Sensing system including layered microprobes

Abstract

A sensing system comprises a microprobe, which comprises a layered structure and an encapsulation portion, wherein: the layered structure comprises: a sensing unit, comprising a sensor, the sensor comprising a working electrode, wherein the sensing unit has a first perimeter when viewed along the layered direction, comprises a first material having a first toughness and comprises a first side and a second side; a deformable layer, configured to deform under stress and positioned on the first side of the sensing unit; a ductile layer, positioned on the deformable layer opposite to the sensing unit and having a second perimeter when viewed along the layered direction, the first perimeter being within the second perimeter, the ductile layer comprising a second material having a second toughness greater than the first toughness; a sensor interface layer, positioned on the second side of the sensing unit; and the encapsulation portion partially encapsulates the layered structure and mechanically isolates the layered structure from the surrounding environment.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This is an International Patent Application (PCT) that is related to and claims the benefit of commonly owned and co-pending U.S. Provisional Patent Application No. 62 / 962,677, filed on January 17, 2020, and entitled “Sensing System Including Layered Microprobes,” the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The disclosure relates to sensing and sensing systems including one or more layered microprobes or microneedles and related methods. Background Art

[0004] Microsensing systems, such as sensors, mounted on microneedles, microprobes, or neural probes are often used in biology and other applications. Summary of the Invention

[0005] This summary is a high-level overview of various aspects of the invention and introduces some concepts that are further described in the detailed description below. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used in isolation to determine the scope of the claimed subject matter. The subject matter should be understood by reference to appropriate portions of the entire specification, any or all of the drawings, and each claim.

[0006] Embodiments of the disclosure relate to a sensing system comprising at least one microprobe. The microprobe comprises a layered structure comprising a sensing cell comprising at least one sensor, wherein the at least one sensor comprises a working electrode, wherein the sensing cell has a first perimeter when viewed along a layering direction of the layered structure, wherein the sensing cell comprises a first material having a first material toughness, and wherein the sensing cell comprises a first side and an opposing second side. The layered structure further comprises a deformable layer positioned on the first side of the sensing cell, wherein the deformable layer is configured to deform under stress. The layered structure further comprises a ductile layer positioned opposite the sensing cell on the deformable layer, wherein the ductile layer has a second perimeter when viewed along the layering direction of the layered structure, wherein the first perimeter is completely within the second perimeter, and wherein the ductile layer comprises a second material having a second material toughness greater than the first material toughness. The deformable layer is further configured to couple the sensing cell to the ductile layer and partially transfer strain resulting from stress applied to the sensor cell to the ductile layer. The layered structure further comprises a sensor interface layer positioned on the second side of the sensing cell. The microprobe further includes at least one encapsulation portion, wherein the at least one encapsulation portion at least partially encapsulates the layered structure, and wherein the at least one encapsulation portion is configured to isolate the layered structure from a surrounding environment.

[0007] In some embodiments, the encapsulation is configured to contain (prevent escape of) debris from at least one of the first material, the second material, the deformable layer material, or the sensor interface material.

[0008] In some embodiments, the encapsulation is at least one of: chemically inert, biocompatible, biodegradable, antifouling, hydrophobic, or hydrophilic.

[0009] In some embodiments, the encapsulation is configured to mechanically isolate the layered structure from the surrounding environment.

[0010] In some embodiments, the encapsulation is configured to electrically isolate the layered structure from the surrounding environment.

[0011] In some embodiments, the encapsulation has a thickness of 100 nanometers to 200 micrometers.

[0012] In some embodiments, the encapsulation includes an opening to the sensor interface layer.

[0013] In some embodiments, the opening is covered or filled with a hydrogel configured to increase in volume when in contact with a liquid.

[0014] In some embodiments, the encapsulation completely encapsulates the layered structure.

[0015] In some embodiments, at least a portion of the tip of the sensing unit is not encapsulated.

[0016] In some embodiments, the encapsulant layer includes polyamide, parylene, polyurethane, or a combination thereof.

[0017] In some embodiments, the sensor interface layer is at least one of: chemically inert, biocompatible, biodegradable, antifouling, hydrophobic, or hydrophilic.

[0018] In some embodiments, the sensor interface layer has a thickness of 10 nanometers to 200 microns.

[0019] In some embodiments, the sensor interface layer comprises a hydrogel.

[0020] In some embodiments, the deformable layer is an adhesive.

[0021] In some embodiments, the deformable layer includes polyurethane, silicone, resin, polyacrylate, polyamide, SU-8, polymethyl methacrylate, parylene, epoxy, silicone, or a combination thereof.

[0022] In some embodiments, the deformable layer is reinforced with a metal oxide such as aluminum oxide, silicon oxide, silicon oxynitride, or a combination thereof.

[0023] In some embodiments, the deformable layer has a thickness of 1 micron to 100 microns.

[0024] In some embodiments, the sensing unit is adhered to the extensible layer by a multi-layer structure comprising a first adhesive, a deformable material, and a second adhesive.

[0025] In some embodiments, the thickness of the deformable layer is less than the surface roughness of each of the sensing unit and the ductile layer.

[0026] In some embodiments, the deformable layer electrically isolates the sensing unit from the stretchable layer.

[0027] In some embodiments, at least one of the sensing unit and the ductile layer is encapsulated by an oxide, a metal oxide, a natural oxide, a polymer, or a combination thereof.

[0028] In some embodiments, the ductile layer includes, for example, stainless steel, cobalt, titanium, aluminum, nickel, chromium, molybdenum, tungsten, and alloys thereof.

[0029] In some embodiments, the ductile layer includes a recess in a surface adjacent to the sensing unit, wherein the sensing unit is received within and at least partially surrounded by the recess.

[0030] In some embodiments, the depth of the recess is equal to a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite the first side.

[0031] In some embodiments, the depth of the recess is greater than a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite the first side.

[0032] In some embodiments, the depth of the recess is less than a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite the first side.

[0033] In some embodiments, the sensing unit includes a shaft and a tip.

[0034] In some embodiments, the ductile layer includes a shaft and a tip.

