration, etc.

Description

[0001] This application is a divisional application of the invention application with the application date of November 13, 2019, international application number PCT / US2019 / 061301, the date of entry into the Chinese national phase of July 1, 2021, application number 201980087485.3, and the invention creation name of "Wearable systems, devices, and methods for measuring and analyzing body fluids".

[0002] Cross-reference to related applications

[0003] This application claims the priority and benefits of U.S. Provisional Application No. 62 / 760,202, titled "Wearable systems, devices, and methods for measure and analysis of body fluids", filed on November 13, 2018, the entire content of which is expressly incorporated by reference for all purposes. Technical field

[0004] The embodiments described herein relate to systems, devices, and methods for near-instantaneous measurement and analysis of body fluids and potential analytes contained therein. The embodiments described herein also relate to implementations of real-time hydration detection systems and hydration strategy development systems for use during activity. Summary of the invention

[0005] Systems, devices, and methods are described herein for various embodiments of a sample analysis system worn by a user, the sample analysis system being configured to collect a sample of a body fluid and measure and analyze the body fluid to determine characteristics of the body fluid and / or health parameters of the user (e.g., degree of hydration, electrolyte loss, sweating rate, etc.). Brief description of the drawings

[0006] Figure 1 is a schematic diagram of an example use of a sample handling device on the surface of a user's skin according to an embodiment.

[0007] Figure 2A and 2B is a schematic diagram of a sample handling device according to an embodiment. The sample handling device can be used with a sample analysis system ("SA system").

[0008] Figure 3 is according to an embodiment including Figure 2A , 2B of a sample analysis system ("SA system") of an example sample handling device.

[0009] Figure 4 is a schematic diagram of the structural components of a sample handling device according to one embodiment.

[0010] Figure 5A Schematic diagram of a perspective view of an exemplary sample handling device according to an embodiment.

[0011] Figure 5B is Figure 5A Schematic diagram of a top view of the exemplary sample handling device in

[0012] Figure 6 is Figure 5A Schematic diagram of an exploded view of the exemplary sample handling device of , illustrating the component layers of the sample handling device.

[0013] Figures 7A-7C Schematically illustrates Figure 5A , 5B and the component layers of the sample handling device of 6.

[0014] Figure 8 is Figure 5A , 5B and a schematic diagram of a part of the electrode and channel layers of the sample handling device of 6.

[0015] Figure 9 is Figure 8 Schematic diagram of a collection of electrodes in the interface layer of .

[0016] Figure 10 Schematic diagram of a perspective view of an exemplary sample handling device of an SA system according to an embodiment.

[0017] Figures 11A-11C Schematic diagrams of a top view, a bottom view, and a perspective view of an exemplary sample handling device of an SA system according to an embodiment.

[0018] Figure 12 is taken along line 12 - 12 of Figure 11A Schematic diagram of a cross-section of the sample handling device of .

[0019] Figure 13 is taken along line 13 - 13 of Figure 11A Schematic diagram of a perspective view of a cross-section of the sample handling device of .

[0020] Figure 14 is taken along line 14 - 14 of Figure 11C Schematic diagram of a perspective view of a cross-section of the sample handling device of .

[0021] Figure 15 Schematic diagram of a top view of a sample handling device that can be used with an exemplary SA system according to an embodiment.

[0022] Figure 16 is Figure 15 Schematic diagram of an exploded view of the sample handling device of , showing the component layers of the sample handling device.

[0023] Figure 17 is according to an embodiment Figures 15-16 Schematic diagram of the electrode and channel layers for sample handling

[0024] Figure 18 Illustrates a schematic flowchart of an example method for measuring and analyzing a user's degree of hydration using an SA system according to an embodiment

[0025] Figure 19 Schematic diagram of a perspective view of an example SA system integrated with an example wearable device according to an embodiment

[0026] Figure 20 is with Figure 19 example wearable device integrated Figure 19 Schematic diagram of a perspective view of the rear part of an SA system

[0027] Figure 21 Schematic diagram of a top view of a sample handling device that can be used with an example SA system according to an embodiment

[0028] Figure 22 is according to an implementation Figure 21 Top view image of a sample handling device

[0029] Figure 23A is according to an implementation Figure 21 Schematic diagram of a perspective exploded view of a sample handling device, illustrating the component layers of the sample handling device

[0030] Figure 23B is according to an implementation Figure 21 Schematic diagram of an exploded view of a sample handling device, illustrating the component layers of the sample handling device

[0031] Figure 24A is according to an implementation Figure 21 Schematic diagram of a perspective side view of a sample handling device

[0032] Figure 24B is Figure 24A Magnified view of the boxed area

[0033] Figure 24C is according to an implementation Figure 21 Schematic diagram of a top view of a part of a sample handling device, where the layers are rendered transparent to show the overlap

[0034] Figure 25A is according to an implementation Figure 21 Schematic diagram of a bottom view of the electrode and channel layers of a sample handling device

[0035] Figures 25B-25D Top views, side views, and bottom views of the electrode layer of a sample handling device according to an embodiment, respectively. Figure 21 Schematic diagrams of the top view, side view, and bottom view of the electrode layer of a sample handling device according to an embodiment.

[0036] Figure 25E Schematic diagram showing a magnified view of a portion of the electrode layer of a sample handling device according to an embodiment, indicating the top and bottom of the electrode layer. Figures 25B-25D Schematic diagram showing a magnified view of a portion of the electrode layer of a sample handling device according to an embodiment, indicating the top and bottom of the electrode layer.

[0037] Figure 26A Schematic diagram of the top view of a sample handling device that can be used with an exemplary SA system according to an embodiment.

[0038] Figure 26B Bottom view image of a sample handling device according to an embodiment after removal of the interface layer. Figure 26A Bottom view image of a sample handling device according to an embodiment after removal of the interface layer.

[0039] Figure 26C Top view image of a sample mounted on a snap ring interface according to an embodiment. Figure 26A Top view image of a sample mounted on a snap ring interface according to an embodiment.

[0040] Figure 27A Is Figure 26A Schematic diagram of a perspective side view of a sample handling device.

[0041] Figure 27B Exploded view schematic diagram of a sample handling device according to an embodiment, illustrating the component layers of the sample handling device. Figure 26A Exploded view schematic diagram of a sample handling device according to an embodiment, illustrating the component layers of the sample handling device.

[0042] Figure 28 Exploded view schematic diagram of a sample handling device according to an embodiment, illustrating the component layers of the sample handling device. Figure 26A Exploded view schematic diagram of a sample handling device according to an embodiment, illustrating the component layers of the sample handling device.

[0043] Figure 29A Perspective top view schematic diagram of a sample handling device according to an embodiment, where the layers are rendered transparent to show overlapping features. Figure 26A Perspective top view schematic diagram of a sample handling device according to an embodiment, where the layers are rendered transparent to show overlapping features.

[0044] Figures 29B-29E Top views of the electrode layer of a sample handling device with the channel layer removed, top views of the channel layer, side views of the channel layer, and bottom views of the spacer portion including the electrode layer according to an embodiment. Figure 26A Top views of the electrode layer of a sample handling device with the channel layer removed, top views of the channel layer, side views of the channel layer, and bottom views of the spacer portion including the electrode layer according to an embodiment.

[0045] Figure 30 Exploded view schematic diagram of a sample handling device according to an embodiment, the sample handling device being coupled to an assembly fixture. Figure 26A Exploded view schematic diagram of a sample handling device according to an embodiment, the sample handling device being coupled to an assembly fixture.

[0046] Figure 31Schematic top view of a sample handling device that can be used with the exemplary SA system according to an embodiment.

[0047] Figure 32 According to an embodiment Figure 31 Schematic top view of a sample handling device that is mounted on a snap ring interface and is to be used with the exemplary SA system.

[0048] Figure 33A and 33B According to an embodiment Figure 31 Schematic perspective top view and top view of a sample handling device, including a cushioning layer for packaging.

[0049] Figure 34 According to an embodiment Figure 31 Schematic exploded view of a sample handling device that is coupled to a mounting interface.

[0050] Figure 35A and 35B Are respectively schematic top view and bottom view of a sample handling device according to an embodiment Figure 31 of.

[0051] Figures 36A-36C According to an embodiment Figure 31 Schematic top view of the electrode layer of a sample handling device, side view of the electrode layer, and bottom view of a spacer portion including the electrode layer.

[0052] Figure 37 According to an embodiment, mounted on a snap ring interface Figure 35A and 35B Schematic perspective side exploded view of a sample handling device, illustrating the component layers of the sample handling device.

[0053] Figure 38 According to an embodiment, mounted on a snap ring interface Figure 35A and 35B Schematic perspective exploded side view of a sample handling device, illustrating the component layers of the sample handling device.

[0054] Figure 39 According to an embodiment Figure 31 Schematic exploded view of a sample handling device that is coupled to a mounting interface.

[0055] Figures 40A-40D Schematic bottom view, top view, side view, and perspective view of a sample handling device according to an embodiment.

[0056] Figure 41 According to an embodiment Figures 40A-40DSchematic of an exploded view of a sample handling device.

[0057] Figure 42 is according to an embodiment Figure 41 Schematic of a top view of a sample handling device according to an embodiment, with layers rendered transparent to show underlying features in the intermediate layer. Detailed embodiments

[0058] The disclosed embodiments generally relate to systems, devices, and methods for near-instantaneous measurement and analysis of body fluids and potential analytes contained therein. The embodiments described herein also relate to embodiments of real-time hydration detection systems and hydration strategy formulation systems for use during activity.

[0059] In one embodiment, a method is disclosed that includes collecting a sample of body fluid from a source of body fluid in a sample collection area of a wearable device and directing a portion of the sample of body fluid from the sample collection area to a set of electrodes. The set of electrodes can include an excitation electrode and a sensing electrode. The method includes applying an excitation signal through the portion of the sample of body fluid and sensing a response signal in response to the excitation signal. The method also includes measuring an impedance associated with the portion of the sample of body fluid based on the response signal and determining a characteristic of the source of body fluid based on the impedance.

[0060] In one embodiment, a wearable device is disclosed that includes a sample collection area having an inlet and configured to receive an initial volume of body fluid via the inlet. The wearable device includes an inlet port in fluid communication with the sample collection area and a flow channel in fluid communication with the inlet port. The flow channel is configured to direct a portion of the initial volume of body fluid to a set of electrodes. The set of electrodes includes an excitation electrode and a sensing electrode. The excitation electrode is configured to apply an excitation signal to the portion of the initial volume of body fluid, and the sensing electrode is configured to receive a response signal from the portion of the initial volume of body fluid in response to the excitation signal. The sensing electrode is configured to transmit the response signal to a processor to calculate an impedance associated with the portion of the initial volume of body fluid.

[0061] In one embodiment, a system is disclosed that includes a memory storing a set of instructions, a processor coupled to the memory and configured to execute the instructions stored in the memory, and a wearable device. The wearable device includes a sample collection area configured to receive an initial volume of body fluid, an inlet port in fluid communication with the sample collection area, and a flow channel in fluid communication with the inlet port. The flow channel is configured to direct a portion of the initial volume of body fluid to a set of electrodes, including an excitation electrode and a sensing electrode. The excitation electrode is configured to apply an excitation signal to the portion of the initial volume of body fluid, and the sensing electrode is configured to receive a response signal from the portion of the initial volume of body fluid in response to the excitation signal.

[0062] In one embodiment, a device for measuring biophysical properties of a sample of body fluid is disclosed, which includes an interface layer, an adhesive layer, an inlet port layer, a channel layer, and an electrode layer. The interface layer includes a pad configured to be released to fix the device to the user's body. The adhesive layer has a predefined thickness, includes an adhesive proximal surface to be fixed to the user's body, and includes an adhesive distal surface to be fixed to the inlet port layer. The adhesive layer defines an opening through which a sample of body fluid is received. The inlet port layer includes a proximal surface configured to be fixed to the distal surface of the adhesive layer, the adhesive layer and the inlet port layer that jointly define a sample collection area, and a distal surface. The inlet port layer defines an inlet port to facilitate the flow of body fluid from the sample collection area. The channel layer defines a flow channel configured to direct the flow of body fluid from the sample collection area. The flow channel includes a test area configured to test the properties of a portion of the sample of body fluid. The electrode layer is configured to define a set of electrodes and interface with the flow channel at the test area. The set of electrodes includes (i) an excitation electrode configured to apply an excitation signal to a portion of the body fluid sample at the test area, and (ii) a sensing electrode configured to receive a response signal from that portion of the body fluid in response to the application of the excitation signal at the test area. The set of electrodes also includes a terminal connection to provide electrical communication between the set of electrodes and a processor to which the response signal to be processed is sent.

[0063] The embodiments described herein relate to systems, devices, and methods for measuring and analyzing body fluids using a wearable system for measurement and analysis. A sample analysis system can be configured to collect a sample of body fluid and measure and analyze the body fluid to determine properties of the body fluid (e.g., osmotic pressure) and / or health parameters of the user (e.g., degree of hydration, electrolyte loss, sweating rate, etc.). For example, the systems and devices described herein can collect a sample of body fluid (e.g., sweat) and measure the impedance of the body fluid. The impedance measurement can then be used to determine and / or predict properties of the sweat (e.g., osmotic pressure). Without wishing to be bound by any particular theory, it is believed that the electrolyte content of sweat is a major contributor to the osmotic pressure of sweat; thus, the determined osmotic pressure can be used to estimate the electrolyte content of the sweat. The sweat data can then be used to determine or predict health parameters of the user (e.g., degree of hydration, electrolyte loss, sweating rate, etc.).

[0064] While the above-described system has been described as being used to determine the electrolyte content of sweat based on impedance measurements, the system can also be used to determine the osmolality of other body fluids and / or secretions, including, for example, saliva, tears, urine, breast milk, etc., which can provide insights into a user's hydration or other health parameters. Additionally, without wishing to be bound by any particular theory, some scientific evidence suggests that the osmolality of breast milk can be used to determine its nutritional composition. Thus, similar to the above analysis, the system can be used to measure the impedance of breast milk, which can be related to the osmolality of breast milk to provide insights into its nutritional composition.

[0065] As described herein, using appropriate metrics of health status, individuals such as athletes, military personnel, laborers, children, the elderly, critically ill patients, and the general population can benefit from timely monitoring of their health and well-being and intervening or correcting in a timely manner based on the monitoring. Some example secondary metrics of health and well-being include degree of hydration, signs of body water loss and electrolyte loss, which can be indicators of electrolyte balance / imbalance.

[0066] Studies have shown that up to 87% of endurance athletes are physically impaired due to dehydration during their workouts and competitions, even though ample fluids are available. Dehydration causes a decrease in blood pressure, an increase in heart rate, an increase in respiratory rate, and a decrease in blood flow to the extremities. These physiological changes can lead to cardiorespiratory stress, impaired thermoregulation, and fatigue - all of which can have a significant impact on a patient's health or athletic performance. Because the symptoms of mild dehydration are subtle - often imperceptible - individuals suffer the consequences without realizing it.

