Wearable device with microneedle integrated sensor for on-demand sensing of interstitial fluid biomarkers

Abstract

A microneedle actuator (108) for monitoring ISF of a user includes a rigid support (112) defining a slot (130), a toothed cam (118) positioned within the rigid support (112) and including a shaft (147) extending through the slot (130), and a spring (114) positioned within the rigid support (112) and configured to rotate the toothed cam (118) about the shaft (147). The microneedle actuator (108) also includes an ISF sensing module (120) and an actuation device (122). An ISF sensing module (120) is attached to the toothed cam (118) and includes a plurality of microneedles (214), each of the plurality of microneedles (214) including at least one sensor (244) for detecting an ISF of a user. An actuation device (122) is attached to the rigid support (112) and the toothed cam (118). Actuation of the actuation device (122) releases the spring (114), rotating the toothed cam (118) to insert the plurality of microneedles (214) into the skin of the user, and wherein the at least one sensor (244) detects a component of ISF of the user.

Description

[0001] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0002] This invention was made with Government support under a development agreement funded by the Air Force Research Laboratory. The Government has certain rights in this invention. Background Art

[0003] The subject matter described herein relates generally to wearable sensing systems, and more particularly to wearable systems for sensing interstitial fluid of a user.

[0004] Continuous monitoring of biochemical data or biomarkers may be important for certain medical conditions. For example, continuous monitoring of biomarkers may enable medical intervention to be performed by the monitored user or medical professional when the biomarker indicates that medical intervention may be beneficial and / or is necessary for the proper management of the medical condition. Poor management of these medical conditions may cause short-term or long-term harm to the user. Similarly, biomarkers can be monitored to assess the performance of the user during sports, military or cognitive activities. The ability to detect and quantify biomarkers in real time on site enables the user or observer to implement changes in the short or long term to enhance performance or prevent performance from deteriorating (e.g., maintaining water, ensuring adequate rest, increasing or decreasing training / task load, using medications or supplements to enhance performance, etc.).

[0005] At least some known biochemical monitoring devices monitor the user's blood. These biochemical monitoring devices typically include at least one needle or microneedle that penetrates the user's skin and directs the blood to a sensing device located on the surface of the skin. The sensing device detects and reports the presence and / or concentration of biomarkers in the blood to the user or a medical professional. However, since the sensing device is located on the surface of the skin, the blood usually needs to be constantly replenished and must be disposed of after the sensing device has analyzed the blood. Typically, the core absorbs the blood and the core is discarded when the core can no longer absorb blood. Therefore, in order to continuously monitor and analyze the blood, the core is usually replaced frequently. In addition, these biochemical monitoring devices may be difficult for the user to use due to blood clots (e.g., the extracted blood may coagulate within the biochemical monitoring device). In addition, since the needle extends through the nerves in the skin, these biochemical monitoring devices may cause pain to the user.

[0006] At least some known biochemical monitoring devices monitor the user's ISF. For certain medical conditions, the concentration of biomarkers in the interstitial fluid (ISF) is correlated with the concentration of biomarkers in the user's blood. Since ISF is not excreted from the body, it is not contaminated by the environment and does not coagulate, making it an excellent source for continuous and on-demand monitoring of biomarkers. These biochemical monitoring devices typically include at least one needle or microneedle that penetrates the user's skin and continuously monitors the user's ISF under the skin. These biochemical monitoring devices typically include at least one needle or microneedle that pierces the user's skin and at least one sensing device located on the microneedle and pierces the skin with the microneedle. The microneedle and sensing device stay in the user's skin for a long time to continuously monitor the user's ISF. However, microneedles and sensor devices inserted into the skin can cause inflammation and / or foreign body reactions, which can introduce artifacts in the measurement of inflammatory cytokines. In addition, for protein biomarker sensing, extremely high affinity binding biorecognition elements (BREs) are used for single-point measurements because they may not be able to effectively respond to a decrease in concentration (debinding). Inflammation and foreign body responses caused by the microneedles and sensing device may distort the results reported by the BRE. Summary of the invention

[0007] In one aspect, a microneedle actuator for monitoring a user's ISF is provided. The microneedle actuator includes a rigid support defining a slot, a geared cam positioned within the rigid support and including an axis extending through the slot, and a spring positioned within the rigid support and configured to rotate the geared cam around the axis. The microneedle actuator also includes an ISF sensing module and an actuating device. The ISF sensing module is attached to the geared cam and includes a plurality of microneedles, each of the plurality of microneedles including at least one sensor for detecting the user's ISF. The actuating device is attached to the rigid support and the geared cam. Actuation of the actuating device releases the spring, causing the geared cam to rotate to insert the plurality of microneedles into the user's skin, and wherein at least one sensor detects the composition of the user's ISF.

[0008] On the other hand, a microneedle actuator for monitoring ISF of a user. The microneedle actuator includes a rigid support defining a slot, a geared cam positioned in the rigid support and including an axis extending through the slot, a spring positioned in the rigid support and configured to rotate the geared cam around the axis, and an ISF sensing module attached to the geared cam. The ISF sensing module includes a first support layer, a sensor layer laminated to the first support layer to form a sensor component, and a plurality of microneedles extending from the sensor component. The sensor layer includes a substrate and at least one sensor positioned on the substrate. Each of the plurality of microneedles includes a microneedle base extending from the sensor component, a body, and a tip extending from the body. The body extends from the microneedle base and defines a slot of the first support layer extending through the body. The slot defines a first opening and a second opening, and at least one sensor is positioned above the second opening, wherein the first opening, the slot, and the at least one sensor define a channel exposed to the environment, wherein the channel is configured to guide the ISF to the at least one sensor. The ISF sensing module includes an actuation device attached to a rigid support and a geared cam, wherein actuation of the actuation device releases a spring, causing the geared cam to rotate to insert a plurality of microneedles into the user's skin, and wherein at least one sensor detects the user's ISF.

[0009] On the other hand, a method for detecting biomarkers in the ISF of a user is provided. The method includes adhering a microneedle actuator to the skin of the user, the microneedle actuator including a rigid support, a geared cam positioned in the rigid support, a spring positioned in the rigid support and configured to rotate the geared cam, an ISF sensing module attached to the geared cam and including a plurality of microneedles, and an actuating device attached to the rigid support and the geared cam. Each of the plurality of microneedles includes at least one sensor for detecting the ISF of the user. The method also includes actuating the actuating device so that the actuating device releases the spring, rotating the geared cam to insert the plurality of microneedles into the skin of the user. The method also includes directing the ISF to at least one sensor and detecting at least one biomarker with at least one sensor. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] These and other features, aspects and advantages of the present disclosure will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like characters refer to like parts throughout, and in which:

[0011] Figure 1 is a top perspective view of an exemplary wearable ISF sensing device.

[0012] Figure 2 yes Figure 1 A cut-away perspective view of an exemplary microneedle actuator is shown in FIG.

[0013] Figure 3 yes Figure 2 A side view of an exemplary microneedle actuator is shown in FIG.

[0014] Figure 4 yes Figure 2 A side view of an exemplary microneedle actuator is shown in , with some parts removed for clarity.

[0015] Figure 5 yes Figure 2 A side view of an exemplary microneedle actuator is shown in FIG. 5 , with portions shown as transparent for clarity.

[0016] Figure 6 yes Figure 2 A side view of an exemplary microneedle actuator is shown in FIG. 5 , with portions shown as transparent for clarity.

[0017] Figure 7 is used with Figure 2 Side view of an exemplary actuation device for use with the microneedle actuator shown in FIG.

[0018] Figure 8 is used with Figure 2 Top view of an exemplary actuation device for use with a microneedle actuator shown in FIG.

[0019] Fig. 9 is a plan view of an exemplary ISF sensing module.

[0020] Fig.10 yes Fig. 9 An exploded perspective view of the ISF sensing module shown in FIG.

[0021] Fig.11 yes Fig. 9 Plan view of the top support layer of the ISF sensing module shown in FIG.

[0022] Fig.12 yes Fig. 9 A plan view of the bottom support layer of the ISF sensing module shown in FIG.

[0023] Fig.13 yes Fig. 9 A plan view of the sensor layer of the ISF sensing module shown in FIG.

[0024] Fig.14 yes Fig. 9 A plan view of the first adhesive layer of the ISF sensing module shown in FIG.

[0025] Fig.15 yes Fig. 9 A plan view of the second adhesive layer of the ISF sensing module shown in FIG.

[0026] Fig.16 yes Fig. 9 An exploded perspective view of the microneedles of the ISF sensing module shown in FIG.

[0027] Fig.17 yes Fig.16 A perspective view of the top support layer of the microneedles shown in FIG.

[0028] Fig.18 yes Fig.16 Plan view of the top support layer of the microneedles shown in .

[0029] Fig.19 yes Fig.16 A plan view of the bottom support layer of the microneedle shown in FIG.

[0030] Fig. 20 yes Fig.16 A plan view of the sensor layer of the microneedle shown in FIG.

[0031] Fig.21 is a block diagram of an exemplary electronic device architecture.