[0035] In some embodiments, the tip of the ductile layer extends distally beyond the tip of the sensing unit such that the ductile layer is configured to absorb axial insertion forces applied thereto during use.

[0036] Embodiments of the disclosure also relate to a microprobe comprising a layered structure. The layered structure includes a sensing cell having at least one sensor, wherein the at least one sensor includes a working electrode, wherein the sensing cell has a first perimeter when viewed along a layering direction of the layered structure, wherein the sensing cell comprises a first material having a first material toughness, and wherein the sensing cell comprises a first side and an opposing second side. The layered structure also includes a deformable layer positioned on the first side of the sensing cell, wherein the deformable layer is configured to deform under stress. The layered structure also includes a ductile layer positioned opposite the sensing cell on the deformable layer, wherein the ductile layer has a second perimeter when viewed along the layering direction of the layered structure, wherein the first perimeter is completely within the second perimeter, and wherein the ductile layer comprises a second material having a second material toughness greater than the first material toughness. The deformable layer is further configured to couple the sensing cell to the ductile layer and partially transfer strain resulting from stress applied to the sensor cell to the ductile layer. The layered structure also includes a sensor interface layer positioned on the second side of the sensing cell. The microprobe further includes at least one encapsulation portion, wherein the at least one encapsulation portion at least partially encapsulates the layered structure, and wherein the at least one encapsulation portion is configured to isolate the layered structure from a surrounding environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Some embodiments of the disclosure are described herein with reference to the accompanying drawings, by way of example only. With specific detailed reference now to the accompanying drawings, the details shown are provided by way of example and are used for the purpose of illustrative discussion of embodiments of the present invention. In this regard, the description in conjunction with the accompanying drawings makes it clear to those skilled in the art how to practice embodiments of the present invention.

[0038] Figure 1A is a top view of a sensing system including a layered microprobe array according to an exemplary embodiment of the disclosure;

[0039] Figure 1B is a perspective view of a patch according to an exemplary aspect of the disclosure, the patch being mounted on the skin and including a sensing system having layered microprobes;

[0040] Figure 2 is a cross-sectional view of a microprobe including a layered structure according to an exemplary embodiment of the disclosure;

[0041] Figure 3 is a top view of a sensing unit shaft and tip according to an exemplary embodiment of the disclosure, obtained using a scanning electron microscope;

[0042] FIG4 is a top view of a microprobe shaft and tip according to a first exemplary embodiment of the disclosure;

[0043] 5 is a top view of a microprobe shaft and tip according to a second exemplary embodiment of the disclosure;

[0044] 6 is a top view of a microprobe shaft and tip according to a third exemplary embodiment of the disclosure;

[0045] Figure 7 is a perspective view of a layered microprojection array having various geometric shapes according to an exemplary embodiment of the disclosure;

[0046] Figure 8 is a cross-sectional view of a tip of a sensing unit and a tip of a ductile layer according to a first exemplary embodiment of the disclosure;

[0047] Figure 9 is a cross-sectional view of a sensing unit tip and a ductile layer tip according to a second exemplary embodiment of the disclosure;

[0048] Figure 10 is a cross-sectional view of a sensing unit tip and a ductile layer tip according to a third exemplary embodiment of the disclosure;

[0049] Figure 11 is a cross-sectional view of a sensing unit tip and a ductile layer tip according to a fourth exemplary embodiment of the disclosure;

[0050] FIG12 is a cross-sectional view of a sensing unit and a ductile layer according to a first exemplary embodiment of the disclosure;

[0051] FIG13 is a cross-sectional view of a sensing unit and a ductile layer according to a second exemplary embodiment of the disclosure;

[0052] FIG14 is a cross-sectional view of a sensing unit and a stretchable layer according to a third exemplary embodiment of the disclosure;

[0053] FIG15 is a side cross-sectional view of a microprobe according to an exemplary embodiment of the disclosure;

[0054] FIG16 is a front cross-sectional view of the microprobe of FIG15 according to an exemplary embodiment of the disclosure;

[0055] 17 is a cross-sectional view of a portion of a tip and a microprobe shaft according to a first exemplary embodiment of the disclosure;

[0056] 18 is a cross-sectional view of a portion of a tip and microprobe shaft according to a second exemplary embodiment of the disclosure;

[0057] 19 is a cross-sectional view of a portion of a tip and a microprobe shaft according to a third exemplary embodiment of the disclosure;

[0058] FIG20 is a cross-sectional view of a portion of a tip and a microprobe shaft according to a fourth exemplary embodiment of the disclosure; and

[0059] Figure 21 is a cross-sectional view of a portion of a tip and a microprobe shaft according to a fifth exemplary embodiment of the disclosure. DETAILED DESCRIPTION

[0060] The following description of the preferred embodiments is merely exemplary in nature and is not intended to limit the present invention, its application or use in any way. As used in the full text, scope is used as a shorthand for describing each value and all values within the scope. Any value within the scope can be selected as the endpoint of the scope. In addition, all references cited herein are incorporated herein by reference in their entirety. In the case of conflict between the definition of the open text and the reference cited, the open text shall prevail.

[0061] The description of the illustrative embodiments according to the principles of the present invention is intended to be read in conjunction with the accompanying drawings, which are considered a part of the entire written description. In the description of the embodiments of the invention disclosed herein, any reference to direction or orientation is intended only to facilitate the description and is not intended to limit the scope of the invention in any way.

[0062] Relative terms such as "lower," "upper," "horizontal," "vertical," "above," "below," "upward," "downward," "left," "right," "top," and "bottom," and their derivatives (e.g., "horizontally," "downwardly," "upwardly," etc.), should be interpreted as referring to the orientation as described or as shown in the figures being discussed. These relative terms are for convenience of description only and do not require that the device be constructed or operated in a particular orientation unless expressly stated.

[0063] As used herein, the term "proximal" refers to in a direction toward a user of a device or system, while the term "distal" refers to in a direction away from the user.