[0067] Dehydration causes athletic performance to deteriorate after only a 1% loss of body weight and deteriorates exponentially as body weight loss increases by 1%. Athletes experience a significant loss of athletic ability and functional impairment when they lose approximately 5% of their body water (by weight). In addition to physical impairment, dehydration can also lead to cognitive impairment. Studies have shown that dehydration also increases the risk of other injuries, such as soft tissue injuries and traumatic brain injuries. If an athlete's dehydration reaches a critical level, medical intervention is required to prevent permanent side effects or shutdown of major body systems. In extreme cases, death can even occur. Because athletes have no way to effectively monitor their hydration status during workouts, they often misunderstand how easily and quickly it can occur. The effects of dehydration on children, the elderly, and critically ill patients can be even more severe and / or devastating.

[0068] Managing hydration is complicated due to the high variability of sweating rates. Each individual can sweat at a different rate based on personal factors such as gender, weight, and fitness level. For any individual athlete, there are many additional variables that can affect the sweating rate, including weather conditions, exercise intensity, and the amount and type of clothing or equipment worn. The same athlete can have different sweating rates when performing the same activity on any given day.

[0069] One method for measuring an athlete's hydration level is to record the nude mass before and after an activity. The difference between the before and after measurements is converted into a percentage of weight loss. Since this method for measuring dehydration can only be performed before and after an activity, athletes currently cannot determine their hydration status during the activity.

[0070] Other methods for measuring hydration status include periodically collecting blood samples during an activity and measuring the osmotic pressure of the plasma with an osmometer. Since current blood sample collection methods cannot be performed during an activity, this method has some of the same problems as the nude mass measurement method. It provides information on the hydration status before or after an activity, but not during the activity. Similar to collecting blood for plasma osmotic pressure measurement, other body fluid collection methods for osmotic pressure measurement are also used as a method for determining hydration status, but the results have been less successful. Other fluids collected include saliva, urine, sweat, and tears. Each of these fluids presents challenges for collection and osmotic pressure measurement.

[0071] Some devices collect sweat with a patch attached to the skin. The sweat can be collected either in an absorbent patch or a reservoir. The patch is then removed from the athlete, and the conductance of the sweat in the patch is measured with a bench-top device. This method requires a large amount of sweat; the athlete must sweat profusely for 15 to 20 minutes to collect this minimum amount. This method does not provide real-time, immediate hydration monitoring for the athlete. In addition, these patches need to be replaced every 15 to 20 minutes in order to collect accurate hydration status throughout the activity being studied. Therefore, systems, devices, and methods for near-instantaneous measurement and analysis of body fluids are needed.

[0072] Sample Analysis System

[0073] The embodiments described herein relate to systems, devices, and methods for near-instantaneous measurement and analysis of body fluids such as sweat and potential analytes contained therein. The disclosed embodiments of the systems and devices are lightweight in nature and can thus be worn by an individual during any form of activity. The disclosed systems, devices, and methods allow for near-instantaneous measurement and analysis of body fluids through their independent, real-time sample collection and analysis nature. Embodiments of the disclosed systems and methods also support repeated instantaneous measurements of samples of body fluids, which are performed over a period of time while the individual is engaged in an activity.

[0074] As used herein, the terms "analyte" and / or "target analyte" refer to any ion, molecule, or compound to be detected and / or that can bind to a binding substance (e.g., a detection molecule or reagent), as described herein. Suitable analytes can include, but are not limited to, metal and non-metal ions (e.g., Na + , Cl - , Ca 2+ , K + or Mg 2+ ions), nitrogen-containing compounds (such as amino acids and urea), metabolites (e.g., lactate and pyruvate), xenobiotics (such as drug molecules, enzymes, metabolic by-products, disease-related biomarkers), small chemical molecules (such as, for example, environmental molecules, clinical molecules, chemicals, pollutants, and / or biomolecules). More specifically, such chemical molecules can include, but are not limited to, pesticides, insecticides, toxins, therapeutic and / or abused 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-biological molecules, as well as fragments and combinations thereof. Some analytes described herein can be proteins, such as enzymes, drugs, cells, antibodies, antigens, cell membrane antigens, and / or receptors or their ligands (e.g., neurotransmitter receptors or their ligands, hormone receptors or their ligands, nutrient receptors or their ligands, and / or cell surface receptors or their ligands).

[0075] As used herein, the term "sample" refers to a composition comprising one or more analytes to be detected. A sample can be heterogeneous, containing multiple components (e.g., different proteins), or homogeneous, containing a single component. In some cases, a sample can be a naturally occurring biological material, and / or an artificial material. Additionally, a sample can be in a native or denatured form. In some cases, a sample can be processed prior to detecting the analyte. For example, a sample can undergo a lysis step, a denaturation step, a heating step, a purification step, a precipitation step, an immunoprecipitation step, a column chromatography step, centrifugation, etc. In some cases, the separation and / or immobilization (via electrophoresis) of a sample can be performed on a native substrate and / or an analyte of interest (e.g., a protein). In other cases, a sample can be denatured to expose its internal hydrophobic groups for immobilization in a fluid path.

[0076] As used in this specification and the claims, unless the context clearly dictates otherwise, the singular forms "a", "an", and "the" include plural referents. Thus, for example, the term "member" is intended to denote a single member or a combination of members, and the term "material" is intended to denote one or more materials, or a combination thereof.

[0077] As used in this specification, unless otherwise indicated, the term "and / or" in the present disclosure means "and" or "or".

[0078] As used herein, "body fluid" can include any fluid obtained from the body of an individual (e.g., an athlete, a patient, etc.). For example, "body fluid" includes but is not limited to sweat, tears, blood, urine, breast milk, saliva, sebum fluid, mucus, vitreous humor, etc., or any combination thereof.

[0079] As used in this application, the terms "about" and "approximate" are used as equivalents. Any number used in this application, with or without about / approximate, is intended to cover any normal fluctuations recognized by a person of ordinary skill in the relevant art. In certain embodiments, unless otherwise stated or apparent from the context, the term "approximate" or "about" refers to a range of values that fall within 10% or less in either direction (greater than or less than) of the stated reference value (unless such a number would exceed 100% of the possible value or be less than 0% of the possible value).

[0080] As used herein, the term "stiffness" relates to an object's resistance to deflection, deformation, and / or displacement caused by an applied force and is generally understood to be the opposite of an object's "flexibility". For example, when subjected to a force, a wall with greater stiffness will resist deflection, deformation, and / or displacement more than a wall with lower stiffness. Similarly, an object with a higher stiffness can be characterized as being stiffer than an object with a lower stiffness. Stiffness can be characterized based on the amount of force applied to the object and the resulting distance by which a first portion of the object deflects, deforms, and / or displaces relative to a second portion of the object. When characterizing the stiffness of an object, the deflection distance can be measured as the deflection of a portion of the object that is different from the portion 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 where the force is applied.

[0081] As used herein, the terms "proximal" and "distal" refer to directions toward and away from a user of a device or system to which the device or system will be placed against the body, respectively. Thus, for example, the end of a device that first contacts the user's body will be the proximal end, while the other end of the device (e.g., the end of the device that is away from the user's body) will be the distal end of the device.

[0082] As described in further detail herein, any system, device, and method can be used to collect and analyze a body fluid sample in a repetitive manner, such as by collecting a first sample or volume of the body fluid, testing the first volume or sample of the body fluid, discharging the first volume or sample of the body fluid, and collecting a subsequent volume or sample of the body fluid after a given duration. Each of the terms "first", "subsequent", and / or "initial" can be used interchangeably to describe and / or refer to the amount, portion, or volume of body fluid that is collected, transported, transferred, directed, and / or discharged during use of the sample analysis system described herein. In some embodiments, the terms "first", "subsequent", and / or "initial" can refer to a predetermined, defined, desired, or given volume, portion, or amount of body fluid, which can depend on several parameters, including device configuration, user needs, and the like.

[0083] The embodiments and / or portions thereof described herein can be formed or constructed from one or more biocompatible materials. In some embodiments, the biocompatible material can be selected based on one or more properties of the constituent materials, such as, for example, stiffness, toughness, hardness, bioreactivity, and the like. Examples of suitable biocompatible materials include metals, glasses, ceramics, or polymers. Examples of suitable metals include medical grade stainless steel, gold, titanium, nickel, iron, platinum, tin, chromium, copper, and / or their alloys.

[0084] The embodiments and / or portions thereof described herein may include assemblies formed by one or more parts, features, structures, etc. When referring to such assemblies, it should be understood that an assembly may be formed by a single part having any number of segments, layers, regions, portions, and / or characteristics, or may be formed by multiple parts or features. For example, when referring to a structure such as a wall or a chamber, the structure may be considered a single structure having multiple parts or multiple different sub-structures, etc., which are coupled to form the structure. Thus, the overall structure may include, for example, a collection of sub-structures. Such a collection of sub-structures may include multiple parts that are either continuous or discontinuous with each other. The collection of sub-structures may also be made of multiple articles or components that are produced separately and subsequently joined together (e.g., via welding, adhesives, or any suitable method).

[0085] According to some embodiments, a sample analysis system (also referred to herein as the "SA system") includes a disposable sample handling device and a durable sample handling device connected to the disposable sample handling device. In some implementations, according to some embodiments, the sample analysis system may include a disposable sample handling device and a disposable sample processing device connected to the disposable sample handling device. The sample handling device is configured to collect a sample of a body fluid, direct the sample to a test and measurement interface, and allow a test stimulus to be applied to the test sample and a response signal from the sample in response to the test stimulus to be measured. After testing the collected sample, the sample handling device is configured to direct the sample to be discharged. The response signal may then be analyzed to determine quantitative characteristics of the sample, such as solute concentration, solvent content, analyte concentration, etc.

[0086] Sample handling device

[0087] Figure 1 A schematic diagram of a section of a user's skin is shown and an example sample handling device positioned on the user's skin is illustrated. The schematic diagram of the skin section shows the density of secretory glands (e.g., sweat glands) that lead to the release of body fluid (e.g., sweat). The sample handling device (also referred to herein as the "SH device") is represented by a disk and is shown positioned on the surface of the user's skin. As shown, the disk covers a subset of the pores that release body fluid and is configured to collect sample body fluid (e.g., sweat) from the user that can be measured and analyzed when the user is engaged in an activity (i.e., 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 that includes the sample handling device may be used without being attached to the user and may be used to analyze any number of other body fluids.

[0088] Figure 2A and 2BFIG. 0 is a schematic diagram of an example sample handling device 110 according to an embodiment, indicating some of the components included in the sample handling device 110. Figure 2B The schematic diagram in FIG. 0 includes illustrations of example configurations of various components of the sample handling device 110, as well as flow paths defined for the flow of a sample of body fluid, indicated by dashed arrows. In some embodiments, the sample handling device 110 may be integrally constructed. In some other embodiments, the sample handling device 110 may be constructed by the assembly of parts or layers, as described in further detail herein. As Figure 2A and 2B shown in FIGS. 0 and 1, the sample handling device 110 includes a sample collection area 112, an inlet port 114, a flow channel 116, one or more test areas 118, a set of electrodes 120, and optionally a temperature sensor 140.

[0089] The sample collection area 112 is a part of the sample handling device 110 that is configured to receive and collect a sample of body fluid, such as sweat, from the user's body when the user wears the sample handling device 110. The sample collection device 112 includes an opening 122, as Figure 2B indicated in FIG. 1, that allows access to the source of the body fluid when the user wears the sample handling device 110. The sample collection area 112 also defines a space or volume that is configured to be fluidly coupled to the opening 122 and that is configured to hold or collect a sample of body fluid when the user wears the sample handling device 110. Although not shown in Figure 2A and 2B FIGS. 0 and 1, 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 increase comfort when using the sample handling device 110. For example, one or more pads may be used to provide a better interface with the user's body and increase comfort during use of the sample handling device 110. Additionally, the interface structures may be used to provide a seal between the sample handling device 110 and the user's body such that pressure generated by the sweat glands causes sweat to pass through the flow channel 116.

[0090] In some embodiments, the sample collection region 112 can be defined by one or more portions of the sample handling device 110. For example, in some embodiments, the sample collection region 112 can be formed by two or more portions or layers of an assembly structure to include an opening 122 for collecting body fluid, and define a specific volume to temporarily hold the collected body fluid sample. The two or more portions or layers can be selected or fabricated such that once assembled, the sample collection region 112 includes the appropriate opening 122, and the body of the assembled portions of the sample handling device 110 defines the volume in the sample collection region 112 that can hold an appropriate amount of the collected body fluid. For example, the thicknesses of the two or more portions can be selected to determine the volume or fluid capacity of the sample collection region 112. The two or more portions can be assembled using any suitable method, such as friction fitting, gluing using an adhesive material (e.g., transfer adhesive), using fasteners, etc. In some other embodiments, the sample collection region 112 can be integrally formed by a single unitary portion or structure to include the opening 122, which is appropriately configured to collect the body fluid sample and define a volume for accommodating the collected body fluid sample.

[0091] The portions forming the sample handling device 110 and / or the sample collection region 112 can have suitable flexibility to provide convenience for the user to wear and provide access to the body fluid source. For example, in some embodiments, the portions or layers forming the sample handling device 110 and / or the sample collection region 112 can have flexible properties such that the sample handling device 110 can be worn on the surface of the user's skin, and the proximal portion of the sample collection region 112 can optimally dock with the user's skin and conform to the contour of the user's body, even when the user is engaged in activities. In some embodiments, the sample handling device 110 and / or the sample collection region 112 can have a relatively rigid construction such that the rigidity allows for better docking with the surface of the user's body and prevents the sample handling device 110 from being misaligned or falling off the user during strenuous activities. In some embodiments, one or more portions or components of the sample handling device 110 can be made rigid to achieve a locally rigid construction. The portions of the locally rigid construction can be designed to avoid deformation of the sample analysis and / or testing region 118. For example, the locally rigid portion can be constructed such that the testing region 118 deforms no more than a few percent (e.g., 0 - 10%) under a load of approximately 1 - 10 Newtons. In some embodiments, the sample handling device 110 can be configured such that portions other than the locally rigid portions of the device and / or the sample collection region 112 are generally flexible and conform to the user's skin and / or body.

[0092] In Figure 2BThe opening 122 defined in the sample collection region 112 as shown can provide access to the source of the body fluid sample (e.g., skin containing sweat pores) and is fluidly connected to a sample configured to temporarily contain the body fluid collected from the source. The sample collection region 112 can be formed such that the volume and the opening 122 are defined in the body of the sample handling device 110 or a portion of the body of the sample handling device 110. In some embodiments, for example, the sample collection region 112 can be configured such that when the sample handling device 110 is positioned on a user's body, the sample collection region 112 is proximal to the user's skin surface and covers a suitable skin area to collect a suitable volume of body fluid (such as sweat) over a suitable period of time. For example, as Figure 1 shown in the schematic diagram in, a section of the user's human skin can have a specific density of sweat pores that release sweat, each pore being spaced from other pores at a specific distance. The sample collection region 112 can be constructed such that the opening 122, when placed on the user's skin, can cover a specific skin area that contains a specific minimum number of sweat pores. Such positioning can allow the initial amount of sweat released from those pores to be collected over a desired period of time. In other words, the opening 122 can be large enough to collect sweat from a sufficient number of sweat glands to substantially fill the sample collection region 112 in a relatively short time, and thus the sweat can be analyzed soon after the user begins to sweat.