[0032] Fig. 22 It is printed on Fig.13 Circuit diagram of multiple sensors on a substrate of a sensor layer is shown in FIG.

[0033] Fig.23 yes Figure 1 FIG. 1 is a diagram of a wearable ISF sensing device positioned on a user's skin, wherein Fig.16 The microneedles shown in are inserted into the dermis of the user's skin.

[0034] Unless otherwise indicated, the drawings provided herein are intended to illustrate features of the embodiments of the present disclosure. These features are believed to be applicable to a variety of systems including one or more embodiments of the present disclosure. Therefore, the drawings are not meant to include all conventional features required for practicing the embodiments disclosed herein known to those of ordinary skill in the art. DETAILED DESCRIPTION

[0035] In the following specification and claims, reference will be made to several terms which shall be defined as having the following meanings.

[0036] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0037] As used herein throughout the specification and claims, approximating language may be applied to modify any quantitative representation that allows variation without causing a change in the basic function associated therewith. Thus, values ​​modified by one or more terms (such as "approximately," "substantially," and "about") are not limited to the exact values ​​specified. In at least some cases, approximate language may correspond to the precision of the instrument used to measure the value. Here and throughout the specification and claims, range limitations may be combined and / or interchanged, and such ranges may be identified and include all subranges contained therein unless otherwise indicated by context or language.

[0038] The system and method described herein provide a wearable interstitial fluid (ISF) sensing device. The wearable ISF sensing device includes a sensor component and a plurality of microneedle actuators positioned on the sensor component. The sensor component is attached to the skin of the user. Each of the microneedle actuators includes a rigid support, a spring, a pressure head, a cam with a gear, an ISF sensing module and an actuating device. The ISF sensing module is attached to the cam with a gear. The pressure head, the spring and the actuating device are configured to rotate the cam with a gear to insert the ISF sensing module into the skin of the user. Specifically, the actuating device is configured to keep the spring in the stored configuration until it is selectively actuated. Once the actuating device has been actuated, the spring is released from the stored configuration to push, press or drive the pressure head against the cam with a gear, thereby rotating the cam with a gear. The rotation of the cam with a gear causes the ISF sensing module to rotate toward the skin of the user, inserting the ISF sensing module into the skin of the user. Then, the ISF sensing module monitors the biochemical markers of the user.

[0039] The ISF sensing module includes a plurality of layers laminated together to form a sensor component and at least one microneedle extending from the sensor component. The layers include a first support layer, a first adhesive layer, a sensor layer, a second adhesive layer, and a second support layer. The first support layer and the second support layer structurally support the sensor layer, and the first adhesive layer and the second adhesive layer laminate the first support layer and the second support layer to the sensor layer. The lamination of the layers ensures that the microneedle remains intact when inserted into the user's skin. Therefore, the microneedle of the ISF sensing module described herein is structurally stronger than previous microneedles and remains intact when monitoring biomarkers in the user's ISF.

[0040] The microneedle comprises a microneedle base, a body and a tip. The microneedle has a substantially flat or planar profile, and a slot is defined in the body of the microneedle. The slot has a first opening and a second opening. The sensor layer comprises a sensor positioned above the second opening, so that the sensor and the slot define a channel for guiding ISF to the sensor. The microneedle and the sensor are inserted into the skin of the user so that the sensor is positioned in the dermis of the user's skin. ISF flows into the channel from adjacent tissues, and the sensor detects and measures biomarkers in the ISF. The user, observer, trainer, coach and / or medical professional can then monitor a medical condition or performance / readiness metric based on the data collected by the sensor.

[0041] Since the sensor is embedded in the dermis, the ISF flowing to the sensor is continuously balanced with the surrounding ISF without the need for a mechanical mechanism to supplement the ISF. In addition, embedding the sensor in the dermis enables the ISF sensing module to detect biomarkers without extracting liquid from the user's body, thereby reducing the body fluid removal and processing work generated by the detection and measurement of biomarkers. In addition, the capillary pressure and compression force generated during insertion will cause the ISF to flow into the channel, so that no fluid power device such as a vacuum pump or mechanical compression is required to supplement the ISF at the sensor. After insertion, the passive diffusion from the ISF and the balance with the ISF inside the channel supplement the ISF at the sensor. Therefore, the ISF sensing module is able to detect biomarkers while reducing body fluid removal and processing work, and reducing the equipment required to measure biomarkers in the ISF. In addition, directly measuring the ISF in the interstitial space reduces the lag time between changes in biomarker concentrations and readings. In addition, the ISF sensing module includes multiple sensors in a single patch, which can monitor multiple analytes on demand at the same time. For example, a sensor may measure a single analyte multiple times, measure multiple analytes at predetermined times, measure a secondary analyte after certain conditions for the primary analyte are met, and / or measure a group of analytes simultaneously.

[0042] Since the wearable ISF sensing device includes multiple microneedle actuators, the wearable ISF sensing device is able to monitor the user's medical condition over a longer period of time compared to a biosensing device with a single set of microneedles. Therefore, the user does not need to replace the wearable ISF sensing device as frequently as other biosensing devices. In addition, the wearable ISF sensing device described herein enables consistent monitoring of ISF because the wearable ISF sensing device can automatically activate another microneedle actuator after the sensor of the first microneedle actuator has been consumed. Therefore, the wearable ISF sensing device described herein enables consistent monitoring of the user's medical / performance condition. In addition, since the wearable ISF sensing device includes multiple microneedle actuators, the wearable ISF sensing device reduces the number of biosensing devices consumed by the user to monitor the medical condition.

[0043] Now referring to the accompanying drawings, Figure 1 1 is a top perspective view of an exemplary embodiment of a wearable ISF detection device 100. The wearable ISF sensing device 100 includes a sensor component 102, which optionally includes an on-chip electronics 104 and a protective foam 106. The wearable ISF sensing device 100 also includes a plurality of microneedle actuators 108 positioned on the sensor component 102 under a plurality of protective covers 111. The wearable ISF sensing device 100 may also include a reusable electronics module 110 positioned on the sensor component 102 and electrically coupled to the microneedle actuators 108. In an exemplary embodiment, portions of the wearable ISF sensing device 100 are disposable (i.e., the sensor component 102 and the microneedle actuators 108 are typically used once), while portions of the wearable ISF sensing device 100 are reusable (i.e., the reusable electronics module 110 is typically used more than once). In an alternative embodiment, at least one of the sensor component 102 and the microneedle actuator 108 is reusable.

[0044] The sensor component 102 is attached to the user's skin using an adhesive surface or foam. Alternatively, in some embodiments, the sensor component 102 can be integrated into clothing and held in place using a suction device or compression clothing. The sensor component 102 can be attached to various parts of the user's body, including but not limited to the trunk, legs, back, neck, arms, etc. For example, the sensor component 102 can be placed on the lower back (e.g., above the waistline, below the rib cage, and adjacent to the spine on either side), on the upper back (e.g., above or above the shoulder blade), on the chest (e.g., below the pectoralis muscle or centered above the sternum), on the calf (e.g., above the gastrocnemius muscle or on the side above the tibialis anterior muscle), or on the thigh (e.g., on the inner thigh). In addition, the sensor component 102 includes an embedded circuit (not shown) to electrically and communicatively couple the on-chip electronic device 104, the reusable electronic device module 110, and / or the microneedle actuator 108.

[0045] The wearable ISF sensing device 100 may also include a clip 113 attached to the sensor component 102 for selectively attaching the microneedle actuator 108 to the sensor component 102. The clip 113 enables the microneedle actuator 108 to be replaced after use, and the sensor component 102 and the reusable electronic module 110 to be reused. The protective cover 111 is positioned on the sensor component 102 and the clip 113, and extends through the protective foam 106 to cover, contain and protect the microneedle actuator 108. The protective foam 106 is positioned on the sensor component 102 to cover and protect the sensor component 102 and the reusable electronic module 110. The sensor component 102 defines a plurality of slots 115 positioned near each microneedle actuator 108 to enable each microneedle actuator 108 to be close to the user's skin.

[0046] In another alternative embodiment, the wearable ISF sensing device 100 may not include the sensor component 102. Instead, the microneedle actuator 108 may be attached to the user's skin separately, and the medical condition and / or performance metric as described herein may be monitored. In yet another alternative embodiment, the wearable ISF sensing device 100 may not include the on-chip electronics 104 and the reusable electronics module 110, but may only include the sensor component 102 and the microneedle actuator 108.

[0047] As described herein, the microneedle actuator 108 includes an actuation mechanism for inserting a microneedle and a sensor into the user's skin so that the sensor is positioned within the dermis of the user's skin. The ISF flows into the sensor and the sensor detects and measures the biomarkers within the ISF. The user and / or medical professional then monitors the medical condition based on the data collected by the sensor. More specifically, each microneedle actuator 108 deploys at least one microneedle as needed so that the microneedle actuator 108 collects data within a predetermined amount of time. The microneedle actuator 108 sends data to the on-chip electronic device 104 and / or a reusable electronic device module 110, which then sends the data to the user.