[0064] Terms such as “attach,” “attach,” “connect,” “couple,” “interconnect,” “mount,” and the like refer to relationships wherein structures are fixed or attached to one another either directly or indirectly through intermediate structures, as well as removable or rigid attachments or relationships, unless expressly described otherwise.

[0065] As used in the specification and claims, the singular form "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0066] As the invention can assume various alternative orientations, spatial or directional terms such as "left", "right", "inner", "outer", "above", "below", etc. should not be considered limiting.

[0067] All numbers used in the specification and claims are to be understood in all instances as being modified by the term “about.” The term “about” means a range of plus or minus ten percent of the stated value.

[0068] Unless otherwise indicated, all ranges or ratios disclosed herein are to be understood to include any and all subranges or subratios encompassed therein. For example, a range or ratio of "1 to 10" is to be understood to include any and all subranges between (and including) a minimum of 1 and a maximum of 10; that is, all subranges or subratios starting with a minimum of 1 or greater and ending with a maximum of 10 or less, such as, but not limited to, 1 to 6.1, 3.5 to 7.8, and 5.5 to 10.

[0069] The terms "first," "second," etc. are not intended to refer to any particular sequential or chronological order, but rather to different conditions, properties, or elements.

[0070] All documents mentioned herein are "incorporated by reference" in their entirety.

[0071] The term "at least" means "greater than or equal to." The term "not greater than" means "less than or equal to."

[0072] The term "comprising" is synonymous with "including."

[0073] As used herein, the term "microprobe" is interchangeable with the terms "microneedle" and "neural probe."

[0074] As used herein, the term "working electrode" is generally an electrode deposited with a metal, such as gold, silver, tin, zinc, copper, cadmium, chromium, nickel, platinum, palladium, rhodium, tantalum, titanium, and titanium nitride, that is connected to a voltage source and at which a redox reaction can occur in an electrochemical sensor.

[0075] As used herein, the term "material toughness" is defined as the energy that can be absorbed per unit volume before fracture.

[0076] As used herein, the term "zero debris" process is defined as a process that produces minimal, near zero, or zero debris. The design of the microprobe is to support a zero debris process, for example, with an encapsulation or by mechanically protecting the brittle material tip and / or by providing a layered structure with compliant materials that can reduce forces and torques on the brittle material.

[0077] As used herein, the term "tip" is defined as the sharp, narrow distal portion of a unit, where the unit may be a microprobe, a sensing unit, a layered structure, or a stretchable layer.

[0078] As used herein, the term "distal end" is defined as the furthest point or line of a unit. For example, the distal end of the tip of a microprojection is the portion of the microprojection that first contacts the skin.

[0079] As used herein, the term "axis" is defined as the portion of a cell that connects its tip to its base. In some embodiments, the tip and axis can be distinguished by a change in geometry. In some cases, the tip and axis converge geometrically so that there is no precise line separating the two.

[0080] For biological and other applications, it is often necessary to use microsensing systems, such as sensors, fabricated or mounted on microneedles, microprobes, or neural probes. It is advantageous to design chip-based sensor systems, which include the sensor and the structure on which the sensor is mounted, and which can be manufactured using standard semiconductor manufacturing processes. In some applications, it is beneficial to place the sensor element as close as possible to the medium being sensed. In the case of chip-based sensor systems, the sensing element can be placed near the tip of the microprobe, allowing for tissue insertion and placement of the sensing element.

[0081] During use, production and / or handling, forces or torques are applied or generated on the chip-based sensor systems and microneedles. For example, Figure 1B As shown, in a chip-based sensor system, for example, an exemplary sensing system 10 having a microprobe 100, the microprobe is inserted through the skin and penetrates the epidermis via, for example, a patch 20 mounted on the skin. During the period when the patch is provided and the microprobe is partially inserted through the epidermis and / or dermis, or while the patch is worn, forces and torques (given by the microprobe) are applied due to, for example, limb movement and / or muscle movement relative to the patch, and when the patch is removed from the skin. Figure 1B ) is applied to the microprobe.

[0082] Generally, the thinner the microprobe and the smaller its size, the less pain is felt during microneedle insertion. This reduction in pain is due to the lower insertion force required for the microprobe to penetrate the skin and the overall smaller number of nerve endings affected by such insertion. However, the mechanical, dimensional, and shape requirements of the microprobe structure can vary depending on the application and often include conflicting design requirements.

[0083] In one example, in order to minimize the insertion force, the microprobe must have a pointed and sharp tip. However, the microprobe is typically formed of a brittle material (eg, silicon), wherein the pointed and sharp tip may not be able to withstand the required insertion force.

[0084] In another example, it may be beneficial to position the sensor element near the microprobe tip to improve sensing, which dictates the shape and minimum dimensions of the microprobe tip. These shape and dimension requirements may conflict with those required to minimize pain during microprobe insertion.

[0085] In addition, material properties are an important contribution to microprobe design. Specifically, because most chip-based sensor systems are made of brittle materials, the size and shape of the microprobe must be increased to form a mechanically reliable structure. Microprobe mechanical reliability is an important design concern. In particular, because microprobe fragments or traces may be toxic or otherwise harmful, the design of the microprobe must ensure that its parts will not break and may break during handling, insertion, application and / or removal.

[0086] The disclosure relates to a novel and reliable sensing system comprising a layered microprobe with a mechanically robust microprobe sensor that can be fabricated using standard semiconductor manufacturing processes. The described sensing system is configured to withstand forces and torques that may be applied or induced during use and handling while minimizing pain during insertion. Furthermore, the sensing system ensures that insertion, application, and removal of the microprobe is a "zero-fragmentation" process.

[0087] As mentioned above, Figure 1A A sensing system 10 is depicted. Figure 1A In the embodiment of the present invention, the sensing system 10 includes a planar array 150 having a base 155 and a plurality of layered microprobes 100. The sensing system 10 also includes electrical components, including a connector 160 and traces 165. However, in other embodiments, the sensing system 10 includes more or less than six layered microprobes. In other embodiments, the sensing system 10 includes a single layered microprobe 100.