[0093] In some embodiments, the SA system can require a minimum amount of body fluid for accurate testing and analysis. The volume of the opening 122 and / or the sample collection region 112 can be configured to determine the volume of the body fluid collected in the initial sample and to ensure that the initial sample collected meets the requirement for the minimum amount of body fluid for accurate testing and analysis. In some implementations, the sample collection region 112 can include one or more structures ( Figure 2A and 2B not shown in) that are constructed to occupy and / or take up volume in the sample collection region 112 such that the volume of the initial sample of body fluid to be collected and directed via the inlet port 114 can be smaller compared to the total volume defined by the sample collection region 112.

[0094] (One or more) space-occupying structures may be defined in the sample collection region 112 in any suitable manner. In some embodiments, (one or more) space-occupying structures may be formed solidly, for example, one or more spacer portions of a spacer film are assembled and / or deposited as a material, such as spacer ink (e.g., ink cured by uv light), on the surface of the sample collection region 112. For example, the space-occupying structure may include (e.g., be deposited) on a layer or portion of the wall used to form the sample collection region 112. In some embodiments, the space-occupying structure may be implemented by assembling one or more spacer layers or portions with one or more other portions to form the sample collection region 112. In some embodiments, (one or more) space-occupying structures may include an outer cover that defines a hollow portion within the outer cover and / or encapsulates a volume defined within the outer cover. In some embodiments, the outer cover of the space-occupying structure may be molded and / or contoured to define a space that may be excluded or isolated from the volume defined by the sample collection region 112.

[0095] In some embodiments, the volume of the initial sample may also determine the ease of collection, the direction of the fluid flow to be tested, and the drainage, thereby determining the rate at which a sample may be collected and tested or analyzed. In other words, in some embodiments of the sample handling device 110, an initial sample of a body fluid (e.g., sweat) may be collected, and the volume of the initial sample is determined by the volume of the sample collection region 112. The collected initial sample may be directed through the inlet port 114 into the flow channel 116 for testing and drained in a continuous flow of the body fluid, thereby leaving room for continuous collection of subsequent body fluids secreted by the user during use. The processes of sample collection, sample testing, and sample drainage may be performed in a continuous manner, with the collected body sample flowing continuously at a suitable rate through the collection region 112, the inlet port 114, the flow channel 116, and (one or more) test regions 118. In such embodiments, the volume of the sample collection region 112 and the dimensions of the opening 122 defined in the sample collection region 112 may determine the rate of the initial amount of the collected sample. The volume of the sample collection region 112 and the dimensions of the opening 122 may partially determine the linear flow rate (i.e., the volumetric flow rate divided by the cross-sectional area of the flow channel 116) of the sample as it is directed through the inlet port 114, the flow channel 116, and (one or more) test regions 118 before being drained.

[0096] In some embodiments, by way of example, the sample collection region 112 can have a volume and / or fluid capacity that is between approximately 0.01 milliliters (mL) and about 5.0 mL. In some embodiments, the sample collection region 112 can have a fluid capacity between about 0.02 mL and about 1 mL, between about 0.03 mL and about 0.5 mL, between about 0.04 mL and about 0.3 mL, between about 0.06 mL and about 0.1 mL, including all ranges or sub-ranges therebetween. In some embodiments, the sample collection region 112 can have a volume sufficient to accommodate as little as microliters or less of body fluid (e.g., as little as 20 drops of body fluid, 10 drops of body fluid, 5 drops of body fluid, 1 drop of body fluid, or any suitable volume therebetween). In other embodiments, the sample collection region 112 can have a volume of up to, for example, about 5.0 mL, 10.0 mL, 15 mL or more. In some embodiments, the sample collection region 112 can have a fluid capacity based on the volume defined by one or more space-occupying structures and / or based on the volume isolated and / or removed by the space-occupying structures, as previously described.

[0097] As Figure 2A and 2B shown, the inlet port 114 of the sample handling device 110 is fluidly coupled to the sample collection region 112. The inlet port 114 can be an opening, through-hole, conduit, fluid flow path, etc., defined in the body of the sample handling device 110 to fluidly connect the sample collection region 112 to the flow channel 116, described in further detail below. In some embodiments, the sample collection region 112 can be formed by assembling two or more parts or structures, as described herein. In some embodiments, one of the parts can be configured to include and / or define an opening 122, while the other part can be configured to include and / or define the inlet port 114. One or more of the assembled parts can be configured to form one or more walls of the sample collection region 112 upon assembly. In embodiments where the sample collection region 112 is defined as a monolithic structure, the inlet port 114 can be an orifice, conduit, and / or flow path defined in the body of the sample handling device 110 to fluidly couple the sample collection region 112 to the flow channel 116.

[0098] The inlet port 114 can be located at any suitable position relative to the sample collection region 112 to mediate a fluid connection between the sample collection region 112 and the flow channel 116. For example, in some embodiments, the inlet port 112 can be an orifice defined on the inner surface of the sample collection region 112. In some embodiments, the inlet port 114 can be defined on the distal portion of the sample collection region 112 (i.e., away from the user's body when using the sample handling device 110). In some embodiments, for example, the inlet port 114 can be defined at a central portion relative to the opening 122 and / or the volume defined by one or more walls of the sample collection region 112 to accommodate the collected body fluid. In some other embodiments, for example, the inlet port 114 can be defined at an eccentric position relative to the opening 122 and / or the volume defined by the walls of the sample collection region 112 to hold the collected body fluid. In some embodiments, the inlet port 114 can be located at any suitable position relative to the sample collection region 112, the opening 122, and / or the flow channel 116 to prevent and / or flush the formation of air bubbles in the sample of the collected body fluid. In some embodiments, the inlet port 114 can be located such that the sample collection region 112 is adapted to form a flow of the collected body fluid, for example, via narrowing of one or more structures, conduits, contour guiding the fluid, etc., towards the inlet port 114.

[0099] The inlet port 114 can be any suitable size to allow the transported collected body fluid sample from the sample collection region 112 to other parts of the sample handling device 110 (e.g., the (one or more) test regions 118, etc.). In an embodiment, the size of the inlet port 114 can range from a few hundred micrometers to a few millimeters. For example, the inlet port 114 can have an internal cross-sectional diameter between approximately 0.05 millimeters (mm) and approximately 5.0 millimeters (mm). In some embodiments, the inlet port 114 can have a cross-sectional area sufficient to allow the collected body fluid sample to flow continuously into the flow channel 116.

[0100] In some embodiments, the inlet port 114 can be configured to allow the collected body fluid sample to flow continuously once the initial sample of the body fluid reaches a minimum volume amount. In some embodiments, the inlet port 114 can be configured such that after the sample collection region 112 reaches a minimum positive pressure from collecting a large or minimum volume of body fluid (e.g., as small as 20 drops of body fluid, 10 drops of body fluid, 5 drops of body fluid, 1 drop of body fluid, 20 μL, 15 μL, 10 μL, 5 μL, or any suitable volume therebetween), the collected body fluid sample is allowed to flow continuously.

[0101] Inlet port 114 can be used with the SA system with sample handling device 110 to determine the flow rate of the collected body fluid to be tested. In some embodiments, inlet port 114 can have wicking properties to draw the collected fluid sample from sample collection area 112 into flow channel 116. In some embodiments, the sample collected in sample collection area 112 can be directed into and beyond inlet port 114 by a pressure differential. For example, a lower pressure in inlet port 114 and flow channel 116 can draw the collected body fluid sample through inlet port 114 and flow channel 116 compared to sample collection area 112. Similarly, as sample collection area 112 becomes increasingly filled with the collected body fluid, an increase in pressure in sample collection area 112 (i.e., generated by sweat glands) can push the collected body fluid sample through inlet port 114 into flow channel 116. In other words, the seal between sample handling device 110 and the user's body is fluid-tight enough such that the pressure generated by the sweat glands causes sweat to pass through flow channel 116. In some other embodiments, inlet port 114 can be configured such that the fluid in sample collection area 112 is drawn out by capillary action.

[0102] Flow channel 116 can have any suitable width, height, diameter, or cross-sectional area to receive the collected body fluid sample from sample collection area 112 through inlet port 114 and appropriately convey the body fluid sample to other parts of sample handling device 110, such as test area(s) 118. For example, flow channel 116 can have a circular cross-section with a suitable diameter, or a rectangular cross-section of flow channel 116 with suitable width and height. The width, height, or diameter of flow channel 116 can range from a few hundred micrometers to a few millimeters. For example, the width, height, and / or diameter of one or more portions of flow channel 116 can be between approximately 0.05 millimeters (mm) and approximately 5.0 mm. Flow channel 116 can extend any suitable length, from a few millimeters to a few centimeters, and is configured to assume any suitable shape along its length. For example, flow channel 116 can extend in length between 5 millimeters (mm) and approximately 15.0 centimeters (cm). Flow channel 116 can be configured to follow any suitable path, such as a linear, straight, curved, or serpentine path.

[0103] In some embodiments, the flow channel 116 may be defined within a monolithic structure that is integrally constructed such that the diameter of the flow channel 116 is at least partially determined by the thickness of the monolithic structure that defines the flow channel 116. In some other embodiments, the flow channel 116 may be constructed by assembling two or more parts or layers of a structure that together define the flow channel 116. In some embodiments, the flow channel 116 may be formed by several layers or parts assembled together to direct the flow of fluid via one or more channels, through-holes, pores, etc. The flow channel 116 may be configured such that external influences during use (such as forces generated by gravity, movement of the user's body, etc.) do not interfere with the fluid flow within the flow channel 116 and / or do not significantly alter the physical shape or dimensions of the flow channel 116 being used.

[0104] In some embodiments, the flow channel 116 may include various portions that are suitably configured to direct the flow of body fluid at a suitable flow rate or flow volume. For example, in some embodiments, the flow channel 116 may include portions constructed with different cross-sectional shapes and / or dimensions. For example, some portions of the flow channel 116 may be circular or rectangular while other portions are not. Similarly, some portions of the flow channel 116 may have a narrower or wider cross-sectional area compared to other portions of the flow channel 116. In some embodiments, the flow channel 116 may include an inlet portion and an outlet portion. The inlet portion of the flow channel 116 may be configured to convey body fluid collected in the sample collection region 112 to the test region 118 described below via the inlet port 114. The outlet portion of the flow channel 116 may be configured to remove the body fluid sample after testing at the test region 118 to discharge it from the sample disposal device 110, e.g., to the environment. For example, in some embodiments, the flow path 116 may be configured to be linear at some portions defined by one or more test regions 118 and the outlet portion of the flow channel 116 may include a tortuous discharge path to reduce and / or avoid air entry. In some embodiments, the tortuous path may be configured to reduce and / or avoid undesirable fluid / air flow due to gravity, acceleration, user movement, etc.

[0105] The inlet and outlet portions of the flow channel 116 can be suitably shaped to allow for optimal flow of the body fluid sample, to access the body fluid sample for testing in an optimal manner, and to optimally expel the sample after testing. In some embodiments, portions of the flow channel 116 can also include structural and / or functional adaptations to overcome or allow for physical forces such as stress and / or strain that may be encountered when the sample disposal device 110 is used by a user engaged in strenuous activity. For example, in some embodiments, the flow channel 116 can be configured to include suitable linear, angular, and / or curved or serpentine portions to better withstand different types of physical forces, including stress and / or strain encountered when the sample disposal device 110 is worn by a user during high-intensity or contact sports activities. In some embodiments, the flow channel 116 can be configured to include one or more curved or serpentine portions to act as local traps to prevent air from outside the sample disposal device 110 from entering the flow channel 116.

[0106] As Figure 2B indicated in the schematic diagrams of, the flow channel 116 can include an outlet 124 to expel the collected and tested body fluid sample. In some embodiments, the body fluid sample can be directed through the outlet portion of the flow channel 116 and via the outlet 124 by means of a series of pressure differentials. In some other embodiments, after testing at the test region(s) 118, the body fluid sample can be directed towards the outlet 124 by one or more suitable physical forces. For example, the body fluid sample can be expelled via the outlet 124 by gravity, capillary action, the movement of the user, etc.

[0107] As Figure 2A and 2B shown in, the sample disposal device 110 includes the test region(s) 118. The test region(s) 118 can include any suitable number of test regions defined along the flow channel 116. For example, in some embodiments, the sample disposal device 110 can include two, three, or more test regions defined at a designated portion of the flow channel 116 such that the body fluid collected at the sample collection region 112 can be directed via the inlet port 114 and through one or more test regions for sequential or parallel processing as described herein. In some embodiments, the test region(s) 118 can be separate from but fluidly coupled to the flow channel 116. In some embodiments, the test region(s) 118 can be defined as part of the flow channel 116. For example, the flow channel 116 can include an inlet portion and an outlet portion separated by the test region(s) 118 which are the third portion. The test region(s) 118 can be configured to intersect the body fluid flow in the flow channel 116. In some embodiments, the test region(s) 118 can be configured to define a volume sufficient to accommodate a portion of the body fluid sample when being tested.

[0108] The (one or more) test areas 118 of the sample handling device 110 may include a set of sample ends of a set of electrodes 120 configured to interface with a body fluid sample flowing through the test area 118. The set of electrodes 120 may include any suitable number of electrodes and the sample end of each electrode may be configured to deliver an excitation signal (e.g., as a current delivery electrode) to the body fluid sample to be tested, or sense a response signal from the body fluid sample tested with the excitation signal (e.g., as a voltage sensing electrode). In some embodiments, the electrodes 120 may include electrodes configured to power one or more components included in the sample handling device 110 (e.g., one or more sensors such as a temperature sensor, etc.) and / or carry signals from one or more components to the sample processing device (e.g., a signal reporting a temperature measurement via a temperature sensor). Parameters such as the number of electrodes required to effectively deliver an excitation signal, the number of electrodes required for a predetermined signal-to-noise ratio in the response signal obtained from a test sample of body fluid, the number of electrodes suitable to meet a predetermined form factor or structural and / or functional constraints, etc. may be considered to appropriately optimize the number of electrodes in different embodiments of the sample handling device. For example, in some embodiments, the set of electrodes may include four electrodes, two of which are configured to deliver an excitation signal in the form of a test current signal, and two of which are allocated to record the response voltage from the body fluid sample after the application of the test current signal. As an example, the electrodes 120 may be configured as a quadrupole impedance cell. As another example, in some other embodiments, the set of electrodes may include two electrodes, one configured to deliver an excitation signal and the other configured to read voltage and / or current from the body fluid sample being tested. For example, the electrodes 120 may be configured as a bipolar impedance unit.