[0048] The wearable ISF sensing device 100 may include an on-chip electronic device 104 or a reusable electronic device module 110. Alternatively, the wearable ISF sensing device 100 may include both the on-chip electronic device 104 and the reusable electronic device module 110, or may not include the on-chip electronic device 104 or the reusable electronic device module 110. Specifically, the on-chip electronic device 104 and / or the reusable electronic device module 110 may be configured to receive data from the microneedle actuator 108 and send and / or display the data to the user. More specifically, the on-chip electronic device 104 and / or the reusable electronic device module 110 may be able to use Bluetooth communication or alternative methods such as direct Wi-Fi to communicate wirelessly with a remote computing device (e.g., a mobile computing device). Therefore, the on-chip electronic device 104 and / or the reusable electronic device module 110 can send and / or display the collected data to the user.

[0049] Figure 2 is a perspective view of the microneedle actuator 108 . Figure 3 is a side view of the microneedle actuator 108 . Figure 4 is a side view of the microneedle actuator 108 with portions of the microneedle actuator 108 removed for clarity. Figure 5 is another side view of the microneedle actuator 108 , wherein portions of the microneedle actuator 108 are shown as transparent for clarity. Figure 6 1 is another side view of the microneedle actuator 108, wherein portions of the microneedle actuator 108 are shown as transparent for clarity. The microneedle actuator 108 includes a rigid support 112, a spring 114, a press head 116, a geared cam 118, an ISF sensing module 120, an actuating device 122, and a sensor flexible connection 123. The ISF sensing module 120 is attached to the geared cam 118. The press head 116, the spring 114, and the actuating device 122 are configured to rotate the geared cam 118 to insert the ISF sensing module 120 into the user's skin through the slot 115. Specifically, the actuating device 122 is configured to hold the spring 114 in the stored configuration until selectively actuated. Once the actuator 122 has been actuated, the spring 114 is released from the stored configuration to push, press or drive the ram 116 against the geared cam 118, thereby rotating the geared cam 118. The rotation of the geared cam 118 causes the ISF sensing module 120 to rotate toward the user's skin, thereby inserting the ISF sensing module 120 into the user's skin. The ISF sensing module 120 then monitors the user's biochemical markers as described herein. The sensor flexible connection 123 electrically couples the ISF sensing module 120 to the on-chip electronics 104 and / or the reusable electronics module 110.

[0050] In an exemplary embodiment, the rigid support 112 includes a base 124, a vertical support 126, and a horizontal support 128. The vertical support 126 extends from the base 124, and the horizontal support 128 is spaced apart from the base 124 and extends between the vertical supports 126. The vertical supports 126 each define a slot 130, and the base 124 defines a plurality of grooves 132. In an exemplary embodiment, the rigid support 112 is formed of a rigid material, such as, but not limited to, a rigid metal, a rigid plastic, and / or any other material that enables the microneedle actuator 108 to operate as described herein. As described herein, the rigid support 112 is configured to position the spring 114, the press head 116, the geared cam 118, and the ISF sensing module 120 relative to each other so that the spring 114 drives into the press head 116, and the press head 116 rotates the geared cam 118 so that the ISF sensing module 120 is inserted into the user's skin.

[0051] In an exemplary embodiment, the spring 114 is formed of an elastic material, such as, but not limited to, spring steel, thermoplastic polyurethane, elastic metal, elastic composite, elastic plastic, and / or any other material that enables the microneedle actuator 108 to operate as described herein. More specifically, the spring 114 is formed of an elastic material that stores and releases an appropriate amount of energy to rotate the geared cam 118 and penetrate the skin of a user with an ISF sensing module 120. The spring 114 is maintained in tension in the stored configuration by the actuating device 122 and the rigid support 112. As described herein, the actuating device 122 is selectively actuated so that the spring 114 is driven into the press head 116, and the press head 116 rotates the geared cam 118 so that the ISF sensing module 120 is inserted into the user's skin. The spring 114 can be a compression spring, a tension spring, a torsion spring, a coil spring, and / or a leaf spring. In an alternative embodiment, the spring 114 can be any mechanical device configured to store and release energy as described herein.

[0052] The ram 116 is positioned between the vertical supports 126 and between the base 124 and the horizontal supports 128. The ram 116 has a face 134 configured to receive the spring 114 and a curved side 136 configured to receive a portion of the geared cam 118. The spring 114 is positioned between the rigid supports 112 and the ram 116 such that a first end 138 of the spring 114 is positioned on the face 134. As described herein, after the actuation device 122 has been actuated, the spring 114 exerts a force on the face 134 and translates the ram 116 toward the geared cam 118 along a direction 140 to rotate the geared cam 118. Specifically, the curved side 136 presses against the geared cam 118, causing the geared cam 118 to rotate.

[0053] The geared cam 118 converts the linear motion of the spring 114 and the ram 116 into the rotational motion of the ISF sensing module 120. In an exemplary embodiment, the geared cam 118 has: a body 142 having an irregular cylindrical shape; a first flat surface 144; a second flat surface 146; a shaft 147 including a pin 148 attached to the body 142; and gear teeth 150 extending from the body 142 and the second flat surface 146. The ISF sensing module 120 is attached to the first flat surface 144. The pin 148 is a cylindrical shaft extending from the body 142, and the geared cam 118 is positioned between the vertical supports 126 so that the pin 148 extends from the body 142 into the slot 130. The pin 148 allows the geared cam 118 to rotate and translate in the direction 140 while holding the geared cam 118 between the vertical supports 126.

[0054] The gear 150 extends from the body 142 and the second planar surface 146 and, in the exemplary embodiment, has a generally circular shape that is complementary to the generally circular shape of the recess 132. Figure 5 and Figure 6 In the first configuration shown, at least one gear tooth 150 is positioned within at least one groove 132. Figure 5 and Figure 6 In the illustrated embodiment, two gear teeth 150 are positioned within two grooves 132. Rotation of the geared cam 118 is accomplished in part by the gear teeth 150 rotating into the grooves 132, such that each gear tooth 150 and groove 132 provides a pivot point about which the geared cam 118 pivots during rotation of the geared cam 118. For example, Figure 5 and Figure 6 As shown, the geared cam 118 includes five gear teeth 150 (a first gear tooth 152, a second gear tooth 154, a third gear tooth 156, a fourth gear tooth 158, and a fifth gear tooth 160), and the base 124 defines five grooves 132 (a first groove 162, a second groove 164, a third groove 166, a fourth groove 168, and a fifth groove 170). Figure 5In the first configuration shown, the first gear tooth 152 is positioned within the first groove 162, and the geared cam 118 pivots around the first gear tooth 152 when it begins to rotate. In addition, when the geared cam 118 rotates, the second gear tooth 154 rotates into the second groove 164 and the first gear tooth 152 rotates out of the first groove 162, so that the geared cam 118 pivots around the second gear tooth 154 instead of the first gear tooth 152. When the geared cam 118 rotates, the pivot point moves sequentially from the first gear tooth 152 to the fifth gear tooth 160. The gear teeth 150 and the groove 132 provide a continuous pivot point around which the geared cam 118 pivots during the rotation of the geared cam 118. Without the gear teeth 150 and the groove 132, the geared cam 118 can slide without rotating so that the ISF sensing module 120 is not inserted into the user's skin. Thus, the gear teeth 150 and the grooves 132 enable the geared cam 118 to rotate, thereby ensuring that the ISF sensing module 120 is inserted into the user's skin.

[0055] The actuator 122 holds the spring 114, the ram 116, the geared cam 118, and the ISF sensing module 120 in the first configuration until the user activates the actuator 122 as described above, releases the spring 114, the ram 116, the geared cam 118, and the ISF sensing module 120, and inserts the ISF sensing module 120 into the user's skin. Figure 7 and Figure 8As shown, in an exemplary embodiment, the actuator 122 includes a heater 172, a first strip 174, a second strip 176, and a sensor 177. The first strip 174 includes a first backing 178 and a first substrate 180 attached to the first backing 178, and the second strip 176 includes a second backing 182 and a second substrate 184 attached to the second backing 182. The first backing 178 and the second backing 182 each include a first side 186, a second side 188, a first end 190, and a second end 192. The first side 186 of the first backing 178 and the second backing 182 faces the spring 114, the ram 116, the geared cam 118, and the ISF sensing module 120, while the second side 188 of the first backing 178 and the second backing 182 faces away from the spring 114, the ram 116, the geared cam 118, and the ISF sensing module 120. A first end 190 of the first backing 178 is attached to the horizontal support 128, and a second end 192 of the first backing 178 is releasably attached to the first end 190 of the second backing 182, as described below. The second end 192 of the second backing 182 is attached to the geared cam 118. In an alternative embodiment, the actuating device 122 does not include the first backing 178 and the second backing 182. Instead, the first substrate 180 and the second substrate 184 are directly attached to the horizontal support 128 and the geared cam 118, respectively. In an exemplary embodiment, the first belt 174 and the second belt 176 each include a porous hydrophobic sheet, a membrane material, paper, a textile, an adhesive-backed textile, a non-woven polymer sheet, a cast polymer sheet, a laser-drilled polymer sheet, and / or a support form of any of the above materials.

