Abstract: The present invention provides a biofluid sensing device capable of concentrating a biofluid sample with respect to a target analyte, so that the analyte can be accurately detected or measured by EAB sensors. Methods for using such a device provide qualitative information about the presence of the analyte, and/or quantitative information about relative concentrations of the analyte in the biofluid. The disclosed device includes a concentration channel for concentrating the biofluid sample, as well as a selectively permeable membrane, one or more EAB sensors, and one or more secondary sensors carried on a water-impermeable substrate. A method for using the disclosed device to collect a biofluid sample, concentrate the sample relative to a target analyte, and measure the target analyte is also disclosed.

Abstract: Electrochemical aptamer-based biosensing devices and methods are described herein that are configured to produce a detectible signal upon target analyte interaction, with reduced reliance on a conformational change by the aptamer. The disclosure includes embodiments of docked aptamer EAB sensors for measuring the presence of a target analyte in a biofluid sample. The sensors include an electrode capable of sensing redox events, and a plurality of aptamer sensing elements with aptamers selected to interact with a target analyte. Each aptamer sensing element includes a molecular docking structure attached to the electrode, and an analyte capture complex that includes an aptamer releasably bound to the docking structure, and an electroactive redox moiety. Upon the aptamer binding with a target analyte, the analyte capture complex separates from the docking structure.

Abstract: Challenges of the sweat medium for electrochemical aptamer-based biosensor (“EAB sensor”) devices can be mitigated through aptamer selection, sensor/device configuration and physiological algorithms that account for the effects of (1) target analyte size, (2) potential concentration ranges, (3) sweat sample pH, and (4) sweat sample salinity. The disclosed invention includes a method of aptamer selection for use in an EAB sensor configured for use in a wearable sweat sensing device. The disclosed invention further provides a sweat sensing device configured to use EAB sensors to detect target analytes in a sweat sample.

Abstract: Embodiments of the disclosed invention provide devices and methods to incorporate suspension-based, i.e., hydrogel-based and thixotropic compound-based, ion-selective electrodes and reference electrodes into a wearable sweat sensing device. Embodiments of this device are configured to monitor sweat electrolyte concentrations, trends, and ratios under demanding use conditions. The accompanying method includes use of the disclosed device to track fluid and electrolyte gain and loss in order to produce an electrolyte estimate, such as a sweat electrolyte concentration, a sweat electrolyte concentration trend, a sweat rate, or a concentration ratio between a plurality of electrolytes.

Abstract: The disclosed invention provides a sweat sensing device configured with self-aligned sweat stimulation means to provide adequate sweat generation for continuous monitoring of sweat. The disclosed device includes one or more analyte-specific sweat sensors that self-align with sweat glands. In one embodiment, the sweat sensing device includes means to protect the self-aligning sensors from abrasion against the skin or device components. In another embodiment, the device includes prolonged sweat stimulation for the self-aligning sensors through diffusion of a sweat stimulating compound into the skin.

Abstract: The present invention provides a biofluid sensing device capable of concentrating a biofluid sample with respect to a target analyte, so that the analyte can be accurately detected or measured by EAB sensors. Methods for using such a device provide qualitative information about the presence of the analyte, and/or quantitative information about relative concentrations of the analyte in the biofluid. The disclosed device includes a concentration channel for concentrating the biofluid sample, as well as a selectively permeable membrane, one or more EAB sensors, and one or more secondary sensors carried on a water-impermeable substrate. A method for using the disclosed device to collect a biofluid sample, concentrate the sample relative to a target analyte, and measure the target analyte is also disclosed.

Abstract: Devices and methods for tuning biofluid sample pH to enable more accurate analyte concentration measurements with pH-sensitive biosensors. In the embodiments, biofluid samples react with a polymer buffering material during transfer to a sensing element. The reaction with the buffering material causes protonation or deprotonation of the sample based upon 1) the pH of the sample, and 2) the selected quantity and pKa of the functional groups in the buffering material. Controlling the H+ content of a biofluid sample has beneficial effects on the accuracy of the biosensor by reducing or eliminating signal changes due to redox moiety variability, thereby isolating signal changes reflecting analyte concentration.

Abstract: The disclosed invention provides sweat sensing devices with smart sweat stimulation and sensing embodiments: which improve the dependability and predictability of sweat sampling rates; achieve a desired number of sweat sampling events per day while minimizing skin irritation and prolonging device lifespan; and use physical, optical or thermal sweat stimulation to augment or replace chemical sweat stimulation.

Abstract: The present disclosure provides a method of using a wearable biofluid sensing device to develop a cytokine profile for an individual. The method includes taking concentration, ratio, and trend measurements of one or more cytokines in the individual's sweat, along with other contemporaneous device measurements to inform sweat rate, skin temperature, sweat sample pH, or other factors. The method further considers these measured values in the context of external information about the individual, and uses such information to develop (1) a baseline cytokine profile characterizing the individual's healthy cytokine levels, or (2) an inflammation profile for a physiological condition, which characterizes the expected cytokine levels for a physiological condition. Also included is a method to use a biofluid sensing device to determine whether an individual has a physiological condition by comparing device measurements to the baseline profile and inflammation profile. Results are then communicated to a device user.

Abstract: The present disclosure provides a method of using a sweat sensing device to determine a kidney profile for an individual. The method includes taking concentration, ratio, and trend measurements of one or more kidney biomarkers in the individual's sweat, along with other contemporaneous device measurements to inform sweat rate, skin temperature, sweat sample pH, or other factors. The method further considers these measured values in the context of external information about the individual, and uses such information to develop a kidney function profile or a kidney injury profile indicative of the physiological state of the individual.