[0109] The set of electrodes can have test ends at the test region(s) 118, configured to interact with a body fluid sample in the test region(s) 118. The set of electrodes can include excitation electrodes and sensing electrodes. In some embodiments, each electrode in the set of electrodes 120 can be configured to function as either an excitation electrode or a sensing electrode. In some embodiments, the set of electrodes 120 can include excitation electrodes designated to deliver an excitation signal to a portion of the body fluid sample at the test region(s) 118, and sensing electrodes designated to sense a response signal from the body fluid sample in response to the application of the excitation signal. The set of electrodes can include terminals (not shown) configured to interact with a portion of the sample processing device described herein and a sample end configured to interact with a portion of the sample fluid at one or more test regions 118. In some embodiments, for example, the excitation electrode can be configured to receive an excitation signal from a power source at the terminal and deliver the excitation signal at the sample end to a portion of the body fluid sample guided by a flow channel and directed to the test region 118. As another example, the sensing electrode can be configured to receive a response signal emitted from a portion of the body fluid sample at the test region 118 at the sample end interfacing with the portion of the body fluid sample at the test region 118 and deliver the received response signal to the terminal interfacing with a portion of the sample processing device such that the response signal can be appropriately processed and / or analyzed by a processor, and / or stored in a memory associated with the sample processing device. In some embodiments, the sample processing device can be configured to receive response signals from electrodes 120 associated with two or more test regions 118 such that response signals from each of the two or more test regions 118 can be compared to determine characteristics of the sample body fluid.

[0110] In some cases, the distance between electrodes 118 associated with two or more test regions 118 can be used to determine characteristics of the sample body fluid. For example, the impedance associated with the response signal from each test region 118 can be used to evaluate the flow rate and / or volumetric flow rate of the sample body fluid. In some embodiments, the known geometry of the flow path connecting the test region(s) 118 can be used to calculate the volumetric flow rate.

[0111] The secretion rate of the sample body fluid (e.g., the rate of sweating) can be estimated or inferred from the volumetric flow rate of the sample body fluid. In some embodiments, known attributes of the user (height, weight, etc.) can be used to calculate the sweating rate of the user. In some embodiments, the sweating rate can be used to estimate the cumulative body fluid loss over time and / or the cumulative electrolyte loss over time.

[0112] In some embodiments, the excitation signal can be a test current signal. In some embodiments, electrode 120 is configured such that the test current signal is in the form of a direct current. In some embodiments, the electrode is configured such that the applied test current signal is in the form of an alternating current (AC). In embodiments where an alternating current is used, electrode 120 can be configured such that the alternating polarity of the test current signal experienced by the electrode allows for a partial reversal of the effect of the salinity of the body fluid sample on the electrode. Thus, using AC for excitation can help prevent rapid corrosion and / or ionization of the electrical interface of the electrode in the test area, which otherwise could be a result of a DC excitation signal. In some embodiments, one or more of electrodes 120 can have a coating with one or more suitable materials (e.g., carbon) to reduce the corrosive effect of the body fluid being tested. In some embodiments, the electrode can be capacitively coupled or AC coupled to the electronics such that no DC can flow through the sample, thereby reducing the risk of corrosion or ionization.

[0113] 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 the presence and / or quantify the amount of one or more of Na + , Cl - , Ca 2+ , K + or Mg 2+ ions in a portion of the initial body fluid volume.

[0114] Although described with reference to detecting the presence of ions, the systems, devices, and methods described herein can equally be suitable and / or used for detecting and / or quantifying the presence of analytes in a body fluid sample. For example, the presence of lactose, glucose, etc. can be detected and / or quantified.

[0115] In some embodiments, the sample handling device 110 may optionally include one or more temperature sensors 140. The temperature sensors 140 may be suitably located at or near one or more test areas 118 and configured such that the temperature sensors 140 can record the temperature of the body fluid sample being tested at the one or more test areas 118. In some embodiments, the temperature sensors 140 may be positioned to monitor and measure the temperature of the body fluid sample during testing in the one or more test areas 118. The temperature sensors 140 may be any suitable temperature sensing device that may be suitably positioned adjacent to the test area 118 and used to measure the temperature of the body fluid sample. For example, the temperature sensors 140 may be a thermistor or a thermistor assembly. In some embodiments, the sample handling device 110 may include additional sensors (not shown) to record environmental conditions. For example, the sample handling device 110 may include a temperature sensor to measure the skin temperature of the user and / or the ambient air temperature. In some embodiments, the sample handling device 110 and / or the sample processing device coupled thereto may include any number of additional sensors to sense pressure, humidity, etc. In some embodiments, the temperature sensors 140 may be used to calculate the temperature of the body fluid sample, from which an estimate of the user's core body temperature may be calculated. In some embodiments, the core body temperature may be used to estimate the user's hydration and / or electrolyte loss and / or cumulative loss rate and / or to estimate the impact of hydration and / or electrolyte loss.

[0116] In use, the sample handling device 110 is positioned on a user's body surface to collect and direct body fluid for testing and analysis to determine the user's health status. For example, the sample handling device 110 can be positioned on the arm of an athlete participating in a sports event to collect and test the user's sweat and analyze the salinity of the collected sweat, from which the user's hydration status, electrolyte loss, and sweating rate can be determined. Sweat is collected in the sample collection region 112 of the sample handling device 110 and is continuously directed through the inlet port 114 to the flow channel 116. In some cases, a spacer portion included in the sample collection region 112 can occupy the space within the sample collection region 112 and reduce the volume of body fluid sample required to initiate or start the flow of body fluid through the flow channel 116. A portion of the flow channel 116 is configured to direct the collected sweat at a continuous flow rate to the (one or more) test regions 118, where the sweat interacts with a collection of electrodes 120. An excitation or test current signal is delivered to the sample sweat in the test region 118 via one or more of the electrodes (current delivery electrodes) in the collection of electrodes 120. A response voltage generated by the sweat sample in response to the excitation or test current signal is read from the collection of electrodes 120 by one or more electrodes (voltage sensing electrodes, different from the current delivery electrodes). In some cases, the excitation or test current signal can be delivered, and the response voltage can be read in a continuous manner. The voltage read from the sweat sample is used to calculate the impedance associated with the sweat sample, and the impedance can be associated with the quantification or measurement of sweat salinity and other physiological information of the user. Thus, the user's sweat can be continuously tested over a period of time, and the measured salinity of the user's sweat can be correlated with the continuous measurement of the degree of hydration electrolyte loss and the user's sweating rate over a period of time while the user is engaged in an activity.

[0117] Exemplary sample analysis system

[0118] Figure 3 is a schematic diagram of a sample analysis system 100 according to an embodiment. The SA system includes the sample handling device 110 and the sample processing device 130 as described above, which are coupled to each other via a connector 125. In some embodiments, the connector 125 can be permanently attached or removable from the sample handling device 110 and / or the sample processing device 130. In some cases, the sample analysis system 100 can be configured to be integrated into a wearable device 145 (e.g., a watch, an odometer, an activity tracker, a heart rate monitor, etc.), integrated with the wearable device 145, or integrated into the wearable device 145. Although Figure 3 the illustrated SA system 100 includes the sample processing device 130 and is coupled to the wearable device 145, in some cases, the sample handling device 110 can be directly integrated with the wearable device 145 without the need for the sample processing device 130.

[0119] The connector 125 can be a mechanical connector defined on the sample processing device 130 and configured to engage a portion of the sample handling device 110 such that the sample handling device 110 can be installed on the sample processing device 130 before being worn by a user. In some embodiments, the sample processing device 130 can be constructed as a durable reusable device, and the sample handling device 110 can be constructed as a disposable device that can be installed and / or connected to the sample processing device for a period of use (e.g., an active period) and discarded to be replaced by another sample handling device 110. The connector 125 can be configured such that it allows for easy removal and replacement of the sample handling device 110. In addition to the physical connection, the connector 125 can also include a suitable set of electrical connections to electrically couple the sample handling device 110 to the sample processing device 130. For example, the connector can be in the form of spring pins and / or flexible contacts that can be engaged to provide an electrical connection when the sample handling device 110 is mechanically coupled to the sample processing device 130, such as using a snap ring interface.

[0120] The sample handling device 130 can have a suitable form factor to be easily worn by a user during strenuous activity such that the sample handling device 110 can properly dock with the user's body (e.g., a portion of the user's skin). The sample processing device 130 can include a processor 132, a memory 136, a communicator 138, and a display 142.

[0121] The processor 132 can be, for example, a hardware-based integrated circuit (IC) or any other suitable processing device configured to run and / or execute instruction sets or code. For example, the processor 132 can be a general-purpose processor, a central processing unit (CPU), a microcontroller, an accelerated processing unit (APU), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), a programmable logic array (PLA), a complex programmable logic device (CPLD), a programmable logic controller (PLC), etc. The processor 132 is operatively 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 to test, measure, and analyze the characteristics of a sample body fluid collected by the sample handling device almost instantaneously or in real time. For example, the processor 132 can be configured to generate a set of excitation signals to probe the body fluid sample, provide instructions for delivering the excitation signals via the electrodes in the sample handling device 110, receive response signals obtained from the body fluid sample read by the electrodes in the sample handling device 110, and interpret the response signals to determine the characteristics of the sample body fluid, thereby indicating the user's health status. In some embodiments, the processor 132 can also be configured to perform additional functions, such as indicating relevant information about the characteristics of the analyzed sample body fluid and / or the user's status during testing to the user via the display 142 (e.g., a graphical display). In some embodiments, the processor 132 can also be configured to transmit a set of signals, interpretations, and / or analysis results to a remote computing device for further processing, as described herein.

[0122] The memory 136 of the sample processing device 130 can be, for example, a random access memory (RAM), a memory buffer, a portable hard disk drive, a read-only memory (ROM), an erasable programmable read-only memory (EPROM), etc. The memory 136 can store, for example, user data for later use / analysis and / or one or more software modules and / or code, which can include instructions that cause the processor 132 to perform one or more of the processes, functions, etc. described herein (e.g., generation of excitation signals, delivery of test signals, reading and analysis of response signals, etc.). In some implementations, the memory 136 can be a portable memory (e.g., a flash drive, a portable hard disk, etc.) that can be operatively coupled to the processor 132. In other cases, at least a portion of the memory can be operatively coupled remotely to the sample processing device 130. For example, a remote database server can be operatively coupled to the sample analysis system 100 via the sample processing device 130.

[0123] The communicator 138 can be a hardware device operably coupled to the processor 132 and the memory 136 and / or software stored in the memory 136 and executed by the processor 132. The communicator 138 can be, for example, a compact network interface card (NIC), a Wi-Fi module, a module, a radio frequency communication module, and / or any other suitable wired and / or wireless communication device. Additionally, the communicator can include a switch, a router, a 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 computing devices. In some cases, the communicator 138 can facilitate the reception and / or transmission of files and / or collections of files to one or more computing devices (e.g., computers, smart phones, remote databases, servers, etc.) via the communication network.

[0124] The display 142 can be a low-power module configured to indicate one or more results of an analysis of a body fluid sample collected and tested by the sample analysis system 100. For example, the display 142 can be configured to have a set of backlit icons that indicate the user's hydration status, or an indication of an increase in the user's hydration, etc. In some embodiments, the display 142 can also be configured to include status indicators related to the sample processing device 130 or the sample disposal device 110. For example, the display 142 can be configured to alert the user that the sample disposal device 110 needs to be replaced or the sample processing device 130 needs to be charged. For example, the sample processing device 130 can be configured to be powered by a disposable or rechargeable battery power unit. In embodiments including a rechargeable power source, the sample processing device 130 can include an adapter for recharging the power unit when plugged into an electrical outlet. In some embodiments, the sample processing device 130 can include a device indicating the charge status.

[0125] Figure 4 An example construction of a sample disposal device 210 according to an embodiment is illustrated. The sample disposal device 210 can be substantially similar in form and / or function to the sample disposal device 110 referenced above Figure 2A and 2B described. For example, the sample disposal device 210 can include a sample collection area, an access port, a flow channel, a test area, and a set of electrodes, as described with reference to the sample disposal device 110. Thus, such similar parts and / or aspects are not described in further detail herein.

[0126] As described above with reference to the sample disposal device 110, one method of constructing the sample disposal device 210 includes assembling elements or parts or layers of a particular shape in a particular configuration to form the various components or elements of the sample disposal device 210. Figure 4Illustrated is an example set of structural layers that can be used to assemble the sample handling device 210 described herein. The layers of the sample handling device 210 can be made of a suitable material to meet the requirements of the sample handling device 210 during use. For example, one or more layers can be rigid, while one or more layers can be flexible. These layers can be made of biocompatible materials (e.g., biocompatible polymers). In some embodiments, these layers can be made of cut sheets of a suitable material to form a specific shape including specific features.

[0127] As Figure 4 shown, the sample handling device 210 can be in the form of a patch composed of a set of layers, which include an interface layer 211, an adhesive layer 213, an access port layer 215, and an electrode and channel layer 217 (either a single layer or two discrete layers). In some embodiments, the sample handling device 210 can include an additional layer 219 to provide interface advantages with the user or with a sample processing device, or to provide additional support during the use of the sample handling device 210, etc. In some embodiments, as described above, the sample handling device 210 can be configured as a disposable device for use with a suitable compatible, durable, reusable sample processing device.

[0128] The interface layer 211 can be a liner layer (e.g., a release liner) having one or more adhesive portions on the proximal and / or distal sides. The interface layer 211 can be configured to be placed on the surface of the user's body, with the proximal side facing the user's body. In some embodiments, the proximal adhesive properties can be used to secure the sample handling device 210 to the user's body. In some embodiments, the distal adhesive properties of the interface layer can be used to secure the interface layer 211 to the subsequent layer in the layer assembly, the adhesive layer 213, to form the sample handling device 210. In some embodiments, the interface layer 211 can include features adapted to allow the user to manipulate the sample handling device 210 while mounting the sample handling device 210 onto the sample processing device or the user. For example, the interface layer 211 can include tabs that protrude or extend beyond the profile of the other layers of the sample handling device 210, which can be used to hold the sample handling device 210.