[0056] The first substrate 180 and the second substrate 184 are fibrous porous substrates attached to the first side 186 of the first backing 178 and the second side 188 of the second backing 182. In an exemplary embodiment, the first substrate 180 and the second substrate 184 include a porous hydrophobic sheet or membrane material, paper, a textile, an adhesive-backed textile, a non-woven polymer sheet, a cast polymer sheet, a laser-drilled polymer sheet, any other porous material and / or a support form of any of the above materials and / or any other porous material. In an exemplary embodiment, the first substrate 180 and the second substrate 184 include a non-woven polyethylene sheet. Figure 7As shown, the first substrate 180 and the second substrate 184 are attached to the first backing 178 and the second backing 182, so that the first substrate 180 and the second substrate 184 contact each other in the first configuration. In addition, in an exemplary embodiment, the first substrate 180 and the second substrate 184 are impregnated with an adhesive material so that the first substrate 180 and the second substrate 184 adhere to each other in the first configuration. The bonding of the first substrate 180 to the second substrate 184 will keep the spring 114, the press head 116, the geared cam 118 and the ISF sensing module 120 in the first configuration until the heater 172 melts the adhesive material, releases the spring 114, the press head 116, the geared cam 118 and the ISF sensing module 120 as described above, and inserts the ISF sensing module 120 into the user's skin.

[0057] In an exemplary embodiment, the adhesive material includes any substance that adheres the first belt 174 to the second belt 176 at a first predetermined temperature, thereby preventing the geared cam 118 and the ISF sensing module 120 from rotating, and disengages the first belt 174 from the second belt 176 at a second predetermined temperature, thereby enabling the geared cam 118 and the ISF sensing module 120 to rotate and enabling the ISF sensing module 120 to be inserted into the user's skin. For example, in an exemplary embodiment, the adhesive material includes wax. Specifically, in one embodiment, the wax includes a polyolefin wax, including eicosane, docosane, tetracosane, hexacosane, octacosane, triacontan, dotriacontan, tetratriacontan, hexatriacontan, octacosane, tetracontan, dotriacontan, tetratriacontan and / or mixtures thereof. In another embodiment, the wax includes a fluoropolymer wax, a fatty acid amide wax, a Fischer-Tropsch wax, a paraffin wax, a polyolefin wax and / or mixtures thereof. In yet another embodiment, the wax comprises a wax of biological origin, such as a plant wax (carnauba wax, palm wax, etc.) or a wax of animal origin (tallow, beeswax, etc.).

[0058] The heater 172 is positioned on the horizontal support 128, near the adhesive material injected into the first substrate 180 and the second substrate 184. In addition, the heater 172 is electrically and communicatively coupled to the on-chip electronic device 104 and / or the reusable electronic device module 110. The on-chip electronic device 104 and / or the reusable electronic device module 110 enable communication between the heater 172 and the user, thereby enabling the user to activate the heater 172. In an exemplary embodiment, the adhesive material is a wax having a melting temperature of about 40°C to about 70°C, and the wax melts when the heater 172 raises the temperature of the wax above the melting temperature. The wax adheres to the first band 174 to the second band 176 at a first predetermined temperature, thereby preventing the geared cam 118 and the ISF sensing module 120 from rotating, and disengages the first band 174 from the second band 176 at a second predetermined temperature, thereby enabling the geared cam 118 and the ISF sensing module 120 to rotate and insert the ISF sensing module 120 into the user's skin. That is, the wax has a predetermined adhesion temperature (approximately the melting temperature) below which the wax adheres the first tape 174 to the second tape 176. However, when the temperature of the wax increases from the first predetermined temperature to the second predetermined temperature such that the temperature of the wax reaches or exceeds the predetermined adhesion temperature, the wax disengages the first tape 174 from the second tape 176.

[0059] In an exemplary embodiment, the heater 172 includes a thin film heater positioned on the horizontal support 128 near the wax injected into the first substrate 180 and the second substrate 184. In an alternative embodiment, the heater 172 may include a thick film heater, an inductively coupled heater, a resistive heater, a photothermal heater, a thermoelectric heater, a piezoelectric heater, an RF / magnetic heater, a laser, a light source and / or a chemical heater. In an alternative embodiment, the heater 172 is formed integrally with the horizontal support 128. The heater 172 is configured to selectively increase the temperature of the wax from a first predetermined temperature to a second predetermined temperature so that the temperature of the wax reaches or exceeds a predetermined adhesion temperature. The sensor 177 is attached to the rigid support 112 to determine the state of the actuator 122. Specifically, the sensor 177 is configured to deactivate the heater 172 after the heater 172 increases the temperature of the adhesive material to above the melting point of the adhesive material. In an exemplary embodiment, the sensor 177 includes a circuit including a conductive link (not shown) that can be mechanically broken. When the actuator 122 is actuated, the conductive link that can be mechanically broken breaks.

[0060] Fig. 9 is a top view of an exemplary embodiment of an ISF sensing module 200, and Fig.10 FIG. 2 is an exploded perspective view of the ISF sensing module 200. Fig. 9 and Fig.10As shown, the ISF sensing module 200 is formed by a plurality of layers 202-210 laminated together to form a sensor component 212 and a plurality of microneedles 214 integrally formed with the sensor component 212 for inserting into the skin of the user and sensing the ISF of the user, as described in detail below. The ISF sensing module 200 is then separated into separate ISF sensing modules 120 and attached to the microneedle actuator 108 as described above for sensing the ISF of the user. The sensor component 212 supports the microneedles 214 during insertion into the skin of the user and adheres the ISF sensing module 200 to the skin of the user, as described below. The microneedles 214 detect and measure at least one biomarker within the ISF of the user, so that the ISF sensing module 200 can monitor medical conditions and / or performance metrics based on data collected by the microneedles 214. In an exemplary embodiment, the ISF sensing module 200 is disposable (i.e., the ISF sensing module 200 is typically used once). In alternative embodiments, at least a portion of the ISF sensing module 200 may be reusable (ie, the ISF sensing module 200 may be used for multiple purposes).

[0061] The ISF sensing module 200 includes a top support layer or first support layer 202, a first adhesive layer 204, a sensor layer 206, a first adhesive layer 208, and a bottom support layer or second support layer 210 laminated together to form the ISF sensing module 200. The adhesive layer 204 and the adhesive layer 208 attach the top support layer 202, the sensor layer 206, and the bottom support layer 210. The top support layer 202 and the bottom support layer 210 structurally support the sensor layer 206, and the sensor layer 206 senses the user's ISF and reports the collected data to the user and / or a medical professional, as described herein. In addition, the size and shape of the microneedle 214 are designed to enable the user's ISF to flow to the sensor layer 206 so that the sensor layer 206 can detect the ISF.

[0062] like Fig.10As shown, the top support layer 202, the first adhesive layer 204, the sensor layer 206, the second adhesive layer 208, and the bottom support layer 210 are arranged and laminated in a layered configuration. The bottom support layer 210 is a base layer attached to the first flat surface 144 of the cam 118 with gears. The second adhesive layer 208 is applied on top of the bottom support layer 210 and adheres the bottom support layer 210 to the sensor layer 206 so that the second adhesive layer 208 is positioned between the bottom support layer 210 and the sensor layer 206. The first adhesive layer 204 is applied on top of the sensor layer 206 and adheres the sensor layer 206 to the top support layer 202 so that the first adhesive layer 204 is positioned between the top support layer 202 and the sensor layer 206. In an exemplary embodiment, the first adhesive layer 204 and the second adhesive layer 208 are curable adhesives positioned between the top support layer 202, the sensor layer 206, and the bottom support layer 210, as described above. Specifically, in the exemplary embodiment, the first adhesive layer 204 and the second adhesive layer 208 are curable adhesive sheets positioned between the top support layer 202, the sensor layer 206, and the bottom support layer 210, as described above. The lamination of the ISF sensing module 200 is achieved by heating the first adhesive layer 204 and the second adhesive layer 208 until the first adhesive layer 204 and the second adhesive layer 208 are thermally cured, bonding the top support layer 202, the sensor layer 206, and the bottom support layer 210.

[0063] In an alternative embodiment, the first adhesive layer 204 and the second adhesive layer 208 are pressure sensitive adhesives applied to the top support layer 202 and the bottom support layer 210. The ISF sensing module 200 is laminated by pressing the top support layer 202 and the first adhesive layer 204 to the sensor layer 206 and pressing the bottom support layer 210 and the second adhesive layer 208 to the sensor layer 206 such that the pressure sensitive adhesive bonds the top support layer 202, the sensor layer 206, and the bottom support layer 210 together.

[0064] In another alternative embodiment, the ISF sensing module 200 does not include the first adhesive layer 204 and the second adhesive layer 208. Instead, the top support layer 202, the sensor layer 206, and the bottom support layer 210 are mechanically laminated together. For example, the top support layer 202, the sensor layer 206, and the bottom support layer 210 are mechanically laminated together in a manner similar to Fig.10 The layer configuration shown in FIG. 2 is arranged, and mechanical fasteners (not shown) couple the top support layer 202 , the sensor layer 206 , and the bottom support layer 210 together.