Abstract: The disclosed invention includes sweat sensing devices configured to periodically measure sweat conductivity and galvanic skin response, devices to measure volumetric sweat flow rate, and devices that combine the three functions. The disclosure further includes methods for using a device configured to perform periodic sweat conductivity measurements, galvanic skin response measurements, and volumetric sweat rate measurements so that each sensor modality informs composite estimates of sweat onset, sweat cessation, sweat ion concentration, and sweat rate. The method uses those measurements to inform other sweat sensing device functions, such as determining the existence of a physiological condition, or performing measurements of concentrations, ratios, and trends of sweat analytes.

Abstract: The disclosed invention provides a biofluid sensing device configured with a membrane-enhanced sensor located in a sweat collector. The disclosed analyte-specific sensor is configured to reduce required biofluid sample volume due to its close proximity to the skin and source of sweat biofluid. The sensor is contained within a pH and salinity-stabilized fluid that, in turn, is contained in a selectively permeable membrane to improve sensor performance in variable biofluids, and to protect the sensor from skin contact. In one embodiment, the biofluid sensing device includes means to protect the self-aligning sensors from abrasion against the skin or device components. Other embodiments of the disclosed invention include a track-etched membrane to provide sensor protection.

Abstract: The disclosed invention includes integrative electrochemical aptamer-based sensors for use in wearable biofluid sensing devices. The disclosed integrative EAB sensors are configured to detect very low concentrations of target analytes in a sweat or biofluid sample by aggregating signals from individual sensing elements over time until a signal threshold is reached. Signal aggregation is accomplished through various retention structures that extend the time sensing elements retain target analyte molecules. Embodiments include attaching complementary primers and functional groups to the aptamer, covering such retention structures with blockers until analyte capture, or coating the sensor electrode with a hydrophilic and hydrophobic monolayer. The invention also includes methods of using the disclosed integrative sensors. Some embodiments of the disclosed method include tracking time to signal threshold to estimate analyte concentration.

Abstract: The disclosed invention addresses an unmet need of biofluid analysis by utilizing the presence of certain nucleotides, e.g., microDNA, eccDNA, DNA fragments, microRNA, RNA fragments, and peptides, in a sample biofluid, such as eccrine sweat, apocrine sweat, blood, serum, saliva or tears, to perform a number of physiological sensing functions. Specifically, the present disclosure provides: (1) a device and method of determining whether a biofluid sensing device is being worn by a specific individual based on a measurement of nucleotides in a biofluid; (2) a device and method of recognizing at least one physiological disease or condition based on nucleotide concentrations, ratios, or trends in a biofluid.

Abstract: The invention includes sweat sensing devices to measure volumetric sweat rate that use alternating current interrogation of electrodes, and embodiments that have a reusable component and a disposable component. The disclosure further includes a method for detecting an air bubble within a volumetric sweat rate device. The disclosure also includes methods, systems, and non-transitory computer-readable storage medium claims for using a device configured to perform periodic volumetric sweat rate measurements to inform estimates of total body water loss, to aid in the avoidance of heat stress or dehydration, and to facilitate comparison of environmental influences on heat stress or dehydration.

Abstract: Embodiments of the disclosed invention provide devices and methods to incorporate suspension-based, i.e., hydrogel-based and thixotropic compound-based, ion-selective electrodes and reference electrodes into a wearable sweat sensing device. Embodiments of this device are configured to monitor sweat electrolyte concentrations, trends, and ratios under demanding use conditions. The accompanying method includes use of the disclosed device to track fluid and electrolyte gain and loss in order to produce an electrolyte estimate, such as a sweat electrolyte concentration, a sweat electrolyte concentration trend, a sweat rate, or a concentration ratio between a plurality of electrolytes.

Abstract: The disclosed invention incorporates sweat sensing devices into headgear so that accurate biofluid analyte measurements may be made during physical activity. As disclosed herein, a sweat sensing device may be incorporated into an inner surface or support structure of headgear, including hardhats, sports headgear, flight helmets, combat helmets, sweatbands, sports caps, visors, and masks. The device is further configured to recognize and alter operational states when the device is not in adequate skin contact for operation. Some embodiments are fully disposable, and other embodiments include a reusable component that may be integrated into, or attached to, the headgear.

Abstract: Methods and systems are disclosed for defining physiological states using sweat-sensing devices. An output of sweat-sensing devices is defined by identifying a set of sweat sensor values. Each sweat sensor value of the set of sweat sensor values includes an electrical-signal value produced by a sensor. For each sweat sensor value of the set of sweat sensor values, the electrical-signal value of the sweat sensor value is translated into a voltage value thereby generating a translated sweat sensor value. Each translated sweat sensor value is calibrated by transforming, upon applying a hardware correction value to the translated sweat sensor value, the voltage value into a physiological value. The calibrated sweat sensor values are aggregated and the calibrated seat sensors values are then modified using received environmental inputs. An output is then generated based on the modified sweat sensor values.

Abstract: The disclosed invention includes: a device and method of performing physiological sweat sensing device calibration; a device and method of indicating an individual's dehydration state; a device and method of indicating an individual's stage in their ovulation cycle; a device and method of indicating that an individual is hypokalemic or hyperkalemic; a device and method of indicating that an individual is entering a hypoglycemic state; a device and method of indicating an individual's glucose trend value; and a device and method of indicating that an individual has experienced toxic substance exposure.

Abstract: The present disclosure includes a device and method of measuring an individual's cortisol awakening response; a device and method of measuring an individual's diurnal cortisone level, including the basal cortisol level; a device and method of indicating an individual's stress profile based on sweat cortisol measurements; a device for measuring and interpreting sweat analytes relevant to risk-taking behavior; and a method of determining an individual's risk-taking propensity based on measurement and development of sweat analyte profiles.