[0129] The adhesive layer 213 is configured to be positioned or assembled on the interface layer 211 and have adhesive properties on its proximal and / or distal sides. The adhesive layer 213 can be assembled on the interface layer 211 using the adhesive properties on the distal side. The adhesive layer 213 is configured to form an opening and a boundary wall of the sample collection region of the sample handling device 210. The adhesive layer 213 can include and / or define an opening of a suitable size corresponding to the opening of the sample collection region of the sample handling device 210. The opening in the adhesive layer can be a portion cut out from the adhesive layer and having no adhesive properties (e.g., a cut-out portion located at the center). The thickness of the adhesive layer 213 can form a boundary wall enabling sample collection and determine the volume or fluid capacity of the sample collection area of the sample handling device 210. For example, the thickness of the adhesive layer 213 can be selected such that the opening defined in the adhesive layer 213 and the thickness of the opening together define a volume or space in which a body fluid sample can be collected to form a sample collection region. Although Figure 4 referring to a single adhesive layer 213, in some embodiments, two or more adhesive layers can be assembled to jointly form a sample collection region having a common thickness of all the adhesive layers. In the assembly of the sample handling device 210, the adhesive properties on the distal side (away from the user's body) of the adhesive layer 213 can be used to fix the adhesive layer 213 to a subsequent layer, the access port layer 215.

[0130] The inlet port layer 215 may have an adhesive property on its proximal side facing the adhesive layer 213, which can be used to assemble the inlet port layer 215 onto the adhesive layer 213. The portion of the inlet port layer 215 near the cutout portion of the adhesive layer 215 forms the bottom or wall portion of the sample collection region defined by the opening and thickness of the adhesive layer 213. The inlet port layer 215 includes an opening defined in the bottom or wall portion of the sample collection region to serve as an inlet port for the sample handling device 210. The opening in the inlet port layer 215 can be positioned at any suitable location such that it provides access to the sample collection region. The opening forming the inlet port of the sample handling device 210 can have a suitable size to form a conduit through the inlet port layer 215 and fluidly connect the sample collection region to the other side or proximal side of the inlet port layer for the flow of the collected body fluid sample. The thickness of the inlet port layer 215 can determine the length of the conduit defined by the inlet port. In some embodiments, the inlet port layer 215 can be made of a flexible material such as polyethylene terephthalate (PET) having a suitable thickness, such as 3 mil PET. In some embodiments, any suitable material (such as polydimethylsiloxane (PET), silicon, polyurethane, glass, or any other suitable material) can be used to form one or more layers of the sample handling device 210. In some embodiments, the material can be selected based on one or more properties such as stiffness, compliance, thickness, thinness, transparency, acceptability of interfacing with various adhesives, acceptability of screen printing one or more conductive traces (e.g., forming electrodes using conductive ink), etc.

[0131] The electrode and channel layer 217 includes a proximal side and a distal side, both of which may include surface portions having an adhesive property to assist in the assembly of the sample handling device 210. The proximal side of the electrode layer may include and / or define flow channels, while the distal side of the electrode and channel layer 217 includes a collection of electrodes. The electrode and channel layer 217 can be configured to form flow channels on the proximal side by defining one or more trenches in the thickness of the electrode and channel layer 217 such that when assembled on the inlet port layer 215, the depth of the trenches determines the cross-sectional area of the flow channels of the sample handling device 210. The remaining portion of the proximal side of the electrode and channel layer 217 in contact with the inlet port layer 215 can have an adhesive property to attach to the distal side of the inlet port layer 215. In such a configuration, the flow channels are formed such that a portion of the wall of the flow channel along its length is formed by the trenches defined in the electrode and channel layer 217, while another portion of the wall of the flow channel is formed by the inlet port of the distal layer 215 layer. The flow channels can be formed to include a test region.

[0132] The distal side of the electrode and the channel layer 217 may include a conductive portion made of etched, printed, coated, or applied conductive ink to form a set of electrodes. For example, the electrode may be formed by printing an ink containing 80% silver and 20% silver chloride. The set of electrodes may include excitation or test current signal delivery electrodes and voltage sensing electrodes. The electrode layer 217 includes a non-conductive portion surrounding the electrode portion to form a defined path or trace for the electrodes. In some cases, the proximal side of the portion of the electrode and the channel layer 217 containing the distal electrode may be coated or applied with a dielectric material to protect the electrode traces in the distal side. The electrode includes a test end located near or in the flow path, at the test area, allowing access to a portion of the sample body fluid that can flow through the flow channel. In other embodiments, another type of material may be selected for the electrode ink depending on the sensing method.

[0133] In use, similar to the sample handling device 110, some embodiments of the sample handling device 210 may be configured to direct the collected sweat from a small area of sweat glands on the user's skin in the sample collection area and at a suitable flow rate for testing. The collected sweat may be continuously directed via the flow channel through the inlet port to the test area and through the set of conductive electrodes in the test area. At the test area, an excitation signal is applied via one set of electrodes (e.g., the current delivery electrodes), and the response is read through the set of electrodes (e.g., the voltage sensing electrodes). The resulting impedance reading is obtained using the sensed voltage and is correlated with the salinity measurement of the collected sweat. After passing through the electrodes, the sweat is continuously directed further through the outlet portion of the flow channel and discharged to the environment at a suitable flow rate. This allows for continuous reading of the salinity measurement of the user's sweat, which can be used to infer the degree of hydration of the user during strenuous activity. The sample handling device 210 may be applied to any part of the body large enough to fit the size of the device 210.

[0134] The sample handling device 210 may be connected via a mechanical connector to a reusable electronic sample processing device. This allows the sample handling device 210 to be disconnected and discarded while retaining the durable electronic sample processing device for use with different sample handling devices 210 in the future. The mechanical connection also allows for an electrical connection between the durable electronic device and the patch having features for preventing sweat contamination of the components. As previously mentioned, the durable electronic sample processing device may be powered via a disposable or rechargeable battery. The durable sample processing device has a simple display and communication means via either an LED or a small screen. The durable electronic sample processing device may also have the ability to communicate wirelessly with a smart phone or a base station, which allows for real-time monitoring of more than one user (e.g., athletes or sports teams participating in an event, etc.).

[0135] Figure 5A and 5BIllustrated is an example sample handling device 310 according to an embodiment. The sample handling device 310 may be substantially similar in form and / or function to the sample handling devices 110 and 210 described above with reference to Figures 2A-2B and 4, respectively. For example, the sample handling device 310 may include a sample collection area, an access port, flow channels, a test area, and a set of electrodes, as described with reference to the sample handling device 110. The sample handling device 310 may be constructed similarly to the sample handling device 210 such that it includes an interface layer 311, an adhesive layer 313, an access port layer 315, and an electrode and channel layer 317, as described with reference to the sample handling device 210. Thus, such similar parts and / or aspects are not described in further detail herein.

[0136] Figure 5A Illustrated is a perspective view of the assembled sample handling device 310, showing the distal side (away from the user's body) of the sample handling device 310 in use. Figure 5B Illustrated is a top view of the distal side of the sample handling device 310 and also shows the outline of features in the more proximal layers of the sample handling device 310. Figure 6 Illustrated is an exploded view of the sample handling device 310, indicating the individual layers and their order and construction. These layers include the interface layer 311 that is the nearest or bottommost, where the adhesive layer 313, the access port layer 315, and the electrode and channel layer 317 form a continuous distal layer.

[0137] The layers for assembling and forming the sample handling device described herein may be generated by cutting a predetermined shape or profile from a suitable sheet along a predetermined contour. Figure 7A 、 7B 7C respectively illustrate the interface layer 311, the adhesive layer 313, and the access port layer 315 of the sample handling device 310, which are generated from materials cut along a predetermined contour for each layer. For example, the cutting profile for generating the adhesive layer 313 includes cutting portions that define the opening and volume of the sample collection area 312. The cutting profile for generating the access port layer 315 includes an opening that defines the access port 314.

[0138] Figure 8 Illustrated is a top view of the distal side or surface of the electrode and channel layer 317. The outline indicates electrode traces etched or marked by printing a conductive ink of 80% silver and 20% silver chloride. The electrode traces follow a path that includes a serpentine shape. This construction may be used to make the electrodes have higher stress tolerance and incorporate flexible electrical and electronic coupling. Figure 8The example electrode traces indicated therein include four electrodes, with four terminals located at the circular probe and four test ends located in the test area. The four electrodes include two current delivery electrodes 320A configured to deliver an excitation signal and two response carrying or voltage sensing electrodes 320B configured to read the voltage or test current across a sample body fluid (e.g., sweat) in response to the applied excitation signal and carry the response signal to the sample processing device. The sample processing device may be electrically coupled to the sample handling device 510 via Figure 8 the circular terminal probe on the electrode trace shown in

[0139] Figure 9 The figure illustrates the proximal or surface of the electrode and channel layer 317, indicating the test ends of the set of flow channels 316, test area 318, current delivery electrodes 320A, and voltage sensing electrodes 320B, as well as an outlet 324 for discharging the sample after testing. Figure 9 The schematic diagram in

[0140] Figure 10 also illustrates an adhesive portion 323 of the electrode and channel layer 317 for securing the electrode and channel layer 317 to an adjacent proximal layer, i.e., the inlet port layer 315. In some embodiments, the portion 323 may be printed with a thickened ink having a thickness of approximately 0.9 mm before applying the adhesive layer. These layers may be assembled such that the inlet ports in the inlet port layer 315 directly cover the test area in the electrode and channel layer 317. In some embodiments, the inlet ports may cover the receiving portion of the flow channel that is upstream of but other than the test area. The receiving portion may direct the collected sample flow to the test area located downstream. The flow channel follows a path including a serpentine shape. Such a configuration may be used to increase stress tolerance and include local traps to prevent air from outside the sample handling device 310 from entering the flow channel.

[0141] Figure 11A The top view of the sample processing device 330 is illustrated, showing the distal surface away from the user's body during use. Figure 11B The bottom view is illustrated, which shows the proximal surface of the sample processing device 330, which is configured to dock with the sample handling device 310 before being worn by the user. Figure 11C The perspective view of the sample processing device 330 is illustrated. Figure 12 、 13 and 14 respectively illustrate cross-sectional views of the sample processing device 330, and the cross-sections are taken along the Figure 11A lines 12-12 and 13-13 in Figure 11C and the line 14-14 in

[0142] Figure 15 The top view of an example sample handling device 510 according to an embodiment is illustrated, and at the same time, the outline of the features in the intermediate layer of the sample handling device 510 is also shown. The sample handling device 510 may be substantially similar in form and / or function to the above-described sample handling devices 110, 210, and 310. For example, the sample handling device 510 may include a sample collection area, an access port, a flow channel, a test area, and a set of electrodes, as described with reference to the sample handling device 110. The sample handling device 510 may be similarly configured to the sample handling device 210 and / or the sample handling device 310 such that it includes an interface layer 511, an adhesive layer 513, an access port layer 515, and an electrode and channel layer 517, as described with reference to the sample handling devices 210 and 310. Therefore, such similar parts and / or aspects will not be further described in detail herein.

[0143] Figure 16 The exploded view of the sample handling device 510 is illustrated, indicating the respective layers and their order and configuration. These layers include the interface layer 511 that is the nearest or the bottommost, and the adhesive layer 513, the access port layer 515, and the electrode and channel layer 517 form a continuous distal layer. Figure 17 The bottom view of the electrode and channel layer 517 is illustrated, showing the proximal surface of the layer 517, which is configured to interface with the adjacent layer (i.e., the access port layer 515) of the sample handling device 510. As described with reference to the electrode and channel layer 317 of the sample handling device 310, the electrode and channel layer 517 includes electrode traces or tracks having serpentine portions configured to better withstand stress.

[0144] Now refer to Figure 18, shows a flowchart of a method 450 of using a sample analysis system that includes 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 body fluid samples (e.g., sweat) at a near-instantaneous real-time rate. In some embodiments, the sample handling device can be similar and / or substantially the same as any of the sample handling devices 110, 210, 310, and / or 510 described herein.

[0145] Method 450 includes collecting a sample of body fluid at 451 via the sample handling device of the sample analysis system. In some cases, for example, the body fluid source can be sweat. As the sample collection area of the sample handling device is filled or when a large amount of sample body fluid has been collected, the sample collected at 453 is directed into contact with an electrochemical interface. In some cases, the collected sample is continuously directed to the electrochemical interface, tested, and discharged as new samples are continuously collected. For example, the sample fluid is directed through an inlet port via a flow channel to a test area where the sample body fluid is brought into contact with the test ends of a set of electrodes.

[0146] The sample analysis system is configured to apply an excitation signal at 455 to the sample body fluid in contact with the electrical interface. For example, the excitation signal is delivered via the test ends of a set of current delivery electrodes. The sample analysis system is configured to receive a response signal from the sample body fluid at 457 after applying the excitation signal at 455. For example, the response voltage is read via the test ends of a set of voltage sensing electrodes.

[0147] At 459, the sample analysis system calculates an impedance measurement via the sample processing device based on the excitation signal applied at 455 and the response signal received at 457. The impedance measurement is then analyzed at 461 to obtain information related to the user's hydration level, electrolyte loss, and / or sweating rate. Based on the analysis, the sample analysis system updates a display or a peripheral device associated with the sample processing device with information related to the user's hydration level at 463. For example, the impedance measurement is related to a salinity measurement of the user's sweat, and the salinity measurement is used to infer the user's hydration level, electrolyte loss, and sweating rate. In some cases, applying the excitation signal at 455, reading the response at 457, calculating the impedance measurement at 459, and inferring the hydration level, electrolyte loss, and / or sweating rate at 463 can be performed in a continuous manner with the sample sweat being directed to flow at a suitable rate. After testing the body fluid sample, the sample is continuously directed to an outlet or a departure port at 465 for discharge into the environment.

[0148] In some embodiments, as described above, the sample handling device of the sample analysis system can be configured to continuously collect samples or volumes of body fluid and direct them to a test area, test the samples, and eject the samples to make room for the next sample. Thus, method 450 can be repeatedly performed for multiple samples, thereby providing intermittent or continuous results from the testing and analysis. The sample analysis system can be configured such that the time taken to collect a body fluid sample sufficient for testing, the time taken to direct the fluid to the test area and test the sample, and the time taken to analyze the test results and eject the sample can be reduced as needed to suit the user's needs. In some cases, one or more parts of the sample handling device can be adjusted to form a series of sample handling devices with different response rates, such that different users can obtain a customized or personalized sample analysis system with a personalized sample handling device or personalized sample processing device. In some embodiments, data from different users (e.g., teams) can be stored, retained, and / or displayed to monitor the hydration level, electrolyte loss, and / or sweating rate of multiple users. In some cases, users can select an appropriate sample analysis system based on the type of activity they may be engaged in or the amount or rate of sample analysis they may require.

[0149] For example, compared to a sample handling device used by a user with little sweating, a user with a higher sweating history can use a sample handling device that includes a sample collection area with appropriately smaller openings that cover a smaller portion of the sweat glands. In some cases, high-performance athletes who require a higher sample analysis rate can use a sample handling device with a sample collection area with a smaller fluid capacity, such that when the high-performance athlete user uses the sample analysis system while engaged in an activity, smaller amounts of sweat are tested more frequently.