[0088] In some embodiments, the sensing system 10 can be integrated into a patch that is worn on the skin for a period of time. Figure 1B An exemplary sensor patch 20 is depicted that includes a sensing system 10 having at least one layered microprobe 100 that is inserted into a user's skin 30. In some embodiments, the sensor patch 20 includes a housing or cover that houses the insertion system, power unit, and electronics. Figure 1B Also depicted are forces F1, F2 and torques T1, T2 that may be applied to patch 20 and microprobe 100 during insertion. Specifically, for example, during insertion and installation, force F1 and torque T1 act on the patch, while force F2 and torque T2 are reaction forces acting on microprobe 100 in the skin due to F1 and T1.

[0089] Figure 2Depicted is a microprobe 100 having a layered structure 101 including a sensing unit 102, a stretchable layer 104, a deformable layer 106, and a sensor interface layer 108. The microprobe 100 also includes at least one encapsulating portion 110 that at least partially encapsulates the layered structure 101 of the microprobe 100, as will be described in further detail below.

[0090] According to some aspects of the disclosure, sensing unit 102 includes at least one sensor 112. For example, in some embodiments, sensor 112 is a field effect transistor (FET)-based sensor comprising a working electrode. In some embodiments, sensor 112 is a silicon-based FET sensor. In other embodiments, sensor 112 is any type of electrochemical sensor, biosensor, temperature sensor, photosensor, acoustic sensor, impedance sensor, electromagnetic sensor, magnetic sensor, or radiation sensor.

[0091] like Figure 3 , in some embodiments, the sensing unit 102 is shaped for insertion into the skin of a subject. Specifically, in some embodiments, the sensing unit 102 includes a base 113 and an elongated shaft 114 extending to a distal tip 116. The distal tip 116 can have a variety of configurations, as will be described in further detail below.

[0092] In some embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.3 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.05 mm and 0.3 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.1 mm and 0.3 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.15 mm and 0.3 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.1 mm and 0.3 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.25 mm and 0.3 mm.

[0093] In some embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.25 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.2 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.15 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.1 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.01 mm and 0.05 mm.

[0094] In some embodiments, the thickness of the sensing unit 102 is between 0.05 mm and 0.25 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.1 mm and 0.15 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.1 mm and 0.25 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.15 mm and 0.2 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.05 mm and 0.25 mm. In other embodiments, the thickness of the sensing unit 102 is between 0.05 mm and 0.1 mm.

[0095] Traditionally, semiconductor-based sensing units include brittle materials. For example, in some embodiments, the brittle material can be any semiconductor material, such as silicon (Si), germanium (Ge), and tin (Sn) in column IV of the periodic table, and selenium (Se) and tellurium (Te) in column VI, as well as compound semiconductors composed of two or more elements (e.g., gallium arsenide (GaAs)) or the ternary compound mercury indium telluride (Hgln2Te4). As well as semiconductor oxides (silicon oxide) and metal oxides (aluminum oxide), semiconductor metal oxides (zinc oxide). These sensing units typically have sharp tips for skin insertion. However, the silicon (Si) building material of such sensing units is brittle, so that small forces or torques will cause the Si to crack, which may result in fractures and release Si fragments. Sharp Si tips are generally unable to withstand axial or other external forces such as those required for skin insertion without cracking or breaking, thereby potentially leaving behind microscopic debris or fragments. In addition, silicon-based tips are very difficult to manufacture and sharpen to a sharp tip.

[0096] To prevent the brittle Si from cracking and / or breaking, in some embodiments, the Si-based sensing unit 102 is mounted on a ductile layer 104. In some embodiments, the ductile layer 104 comprises a material capable of absorbing most of the external forces applied to the microprobe 100 during operation and insertion. In some embodiments, the ductile layer 104 comprises, for example, any metal, metal alloy, or composite material. In some embodiments, the ductile layer 104 comprises stainless steel. In some embodiments, the material toughness of the ductile layer material is significantly greater than the material toughness of the silicon-based sensing unit, such that the combined structure of the sensing unit 102 and the ductile layer 104 can withstand higher external forces / torques than either of the individual materials alone. For example, in some embodiments, the material toughness of the ductile layer material is orders of magnitude greater than the material toughness of the sensing unit material. Thus, the ductile layer 104 serves to support the brittle sensing unit 102, enabling the functionality of such a sensing unit microstructure made of such a brittle material to be realized. Additionally, the combined toughness of the sensing unit 102 and the ductile layer 104 allows for thinner microprobe designs than microprobes using a brittle material (eg, Si) for the sensing unit 102 alone.

[0097] As described above, in some embodiments, the ductile layer 104 is configured to absorb forces and torques applied to the microprobe 100 during its use and / or handling. Thus, the ductile layer 104 is shaped to reduce or distribute the forces and torques applied to the microprobe 100 during use and / or handling. Specifically, as depicted in FIG4 , the ductile layer 104 substantially traces the shape of the sensing unit 102 in some planes, thereby providing support for the sensing unit 102, while being shaped to provide protection in other aspects.

[0098] See Figures 4 to Figure 7 In an exemplary embodiment, the ductile layer 104 includes an elongated shaft 120 extending from a base 121 of the ductile layer 104 to a tip 122 that partially coincides with the sensing unit 102. The shafts 114, 120 of the sensing unit 102 and the ductile layer 104 together form an axis 124 of the layered structure 101, as shown. Figure 7 In some embodiments, the shaft 114 of the sensing unit is connected to the shaft 120 of the extensible layer 104 along its entire length so as to provide support to the sensing unit 102 along its length so that the sensing unit 102 is mechanically constrained, thereby minimizing the forces acting on the sensing unit shaft 120. In addition, in some embodiments, when the sensing unit 102 is moved along the layering direction D of the layered structure 101, the sensing unit 102 is mechanically constrained. L ( Figure 2 When viewed along the layering direction D of the layered structure 101, the ductile layer 104 has an increased area relative to the sensing unit 102. L When observed, the sensing unit 102 has a first perimeter P S , and when along the layering direction D of the layered structure 101 L When observed, the ductile layer 104 has a second perimeter P D , so that the first perimeter P S Completely on the second perimeter P D 4 to 6 depict various shapes and sizes of the ductile layer 104 with the sensing unit 102 attached thereto.