[0065] The sensor component 212 of the bottom support layer 210 is attached to the first flat surface 144 of the geared cam 118 using an adhesive surface 216 or foam. Alternatively, in some embodiments, the sensor component 212 can be integrated into the first flat surface 144 of the geared cam 118. In an exemplary embodiment, the sensor component 212 of the top support layer 202 and the bottom support layer 210 is formed of a pliable material, such as, but not limited to, a pliable metal, a pliable plastic, and / or any other material that enables the ISF sensing module 200 to operate as described herein. In some embodiments, the sensor component 212 of the top support layer 202 and the bottom support layer 210 is formed by additively manufacturing, casting, and / or molding a pliable metal or plastic into the sensor component 212 of the top support layer 202 and the bottom support layer 210. In other embodiments, the sensor components 212 of the top supporting layer 202 and the bottom supporting layer 210 are formed by machining (eg, laser cutting) a pliable metal or plastic into the sensor components 212 of the top supporting layer 202 and the bottom supporting layer 210 .

[0066] The ISF sensing module 200 includes a plurality of ISF sensing modules 120 that are separable from one another such that each ISF sensing module 120 operates independently of the other ISF sensing modules 120. In the illustrated embodiment, the ISF sensing module 200 includes four ISF sensing modules 120 that are separable from one another. In alternative embodiments, the ISF sensing module 200 may include any number of ISF sensing modules 120 that enable the ISF sensing module 200 to operate as described herein. After the layers 202-210 have been laminated together to form the ISF sensing module 120, the ISF sensing modules 200 are separated from one another. The ISF sensing modules 120 are separated from one another and attached to the first flat surface 144 of the geared cam 118. In alternative embodiments, after the ISF sensing module 200 is shipped to a user, the ISF sensing modules 120 are separated from one another by the user and / or a medical professional, and the user and / or a medical professional attaches the ISF sensing modules 120 to the first flat surface 144 of the geared cam 118. Figures 9 to 11 and Fig.15 As shown, the top support layer 202 and the bottom support layer 210 define a plurality of separation slots 220 between the ISF sensing modules 120 and enable the ISF sensing modules 120 to be separated from each other.

[0067] The sensor component 212 of the top support layer 202 includes a plurality of cutouts 222 to allow a user and / or medical professional to access the sensor layer 206 positioned between the top support layer 202 and the bottom support layer 210. Figures 9 to 11As shown, the cutout 222 is formed so that portions of the sensor layer 206 are accessible by a user and / or a medical professional. The size and shape of the cutout 222 are designed to allow a user, a medical professional, a battery, and / or an electronic device to access the sensor layer 206. In an exemplary embodiment, the cutout 222 has an oval shape. However, the cutout 222 can have any shape that enables the ISF sensing module 200 to operate as described herein.

[0068] In an exemplary embodiment, sensor component 212 may have a sensor component length 224 of about 25 millimeters (mm) and a sensor component height 226 of about 13 mm, microneedles 214 may have a microneedle length 228 of about 800 micrometers (μm) and a microneedle width 230 of about 100 μm, and incision 222 may have an incision length 232 of about 7.5 mm and an incision width 234 of about 2.25 mm. Alternatively, sensor component 212, microneedles 214, and / or incision 222 may have any dimensions that enable ISF sensing module 200 to function as described herein. In addition, the top support layer 202 and the bottom support layer 210 each have a patch layer thickness 236 of approximately 75 μm, the sensor layer 206 has a sensor layer thickness 238 of approximately 25 μm, and the first adhesive layer 204 and the second adhesive layer 208 each have an adhesive layer thickness 240 of approximately 25 μm, so that the sensor component 212 and the microneedle 214 have a thickness 242 of approximately 325 μm.

[0069] In the exemplary embodiment, sensor component 212 has a rectangular shape. In alternative embodiments, sensor component 212 may have any shape that enables ISF sensing module 200 to operate as described herein, including but not limited to oval, elongated, circular, and / or any other shape that enables ISF sensing module 200 to operate as described herein.

[0070] In the illustrated embodiment, the ISF sensing modules 120 each include three microneedles 214 attached to the sensor component 212. In alternative embodiments, the ISF sensing modules 120 may include any number of microneedles 214 that enable the ISF sensing module 200 to operate as described herein. Specifically, as described in detail below, at least one sensor 244 (i.e., electrode) is attached to each microneedle 214 to detect biomarkers within the ISF. Some medical conditions may require monitoring of multiple biomarkers in order to properly monitor and manage the medical condition. Therefore, each ISF sensing module 120 may include any number of microneedles 214 and sensors 244 that enable the ISF sensing module 200 to properly monitor the medical condition.

[0071] The microneedles 214 each include a microneedle base 246, a body 248, and a tip 250. The microneedle base 246 is attached to the sensor component 212, the body 248 is attached to the microneedle base 246, and the tip 250 is attached to the body 248. The ISF sensing module 200 is formed such that the microneedle base 246 extends from the sensor component 212 and is substantially coplanar with the sensor component 212. In addition, the body 248 extends from the microneedle base 246, and the tip 250 extends from the body 248, so that the microneedle base 246, the body 248, and the tip 250 are substantially coplanar with the sensor component 212.

[0072] In an exemplary embodiment, each of the microneedles 214 includes a first surface 252, a second surface 254 opposite the first surface 252, a third surface 256, and a fourth surface 258 opposite the third surface 256. The first surface 252 and the second surface 254 each have a length equal to the microneedle length 228 and a width equal to the microneedle width 230. The third surface 256 and the fourth surface 258 each have a length equal to the microneedle length 228 and a width equal to the thickness 242. In an exemplary embodiment, the first surface 252, the second surface 254, the third surface 256, and the fourth surface 258 each have a flat or planar profile. Therefore, each of the microneedles 214 includes at least one surface having a flat or planar profile. In an exemplary embodiment, each microneedle 214 includes four surfaces, each of which has a flat or planar profile.

[0073] In an exemplary embodiment, the microneedle base 246 is formed of a flexible material to enable the microneedle base 246 to bend. In some embodiments, the sensor component 212 and the microneedle 214 are formed of the same flexible material. In an alternative embodiment, the sensor component 212 is formed of a first material, and the microneedle 214 is formed of a second material different from the first material. In yet another alternative embodiment, the sensor component 212 and the microneedle 214 may be formed of multiple materials. For example, the sensor component 212 may be formed of a first material, the microneedle base 246 may be formed of a second flexible material, the body 248 may be formed of a third material different from the first material and the second material, and the tip 250 may be formed of a fourth material different from the first material, the second material, and the third material.

[0074] In an exemplary embodiment, the first material, the second material, the third material and the fourth material are the same material. Specifically, in an exemplary embodiment, the first material, the second material, the third material and the fourth material can be stainless steel or a stainless steel alloy. In an alternative embodiment, the first material, the second material, the third material and the fourth material can be a polymer. In another alternative embodiment, each of the first material, the second material, the third material and the fourth material can be selected based on the function of the component they form. For example, the third material and the fourth material that form the body 248 and the tip 250, respectively, can be a material whose hardness (a measure of the resistance to local plastic deformation caused by mechanical indentation or wear) is greater than the hardness of the second material, because the body 248 and the tip 250 pierce the user's skin. Since the microneedle base 246 is bent, the second material can be a material with greater flexibility than the first material, the third material and the fourth material.

[0075] In an exemplary embodiment, each top support layer 202 of each microneedle 214 defines a slot 260 extending through the microneedle base 246 and the body 248. In the illustrated embodiment, the slot 260 does not extend into the tip 250. In an alternative embodiment, the slot 260 extends through only a portion of the body 248. In another alternative embodiment, the slot 260 extends through the microneedle base 246, the body 248, and the tip 250. However, the slot 260 may extend through any portion of each top support layer 202 of each microneedle 214 that enables the ISF sensing module 200 to operate as described herein. The slot 260 has a slot length 262 and a slot width 264. In an exemplary embodiment, the slot length 262 is substantially greater than the slot width 264, and the slot 260 forms a channel that guides the ISF to the sensor 244 to detect biomarkers, as described herein. Slot 260 extends through top support layer 202 of microneedle 214, and thus, slot 260 has a slot depth 266 approximately equal to patch layer thickness 236 of approximately 75 μm. In alternative embodiments, slot 260 may have any size and shape that enables ISF sensing module 200 to operate as described herein.

