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.
Devices and methods are described herein for separating electrically charged particles in a biofluid sensing device employing electrochemical aptamer-based ("EAB") sensors to limit ion-induced variability in the sensor outputs. In the disclosed embodiments, charge separation is accomplished with continuous biofluid sample flow in a sensor channel in order to limit ion exposure without decreasing the flow rate of biofluid through the device or increasing the biofluid volume required for sampling. Certain embodiments create an electric field to deflect ions away from sensors. Other embodiments create a magnetic field to accomplish charge separation. Y et other embodiments use a charged polymer membrane to electrostatically draw certain ions away from sensors. A method for reducing EAB sensor variability due to ions is also disclosed that uses such charge separation techniques within a biofluid channel.
A method for measuring analyte concentrations in a biofluid sample to determine patient compliance with a drug regimen. These analytes include a tracer having a half-life that is longer than the drug dosage interval, the drug, or a second tracer with a half-life similar to that of the drug. Further, a method for measuring biofluid concentrations of an analyte and correlating those measurements to plasma concentrations of a drug. The biofluid concentrations are then used to compare drug plasma concentrations to toxic or minimum effective drug levels. Furthermore, a method for selecting tracer compounds for medication monitoring by biofluid sensing devices. Such tracer selection includes the following factors: percentage and molarity of dosed tracer that emerges in biofluid; timing and mechanism of the tracer emerging in biofluid; suitability of the tracer or its characteristics for drug monitoring requirements; and amenability of the tracer to interact with a randomized aptamer sequence.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
4.
INTEGRATED DEVICES TO CONTINUOUSLY MEASURE BOUND AND UNBOUND ANALYTE FRACTIONS IN BIOFLUIDS
Embodiments of the disclosed invention provide devices for measuring concentrations of bound and unbound fractions of a target analyte in a biofluid sample. Analytes present in biofluid may be found in a free state, or bound to a binding solute, presenting difficulties for wearable analyte sensors to measure physiologically significant concentrations of the analyte in biofluid. The disclosed devices feature sensors configured to measure both the bound and unbound fractions of the analyte, as well as analyte releasers that cause a portion of the bound fraction of analytes to be released to facilitate measurement. Some embodiments include a collector and or a sample conduit. Other embodiments include a plurality of fluid pathways.
G01N 33/62 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving urea
G01N 33/66 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
G01N 33/70 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving creatine or creatinine
G01N 33/84 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH
G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
G01N 35/02 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
5.
FLEXIBLE SWEAT SAMPLE COLLECTION AND SENSING DEVICES
Embodiments of the disclosed invention include flexible, body-conforming sweat sensing devices configured to measure a sweat rate, or a concentration of one or more analytes in a sweat sample that correlate to physiological conditions in the device wearer. The disclosed devices improve upon existing devices by providing determined sweat collection regions that allow measured sweat rates to be correlated to total body sweat rates or other relevant metric, and provide automatic electronic reporting of measurements taken by the device.
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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
Embodiments of the disclosed invention provide devices that mitigate salinity-based EAB sensor output variability by improving aptamer structural rigidity or sensing performance through the pretreatment of aptamers with ions or buffering molecules. Other embodiments provide devices that mitigate salinity- based EAB sensor output variability through the pretreatment of additional device components with ions or buffering molecules thereby reducing ion uptake from, or output to, a biofluid sample.
C23C 16/00 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition (CVD) processes
G01N 21/75 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
8.
REFERENCE APTAMER SENSING ELEMENTS FOR EAB BIOSENSORS
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.
A device (10) for determining the amount or concentration of an analyte (1700) in a fluid sample (1500) and a flow rate (1000) of the fluid sample (1500) in a channel (14) is provided. The device (10) includes a chamber (20) including a channel (14) and an opening (12a), the channel (14) in fluid communication with the opening (12a). The device further includes a wicking component (16) positioned adjacent to the opening (12a) configured to receive an amount of fluid (1500) from the channel (14). The device may further include an analyte sensor (18) positioned on the wicking component (16), the analyte sensor (18) configured to detect an analyte (1700) in fluid ((1500) in contact with the analyte sensor (18), wherein the wicking component (16) is configured to contact the amount of fluid (1500) with the analyte sensor (18). Alternatively the device (10) may include at least one pair of electrodes (130, 132) configured to determine a flow rate (1000) of the fluid (1500) in the channel (14).
Methods are disclosed for using click chemistry techniques to functionalize aptamer sequences for use in electrochemical aptamer-based biosensors, and in particular such sensors for use in sweat sensing environments. Specifically, such techniques include preparing a portion of the aptamer sequence to interact with a functionalization component through a bio-orthogonal chemistry reaction, preparing the functionalization component to interact with the aptamer sequence through the click chemistry reaction, and attaching the aptamer sequence to the functionalization component through the click chemistry reaction. The functionalization component may be one or more of an oligonucleotide primer, an anchor molecule, a redox moiety, an oligonucleotide dock, or an electrode surface. Disclosed bio-orthogonal chemistry reactions include an azide-alkyne cycloaddition reaction, and a thiol-maleimide reaction.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
11.