[0099] In the first exemplary embodiment depicted in FIG. 4 , when the delamination direction D L When viewed, the width of the ductile layer 104 is substantially the same as the width of the sensing cell 102. However, the shaft 120 and / or tip 122 of the ductile layer 104 is longer than that of the sensing cell 102, such that the ductile layer 104 extends beyond the distal end 118 of the sensing cell 102.

[0100] In the second exemplary embodiment depicted in FIG. 5 , when the delamination direction D LWhen viewed, the width of the ductile layer 104 tapers toward its distal end. However, as seen in the figure, the width of the ductile layer 104 is greater than the width of the sensing element axis 114 at the proximal base of the ductile layer axis 120.

[0101] In the third exemplary embodiment depicted in FIG. 6 , when the layering direction D L When viewed, the width of the ductile layer 104 is substantially uniform for a portion and then tapers toward its distal end. However, the width of the ductile layer along its entire length is greater than the width of the sensing unit 102.

[0102] In some embodiments, the shape of the ductile layer 104 can be customized based on the application to protect the tip of the sensing unit 102 from foreseeable and / or unforeseeable forces that may cause cracking or fracture. Specifically, as described above, in some embodiments, the distal portion of the ductile layer 104 extends beyond the distal end 118 of the tip 116 of the sensing unit 102. In these embodiments, because the ductile layer 104 extends distally beyond the distal end 118 of the sensing unit 102, the ductile layer 104 is inserted into the skin before the sensing unit 102, thereby protecting the sensing unit 102 from axial and lateral insertion forces and minimizing the risk of fracture of the sensing unit tip 116. Figures 7 to 11 Various exemplary designs are depicted in which the ductile layer 104 is shaped to protect the sensing unit tip 116 and distal end 118, as will be described in further detail below.

[0103] In some embodiments, for example Figures 8 and 9 , the tips 116, 122 of a respective one of the sensing unit 102 and the ductile layer 104 are sharpened for insertion into the skin of a subject. In this embodiment, the ductile layer tip 122 is configured to protrude or extend beyond the distal end 118 of the sensing unit 102. Thus, the ductile layer 104, rather than the sensing unit 102, is first subjected to the majority of the insertion force. Furthermore, because the ductile layer 104 is inserted into the skin before the sensing unit 102, the ductile layer 104 forms an initial hole or opening in the skin. As a result, the tip 116 of the sensing unit 102 is inserted into the previously formed hole, minimizing the axial force applied thereto, thereby reducing the risk of cracking, breaking, or shattering the relatively brittle sensing unit 102. Figure 7 A perspective view of a layered structure shaft 124a having similar tip 116, 122 configurations is depicted.

[0104] In other embodiments, for example Figures 10 and 11In the depicted embodiments, the tip 116 of the sensing element 102 is shielded in two planes from potential insertion / handling forces of the ductile layer 104. First, the ductile layer 104 includes a sharp tip 122 that extends beyond the distal end 118 of the sensing element 102, as shown in FIG. Figure 8 and Figure 10 Second, the ductile layer 104 is arranged in the layering direction D L The upper portion covers or surrounds the distal end 118 or face of the sensing unit tip 116. Thus, the tip 116 of the sensing unit 102 is almost completely shielded from axial insertion forces because the ductile layer 104 alone creates and widens the opening in the subject's skin. Figure 7 A perspective view of a layered structure shaft 124b is depicted having a similar tip 116, 122 configuration that provides complete shielding of the tip 116 from axial insertion forces.

[0105] In some embodiments, the sensing cell 102 is also protected by the stretch layer 104 on its lateral sides 142, as depicted in Figures 12 to 14. Specifically, the stretch layer 104 covers at least a portion of the lateral sides of the sensing cell shaft 114 and the tip 116 to minimize oblique or lateral forces applied thereto during handling and use. In some embodiments, the stretch layer 104 includes a recess 134 in a surface 136 thereof adjacent to the sensing cell 102, such that the sensing cell 102 is received within and at least partially surrounded by the recess 134. In some embodiments, the recess 134 has a depth D that is equal to a dimension W between a first side 126 of the sensing cell 102 adjacent to the stretch layer 104 and a second side 128 of the sensing cell 102 that is opposite (e.g., opposite) the first side 126, as depicted in Figure 12. In other embodiments, recess 134 has a depth D that is less than dimension W of sensing cell 102, as depicted in FIG13. In these embodiments, as can be seen in FIG13, ductile layer 104 covers only a portion of the side surface of sensing cell 102. In other embodiments, recess 134 has a depth D that is greater than dimension W of sensing cell 102, as depicted in FIG14. In these embodiments, as can be seen in FIG14, ductile layer 104 covers and extends beyond the side surface of sensing cell 102. Figure 7 Depicted is a perspective view of a layered structure shaft 124c having a tip 116, 122 configuration protecting the tip 116 on the lateral side. Note that Figure 7 An array of layered microprobes 100 having different microprobe designs is depicted. In other embodiments, each microprobe 100 of the array will have the same design.

[0106] In some embodiments, the length of the ductile layer, i.e., the dimension from the base 121 to the tip 122 of the ductile layer 104, is between 0.8 mm and 2.0 mm. In other embodiments, the length of the ductile layer 104 is between 0.8 mm and 1.8 mm. In other embodiments, the length of the ductile layer 104 is between 0.8 mm and 1.6 mm. In other embodiments, the length of the ductile layer 104 is between 0.8 mm and 1.4 mm. In other embodiments, the length of the ductile layer 104 is between 0.8 mm and 1.2 mm. In other embodiments, the length of the ductile layer 104 is between 0.8 mm and 1.0 mm.

[0107] In some embodiments, the ductile layer 104 has a length of 1.0 mm to 2.0 mm.

