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1. 发明申请

WO2017070640A1 DEVICES CAPABLE OF SAMPLE CONCENTRATION FOR EXTENDED SENSING OF SWEAT ANALYTES 审中-公开
标题翻译：可用于样品浓度的设备用于扩展SWEAT分析的检测
公开(公告)号：WO2017070640A1
公开(公告)日：2017-04-27
申请号：PCT/US2016/058356
申请日：2016-10-23
申请人： ECCRINE SYSTEMS, INC. , UNIVERSITY OF CINCINNATI
发明人： HEIKENFELD, Jason , BERTRAND, Jacob, A. , BROTHERS, Michael , JAJACK, Andrew
IPC分类号： A61B5/00 , A61B5/05 , A61B5/053 , A61B10/00 , G01N33/48 , G01N33/50
CPC分类号： A61B5/4266 , A61B5/0002 , A61B5/14517 , A61B5/14521 , A61B5/14546 , A61B5/1468 , A61B5/6833 , A61B10/0012 , A61B10/0064 , A61B2010/0016 , G01N33/50
摘要： 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.
摘要翻译：所公开的发明提供了能够收集汗液样品，相对于目标分析物浓缩样品并测量浓缩样品中的目标分析物的汗液感测装置和方法。当样品被装置浓缩时，本发明还能够测定汗样品相对于目标分析物的摩尔浓度的变化。

2. 发明申请

WO2018057695A1 ACCURATE ENZYMATIC SENSING OF SWEAT ANALYTES 审中-公开
标题翻译：甜味分析的准确酶学检测
公开(公告)号：WO2018057695A1
公开(公告)日：2018-03-29
申请号：PCT/US2017/052651
申请日：2017-09-21
申请人： UNIVERSITY OF CINCINNATI , ECCRINE SYSTEMS, INC.
发明人： HEIKENFELD, Jason, C. , BERTRAND, Jacob, A. , BROTHERS, Michael, Charles , GOMEZ, Eliot
IPC分类号： A61B5/00 , A61B5/05 , A61B5/145 , C12Q1/00 , C12Q1/70
摘要： 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.
摘要翻译：用于感测生物流体（18）的装置（200）包括至少一个消耗分析物的传感器（220），用于测量生物流体（18）中的分析物的至少第一分析物浓度以及至少一个附加组件（248）。如果生物流体（18）样品流速小于或等于第一生物流体（18）样品的2倍，那么至少一个附加部件（248）将分析物消耗传感器（220）测量结果保持在第一浓度测量结果的20％如由设备（200）所测量的流量测量。用于感测生物流体（18）的方法包括使用消耗分析物的传感器（220）测量生物流体（18）中的分析物的第一分析物浓度，测量第一生物流体样本流速并将后续分析物浓度测量保持在当随后测量的生物流体（18）流速小于或等于第一生物流体样品流速的2倍时，20％的第一分析物浓度测量。

3. 发明申请

WO2018237094A1 BIOFLUID SENSING DEVICES WITH PH-BUFFERED EAB SENSORS 审中-公开
公开(公告)号：WO2018237094A1
公开(公告)日：2018-12-27
申请号：PCT/US2018/038633
申请日：2018-06-20
申请人： ECCRINE SYSTEMS, INC.
发明人： BERTRAND, Jacob, A. , HANLEY, Brian , LARSON, Mikel , BEGTRUP, Gavi
IPC分类号： A61B5/00 , A61B5/145 , A61B5/1477
摘要： 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.

4. 发明申请

WO2018112024A1 THIOLATED AROMATIC BLOCKING STRUCTURES FOR EAB BIOSENSORS 审中-公开
公开(公告)号：WO2018112024A1
公开(公告)日：2018-06-21
申请号：PCT/US2017/066069
申请日：2017-12-13
申请人： ECCRINE SYSTEMS, INC.
发明人： BERTRAND, Jacob, A. , HANLEY, Brian , SAFAZADEH HAGHIGHI, Leila , BROTHERS, Michael
IPC分类号： G01N33/543 , C12N15/115 , H01L23/532
摘要： 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.

5. 发明申请

WO2018017619A1 SWEAT CONDUCTIVITY, VOLUMETRIC SWEAT RATE AND GALVANIC SKIN RESPONSE DEVICES AND APPLICATIONS 审中-公开
标题翻译：卫星电导率，体积速率和皮肤电声响应装置及应用
公开(公告)号：WO2018017619A1
公开(公告)日：2018-01-25
申请号：PCT/US2017/042677
申请日：2017-07-18
申请人： ECCRINE SYSTEMS, INC.
发明人： BEGTRUP, Gavi , BERTRAND, Jacob, A. , HEIKENFELD, Jason , MORGAN, Austin , WEINLE, Nathan
IPC分类号： A61B5/00 , A61B5/05 , A61B5/145
摘要： 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.
摘要翻译：所公开的发明包括配置为周期性地测量汗液传导性和皮肤电流响应的汗液感测设备，测量体积汗液流速的设备以及组合这三种功能的设备。本公开还包括用于使用被配置为执行周期性汗液电导率测量，电流皮肤响应测量和体积汗液率测量的装置的方法，以便每个传感器形式通知汗水开始，汗液中止，汗液浓度和出汗率的综合估计。该方法使用这些测量值来通知其他汗液感测设备功能，例如确定生理状况的存在，或者执行汗液分析物的浓度，比率和趋势的测量。