BIOFLUID SENSING DEVICES WITH PH-BUFFERED EAB SENSORS
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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
Electrochemical aptamer-based biosensing devices and methods 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 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 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 aptamer binding with a target analyte, the analyte capture complex separates from the docking structure. The separation of the analyte capture complex from the docking structure produces a positional change in the redox moiety that is detectable by the sensing device on interrogation of the electrode.
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.
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
14.
THIOLATED AROMATIC BLOCKING STRUCTURES FOR EAB BIOSENSORS
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.
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
H01L 23/532 - Arrangements for conducting electric current within the device in operation from one component to another including external interconnections consisting of a multilayer structure of conductive and insulating layers inseparably formed on the semiconductor body characterised by the materials
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.
A61B 5/04 - Measuring bioelectric signals of the body or parts thereof
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
17.
AUTONOMOUS SWEAT ELECTROLYTE LOSS MONITORING DEVICES
The disclosed invention comprises a wearable sweat sensing device configured to monitor sweat electrolyte concentrations, trends, and ratios under demanding use conditions. The disclosed method includes use of the disclosed device to track fluid and electrolyte gain and loss in order to produce an electrolyte estimate for the device wearer, such as a sweat electrolyte concentration, a sweat electrolyte concentration trend, a sweat rate, or a concentration ratio between a plurality of electrolytes.
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
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.
G01N 27/26 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by using electrolysis or electrophoresis
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/1468 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means
A device (200) for sensing a biofluid (18) includes at least one analyte-consuming sensor (220) for measuring at least a first analyte concentration of an analyte in the biofluid (18) and at least one additional component (248). The at least one additional component (248) maintains analyte-consuming sensor (220) measurements within 20% of the first concentration measurement if a biofluid (18) sample flow rate is less than or equal to 2 times a first biofluid (18) sample flow rate measurement as measured by the device (200). A method for sensing a biofluid (18) includes measuring a first analyte concentration of an analyte in the biofluid (18) using an analyte-consuming sensor (220), measuring a first biofluid sample flow rate, and maintaining a subsequent analyte concentration measurement within 20% of the first analyte concentration measurement when a subsequently measured biofluid (18) flow rate is less than or equal to 2 times the first biofluid sample flow rate.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
20.
BIOFLUID SENSING DEVICES WITH TEMPERATURE REGULATION
The disclosed invention includes a biofluid sensing device capable of passively or actively regulating an operating temperature of one or more sensors. The device includes at least one biofluid sensor in a thermally isolated environment and at least one temperature sensor to measure sensor environment temperature. Some embodiments include at least one thermal component to regulate the sensor temperature by actively adjusting the sensor environment temperature in response to a signal from the temperature sensor. The invention also includes a method of regulating temperature for a biofluid sensing device having a sensor for measuring an analyte in the biofluid. The method includes measuring a biofluid sensor temperature, regulating the sensor temperature to within a selected range of the measured sensor temperature, and maintaining sensor temperature within the selected range of the measured temperature throughout device operation. In some embodiments, the measured temperature is a calibration temperature.
A61B 5/02 - Measuring pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography; Heart catheters for measuring blood pressure
A61B 5/04 - Measuring bioelectric signals of the body or parts thereof
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
21.
BIOFLUID SENSING DEVICES WITH INTEGRATIVE EAB BIOSENSORS
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.
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
A61N 1/30 - Apparatus for iontophoresis or cataphoresis
A61N 1/32 - Applying electric currents by contact electrodes alternating or intermittent currents
The disclosed invention includes methods to employ wearable biosensing devices to accomplish the following: 1) screen for the presence of a disease or infection, including pre-symptomatic detection, and determination of the type (e.g., viral, bacterial, or fungal) of disease or infection present; 2) confirm the antigen and monitor the progress of an active infection; and 3) monitor the efficacy of a treatment program for a disease or infection. Such methods rely on the detection, in sweat or other biofiuids, of proteins, nucleotides, DNA polymerases, proteases, group-specific antigens, antibodies, cytokines, or other molecules, that are produced by the body as part of the innate or adaptive immune responses to an infectious agent, or the infectious agent itself, its products, or derivatives. Some embodiments comprise a method of using such a biosensing device as a biosentinel against biological threats.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
24.
DEVICES WITH REDUCED MICROFLUIDIC VOLUME BETWEEN SENSORS AND SWEAT GLANDS
A sweat sampling and sensing device (100) for sensing sweat on skin (12) includes an analyte- specific sensor (120, 122) for sensing a first analyte in sweat; a sweat collector (110) placed on or adjacent to skin (12) with a plurality of pores or pathways for entry of sweat from skin (12) into said sweat collector (110), said sweat collector (110) at least partly defining a sweat volume (190) between said analyte-specific sensor (120, 122) and the skin (12); and a pressure element (112, 170) capable of holding said sweat collector (110) against the skin (12) with a pressure and reducing the sweat volume (190) between said sweat collector (110) and the skin (12).
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
Challenges of the sweat medium for EAB biosensing 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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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.