[0076] Turning now to the sensor layer 206, the sensor layer 206 includes a substrate 268, at least one circuit 270, a sensor 244, and communication and energy management components. Fig.212 is a block diagram of an exemplary electronic device architecture of a communication and energy management component. The communication and energy management component described above may include an on-chip control module 272, an off-chip control module 274, and a cable (not shown) that couples the circuit 270, the sensor 244, and / or the on-chip control module 272 to the off-chip control module 274 in a communication manner. The sensor layer 206 may include any one of the on-chip control module 272, the off-chip control module 274, and the cable. The off-chip control module 274 may be a reusable electronic device module 110, and may include a data storage device, power management, and communication components, as described herein. The on-chip control module 272 may also be referred to as an analog-digital signal module in this article. Performing analog-to-digital conversion near the sensor 244 minimizes noise and stray signals that may interfere with the signal generated by the sensor 244 and the piezoelectric voltage generated in the connecting cable. The distributed configuration of the sensor layer 206 enables the area and weight of the portion of the sensor layer 206 that is in direct contact with the skin (i.e., the on-chip control module 272) to be reduced. Specifically, the on-chip control module 272 may have a lighter weight and a thin profile so that the ISF sensing module 120 is attached to the geared cam 118. In addition, because the on-chip control module 272 is separated from the off-chip control module 274, the off-chip control module 274 may be positioned away from the sensor assembly 212. Alternatively, the on-chip control module 272 and the off-chip control module 274 are incorporated in the same component and are not far from each other. As another alternative, in some embodiments, the on-chip control module 272 and the off-chip control module 274 are far from each other, but are not coupled in a communication manner using a cable. On the contrary, in such embodiments, the on-chip control module 272 and the off-chip control module 274 communicate with each other in a wireless communication manner using any suitable wireless communication protocol.

[0077] If the off-chip control module 274 is not a reusable electronics module 110, a cable may be used to position the off-chip control module 274 away from the on-chip control module 272. For example, the off-chip control module 274 may be stored in a pocket of clothing (e.g., pants or a shirt), or may be attached to, for example, a belt or heart rate monitor strap (e.g., using a clip or hook-and-loop fastener). In an embodiment where the off-chip control module 274 is incorporated into clothing (e.g., an elastic and form-fitting garment), the cable may be a flexible conductor that is sewn or otherwise incorporated into the garment to allow the ISF sensing module 200 to be attached to a specific location, while the off-chip control module 274 is located in an inconspicuous location (e.g., on the back of a collar or on a sleeve of a shirt, on the sternum, on the hem of pants, in a waistband, in a pocket, etc.) or distributed on other parts of the garment.

[0078] In addition, in an exemplary embodiment, the off-chip control module 274 includes a memory device and a microcontroller (MCU) 280. The off-chip control module 274 may also include a wireless communication unit 282 (e.g., a Bluetooth unit), a sensor data interface unit 284, a battery unit 286, and a microneedle actuation unit 288. The battery unit 286 may be rechargeable, for example, using inductive charging. In some embodiments, the memory device 280 may be a microSD card or other data storage device that is removably inserted into or permanently installed in the off-chip control module 274.

[0079] The off-chip control module 274 may be able to wirelessly communicate with a remote computing device (e.g., a mobile computing device) using Bluetooth communication or an alternative method (such as direct Wi-Fi). In addition, the off-chip control module 274 may have a two-way communication capability, allowing the off-chip control module 274 or the remote computing device to store and recall previous data in the event of a communication failure.

[0080] In some embodiments, the off-chip control module 274 communicates with the relevant software applications installed on the computing device. The software application may include multiple functions that help users use the ISF sensing module 200. The software application can upload all data to the cloud storage system, including algorithms for analyzing trends in data, and enables users to customize data analysis. The software application can also enable data (in original form or subsequent analysis) to be displayed on the computing device. For example, in some embodiments, the software application (or the off-chip control module 274 itself) can analyze the biochemical data collected by the ISF sensing module 200. In addition, when biomarkers deviate from the expected range, the software application can generate an alarm. In addition, data can be stored as a backup on the off-chip control module 274, and downloaded to the computing device when reestablishing communication.

[0081] In an exemplary embodiment, the substrate 268 includes a patch of sensor components 212 attached to the top support layer 202 and the bottom support layer 210. Specifically, in an exemplary embodiment, the substrate 268 is formed of polyethylene terephthalate (PET) and is attached to the sensor components 212 of the top support layer 202 and the bottom patch layer 210 as described above. The circuit 270, the sensor 244, and / or the on-chip control module 272 can be printed on the substrate 268, and the substrate 268 can be attached to the sensor components 212 of the top support layer 202 and the bottom patch layer 210. In addition, after the substrate 268 has been attached to the sensor component 212 of the top support layer 202 and the bottom patch layer 210, at least a portion of the substrate can be laminated to the sensor component 212 of the top support layer 202 and the bottom patch layer 210 to maintain the position of the circuit 270, sensor 244 and / or on-chip control module 272 on the substrate 268 and / or the sensor component 212 of the top support layer 202 and the bottom patch layer 210 during use. In an alternative embodiment, the ISF sensing module 200 does not include the substrate 268. Instead, the circuit 270, sensor 244 and / or on-chip control module 272 can be printed directly on the sensor component 212 of the top support layer 202 and / or the bottom patch layer 210.

[0082] In another alternative embodiment, the circuit 270, sensor 244, and / or on-chip control module 272 are printed on both sides of the substrate 268, and the size and shape of the bottom patch layer 210 are similar to the top support layer 202, so that the circuit 270, sensor 244, and / or on-chip control module 272 are accessible on both sides of the substrate 268. That is, the substrate 268 can have the circuit 270, sensor 244, and / or on-chip control module 272 on both sides of the substrate 268, so that the ISF sensing module 200 is double-sided, thereby improving the monitoring capabilities of the ISF sensing module 200. The sensors 244 positioned on opposite sides of the substrate 268 can be configured to monitor the same biomarker or different biomarkers.

[0083] Circuit 270 communicatively couples sensor 244 to on-chip control module 272 and / or off-chip control module 274. Specifically, circuit 270 may be any circuit that transmits data from sensor 244 to on-chip control module 272 and / or off-chip control module 274.

[0084] In the illustrated embodiment, each ISF sensing module 200 includes twelve microneedles 214, and each microneedle 214 includes at least one sensor 244 positioned at least partially on a body 248 and a tip 250. Each sensor 244 is positioned on the body 248 and / or the tip 250 so that when the microneedle 214 is inserted into the skin of the user, the sensor 244 is embedded in the dermis of the user's skin. In an exemplary embodiment, each sensor 244 includes a biosensor for sensing biomarkers within the ISF. Specifically, the sensor 244 detects and measures metabolites, small molecules, proteins, ions, electrolytes, enzymes, hormones, one or more biochemical parameters, and / or any other biomarker that helps monitor and control medical conditions and / or the performance of athletes.

[0085] In the illustrated embodiment, each ISF sensing module 120 includes three microneedles 214, and each microneedle 214 includes at least one sensor 244, so that the sensor layer 206 of each ISF sensing module 120 includes a first sensor 290, a second sensor 292, and a third sensor 294. In some embodiments, the first sensor 290, the second sensor 292, and the third sensor 294 are the same sensors for detecting and measuring the same biomarker. More specifically, the first sensor 290, the second sensor 292, and the third sensor 294 can be configured to measure the same biochemical substance and report the results (data from all three sensors 290, 292, and 294 or the average of all three sensors 290, 292, and 294) to the user and / or medical professional. In an alternative embodiment, the first sensor 290, the second sensor 292, and the third sensor 294 are different sensors for detecting and measuring different biomarkers.

[0086] Fig. 22 is a circuit diagram of the sensor 244 printed on the substrate 268. Fig.15In the illustrated embodiment, each sensor 244 comprises a 2-electrode and / or 3-electrode biosensor for detecting biomarkers within the ISF. More specifically, the sensor layer 206 may include a 2-electrode biosensor 296 and / or a 3-electrode biosensor 298. The 2-electrode biosensor 296 is a 2-electrode system including a working electrode 300 and a counter / reference electrode 302 for detecting a specific biomarker. The 3-electrode biosensor 298 is a 3-electrode system including a working electrode 304, a reference electrode 306, and a counter electrode 308 for detecting a specific biomarker. The 2-electrode biosensor 296 and / or the 3-electrode biosensor 298 may detect the ISF using a variety of electroanalytical detection methods including, but not limited to, chronoamperometry, cyclic voltammetry, square wave voltammetry, and / or any other electroanalytical detection method that enables the sensor 244 to operate as described herein. In addition, the biomarker to be detected at least partially determines the type of sensor 244 embedded in the microneedle 214. Additionally, sensor 244 may include other types and / or classes of biosensors. For example, sensor 244 may include a field effect transistor biosensor (not shown) and / or any other type of sensor that enables ISF sensing module 200 to operate as described herein.

[0087] For each of the biosensors described herein, the working electrode 300 and the working electrode 304 include a biological recognition element (BRE) (not shown). For example, when the working electrodes 300 and 304 detect metabolites, the BRE includes a metabolite sensing enzyme immobilized on the surface (not shown) of the working electrode 300 and the working electrode 304. The selection of BRE and its kinetics are key to achieving a sustained balance with biomarkers within the ISF, where high binding affinity (necessary for sensing low concentrations) is generally associated with poor reversibility (multiple sensor uses). Antibodies, short peptides, aptamers, and non-natural peptide-based BREs can also be used to achieve a target on / off equilibrium rate compatible with the dynamics of fluctuations in the concentration of the target biomarker in vivo. Aptamers and short peptide BREs can replace more commonly used antibodies to selectively and specifically recognize protein and hormone biomarkers. The use of aptamers and peptides as recognition elements will reduce costs and improve the simplicity and effectiveness of biosensor manufacturing. In particular, peptide and aptamer BREs enable the binding of target analytes (compared to much larger antibodies) in close proximity to the sensor surface, providing an effective approach to overcome the challenges associated with sensing in conductive biological media such as ISF. In addition, aptamer and peptide BREs are much more stable than commonly used antibodies, providing distinct advantages for in vivo monitoring in biological fluids. Other examples of BREs include non-natural peptides that provide thermal and enzymatic stability.