[0108] In other embodiments, the length of the ductile layer 104 is between 1.2 mm and 2.0 mm. In other embodiments, the length of the ductile layer 104 is between 1.4 mm and 2.0 mm. In other embodiments, the length of the ductile layer 104 is between 1.6 mm and 2.0 mm. In other embodiments, the length of the ductile layer 104 is between 1.8 mm and 2.0 mm.

[0109] In some embodiments, the extensible layer 104 has a length of 1.2 mm to 1.6 mm.

[0110] In other embodiments, the length of the ductile layer 104 is 1.0 mm to 1.4 mm. In other embodiments, the length of the ductile layer 104 is 1.4 mm to 1.6 mm. In other embodiments, the length of the ductile layer 104 is 1.6 mm to 1.8 mm. In other embodiments, the length of the ductile layer 104 is 1.2 mm to 1.8 mm.

[0111] In some embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.3 mm. In other embodiments, the ductile layer 104 has a thickness of 0.05 mm to 0.3 mm. In other embodiments, the ductile layer 104 has a thickness of 0.1 mm to 0.3 mm. In other embodiments, the ductile layer 104 has a thickness of 0.15 mm to 0.3 mm. In other embodiments, the ductile layer 104 has a thickness of 0.1 mm to 0.3 mm. In other embodiments, the ductile layer 104 has a thickness of 0.25 mm to 0.3 mm.

[0112] In some embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.25 mm. In other embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.2 mm. In other embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.15 mm. In other embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.1 mm. In other embodiments, the ductile layer 104 has a thickness of 0.01 mm to 0.05 mm.

[0113] In some embodiments, the ductile layer 104 has a thickness of 0.05 mm to 0.25 mm. In other embodiments, the ductile layer 104 has a thickness of 0.1 mm to 0.15 mm. In other embodiments, the ductile layer 104 has a thickness of 0.1 mm to 0.25 mm. In other embodiments, the ductile layer 104 has a thickness of 0.15 mm to 0.2 mm. In other embodiments, the ductile layer 104 has a thickness of 0.15 mm to 0.25 mm. In other embodiments, the ductile layer 104 has a thickness of 0.05 mm to 0.1 mm.

[0114] In the above exemplary configuration, the width and thickness of the Si of the sensing unit 102 can be reduced due to the reduction in external forces and torques applied thereto. Thus, in some embodiments, the combined thickness and / or width of the sensing unit 102 and the ductile layer 104 can be less than the thickness and / or width required for the sensing unit alone to withstand handling and insertion forces. These smaller dimensions are beneficial because they allow for insertion into the skin or other tissue with less force, resulting in less pain.

[0115] In some embodiments, the layered structure of the microprobe 100 includes a deformable layer 106 positioned on the first side 126 of the sensing cell 102, between the sensing cell 102 and the ductile layer 104. In some embodiments, the deformable layer 106 is also positioned on the lateral side 142 of the sensing cell 102. As used herein, the deformable layer 106 is defined as a layer comprising a material having sufficient material properties (e.g., elasticity) to perform at least one desired function (e.g., deform under stress applied to the sensing system 10) during normal operation of the sensing system 10. In some embodiments, the deformable layer 106 electrically isolates the Si of the sensing cell 102 from the material of the ductile layer 104. In some embodiments, the ductile layer 104 shields the sensing cell 102 from electrical noise and / or serves as a ground for the at least one sensor 112. In other embodiments, where it is preferred to have the sensing cell 102 and the ductile layer 104 in contact with each other, for example to precisely position the sensing cell 102 and the ductile layer 104 relative to each other when there is less process control over the thickness of the deformable layer 106, recesses or channels can be incorporated into the surfaces of the Si of the ductile layer 104 and the sensing cell 102. The deformable layer 106 can then be positioned within the channels while the remaining portions of the sensing cell 102 and the surface of the ductile layer 104 are in physical contact.

[0116] In some embodiments, the deformable layer 106 comprises, for example, a polymeric material such as polyurethane, silicone, polyacrylate or methacrylate, polymethyl methacrylate, polyamide, SU-8, parylene, or epoxy resin, polydimethylsiloxane. In some embodiments, the deformable layer 106 is reinforced with a metal oxide (e.g., aluminum oxide), silicon oxide, or silicon oxynitride. In some embodiments, the deformable layer 106 comprises a viscoelastic material, such as an amorphous polymer, a semi-crystalline polymer, or a biopolymer.

[0117] In some embodiments, the deformable layer 106 is an adhesive. In some embodiments, the deformable layer 106 includes a first adhesive, a deformable material, and a second adhesive. Specifically, in some embodiments, the deformable layer 106 includes a deformable material positioned between the first adhesive and the second adhesive.

[0118] In some embodiments, the deformable layer 106 has a thickness of 1 micron to 100 microns. In other embodiments, the deformable layer 106 has a thickness of 5 microns to 100 microns. In other embodiments, the deformable layer 106 has a thickness of 10 microns to 100 microns. In other embodiments, the deformable layer 106 has a thickness of 50 microns to 100 microns. In other embodiments, the deformable layer 106 has a thickness of 90 microns to 100 microns. In other embodiments, the deformable layer 106 has a thickness of 95 microns to 100 microns.

[0119] In some embodiments, the thickness of the deformable layer 106 is between 1 micron and 100 microns. In other embodiments, the thickness of the deformable layer 106 is between 1 micron and 95 microns. In other embodiments, the thickness of the deformable layer 106 is between 1 micron and 75 microns. In other embodiments, the thickness of the deformable layer 106 is between 1 micron and 50 microns. In other embodiments, the thickness of the deformable layer 106 is between 1 micron and 10 microns. In other embodiments, the thickness of the deformable layer 106 is between 1 micron and 5 microns.

[0120] In some embodiments, the deformable layer 106 has a thickness of 5 to 10 microns. In other embodiments, the deformable layer 106 has a thickness of 10 to 50 microns. In other embodiments, the deformable layer 106 has a thickness of 50 to 75 microns. In other embodiments, the deformable layer 106 has a thickness of 5 to 50 microns. In other embodiments, the deformable layer 106 has a thickness of 10 to 95 microns. In other embodiments, the deformable layer 106 has a thickness of 25 to 50 microns.