[0150] In some cases, the sample processing device can be personalized to store and retain a history of results from the analysis of a user's health condition for future use by the sample analysis system. In some embodiments, the sample analysis system can be configured to output a collection of data and / or analysis from the memory of the sample processing device to a remote device after a predetermined intermittent period. For example, in some implementations, the sample analysis system can export data and / or analysis results to a wearable device or a smart phone each time there is a change or replacement of the sample handling device. 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 chart the progress of the user's health, performance, etc. and, in some cases, to predict their health status prior to the individual user undertaking a planned activity. In some implementations, the sample analysis system can include a remote application running on a remote server or computing device to provide a plan to the user, such as a hydration strategy that might be most suitable for the user (such as a performing athlete) when a major sporting event is planned. The remote application can include predictive algorithms that can be used to develop strategic plans for rehydration, maintaining electrolyte balance, etc.

[0151] As previously described, the sample analysis system and / or sample handling device described herein can be integrated with wearable devices such as smart watches, pedometers, GPS systems, etc. Figure 19 and 20Illustrates an example embodiment of a sample analysis system 600, including a sample handling device 610, which is integrated with a wearable smartwatch device 645. In some cases, when a sample analysis system including a sample processing device is integrated with a wearable device, the sample processing device may include interface elements for physical and electrical connection to the sample handling device. The sample processing device may perform functions such as providing instructions regarding the delivery of an excitation signal, providing the excitation signal to the terminals of an electrode in the form of a test current, and receiving a response signal obtained from the sample to be tested via the electrode. The sample processing device may include the electronics required to analyze the response signal and / or transfer data to a remote computing device, etc. For example, the electronics may be programmed with a unique analysis code to interpret the collected readings. The interpreted readings may be output to a display of the sample processing device to provide information to the wearer regarding the sweating rate and overall hydration status. In cases where the sample handling device can interface directly with the wearable device, the wearable device may be configured to physically and electrically engage directly with the sample handling device and perform functions such as providing instructions, providing an excitation signal, receiving and analyzing a response signal, etc. The electronics included in the wearable device may be used to execute a program with a unique analysis code to interpret the collected readings. The interpreted readings may be output to a display of the wearable device or a display associated with a remote computing device (e.g., a smartphone) to provide information to the wearer regarding the sweating rate and overall hydration status.

[0152] Figure 21 Is a schematic top view of a sample handling device 710 according to an embodiment, with the layers rendered transparent to show the underlying features in the intermediate layer of the sample handling device 710. Figure 22 Is Figure 21 A top view image of an example implementation of the sample handling device 710. Figure 23A Is a schematic exploded view of a sample handling device 710 according to an example implementation. Figure 23B Is a schematic exploded view of a sample handling device 710 according to another example implementation. Figure 24A Shows a perspective view of the device 710, and 24B shows Figure 24A An enlarged view of a portion indicated by the dashed box of Figure 24C Which is also shown in the top view of

[0153] The sample handling device 710 may be substantially similar in structure and / or function to the sample handling devices 110, 210, 310, and / or 510 described herein. For example, the sample handling device 710 may include a sample collection area 712, an inlet port 714, a flow channel 716, a test area 718, a set of electrodes 720, and a temperature sensor 740, which may be substantially similar to those described for the reference sample handling device 110. The sample handling device 710 may be constructed similarly to the sample handling device 210 and / or the sample handling device 310 such that it includes an interface layer 711 that may be a release liner, an adhesive layer 713 that includes an opening 722 for the sample collection area 712, an inlet port layer 715 that defines the inlet port 714, and an electrode and channel layer 717, as described for the reference sample handling devices 210 and 310. Thus, such similar parts and / or aspects are not described in further detail herein.

[0154] In some embodiments, the flow channel 716 may be defined by a meandering shape as Figure 21 shown to reduce and / or prevent air entry and / or unwanted fluid movement, such as backflow or "mixing" in the flow channel. In some embodiments, the meandering shape of the flow channel 716 may be configured such that the flow rate of the body fluid sample being tested is determined by the supply rate of the body fluid (e.g., sweating rate) and is not affected by other lateral effects such as gravity, the user's body movement, etc. The sample handling device 710 may include a reinforcement layer 727A that is configured to provide structural support to a portion of the electrode and channel layer 717, e.g., at the portion that will be contacted by a sample processing device (e.g., sample processing devices 130, 330, etc.). In some embodiments, as shown, the sample handling device 710 may include a reinforcement layer 727B that is configured to provide support to the cell portions of the covered area that includes the inlet port 714, the test area 718, etc. As Figure 23A and 23BAs can be seen, the reinforcement layer 727B may include holes that are defined to allow space for the temperature sensor 740 when the layers are assembled. In some embodiments and / or in some examples, the sample handling device 710 may include one or more spacer portions 729 that are included to occupy space in the sample collection region 712 such that the initial volume of body fluid required to push fluid through the flow path 716 can be reduced compared to embodiments without the spacer layer 729. In some examples, the spacer portion 729 may be included in the inlet port layer 715. For example, the inlet port layer 715 may be made of a transparent polyester (PET) material (such as Melinex 454 or equivalent material) having a specified thickness (e.g., 3 mils (75 microns)). The inlet port layer 715 may include spacer portions 729 defined by an increased thickness via printed spacer ink (e.g., a thickness of 4 mils (0.10 mm) spacer ink). As shown, the spacer portion 729 may define through-holes aligned with the inlet ports 714 such that the fluid capacity of the sample collection region is reduced (e.g., reducing the volume of the spacer portion 727) and the fluid collected in the available portion of the sample collection region 712 can be pushed via the holes and the inlet ports 714 toward the test region 718 defined on the electrode and channel layer 717.

[0155] Figure 25A is a schematic bottom view of the electrode and channel layer 717, showing the channel layer 717B. Figure 25B and 25C are schematic bottom and side views, respectively, of the electrode layer with the channel layer removed. Figure 25B shows the electrode layer 717A, which includes electrode tracks 717C and electrical vias 717D on the bottom surface of the electrode layer 717A. Figure 25D is a top view of the electrode layer 717A, showing the electrode traces 717C on the top surface of the electrode layer 717A. Figure 25E is a schematic enlarged view of a cell portion of the electrode layer 717A, indicating the electrode tracks 717C on the top and bottom surfaces of the electrode layer 717A and the electrical vias 717D.

[0156] The electrode and channel layer 717 may be made of the electrode layer 717A and the channel layer 717B, as Figure 23BAs shown. The electrode layer 717A and / or the channel layer 717B can be made of any suitable material with a suitable thickness. For example, the electrode and channel layer 717 can be formed using transparent 5 mil PET. The channel layer 717B can be defined on the bottom or proximal surface of the electrode and channel layer 717, closer to the user's body during use, and includes a cell portion and an electrode track portion. The cell portion of the channel layer 717B can be formed using spacer ink such that the profile of the flow channel 7176 defines the grooves forming the flow channel 716. The spacer ink can have any suitable thickness, which can at least partially determine the cross-sectional thickness of the flow channel. The spacer ink thickness can be, for example, 2 mils (0.05 mm). In some embodiments, the spacer ink can be applied to the channel layer 717B and then an adhesive can be sprayed within a suitable specified maximum thickness (e.g., maximum 1 mil (0.025 mm)). The channel layer 717B can include an electrode track portion 717E, which is printed on the proximal or bottom surface (towards the user's body) with a dielectric ink of a specified thickness (e.g., 1 mil (0.025 mm)). In some embodiments, the electrode track portion can be substantially straight to avoid entanglement with the user's clothing, etc. during use. The electrode layer 717A can be defined on the top or distal portion of the electrode and channel layer 717, as Figures 25B-25D shown. The electrode track portion 717A of the electrode layer can include electrode tracks 717C defined on the bottom or proximal surface (closer to the user's body during use) to form a sample end of the electrode 720, which can be in fluid communication with at least a portion of the flow channel 716 at the collection of the test area 718 such that a body fluid flowing through the flow channel 716 at the test area 718 can be tested. The electrode tracks can be configured to provide an electrical connection between the sample end of the collection of the electrodes 720 and their respective terminals configured to be connected to a part of a sample processing device (e.g., sample processing devices 130, 330, etc.). In some embodiments, the sample handling device 710 can include a temperature sensor 740 and the electrode layer 717A can include an electrical via or through-hole 717D and electrode tracks defined in the top or distal surface (away from the user's body during use) to communicate with the electrical via 717D, as Figure 25D shown. The electrode tracks on the distal surface and in communication with the electrical via 717D can be configured to provide an electrical connection to the temperature sensor 740 to send and / or receive signals from the temperature sensor 740. Figure 25E Shows enlarged views of the top (distal) and bottom (proximal) surfaces of the cell portion of the electrode layer 717A according to some embodiments.

[0157] The electrode 720 may include an excitation electrode 720A and a sensing electrode 720B that are positioned to define a test region 718. In use, a body fluid sample may be collected at the sample collection region 712 and directed to flow through the flow channel 716 and past the test region 718 via the inlet port 714. A temperature sensor 740 may be appropriately positioned to measure the fluid temperature at the test region 718. An excitation signal (e.g., current) may be applied via the excitation electrode 720A and a response signal (e.g., voltage response) may be received by the sensing electrode 720B to calculate the impedance associated with the body fluid sample at the test region. The temperature associated with the body fluid sample may be measured by the temperature sensor 740. At each test time point, the response signal and the measured temperature may be sent to the sample processing device via the electrode tracks. As body fluid is collected, tested, and ejected at the outlet 724 in a continuous manner, multiple body fluid samples may be tested at multiple time points. The sample processing device may receive the response signals and / or temperature measurements associated with the body fluid samples over a period of time and analyze the signals and / or measurements, or store / transmit the signals for further processing.

[0158] Figure 26A is a schematic top view of a sample handling device 810 according to an embodiment, where layers are rendered transparent to show underlying features. The sample handling device 810 may be substantially similar in structure and / or function to the sample handling devices 110, 210, 310, 510, and / or 710 described herein. For example, the sample handling device 810 may include a sample collection region 812, an inlet port 814, a flow channel 816, a test region 818, and a set of electrodes 820, which may be substantially similar to those described with reference to the above sample handling devices. In some embodiments, the sample handling device 810 may include a temperature sensor (not shown). In some embodiments, the temperature sensor may be included in the sample processing device to couple to the sample handling device 810.

[0159] The sample handling device 810 may be constructed similarly to the sample handling devices 210, 310, and / or the sample handling device 710. For example, the sample handling device 810 includes an interface layer 811 that may be a release liner, and an adhesive layer 813 that is configured to be peeled and adhered to the user's skin. The adhesive layer 813 includes an opening 822 of the sample collection region 812. The sample handling device 810 includes an inlet port layer that defines the inlet port 814 and an electrode and channel layer 817, as described with reference to the sample handling devices 210, 310, and / or 710. In some embodiments, the inlet port layer may be combined with the electrode and channel layer to form an intermediate layer 817. Thus, such similar parts and / or aspects are not described in further detail herein.

[0160] One or more layers of the sample handling device 810 may include alignment aids, such as alignment holes 837.Figure 26B It is a schematic bottom view of the sample handling device 810 after removing the release liner that forms the interface layer 811. Figure 26C It shows a top view of the sample handling device 810 mounted on an installation interface 835 (e.g., a snap ring interface) according to an embodiment. Figure 27A Is Figures 26A-26C A perspective top view of an exemplary embodiment of the sample handling device 810. Figure 27B Is according to an exemplary embodiment Figure 27A A schematic exploded view of the sample handling device 810. Figure 28 It is a schematic exploded view of the sample handling device 810 according to an embodiment.

[0161] FIG. 29 shows a perspective top view of the device 810. Figure 30 It shows an exploded view of the sample handling device 810 mounted on an installation structure according to one embodiment.

[0162] The interface layer 811 and / or the adhesive layer 813 may be substantially similar to the interface layer and / or the adhesive layer described herein (e.g., interface layers 211, 711, etc. and adhesive layers 213, 713, etc.). In some embodiments, the access port 814 may be formed on the access port layer 817 and at a suitably defined position relative to the sample collection region 812 and its opening 822, as shown in FIGS. 26 and 29. For example, the access port 814 may be positioned at an off - center position relative to the opening 822 of the sample collection region 812 to reduce and / or prevent the formation of air bubbles in the collected body fluid sample. The opening 822 may be suitably shaped to accommodate the eccentric positioning of the access port 814, as shown by the notch in FIGS. 26 and 29.

[0163] In some embodiments, the intermediate layer 817 defines the access port 814 as a through - hole and includes flow channels defined on the distal surface and electrode tracks and test regions defined on the proximal surface. In some embodiments, the intermediate layer 817 may be made of a suitable material, such as polyester (PET), PDMS, etc. In some embodiments, the intermediate layer 817 may be made of a suitably coated material such that one or both surfaces are hydrophilic. For example, the intermediate layer 817 may be made of (e.g., It is made of 0.100 mm (4 mil) HNW and includes a surface with a hydrophilic coating. The hydrophilic coating can improve the capillary action of fluids and guide body fluids to flow through the defined flow channel 816 during use. In some embodiments, the hydrophilic coating can be applied on the proximal surface and the electrode layer 817A can be printed on the hydrophilic surface. In some embodiments, the hydrophilic coating can be added to any surface or surface portion in contact with the fluid. The hydrophilic coating can be configured to reduce bubble formation and / or improve the flushing of any bubbles entering the system.

[0164] In some embodiments, the hydrophilic coating can be applied on the distal surface and the channel layer 817B can be printed on the hydrophilic surface. The hydrophilic coating can be applied in any suitable shape. For example, in some embodiments, the hydrophilic coating can be preferentially applied to the portion of the inner surface defining the flow channel 816 to assist the flow of the body fluid sample.

[0165] The sample handling device 810 can include three test areas 818A, 818B, and 818C, as Figure 26A shown in FIGS. 28 and 29. Each test area respectively includes a set of electrodes 820A, 820B, and 820C. The test areas 818A, 818B, and 818C are positioned at increasing distances from the inlet port 814 and along the flow path 816 before the body fluid sample is ejected at 824. The sample handling device 810 can include a reinforcement layer 827A, which is configured to provide structural support to a portion of the electrodes and the channel layer 817. For example, the reinforcement layer 827A can be configured to provide the wall of the flow path 816 and support to the unit portion covering area, which includes the inlet port 814, the test areas 818A, 818B, 818C, etc.

[0166] The electrode layer 817A can include a set of electrodes 820A, 820B, and 820C and electrode tracks connecting the electrodes to the terminals. In some embodiments, the set of electrodes 820 can be configured such that each test area is assigned one or more excitation electrodes to apply an excitation signal and one or more sensing electrodes to receive a response signal from the fluid sample being tested. In some embodiments, the electrodes 820 can be configured such that each test area is equipped with bipolar electrodes to excite and sense a response from the sample body fluid being tested. The electrodes 820 and the electrode tracks can be printed using any suitable conductive and / or electrode ink. For example, Ercon (80 / 20 silver / silver chloride ink) or any other electrode material can be used to print the electrodes and / or the electrode tracks with any suitable thickness (e.g., 0.015 mm). The terminals of the electrodes can be in any suitable configuration to be electrically connected to a part of the sample processing device. For example, the terminals can be configured to be connected via spring pins, spring-loaded pins, etc.

