Abstract: A device for determining the amount or concentration of an analyte in a fluid sample and a flow rate of the fluid sample in a channel is provided. The device includes a chamber including a channel and an opening the channel in fluid communication with the opening. The device further includes a wicking component positioned adjacent to the opening configured to receive an amount of fluid from the channel. The device may further include an analyte sensor positioned on the wicking component, the analyte sensor configured to detect an analyte in fluid in contact with the analyte sensor, wherein the wicking component is configured to contact the amount of fluid with the analyte sensor. Alternatively the device may include at least one pair of electrodes configured to determine a flow rate of the fluid in the channel.

Abstract: A sweat sampling and sensing device for sensing sweat on skin includes an analyte-specific sensor for sensing a first analyte in sweat; a sweat collector placed on or adjacent to skin with a plurality of pores or pathways for entry of sweat from skin into said sweat collector, said sweat collector at least partly defining a sweat volume between said analyte-specific sensor and the skin; and a pressure element capable of holding said sweat collector against the skin with a pressure and reducing the sweat volume between said sweat collector and the skin.

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: Embodiments of the disclosed invention provide wearable devices that use a humidity sensor to measure sweat rate generated from an area of skin. A sensing chamber is continuously filled with a sweat sample, which forms a droplet and alters the humidity measured within the chamber. Once the sweat sample droplet expands to the edge of the chamber, the droplet contacts a wick and is drawn away, so the chamber can fill with a subsequent droplet. The device uses a droplet volume and the time required to reach a maximum humidity to calculate a sweat rate. A pump is used to draw old sweat sample out of the wick to allow extended device operation. Some embodiments also include capacitive sensors to perform back up measurements. Another set of embodiments includes alternatively shaped sensing chambers configured to reduce sample volumes or improve function. A method for determining sweat rate based on humidity sensor measurements is also included.

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: Electrochemical aptamer-based (EAB) biosensing devices are described that provide drift correction and calibration to EAB sensor measurements of biofluid analyte concentrations by disclosing reference sensors that are configured to not interact with a target analyte, but otherwise mirror the performance of active EAB sensors within the expected application parameters of the device. Such reference sensors are configured to allow comparisons with their companion active sensors to track aptamer sensing element dissociation from an electrode surface, temperature-induced effects, redox moiety dissociation, and/or the effects of surface fouling. Some embodiments include separate electrodes for active and reference aptamer sensing elements. Other embodiments include a single electrode for both active and reference aptamer sensing elements. Single electrode embodiments include two or more distinct redox moieties.

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 disclosed invention provides a fluid sensing device capable of collecting a biofluid sample, such as interstitial fluid, blood, sweat, or saliva, concentrating the sample with respect to a target analyte, and measuring the target analyte in the concentrated sample. Embodiments of the invention can also determine the change in molarity of the fluid sample with respect to the target analyte, as the sample is concentrated by the device. Some embodiments of the disclosed invention provide a fluid sensing device comprising minimally invasive, microneedle-enabled extraction of interstitial fluid or other biofluid for continuous or prolonged on-body monitoring of biomarkers. Some embodiments allow the collection and measurement of analytes in of non-biological fluids, such as fuels, or bodies of water.

Abstract: The disclosed invention provides a sensing device capable of concentrating a fluid sample with respect to a target analyte and a reference analyte, and measuring the target analyte and reference analyte in the concentrated sample. The invention includes a concentrator that may include a selectively permeable membrane, or a gel having an increasing density gradient. In another embodiment, the invention includes an air or gas gap between a fluid transport channel and the concentrator. In another embodiment, the sensing device includes a driver for electronically moving a fluid sample through the channel and membrane to cause concentration. In some embodiments, the invention may also determine the change in molarity of the fluid sample with respect to the target analyte, as the sample is concentrated by the device.

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 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: An electrochemical sensor is provided for use in a wearable device for measuring analytes in a pH-variable biofluid. The sensor includes a plurality of aptamer sensing elements which have biorecognition elements, such as aptamers, that experience a conformational change on interaction with a target analyte in the biofluid. Each aptamer sensing element forms a first configuration before target analyte capture and a second configuration after target analyte capture. A redox moiety is paired with each aptamer sensing element. The redox moiety has a reaction potential that is at least partially independent of a pH value of the biofluid. The EAB sensor further includes an electrode operative in conjunction with the plurality of aptamer sensing elements to produce a variable signal depending upon the configuration of the aptamer sensing elements.

Abstract: The present invention provides self-assembled monolayers (SAM) configured for use with electrochemical aptamer-based biosensors, which allow sensing devices to detect very low concentrations of target analytes in a biofluid sample. Embodiments of the disclosed invention include SAMs with improved long-term stability in sweat through persistent thiolate bonds between the sensor electrode and disclosed blocker groups, or between the sensor electrode and aptamer sensing elements via disclosed binder molecules. Embodiments of the invention also include blocker groups configured to form densely packed and persistent SAMs on sensor electrodes.

Abstract: The disclosed invention provides a fluid sensing device and method capable of collecting a fluid sample, concentrating the sample with respect to one or more target analytes, and measuring the target analyte(s) in the concentrated sample. The invention is also capable of determining the change in molarity of the fluid sample with respect to the target analyte(s), as the sample is concentrated by the device. The invention further includes a method for using a fluid sensing device to concentrate a fluid sample with respect to one or more target analytes. The disclosed method further includes the ability to correlate the measured target analyte concentration to a physiological condition of a device wearer, or of a fluid source.

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.