[0088] like Fig. 9 , Fig.10and Fig.16 As shown in FIG. 1 , substrate 268 is positioned on sensor component 212 such that electrodes 300, 302, 304, 306, and / or 308 are positioned within slot 260, and substrate 268 and slot 260 define a channel 310 for directing ISF to electrodes 300, 302, 304, 306, and / or 308. Fig.17 As shown, the slot 260 extends through the body 248 of the top support layer 202 to form a first opening 312 and a second opening 314. Fig.16 As shown, substrate 268 is positioned on sensor component 212 so that second opening 314 is covered by substrate 268. First opening 312 remains uncovered and allows ISF to flow into channel 310. More specifically, the pressure of the ISF causes the ISF to flow into channel 310 and flow to electrodes 300, 302, 304, 306 and / or 308 to be detected and measured. Since microneedles 214 penetrate the skin of the user, cells near microneedles 214 can be stimulated by microneedles 214 and / or sensor 244. Cells near sensor 244 can respond to stimulation by producing different biomarkers that can change the ISF near microneedles 214. Therefore, if sensor 244 is in close proximity to stimulated cells, the measurement results reported by sensor 244 may have errors caused by the reaction of stimulated cells.

[0089] The slotted design of microneedle 214 reduces errors caused by stimulated cells. Specifically, electrodes 300, 302, 304, 306 and / or 308 are positioned in slots 260 and channels 310, and are not adjacent to stimulated cells. In addition, since ISF flows into channel 310, the ISF detected by electrodes 300, 302, 304, 306 and / or 308 includes ISF surrounding cells adjacent to and away from microneedle 214. Therefore, electrodes 300, 302, 304, 306 and / or 308 detect average biomarker concentrations from cells that vary in position relative to microneedle 214. In addition, guiding ISF into channel 310 enables electrodes 300, 302, 304, 306 and / or 308 to detect and measure ISF around different types of cells in the dermis. Thus, the slotted design of the microneedle 214 reduces errors caused by stimulated cells by directing the ISF into the electrodes 300 , 302 , 304 , 306 , and / or 308 .

[0090] Fig.23318 is a diagram of an ISF sensing module 200 positioned on a user's skin 316, with microneedles 214 inserted into the dermis 318 of the user's skin 316. During operation, the user attaches the ISF sensing module 200 to their skin 316 so that the microneedles 214 pierce and penetrate the epidermis 320 and dermis 318 of the user's skin 316. Specifically, when the microneedles 214 are inserted into the user's skin 316 by the microneedle actuator 108, the sensor 244 is embedded in the dermis 318 of the user's skin 316, as described above. Once inserted into the dermis 318, ISF from the vicinity of the cells surrounding the microneedles 214 flows into the channel 310 and contacts the electrodes 300, 302, 304, 306, and / or 308. The electrodes 300, 302, 304, 306, and / or 308 detect and measure at least one specific biomarker within the ISF. The electrodes 300, 302, 304, 306, and / or 308 then send electrical signals to the on-chip control module 272 and / or the off-chip control module 274. The on-chip control module 272 and / or the off-chip control module 274 may analyze the data from the electrodes 300, 302, 304, 306, and / or 308 and / or may transmit the data from the electrodes 300, 302, 304, 306, and / or 308 to a computing device. The user and / or a medical professional may then analyze the data to determine whether further medical care is needed.

[0091] Because the sensor 244 is embedded in the dermis 318, the ISF flowing to the sensor 244 is constantly replenished, and no mechanical mechanism for replenishing the ISF is required to enable the ISF sensing module 200 to operate as described herein. In addition, embedding the sensor 244 in the dermis 318 enables the ISF sensing module 200 to detect biomarkers without extracting liquid from the user's body, thereby reducing the body fluid removal and processing work generated by the detection and measurement of the biomarkers, and reducing the equipment required for measuring the biomarkers in the ISF. In addition, because the pressure of the ISF causes the ISF to flow into the channel 310, a fluid power device such as a vacuum pump is not required to continuously replenish the ISF flowing to the electrodes 300, 302, 304, 306 and / or 308. Therefore, the ISF sensing module 200 enables the detection of biomarkers while reducing the body fluid removal and processing work, and reducing the equipment required for measuring the biomarkers in the ISF.

[0092] After a predetermined amount of time, the BRE within the sensor 214 may be consumed so that the sensor 214 no longer detects biomarkers within the ISF. To continue monitoring the biomarkers within the ISF, at least one of the remote computing device, the on-chip electronics 104, and / or the reusable electronics module 110 activates at least one other microneedle actuator 108 of the plurality of microneedle actuators 108, and the wearable ISF sensing device 100 continues to monitor the user's medical condition. The microneedle actuators 108 may be activated sequentially until all of the ISF sensing modules 120 of the microneedle actuators 108 have been consumed. Once all of the ISF sensing modules 120 have been consumed, the user removes any reusable portion of the wearable ISF sensing device 100 and discards the remaining portion of the wearable ISF sensing device 100. The user then attaches a second wearable ISF sensing device 100 to their skin and attaches any reusable portion of the wearable ISF sensing device 100 to the second wearable ISF sensing device 100. The user then operates the second wearable ISF sensing device 100 as described herein.

[0093] Since the wearable ISF sensing device 100 includes a plurality of microneedle actuators 108, each of which includes an ISF sensing module 120, the wearable ISF sensing device 100 is capable of monitoring the user's medical condition over a longer period of time compared to a biosensing device having a single ISF sensing module 120. Therefore, the user does not need to replace the wearable ISF sensing device 100 as frequently as other biosensing devices. In addition, the wearable ISF sensing device 100 described herein enables consistent monitoring of ISF because the wearable ISF sensing device 100 can automatically activate another microneedle actuator 108 after the sensor 214 of the first ISF sensing module 120 has been consumed. Therefore, the wearable ISF sensing device 100 described herein enables consistent monitoring of the user's medical condition. In addition, since the wearable ISF sensing device 100 includes a plurality of microneedle actuators 108, each of which includes an ISF sensing module 120, the wearable ISF sensing device 100 reduces the number of biosensing devices consumed by the user to monitor the medical condition.

[0094] Embodiments described herein include systems and methods for wearable ISF sensing devices. The wearable ISF sensing device includes a sensor component and a plurality of microneedle actuators positioned on the sensor component. The sensor component is attached to the skin of the user. Each of the microneedle actuators includes a rigid support, a spring, a pressure head, a geared cam, an ISF sensing module, and an actuating device. The ISF sensing module is attached to the geared cam, and the pressure head, the spring, and the actuating device are configured to rotate the geared cam to insert the ISF sensing module into the skin of the user. Specifically, the actuating device is configured to keep the spring in a stored configuration until it is selectively actuated. Once the actuating device has been actuated, the spring is released from the stored configuration to push, press, or drive the pressure head against the geared cam, thereby rotating the geared cam. The rotation of the geared cam causes the ISF sensing module to rotate toward the skin of the user, inserting the ISF sensing module into the skin of the user. Then, the ISF sensing module monitors the biochemical markers of the user.

[0095] The ISF sensing module includes a plurality of layers laminated together to form a sensor component and at least one microneedle extending from the sensor component. The layers include a first support layer, a first adhesive layer, a sensor layer, a second adhesive layer, and a second support layer. The first support layer and the second support layer structurally support the sensor layer, and the first adhesive layer and the second adhesive layer laminate the first support layer and the second support layer to the sensor layer. The lamination of the layers ensures that the microneedle remains intact when inserted into the user's skin. Therefore, the microneedle of the ISF sensing module described herein is structurally stronger than previous microneedles and remains intact when monitoring biomarkers in the user's ISF.

[0096] The microneedle comprises a microneedle base, a body and a tip. The microneedle has a substantially flat or planar profile, and a slot is defined in the body of the microneedle. The slot has a first opening and a second opening. The sensor layer comprises a sensor positioned above the second opening, so that the sensor and the slot define a channel for guiding ISF to the sensor. The microneedle and the sensor are inserted into the skin of the user so that the sensor is positioned in the dermis of the user's skin. ISF flows into the channel from adjacent tissues, and the sensor detects and measures biomarkers in the ISF. The user, observer, trainer, coach and / or medical professional can then monitor a medical condition or performance / readiness metric based on the data collected by the sensor.