A method of collecting and sensing a biofluid with enhanced concentration of analytes due to electroporation comprises electroporating biofluid glands (14) that are generating a biofluid and specifically sensing at least one analyte in said biofluid, the at least one analyte having a molecular weight greater than 50 Da. A device (100) wearable on a user's skin (12) for receiving an advective flow of a biofluid comprises at least one of a biofluid stimulation component (140), a biofluid sensor (220, 222) specific to an analyte, or a biofluid collection element (230, 232), at least one electroporation electrode (290) for enhancing concentration of at least one analyte in the biofluid having a molecular weight of greater than 50 Da, a counter electrode (195), and an electroporation waveform generator configured to cause the electroporation electrode (290) to generate and direct a plurality of electroporation pulses into the skin (12).
Embodiments of the disclosed invention provide devices and methods for buffering sweat samples to enable accurate concentration measurements of sweat analytes by salinity - sensitive or pH- sensitive sensors. The buffering capabilities of the device include the ability to control the salinity and pH of a sweat sample, specifically, through the management of solutes in sweat such as salts, H+, other ions, and other sweat contents. The purpose of such control is to enhance particular sweat sensing device applications by improving detectability of the targeted analyte, or improving performance of analyte sensors. Some embodiments also include components to enable sample concentration to enhance the measurement of low- concentration sweat solutes.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
29.
DEVICES CAPABLE OF SAMPLE CONCENTRATION FOR EXTENDED SENSING OF SWEAT ANALYTES
The disclosed invention provides a sweat sensing device and method capable of collecting a sweat sample, concentrating the sample with respect to a target analyte, and measuring the target analyte in the concentrated sample. The invention is also capable of determining the change in molarity of the sweat sample with respect to the target analyte, as the sample is concentrated by the device.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/05 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
A61B 5/053 - Measuring electrical impedance or conductance of a portion of the body
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
Sweat sensing devices hold tremendous promise as biological monitoring systems for workplace safety, athletic, and military settings. The disclosed invention addresses a difficulty involving such use of sweat sensing devices by incorporating them 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.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
The disclosed invention provides a sweat sensing device configured with reduced volume between sweat sensors and sweat glands, which decreases the chronologically assured sampling interval. In one embodiment, a sweat sensing device placed on the skin for measuring a property of a sweat analyte includes one or more sweat sensors and a volume-reducing component. The volume-reducing component provides a volume-reduced pathway for sweat between the one or more sweat sensors and sweat glands when the device is positioned on the skin. The volume-reducing component may include a wicking material or other component that at least partially creates the volume-reduced pathway.
A device (100) for sensing biofluid placed on skin (12) with at least one pre-existing pathway (14) includes a first analyte-specific sensor (120) for sensing a first analyte in the biofluid and a volume-reduced pathway between skin (12) and the first analyte-specific sensor (120) configured to allow an advective flow of the biofluid from the at least one pre-existing pathway (14) toward the first analyte-specific sensor (120). The first analyte-specific sensor (120) does not consume the first analyte. The device (100) further includes an iontophoresis electrode (150) and a counter electrode (152) for bringing the first analyte into the at least one pre-existing pathway. The biofluid may be more than 50% interstitial fluid or more than 50% sweat. The device (100) may also include at least one of a wicking collector (136), a wicking coupler (130), or a wicking pump (138).
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1477 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using chemical or electrochemical methods, e.g. by polarographic means non-invasive
A61B 5/1486 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using enzyme electrodes, e.g. with immobilised oxidase
A61N 1/30 - Apparatus for iontophoresis or cataphoresis
G01N 27/26 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by using electrolysis or electrophoresis
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.
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.
The disclosure provides: a two-way communication means between a sweat sensing device and a user; at least one means of activating, deactivating, controlling the sampling rate, and controlling the electrical power applied to a particular sweat sensor or group of sensors; a means of isolating a sweat sensor from sweat until needed; a means of selectively stimulating sweat for a particular sweat sensor or group of sensors to manage sweat flow or generation rate; a means of monitoring the power consumption of a sensor device, individual sensors or groups of sensors; a means of monitoring an individual sweat sensor or group of sensors for optimal performance; a means of monitoring whether a sweat sensing patch is in adequate proximity to a wearer's skin to allow device operation; and the ability to use aggregated sweat sensor data correlated with external information to enhance the device's management capabilities.
The invention addresses confounding difficulties involving continuous sweat analyte measurement. Specifically, the present invention provides: at least one component capable of monitoring whether a sweat sensing device is in sufficient contact with a wearer's skin to allow proper device operation; at least one component capable of monitoring whether the device is operating on a wearer's skin; at least one means of determining whether the device wearer is a target individual within a probability range; at least one component capable of generating and communicating alert messages to the device user(s) related to: wearer safety, wearer physiological condition, compliance with a requirement to wear a device, device operation; compliance with a behavior requirement, or other purposes that may be derived from sweat sensor data; and the ability to utilize aggregated sweat sensor data that may be correlated with information external to the device to enhance the predictive capabilities of the device.
A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
A61B 5/1455 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using optical sensors, e.g. spectral photometrical oximeters
patents