[0121] In some embodiments, the thickness of the deformable layer 106 is greater than the larger of the surface roughness Ra of the sensing unit 102 and the surface roughness Ra of the ductile layer 104 , such that the sensing unit 102 and the ductile layer 104 do not contact each other.

[0122] In some embodiments, the layered structure of the microprobe 100 further includes a sensor interface layer 108. In some embodiments, the sensor interface layer 108 provides specific functionality to the sensor 112, such as analyte specificity. Specifically, the sensor interface layer 108 may include enzyme antibodies, small molecules, and hydrogels. In some embodiments, the sensor interface layer also provides a barrier between the sensor 112 and the surrounding environment. In some embodiments, the sensor interface layer 108 is biodegradable and changes properties over time or its application life. Figure 2 , the sensor interface layer 108 is positioned on the second side 128 of the sensing cell 102 and opposite the first side 126. In some embodiments, the sensor interface layer 108 is in contact with the material of the sensing cell 102 (e.g., Si) and components of the sensor 112. In one embodiment, the sensor interface layer 108 is applied to the sensing cell 102 as part of the sensor manufacturing process using a semiconductor coating process such as spin coating, spray coating, brush coating, dipping, chemical vapor deposition, or physical vapor deposition.

[0123] In some embodiments, the sensor interface layer 108 comprises, for example, polyamide, polyurethane, or other materials. In some embodiments, the sensor interface layer 108 comprises a material having high tensile strength. In other embodiments, the sensor interface layer 108 comprises a flexible material.

[0124] In some embodiments, the material of sensor interface layer 108 allows for patterning to form planar structures including gaps, holes, openings, vias, traces, crevices, or channels. In some embodiments, the openings or gaps are circular, oval, rectangular, or other shapes. In some embodiments, the openings are located over portions of sensor 112. In some embodiments, the openings are located over electrical, electrochemical, or optoelectronic components of sensor 112 (e.g., electrodes, conductive traces, or nanowires). In some embodiments, the openings are located over portions of field effect transistor sensors.

[0125] In some embodiments, the sensor interface layer 108 will be one or more of the following: chemically inert, biocompatible, biodegradable, antifouling, hydrophobic, hydrophilic, or have a low coefficient of friction.

[0126] In some embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 200 microns. In other embodiments, the sensor interface layer 108 has a thickness of 100 nanometers to 200 microns. In other embodiments, the sensor interface layer 108 has a thickness of 1 micron to 200 microns. In other embodiments, the sensor interface layer 108 has a thickness of 10 microns to 200 microns. In other embodiments, the sensor interface layer 108 has a thickness of 50 microns to 200 microns. In other embodiments, the sensor interface layer 108 has a thickness of 100 microns to 200 microns.

[0127] In some embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 150 micrometers. In other embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 100 micrometers. In other embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 50 micrometers. In other embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 10 micrometers. In other embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 1 micrometer. In other embodiments, the sensor interface layer 108 has a thickness of 10 nanometers to 100 nanometers.

[0128] In some embodiments, the sensor interface layer 108 has a thickness of 100 nanometers to 1 micron. In other embodiments, the sensor interface layer 108 has a thickness of 1 micron to 10 microns. In other embodiments, the sensor interface layer 108 has a thickness of 10 microns to 50 microns. In other embodiments, the sensor interface layer 108 has a thickness of 50 microns to 100 microns.

[0129] In some embodiments, as depicted in FIG15-16 , the sensor interface layer 108 covers only the sensor 112 of the sensing unit 102. Specifically, when the layer direction D L When viewed from above, the perimeter of the sensor interface layer 108 is substantially the same as the perimeter of the sensor 112, such that other portions of the sensing unit 102 are not covered by the sensor interface layer 108. In some embodiments, the sensor interface layer 108 covers the sensor 112 of the sensing unit 102 and a portion of the sensing unit 102. Specifically, when the sensor interface layer 108 is disposed in the layer direction D L When viewed from above, the perimeter of the sensor interface layer 108 is smaller than the perimeter of the sensor.

[0130] In some embodiments, as Figure 2 , the microprobe 100 includes at least one enclosure 110 that at least partially encapsulates the layered structure of the microprobe 100. In some embodiments, the enclosure 110 is configured to contain any debris that may be formed by (e.g., may originate from) the components of the layered structure encapsulated therein. In some embodiments, the enclosure 110 is also configured to ensure that any debris formed by the layered structure can be removed using the sensing system 10 during removal from the skin of a subject.

[0131] In some embodiments, the enclosure 110 is designed to isolate the microprobe components from the surrounding environment to increase their useful life. In some embodiments, the enclosure 110 provides electrical isolation. In other embodiments, the enclosure 110 provides mechanical or spatial isolation, but does not provide electrical isolation. In some embodiments, the enclosure 110 provides a uniform coefficient of friction on all aspects of the surface of the microprobe 100. The uniform coefficient of friction on all aspects of the microprobe surface can reduce asymmetric lateral forces that may cause buckling or twisting of the microprobe shaft 124. In other embodiments, the enclosure 110 provides mechanical isolation but allows liquids, gases, chemicals and / or biochemicals to pass through or diffuse.

[0132] In some embodiments, encapsulation 110 partially encapsulates layered structure 101. For example, in some embodiments, encapsulation 110 covers 10% to 99% of the surface of layered structure 101. In other embodiments, encapsulation 110 covers 20% to 99% of layered structure 101. In other embodiments, encapsulation 110 covers 25% to 99% of layered structure 101. In other embodiments, encapsulation 110 covers 50% to 99% of layered structure 101. In other embodiments, encapsulation 110 covers 75% to 99% of layered structure 101. In other embodiments, encapsulation 110 covers 90% to 99% of layered structure 101.