[0167] In some embodiments, the flow channel 816 may be defined by an annular shape as shown in Figure 26A to reduce and / or prevent air entry. The channel layer 817B may be formed by printing a thickened ink in a predetermined area to form the flow path 816. For example, the channel layer 817B may be formed by printing NAZDAR NFX52 ink with a thickness of 0.05 mm. The flow path 816 may be jointly formed when the intermediate layer 817 and the reinforcing layer 827A are assembled, and the reinforcing layer 827A forms the far side wall of the flow path 816. The channel layer 817B may include test areas 818A, 818B, and 818C defined at specified portions along the flow path 816. The test areas 818A, 818B, and 818C and the flow path 816 may be defined on the far side surface of the intermediate layer 817, and the sample ends of the electrode tracks and the electrodes 820A, 820B, and 820C may be defined on the near side surface of the intermediate layer. The test area may be configured to include one or more through holes that provide electrical connection between the far side surface of the intermediate layer 817 defining the flow path 816 and the near side surface of the intermediate layer 817 defining the electrodes, such that when body fluid flows through the flow path 816 and through each test area, the excitation signal applied by the excitation electrode can be delivered to the fluid sample at the test area and can elicit a response from the body fluid sample, and this response can be sensed by the sensing electrode located at that test area. In some embodiments, a temperature sensor may be configured to be housed in the sample processing device and measure the temperature of the fluid sample being tested at one or more test areas defined on the channel layer 817B.

[0168] Figure 29B is a schematic top view with the channel layer removed and shows the near side of the intermediate layer 817 including the electrode layer 817A. Figure 29C Illustrates the top or far side of the intermediate layer 817 including the channel layer 817B. Figure 29D is a side view and Figure 29E shows a bottom view of the spacer portion 829 that will be covered on the near side surface of the intermediate layer 817 including the electrode layer 817A.

[0169] In some embodiments, the sample handling device 810 may include a spacer portion 829, as described previously with reference to the spacer portion 729, and the spacer portion 829 is bonded to occupy the space in the sample collection area 812. The spacer area 829 may be formed by printing a thickened ink (e.g., 0.10 mm NAZDAR NFX52). In some embodiments, the device 810 may include an additional adhesive layer 833 to assist in adhering to an alignment and / or mounting interface (e.g., a snap ring interface).

[0170] Figure 30FIG. shows an exploded view of a set of a sample handling device 810 mounted to a ferrule interface 835 and an assembly fixture 871 using an alignment structure 869 interfacing with an alignment aid, according to an example embodiment. Figure 30 Also shown is an electrical interface assembly 872, which in some embodiments can be used to test and / or optimize the functionality of the sample handling device 810.

[0171] Figure 31 is a schematic top view of a sample handling device 910 according to an embodiment, where the layers are rendered transparent to show underlying features. Figure 32 is a schematic top view of a sample handling device 910 mounted to an interface 967 (e.g., a ferrule interface) in an example embodiment. The sample handling device 910 can be substantially similar in structure and / or function to the sample handling devices 110, 210, 310, 510, 710, and / or 810 described herein. For example, the sample handling device 910 can include a sample collection area 912, an inlet port 914, flow channels 916, test areas 918A and 918B, and a set of electrodes 920, which can be substantially similar in structure and / or function to those described with reference to the above sample handling devices. In some embodiments, the sample handling device 910 can include a temperature sensor (not shown). In some embodiments, the temperature sensor can be included in a sample processing device to be coupled with the sample handling device 910, and the temperature sensor can be configured such that the temperature of the sample fluid being tested at one or more test areas 918 can be measured. Figure 33A and 33B is a schematic perspective top view and top view of a sample handling device 910 according to one embodiment, showing layers for packaging.

[0172] Figure 34 is according to one embodiment Figure 33A 、 33B of an exploded view schematic of a sample handling device 910. Figure 35A and 35B are schematic bottom view and top view of a sample handling device 910 according to one embodiment. FIGS. 36 and 37 are exploded views of two perspective views of a sample handling device 910 mounted on a mounting structure according to one embodiment. Figure 38 is an exploded view of a sample handling device 910 mounted to a mounting structure according to another embodiment.

[0173] In some embodiments, the sample handling device 910 may be constructed similarly to the sample handling devices 210, 310, 710, and / or the sample handling device 810. For example, the sample handling device 910 includes an interface layer 911 that may be a release liner and an adhesive layer 913 configured to be peeled off and adhered to the user's skin. The adhesive layer 913 includes an opening 922 of the sample collection area 912. The sample handling device 910 includes an access port layer that defines an access port 914 in combination with the electrode and channel layer 817, as described with reference to the sample handling devices 210, 310, 710, and / or 810. Thus, such similar parts and / or aspects will not be described in further detail herein.

[0174] One or more layers of the sample handling device 910 may include an alignment aid 937. The interface layer 911 and / or the adhesive layer 913 may be substantially similar to the interface layer and / or the adhesive layer described herein (e.g., interface layers 211, 711, 811, etc. and adhesive layers 213, 713, 813, etc.). In some embodiments, the access port 914 may be formed on the electrode layer 917A (which also serves as an access port layer) and at a properly defined position relative to the opening 922 of the sample collection area 812, as Figure 35A and 35B shown. For example, the access port 914 may be positioned at an off-center position relative to the opening 922 of the sample collection area 912 to reduce, flush, and / or prevent the formation of air bubbles in the collected body fluid sample and / or the flow of the prepared body fluid during use.

[0175] In some embodiments, the electrode layer 917A defines the access port 914 that is defined to pass through the opening. In some embodiments, the electrode layer 917A may be made of a suitable material, such as transparent polyester (PET), PDMS, etc. In some embodiments, the intermediate layer 817 may be made of a properly coated material such that one or both surfaces are hydrophilic. For example, the electrode layer 917A may be made of (e.g., 0.100 mm (4 mil) HNW), which includes one surface having a hydrophilic coating. The hydrophilic coating may improve the capillary action of the fluid and guide the body fluid to flow through the defined flow channels 916 during use. The electrode tracks and the test area may be defined on the proximal surface of the electrode layer 917A. The hydrophilic coating may be applied on the proximal surface and the electrode layer 917A may be printed on the hydrophilic surface.

[0176] The sample handling device 910 may include a channel layer 917B having an exact predefined thickness and determining the cross-sectional dimensions and volume of a portion of the flow channel 916. In some embodiments, the channel layer 917B may include an adhesive surface that may be configured to attach to a portion of a sample handling device (e.g., sample handling devices 130, 330, etc.). In some implementations, the sample handling device 910 may be a disposable portion for use with a durable portion, where the adhesive surface of the channel layer 917B is used to attach the sample handling device 910 to the durable portion (e.g., attached to a plastic portion). In some implementations, the sample handling device 910 may be used with and attached to a plastic portion or surface of a disposable sample handling device via the adhesive surface of the channel layer 917B. In some embodiments, the adhesive surface of the channel layer 917B may be configured to attach to a reinforcement layer 927A. The reinforcement layer 927A may be made of any suitable plastic material. In some embodiments, the flow channel 916 may be defined by a linear portion in the channel layer 917B that extends via a through hole in the reinforcement layer 927A and via a flow path defined by an interface (e.g., Figure 37 and 38 as shown in the snap ring interface 924). An outlet 924 may be defined in the snap ring interface 935 to eject the fluid sample being tested. The flow path 916 may be formed jointly on the assembly of the adhesive layer 912, the electrode layer 917A, the channel layer 917B, the reinforcement layer 927A, and the snap interface 935. The channel layer 917B may include test regions 918A and 918B defined at designated portions along the flow path 816. The electrode tracks and the sample ends 920C of the electrodes 920A, 920B, and 920B may be defined proximal to the electrode layer 917A and the test regions 918A and 918B, and the flow path 916 may be defined on the distal surfaces of the electrode layer 917A and the channel layer 917B such that when a body fluid sample flows through the flow path 916 and through each test region, an excitation signal applied by the excitation electrode 920B may be delivered to the fluid sample at the test region and may elicit a response from the body fluid sample, which may be sensed by the sensing electrodes 920A, 920C located at that test region 918A, 918B, respectively. In some embodiments, a temperature sensor may be configured to be housed in the sample handling device and measure the temperature of the fluid sample being tested at one or more of the test regions 918A and 918B defined on the channel layer 917B.

[0177] In some embodiments of the sample handling device, the electrodes 920 may be configured such that multiple electrode pairs may share one or more electrodes. The multiple electrode pairs may be directed to multiple test areas such that the shared electrode may have a common terminal and multiple sample terminals located at or near the multiple test areas. For example, the electrodes 920 may be configured such that two or more electrode pairs share an excitation electrode rather than having one excitation electrode per pair of electrodes. The sample handling device 910 may include two predefined test areas 918A and 918B, as Figure 35A shown. The test area 918A includes a set of electrodes 920A and 920B, and the test area 918B includes electrodes 920B and 920C respectively, where the electrode 920B serves both test areas. The test areas 918A and 918B are positioned at increasing distances from the inlet port 914 and at a known distance from each other along the flow path 916 before the body fluid sample is ejected at 924. The sample handling device 910 may include a reinforcement layer 927A that is configured to form the far sidewall of the flow path 916 (away from the user's body in use), and the far side surface of the electrode layer 917A forms the near sidewall of the flow path 916. The reinforcement layer 927A is also configured to provide structural support to a portion of the electrode and channel layers 917A and 917B, such as covering the cell portion of the area including the inlet port 914, the test areas 918A and 918B.

[0178] In some embodiments, the electrode 920B may be a common excitation electrode serving both test areas 918A and 918B, and the electrodes 920A and 920C may be configured as sensing electrodes that operate in combination with the electrode 920B. An excitation signal may be applied via the electrode 920B, and the electrodes 920A and 920C may receive response signals from the fluid samples being tested at each test area. In some embodiments, the electrodes may be configured to operate as bipolar electrodes to both excite and sense responses from the sample body fluid being tested. The electrodes 920A, 920B, and 920C, as well as the electrode tracks, may be printed using any suitable conductive and / or electrode ink. For example, the electrodes and / or electrode tracks may be printed using Ercon (80 / 20 silver / silver chloride ink) or any other electrode material of a suitable thickness. The terminals of the electrodes may be of any suitable configuration to electrically connect to a portion of the sample processing device. For example, the terminals may be configured to connect via spring pins, spring needles, etc.

[0179] Figure 36A is a schematic view of the top or far side of the electrode layer 917A. Figure 36B is a side view and Figure 36CIllustrates the bottom or proximal side of electrode layer 917B and shows a bottom view of spacer portion 929 that will be covered on the proximal surface of electrode layer 917A. As shown, channel layer 917B includes vias that permit an electrical path between a sample processing device attached to the distal side of sample handling device 910 and connection points of electrodes 920A, 920B, and 920C on the distal side of electrode layer 917A.

[0180] In some embodiments, sample handling device 910 may include spacer portion 929, as previously described with reference to spacer portions 729 and / or 829, which is incorporated to occupy space in sample collection region 912. Spacer region 929 may be formed by printing a thickened ink (e.g., 100 μm or approximately 0.004” NAZDAR NFX52). In some embodiments, device 910 may include an additional adhesive layer (not shown) to aid in adhesion to an alignment and / or mounting interface (e.g., a retaining ring interface).

[0181] Figure 37 and 38 Illustrates two perspective exploded views of sample handling device 910 mounted to retaining ring interface 935 according to one embodiment. Figure 39 Shows an exploded view of sample handling device 910 mounted to a retaining ring interface and an assembly of mounting structure 971 that interfaces with alignment aid 935 using alignment structure 969 according to an example embodiment.

[0182] Figures 40A-40D Are schematic diagrams of a bottom view, a top view, a side view, and a perspective side view, respectively, of sample handling device 1010 according to an embodiment. Figure 41 Is a schematic diagram of an exploded view of sample handling device 1010 according to an example embodiment. Figure 42 Is a schematic diagram of a top view of sample handling device 1010 according to an embodiment, with layers rendered transparent to show underlying features in intermediate layers.

[0183] The sample handling device 1010 can be substantially similar in structure and / or function to the sample handling devices 110, 210, 310, 510, 710, 810, and / or 910 described herein. For example, the sample handling device 1010 can include a sample collection area 1012, an access port 1014, a flow channel 1016, test areas 1018A and 1018B, and a set of electrodes 1020, which can be substantially similar in structure and / or function to those described with reference to the above sample handling devices. In some embodiments, the sample handling device 1010 can include a temperature sensor (not shown). In some embodiments, the temperature sensor can be included in the sample processing device to be coupled to the sample handling device 1010, and the temperature sensor can be configured such that the temperature of the sample fluid being tested at one or more of the test areas 1018A, 1018B can be measured.

[0184] Figure 41 FIG. is a schematic diagram of an exploded view of a sample handling device 1010 according to one embodiment. In some embodiments, the sample handling device 1010 can be constructed similarly to the sample handling devices 210, 310, 710, 810, and / or the sample handling device 910. For example, the sample handling device 1010 includes an interface layer 1011 that can be a release liner, and interface and adhesive layers 1013A and 1013B. The adhesive layer 1013A can be constructed to be peeled off and adhered to the user's skin. The adhesive layers 1013A and 1013B include an opening 1022 of the sample collection area 1012. The sample handling device 1010 includes an additional electrode layer adhesive 1019A to attach the electrode layer 1017A to a distal layer (e.g., the interface layer 1011, the adhesive layers 1013A, 1013B, etc.). The sample handling device 1010 includes an access port layer that defines the access port 1014 in combination with the electrode layer 1017A, as described with reference to the sample handling devices 210, 310, 710, 810, and / or 910. Thus, such similar parts and / or aspects are not described in further detail herein.

[0185] The interface layer 1011 and / or the adhesive layers 1013A, 1013B can be substantially similar to the interface layer and / or the adhesive layers described herein (e.g., the interface layers 211, 711, 811, 911, etc. and the adhesive layers 213, 713, 813, 913, etc.). In some embodiments, the access port 1014 can be formed on the electrode layer 1017A (which also serves as the access port layer) and at an appropriately defined position relative to the opening 1022 of the sample collection area 1012, as Figure 41 and 42As shown in. For example, the inlet port 1014 can be positioned off - center relative to the opening 1022 of the sample collection area 1012 to reduce, flush, and / or prevent the formation of air bubbles in the collected body fluid sample and / or to condition the flow of the body fluid during use.

[0186] In some embodiments, the electrode layer 1017A defines the inlet port 1014 that is defined as a through - hole. In some embodiments, the electrode layer 1017A can be substantially similar in structure and / or function to the electrode layers described herein (e.g., electrode layer 917A). Thus, the similar aspects of the electrode layer 1017A are not described in further detail.