[0097] Since the sensor is embedded in the dermis, the ISF flowing to the sensor is continuously balanced with the surrounding ISF without the need for a mechanical mechanism to supplement the ISF. In addition, embedding the sensor in the dermis enables the ISF sensing module to detect biomarkers without extracting liquid from the user's body, thereby reducing the body fluid removal and processing work generated by the detection and measurement of biomarkers. In addition, the capillary pressure and compression force generated during insertion will cause the ISF to flow into the channel, so that there is no need for a fluid power device such as a vacuum pump or mechanical compression to supplement the ISF at the sensor. After insertion, the passive diffusion from the ISF and the balance with the ISF inside the channel supplement the ISF at the sensor. Therefore, the ISF sensing module is able to detect biomarkers while reducing body fluid removal and processing work, and reducing the equipment required to measure biomarkers in the ISF. In addition, directly measuring the ISF in the interstitial space reduces the lag time between changes in biomarker concentrations and readings.

[0098] Since the wearable ISF sensing device includes multiple microneedle actuators, the wearable ISF sensing device is able to monitor the user's medical condition over a longer period of time compared to a biosensing device with a single set of microneedles. Therefore, the user does not need to replace the wearable ISF sensing device as frequently as other biosensing devices. In addition, the wearable ISF sensing device described herein enables consistent monitoring of ISF because the wearable ISF sensing device can automatically activate another microneedle actuator after the sensor of the first microneedle actuator has been consumed. Therefore, the wearable ISF sensing device described herein enables consistent monitoring of the user's medical condition. In addition, since the wearable ISF sensing device includes multiple microneedle actuators, the wearable ISF sensing device reduces the number of biosensing devices consumed by the user to monitor the medical condition.

[0099] Exemplary technical effects of the methods, systems, and devices described herein include at least one of the following: (a) detecting biomarkers within ISF; (b) reducing body fluid clearance and handling associated with biomarker detection; (c) reducing equipment required to measure biomarkers within ISF, and (d) reducing errors associated with the detection of biomarkers within ISF.

[0100] Exemplary embodiments of wearable ISF sensing devices are described herein. These systems and methods are not limited to the specific embodiments described herein, but rather, components of the systems and / or steps of the methods may be used independently and separately from other components and / or steps described herein. For example, these methods may also be used in combination with other systems and are not limited to practice with only the systems described herein. Rather, the exemplary embodiments may be implemented and utilized in conjunction with many other systems.

[0101] Although specific features of various embodiments of the present disclosure may be shown in some drawings and not in other drawings, this is for convenience only. According to the principles of the present disclosure, any feature of a drawing may be referenced and / or claimed in combination with any feature of any other drawing.

[0102] This written description uses examples to disclose embodiments, including the best mode, and also to enable those skilled in the art to practice the embodiments, including making and using any devices or systems and performing any included methods. The patentable scope of the disclosure is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to fall within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with minor differences from the literal language of the claims.

Claims

1. A microneedle actuator (108) for monitoring interstitial fluid (ISF) of a user, the microneedle actuator (108) comprising: a rigid support member (112) defining a slot (130); a geared cam (118) positioned within the rigid support (112) and including a shaft (147) extending through the slot (130); a spring (114) positioned within the rigid support (112) and configured to rotate the geared cam (118) about the shaft (147); an ISF sensing module (120) attached to the geared cam (118) and comprising a plurality of microneedles (214), each of the plurality of microneedles (214) comprising at least one sensor (244) for detecting the ISF of the user; and an actuation device (122) attached to the rigid support (112) and the geared cam (118), wherein actuation of the actuation device (122) releases the spring (114), thereby rotating the geared cam (118) to insert the plurality of microneedles (214) into the skin of the user, and wherein the at least one sensor (244) detects a composition of the ISF of the user.

2. The microneedle actuator (108) of claim 1, wherein the spring (114) comprises at least one of a compression spring, a tension spring, a torsion spring, a coil spring, and a leaf spring.

3. The microneedle actuator (108) according to claim 1, further comprising a pressure head (116) positioned within the rigid support (112) between the spring (114) and the geared cam (118), wherein actuation of the actuating device (122) releases the spring (114) so ​​that the spring (114) presses on the pressure head (116), so that the pressure head (116) rotates the geared cam (118), and the geared cam (118) inserts the plurality of microneedles (214) into the skin of the user, and wherein the pressure head (116) comprises a curved surface (136) configured to receive a portion of the geared cam (118) and a face (134) configured to receive the spring (114).

4. The microneedle actuator (108) of claim 1, wherein the geared cam (118) comprises a body (142), a first flat surface (144), a second flat surface (146), and a plurality of gear teeth (150) extending from the body (142) and the second flat surface (146).

5. The microneedle actuator (108) of claim 4, wherein the ISF sensing module (120) is attached to the first planar surface (144).

6. The microneedle actuator (108) of claim 4, wherein the rigid support (112) defines a plurality of grooves (132), and wherein rotation of the geared cam (118) causes a gear tooth of the plurality of gear teeth (150) to rotate into a groove (132) of the plurality of grooves (132).

7. The microneedle actuator (108) of claim 6, wherein each gear tooth (150) within each groove (132) defines a pivot point about which the geared cam (118) pivots during rotation of the geared cam (118).

8. A microneedle actuator (108) according to claim 1, wherein the rigid support member (112) defines a plurality of grooves (132) imprinted in the rigid support member (112) along a first plane, and wherein the narrow groove (130) is a pair of narrow grooves defined in the rigid support member (112) to cooperatively define a second plane extending through the pair of narrow grooves (130), and the second plane is parallel to the first plane.

9. The microneedle actuator (108) of claim 8, wherein the geared cam (118) comprises a body (142) and a plurality of gear teeth (150) extending from the body (142), and wherein a first distance between a centerline of the pair of slots (130) and the first plane is the same as a radius of the body (142) of the geared cam (118).

10. The microneedle actuator (108) according to claim 1, wherein the actuating device (122) comprises a first tape (174) and a second tape (176), wherein the first tape (174) and the second tape (176) are impregnated with an adhesive material so that the first tape (174) and the second tape (176) adhere to each other, wherein the adhesive material comprises at least one of fluoropolymer wax, fatty acid amide wax, Fischer-Tropsch wax, paraffin wax, biowax, polyolefin wax and / or polyolefin waxes including eicosane, docosane, tetracosane, hexacosane, octacosane, triacontan, dotriacontane, tetratriacontane, hexatriacontane, octacosane, tetracontane, dotriacontane and / or tetratriacontane, and wherein the first tape (174) and the second tape (176) each comprise a porous hydrophobic sheet, a membrane material, paper, a textile, an adhesive-backed textile, a non-woven polymer sheet, a cast polymer sheet and / or a laser-drilled polymer sheet.

11. A microneedle actuator (108) for monitoring interstitial fluid (ISF) of a user, the microneedle actuator (108) comprising: a rigid support member (112) defining a slot (130); a geared cam (118) positioned within the rigid support (112) and including a shaft (147) extending through the slot (130); a spring (114) positioned within the rigid support (112) and configured to rotate the geared cam (118) about the shaft (147); An ISF sensing module (120) is attached to the geared cam (118), the ISF sensing module (120) comprising: A first supporting layer (202); a sensor layer (206) laminated to the first support layer (202) to form a sensor component (212); and A plurality of microneedles (214) extending from the sensor component (212), the sensor layer (206) comprising a substrate (268) and at least one sensor (290) positioned on the substrate (268), each microneedle in the plurality of microneedles (214) comprising: a microneedle base (246) extending from the sensor component (212); A body (248) extending from the microneedle base (246), the body (248) defining a slot (130) extending through the first support layer (202) of the body (248), the slot (130) defining a first opening (312) and a second opening (314), the at least one sensor (290) is positioned above the second opening (314), wherein the first opening (312), the slot (130) and the at least one sensor (244) defining a passageway (310) exposed to the environment; and a tip extending from the body (248), wherein the channel (310) is configured to direct (310) the ISF to the at least one sensor (244); and an actuation device (122) attached to the rigid support (112) and the geared cam (118), wherein actuation of the actuation device (122) releases the spring (114), thereby rotating the geared cam (118) to insert the plurality of microneedles (214) into the skin of the user, and wherein the at least one sensor (244) detects the ISF of the user.

12. The microneedle actuator (108) of claim 11, wherein the ISF sensing module (120) further comprises a second support layer (210) laminated to the first support layer (202) and the sensor layer (206), wherein the sensor layer (206) is positioned between the first support layer (202) and the second support layer (206), and wherein the first support layer (202) and the second support layer (210) structurally support the sensor layer (210).

13. The microneedle actuator (108) of claim 12, wherein the ISF sensing module (120) further comprises a second support layer (210) laminated to the sensor layer (206), a first adhesive layer (204) positioned between the first support layer (202) and the sensor layer (206), and a second adhesive layer (208) positioned between the second support layer (210) and the sensor layer (206), and wherein the first adhesive layer (204) laminates the first support layer (202) to the sensor layer (206).

14. The microneedle actuator (108) of claim 13, wherein the first adhesive layer (204) and the second adhesive layer (208) each comprise a sheet of curable adhesive.

15. The microneedle actuator (108) of claim 13, wherein the first adhesive layer (204) and the second adhesive layer (208) each comprise a pressure sensitive adhesive.

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