6. 发明申请

WO2019183529A1 HUMIDITY-BASED SWEAT RATE SENSING DEVICES 审中-公开
公开(公告)号：WO2019183529A1
公开(公告)日：2019-09-26
申请号：PCT/US2019/023665
申请日：2019-03-22
申请人： ECCRINE SYSTEMS, INC.
发明人： HOFFMAN, Michelle , HEIKENFELD, Jason , BERTRAND, Jacob, A. , BAILEY, Nicholas
IPC分类号： A61B5/00 , A61B5/145 , A61B10/00
摘要： 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.

7. 发明申请

WO2018031559A1 BIOFLUID SENSING DEVICES WITH INTEGRATIVE EAB BIOSENSORS 审中-公开
标题翻译：具有集成EAB生物传感器的生物流体传感装置
公开(公告)号：WO2018031559A1
公开(公告)日：2018-02-15
申请号：PCT/US2017/045926
申请日：2017-08-08
申请人： ECCRINE SYSTEMS, INC.
发明人： BEECH, Robert , BEGTRUP, Gavi , HEIKENFELD, Jason , BERTRAND, Jacob, A.
IPC分类号： A61B5/00 , A61B5/01 , A61B5/053 , A61B5/145 , A61B10/00 , A61N1/30 , A61N1/32
摘要： 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.
摘要翻译：所公开的发明包括用于可佩戴生物流体感测装置的基于集成电化学适体的传感器。所公开的集成EAB传感器被配置为通过聚集来自各个感测元件的信号随着时间的过去来检测汗液或生物流体样品中的非常低浓度的目标分析物，直到达到信号阈值。信号聚集是通过各种保留结构完成的，延长了感应元件保留目标分析物分子的时间。实施方案包括将互补的引物和官能团连接至适体，用阻断剂覆盖这些保留结构，直到分析物捕获，或者用亲水性和疏水性单层涂覆传感器电极。本发明还包括使用所公开的集成传感器的方法。所公开的方法的一些实施例包括追踪时间到信号阈值以估计分析物浓度。

8. 发明申请

WO2017189122A1 EAB BIOSENSORS FOR DETECTING SWEAT ANALYTES 审中-公开
标题翻译： EAB生物传感器用于检测蛋白质分析
公开(公告)号：WO2017189122A1
公开(公告)日：2017-11-02
申请号：PCT/US2017/023399
申请日：2017-03-21
申请人： ECCRINE SYSTEMS, INC.
发明人： BERTRAND, Jacob, A. , BEGTRUP, Gavi , HAGHIGHI, Leila, Safazadeh , HEIKENFELD, Jason
IPC分类号： A61B5/00 , A61B5/145 , A61B5/05 , C12Q1/68
摘要： 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.
摘要翻译：（1）目标分析物大小，（2）潜在的浓度范围，（2）潜在的浓度范围等的影响，通过适体选择，传感器/装置配置和生理学算法可以缓解汗液培养基对EAB生物传感的挑战。（3）出汗样品的pH，和（4）出汗样品的盐度。所公开的发明包括适用于EAB传感器中的适配体选择方法，所述EAB传感器被配置用于可穿着汗水感测装置中。所公开的发明进一步提供了一种汗液感测设备，其被配置为使用EAB传感器来检测汗液样品中的目标分析物。

9. 发明申请

WO2020061552A1 BIOFLUID SENSING DEVICES WITH INTEGRATED CHARGE SEPARATION BUFFERING 审中-公开
公开(公告)号：WO2020061552A1
公开(公告)日：2020-03-26
申请号：PCT/US2019/052334
申请日：2019-09-23
申请人： ECCRINE SYSTEMS, INC.
发明人： BERTRAND, Jacob, A. , HANLEY, Brian
IPC分类号： G01N27/26
摘要： 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.

10. 发明申请

WO2019099856A1 REFERENCE APTAMER SENSING ELEMENTS FOR EAB BIOSENSORS 审中-公开
公开(公告)号：WO2019099856A1
公开(公告)日：2019-05-23
申请号：PCT/US2018/061557
申请日：2018-11-16
申请人： ECCRINE SYSTEMS, INC.
发明人： LARSON, Mikel , SAFAZADEH HAGHIGHI, Leila , BERTRAND, Jacob, A. , MACAZO, Florika
IPC分类号： C12N15/115 , G01N27/30 , G01N27/327 , G01N33/53 , G01N33/543
摘要： 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.

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