[0187] The sample handling device 1010 can include a channel layer 1017B that has a precise predefined thickness and determines the cross - sectional dimensions and volume of a portion of the flow channel 1016. In some embodiments, the sample handling device 1010 can include a vent hole layer 1073 that is configured to define vent holes 1024. In some embodiments, the vent hole layer 1073 can be adjacent to a vent hole layer adhesive 1019B that also defines the vent holes 1024 and has an adhesive surface that can be configured to attach to a part of a sample processing device (e.g., sample processing device 130, 330, etc.). In some embodiments, the sample handling device 1010 can be a disposable part for use with a durable part, and the adhesive surface of the channel layer 1017B is used to attach the sample handling device 1010 to the durable part (e.g., attach to a plastic part). In some embodiments, the sample handling device 1010 can be used in conjunction with and attached to a plastic part or surface of a disposable sample handling device through the adhesive surface of the channel layer 1017B.

[0188] In some embodiments, the adhesive surface of the channel layer 1017B can be configured to attach to a release liner layer 1027A. The release liner layer 1027A can be made of any suitable material that is to be peeled off before attaching the sample handling device 1010 to a sample processing device (e.g., sample processing device 130, 330, etc.). In some embodiments, the flow channel 1016 can be defined by a curved portion in the channel layer 1017B that extends to the vent holes 1024 defined by the vent hole layer 1073.

[0189] As described previously with reference to the reference device 910, the channel layer 1017B can include test regions 1018A and 1018B defined at specified portions along the flow path 1016. The electrode tracks and the sample ends of the electrodes 1020A, 1020B, and 1020C can be defined proximal to the electrode layer 1017A and the test regions 1018A and 1018B. The flow path 1016 can be defined by the distal surfaces of the electrode layer 1017A and the channel layer 1017B such that when a body fluid sample flows through the flow path 1016 and through each test region, an excitation signal (shared between the test regions 1018A and 1018B) applied by the excitation electrode 1020B can be delivered to the fluid sample at the test region and can elicit a response from the body fluid sample, which can be sensed by the sensing electrodes 1020A, 1020C located at that test region 1018A, 1018B, respectively. In some embodiments, a temperature sensor can be configured to be housed in the sample handling device and measure the temperature of the fluid sample being tested at one or more of the test regions 1018A and 1018B defined on the channel layer 1017B.

[0190] In some embodiments of the sample handling device, the electrodes 1020 can be configured such that multiple electrode pairs can share one or more electrodes. Multiple electrode pairs can be directed to multiple test regions such that the shared electrode can have a common terminal and multiple sample ends located at or near the multiple test regions. For example, the electrodes 1020 can be configured such that two or more electrode pairs share one excitation electrode instead of one excitation electrode per pair of electrodes. The sample handling device 1010 can include two predefined test regions 1018A and 1018B, as Figure 35A shown. Test region 1018A includes a set of electrodes 1020A and 1020B, and test region 1018B includes electrodes 1020B and 1020C, respectively, with electrode 1020B serving both test regions. The test regions 1018A and 1018B are positioned at increasing distances from the inlet port 1014 and at a known distance from each other along the flow path 1016 before the body fluid sample is ejected at 1024.

[0191] The sample handling device 1010 can include a top release liner 1027A that is configured to be peeled off before attaching the device to the sample processing device as described herein.

[0192] In some embodiments, electrode 1020B can be a common excitation electrode serving both test regions 1018A and 1018B, and electrodes 1020A and 1020C can be configured as sensing electrodes that operate in combination with electrode 1020B. An excitation signal can be applied via electrode 1020B and electrodes 1020A and 1020C can receive response signals from the fluid samples being tested at each test region. In some embodiments, the electrodes can be configured to operate as bipolar electrodes to both excite and sense responses from the sample body fluid being tested. Electrodes 1020A, 1020B, and 1020C, as well as the electrode tracks, can be printed using any suitable conductive and / or electrode ink, as previously described. The terminals of the electrodes can be of any suitable construction to electrically connect to a part of the sample handling device. For example, the terminals can be configured to connect via spring pins, spring-loaded pins, flexible electrical connections, etc.

[0193] In some embodiments, the sample handling device 1010 can include a spacer portion 1029 that is incorporated to occupy space in the sample collection region 1012, as previously described with reference to spacer portions 729, 829, and / or 929. The spacer region 1029 can be formed by printing a thickening ink as previously described. In some embodiments, the device 1010 can include an additional adhesive layer (not shown) to aid in adhesion to an alignment and / or mounting interface (e.g., a snap ring interface).

[0194] Conclusion

[0195] In summary, the systems and methods described herein are for the instantaneous measurement and analysis of body fluid samples to evaluate the properties and / or health parameters of body fluids (e.g., degree of hydration, electrolyte loss, sweating rate, etc.).

[0196] Although various embodiments have been described above, it should be understood that they are presented by way of example only and not limitation. In cases where the above schematic diagrams and / or embodiments indicate certain components arranged in certain orientations or positions, the arrangement of the components can be modified. Although the embodiments have been specifically shown and described, it should be understood that various changes can be made in form and detail. Although the various embodiments have been described as having combinations of specific features and / or components, other embodiments having any combination of any features and / or components from any of the above embodiments are also possible. Except for mutually exclusive combinations, any part of the devices and / or methods described herein can be combined in any combination. The embodiments described herein can include various combinations and / or sub-combinations of the functions, components, and / or features of the different embodiments described.

[0197] In cases where the above method indicates specific events that occur in a specific order, the ordering of the specific events can be modified. Additionally, certain events can be executed concurrently in parallel processes where possible, as well as sequentially as described above.

Claims

1. A method, comprising: Collecting a sample of a user's body fluid from a source of the body fluid in a sample collection area of a wearable device; Guiding a portion of the sample of the body fluid from the sample collection area to a set of electrodes, the set of electrodes including an excitation electrode and a sensing electrode; Applying an excitation signal through the portion of the sample of the body fluid; Sensing a response signal in response to the excitation signal; Measuring an impedance associated with the portion of the sample of the body fluid based on the response signal; Determining a characteristic of the body fluid based on the impedance; And Estimating a health parameter of the user based on the characteristic of the body fluid.

2. The method according to claim 1, wherein the body fluid is sweat, the characteristic is the molar concentration of the sweat, and the health parameter is the hydration state of the user.

3. The method according to claim 2, the method further comprising: Predicting a hydration replenishment plan for the user based on the molar concentration.

4. The method according to claim 1, wherein the body fluid is sweat, the portion of the sample of the body fluid is a first portion, the excitation signal is a first excitation signal generated at a first time point, and the response signal is a first response signal, the method further comprising: Applying a second excitation signal through a second portion of the sample of the body fluid; Sensing a second response signal in response to the second excitation signal; Measuring an impedance associated with the second portion of the sample of the body fluid based on the second response signal; Determining a volumetric flow rate associated with the portion of the initial sample of the body fluid based on the impedances of the first and second portions of the sample of the body fluid; And Determining the sweating rate of the user based on the volumetric flow rate.

5. The method according to claim 4, further comprising: Estimating the electrolyte loss rate of the user; And Indicating to the user a signal for replenishing electrolytes via the wearable device.

6. The method according to claim 1, further comprising: Providing a recommended hydration replenishment plan.

7. The method according to claim 1, further comprising: Measuring the temperature of the portion of the sample of the body fluid; And Calculating the core body temperature of the user based on at least one of the impedance or the measured temperature.

8. The method according to claim 7, wherein the characteristic is the molar concentration of the body fluid, the method further comprising: Determining the molar concentration of the body fluid based on the impedance and the measured temperature.

9. A wearable device, comprising: A processor; A sample collection area having an inlet and configured to receive an initial volume of a user's body fluid via the inlet; An inlet port in fluid communication with the sample collection area; A flow channel in fluid communication with the inlet port and configured to direct a portion of the initial volume of the body fluid towards a set of electrodes, The set of electrodes including an excitation electrode and a sensing electrode, the excitation electrode being configured to apply an excitation signal to the portion of the initial volume of the body fluid, and the sensing electrode being configured to receive a response signal in response to the excitation signal from the portion of the initial volume of the body fluid, the sensing electrode being configured to transmit the response signal to the processor, The processor being configured to: Calculate an impedance associated with the portion of the initial volume of the body fluid based on the response signal; Determine a characteristic of the body fluid based on the impedance; And Estimate a health parameter of the user based on the characteristic of the body fluid.

10. The method according to claim 9, wherein the body fluid is sweat, the characteristic is the molar concentration of the sweat, and the health parameter is the hydration status.

11. The wearable device according to claim 9, wherein the flow channel is further configured to direct the portion of the initial volume of the body fluid to the outlet.

12. The wearable device according to claim 9, wherein the set of electrodes includes two pairs of electrodes, each of the two pairs of electrodes includes at least one excitation electrode and at least one sensing electrode, and the two pairs of electrodes are located at a predefined distance from each other.

13. The wearable device according to claim 12, wherein the flow channel is further configured to direct the portion of the initial volume of the body fluid to each of the two pairs of electrodes such that the portion of the initial volume of the body fluid passes through the two pairs of electrodes in a sequential manner.

14. The wearable device according to claim 9, wherein at least a portion of the flow channel is defined to include at least one of a linear, curved, annular, planar, non-planar, serpentine or meandering shape.

15. The wearable device according to claim 9, wherein at least one of the flow channel or the set of electrodes includes a hydrophilic coating configured to facilitate the flow of the body fluid.

16. The wearable device according to claim 9, wherein the flow channel has a cross-sectional area defined by a diameter between 0.2 mm and 5.0 mm.

17. The wearable device according to claim 9, wherein at least a portion of the set of electrodes is formed of a printing ink that includes 80% silver by weight and 20% silver chloride by weight.

18. The wearable device according to claim 9, wherein the set of electrodes includes bipolar electrodes configured to provide an electric current to the portion of the initial volume of the body fluid and sense a voltage associated with the portion of the initial volume of the body fluid.

19. The wearable device according to claim 9, wherein the sample collection area is configured such that after the initial volume of the collected body fluid exceeds a threshold volume, the portion of the initial volume of the body fluid is pushed from the sample collection area to the flow channel via the inlet port in a continuous manner.

20. The wearable device according to claim 19, wherein the threshold volume is a first threshold volume, and the wearable device further includes a spacer portion defined in the sample collection area and configured to reduce the fluid capacity of the sample collection area such that after the initial volume of the collected body fluid exceeds a second threshold volume less than the first threshold volume, the portion of the initial volume of the body fluid is pushed from the sample collection area via the inlet port and via the flow channel.

21. The wearable device according to claim 9, wherein the set of electrodes is configured to sense a signal indicative of the presence of an amount of at least one of Na + , Cl - , Ca 2+ , K + or Mg 2+ ions in the portion of the initial volume of the body fluid.

22. The wearable device according to claim 9, wherein at least one electrode in the set of electrodes includes a carbon coating configured to reduce corrosion of the set of electrodes.

23. The wearable device according to claim 9, wherein the set of electrodes is configured to sense a signal indicating the presence of at least one of a certain amount of lactase, glucose, lactic acid or pyruvic acid in the portion of the initial volume of the body fluid.

24. The wearable device according to claim 12, wherein the first pair of electrodes of the two pairs of electrodes is configured to transmit a first response signal of a portion of the initial volume of body fluid to the processor at a first time, and the second pair of electrodes of the two pairs of electrodes is configured to transmit a second response signal of a portion of the initial volume of body fluid to the processor at a second time, and the processor is further configured to calculate the impedance associated with the first response signal and the second response signal; determine the volumetric flow rate associated with a portion of the initial sample of body fluid based on the impedance from the first response signal and the second response signal; and determine the user's sweating rate based on the volumetric flow rate.

25. The wearable device according to claim 9, further comprising: a temperature sensor configured to measure the temperature associated with a portion of the initial volume of body fluid, the temperature sensor being configured to transmit the measured temperature to the processor to perform at least one of the following: (a) estimate the user's core body temperature based on the measured temperature, or (b) estimate the user's hydration loss rate based on the calculated impedance and the measured temperature.

26. A system, comprising: a memory storing a set of instructions; a processor coupled to the memory and configured to execute the instructions stored in the memory; and a wearable device operatively coupled to the processor and comprising: a sample collection area configured to receive an initial volume of a user's body fluid; an inlet port in fluid communication with the sample collection area; and a flow channel in fluid communication with the inlet port and configured to direct a portion of the initial volume of body fluid towards a set of electrodes, the set of electrodes including an excitation electrode and a sensing electrode, the excitation electrode being configured to apply an excitation signal to the portion of the initial volume of body fluid, and the sensing electrode being configured to receive a response signal in response to the excitation signal from the portion of the initial volume of body fluid; wherein the instructions, when executed, are configured to cause the processor to: send an excitation signal to the excitation electrode, receive a response signal from the sensing electrode, calculate the impedance associated with the portion of the initial volume of body fluid based on the response signal; determine the characteristics of the body fluid based on the impedance; and estimate the user's health parameter based on the characteristics of the body fluid.

27. The system according to claim 26, wherein the body fluid is sweat, the characteristic is the molar concentration of the sweat, and the health parameter is the hydration status.

28. The system according to claim 26, wherein the portion of the initial volume of body fluid is a first portion, and the flow channel is further configured to direct the first portion to an outlet and sequentially push a second portion of the initial volume of body fluid towards the set of electrodes.

29. The system according to claim 26, wherein the instructions, when executed, are further configured to cause the processor to: identify that the hydration status is below a predefined value, and generate an alert recommending a source of fluid replenishment based on the identification result and via the wearable device.

30. The system according to claim 26, further comprising: an accelerometer, wherein the instructions, when executed, are further configured to cause the processor to: identify the status of the acceleration of the system, and Predict an optimal replenishment rate of a source of body fluid based on an acceleration state.

31. An apparatus for measuring a biophysical property of a sample of body fluid, comprising: An interface layer including a pad configured to be peeled to secure the apparatus to a user's body; An adhesive layer having a predefined thickness, including an adhesive proximal surface to be secured to the user's body and including an adhesive distal surface to be secured to an inlet port layer, the adhesive layer defining an opening through which a sample of body fluid is received; An inlet port layer including a proximal surface and a distal surface, the proximal surface configured to be secured to the distal surface of the adhesive layer, the adhesive layer and the inlet port layer together defining a sample collection area, the inlet port layer defining an inlet port to drive a flow of body fluid from the sample collection area; A channel layer defining a flow channel configured to direct a flow of body fluid from the sample collection area, the flow channel including a test area configured to test a body fluid property of a portion of the sample of body fluid; And An electrode layer configured to define a collection of electrodes and interface with the flow channel at the test area, the collection of electrodes including (i) an excitation electrode configured to apply an excitation signal to the portion of the sample of body fluid at the test area, and (ii) a sensing electrode configured to receive a response signal in response to the application of the excitation signal at the test area from the portion of the sample of body fluid, The collection of electrodes further includes terminal connections to provide electrical communication between the collection of electrodes and a processor to which the response signal to be processed is sent.

Images