[0133] In some embodiments, encapsulation 110 covers 10% to 90% of layered structure 101. In other embodiments, encapsulation 110 covers 10% to 75% of layered structure 101. In other embodiments, encapsulation 110 covers 10% to 50% of layered structure 101. In other embodiments, encapsulation 110 covers 10% to 25% of layered structure 101. In other embodiments, encapsulation 110 covers 10% to 20% of layered structure 101.

[0134] In some embodiments, encapsulation 110 covers 20% to 90% of layered structure 101. In other embodiments, encapsulation 110 covers 25% to 75% of layered structure 101. In other embodiments, encapsulation 110 covers 50% to 75% of layered structure 101. In other embodiments, encapsulation 110 covers 20% to 5% of layered structure 101. In other embodiments, encapsulation 110 covers 75% to 90% of layered structure 101.

[0135] In some embodiments, encapsulating portion 110 encapsulates portions of some surfaces of layered structure 101. In other embodiments, encapsulating portion 110 encapsulates portions of the top surface of layered structure 101. In other embodiments, encapsulating portion 110 encapsulates portions of the top and side surfaces of layered structure 101. In further embodiments, encapsulating portion 110 encapsulates the entire layered structure 101 except for a portion of its tip 122, as will be described in further detail below.

[0136] In some embodiments, encapsulation 110 includes a hydrogel located in a portion that increases in volume when in contact with a liquid environment. For example, in some embodiments, encapsulation 110 includes hydrogel in a fixed region surrounding sensor 112. In some embodiments, the hydrogel is not part of the encapsulation material. This change in volume has many potential benefits, including, for example, enabling diffusion of analytes and biomolecules from tissue or the liquid environment to the sensor, volumetric tissue displacement, easier anchoring of the microprobe 100 into tissue, and anti-occlusive, anti-inflammatory, and anti-proliferative properties, the latter of which prevents growing tissue from clogging the sensor. In some embodiments, the volume of the hydrogel may increase by 1% to 1000%. In other embodiments, the volume of the hydrogel may increase by 10% to 1000%. In other embodiments, the volume of the hydrogel may increase by 100% to 1000%. In other embodiments, the volume of the hydrogel may increase by 500% to 1000%.

[0137] In some embodiments, the volume of the hydrogel may increase by 1% to 500%. In other embodiments, the volume of the hydrogel may increase by 1% to 100%. In other embodiments, the volume of the hydrogel may increase by 1% to 10%. In other embodiments, the volume of the hydrogel may increase by 1% to 5%.

[0138] In some embodiments, the volume of the hydrogel may increase by 10% to 100%. In other embodiments, the volume of the hydrogel may increase by 100% to 500%. In other embodiments, the volume of the hydrogel may increase by 5% to 10%. In other embodiments, the volume of the hydrogel may increase by 10% to 500%.

[0139] In some embodiments, the thickness of the encapsulation portion 110 is between 100 nanometers and 200 microns. In other embodiments, the thickness of the encapsulation portion 110 is between 1 micron and 200 microns. In other embodiments, the thickness of the encapsulation portion 110 is between 10 microns and 200 microns. In other embodiments, the thickness of the encapsulation portion 110 is between 50 microns and 200 microns. In other embodiments, the thickness of the encapsulation portion 110 is between 100 microns and 200 microns.

[0140] In some embodiments, the thickness of the encapsulation portion 110 is between 100 nanometers and 100 micrometers. In other embodiments, the thickness of the encapsulation portion 110 is between 100 nanometers and 50 micrometers. In other embodiments, the thickness of the encapsulation portion 110 is between 100 nanometers and 10 micrometers. In other embodiments, the thickness of the encapsulation portion 110 is between 100 nanometers and 1 micrometer.

[0141] In some embodiments, the thickness of the encapsulation portion 110 is 1 micron to 100 microns. In other embodiments, the thickness of the encapsulation portion 110 is 10 microns to 50 microns. In other embodiments, the thickness of the encapsulation portion 110 is 50 microns to 150 microns. In other embodiments, the thickness of the encapsulation portion 110 is 1 micron to 10 microns.

[0142] In some embodiments, the encapsulation portion includes at least one of the following materials: an oxide, a metal oxide, a natural oxide, a polymer, parylene, a primer, polytetrafluoroethylene, or a polyamide. In some embodiments, the encapsulation portion 110 includes more than one material.

[0143] The encapsulant 110 may be applied to the layered structure 101 of the microprobe 100 via dipping, chemical vapor deposition, physical vapor deposition, brushing, spraying, or other methods.

[0144] In some embodiments, the enclosure 110 will be one or more of the following: chemically inert, biocompatible, biodegradable, antifouling, hydrophobic, hydrophilic, or have a low coefficient of friction.

[0145] In some embodiments, the material of encapsulation 110 will allow it to be patterned so that a planar structure including gaps, holes, openings, vias, traces, crevices, or channels can be formed. In some embodiments, the openings or gaps are circular, oval, rectangular, or other shapes. In some embodiments, there is an opening 140 above a portion of sensor 112, such as Figure 3 In some embodiments, opening 140 is positioned on the shaft of microprobe 100. In other embodiments, opening 140 is positioned on the tip of microprobe 100.

[0146] In some embodiments, the microprobe 100 is selectively encapsulated. For example, in some embodiments, the bottom and vertical surfaces of the layered structure 101 of the microprobe 100 are encapsulated, while the sensing unit 102 and the sensor interface layer 108 are not encapsulated. In another embodiment, the bottom and vertical surfaces of the layered structure 101 are encapsulated with a first encapsulating material, while the sensing unit 102 and the sensor interface layer 106 are encapsulated with a second encapsulating material.

[0147] In some embodiments, different layers or components within the layered structure 101 can also be selectively encapsulated. For example, some layers can be encapsulated to prevent debris from electrically isolating the layers or to isolate the layers from the environment. In some embodiments, one or both of the sensing element 102 and the ductile layer 104 are encapsulated with an oxide, a metal oxide, a natural oxide, a polymer, a primer, parylene, polytetrafluoroethylene, or a polyamide.

[0148] The thickness of the encapsulation 110 may also vary around the layered structure 101. For example, in some embodiments, the thickness of the encapsulation 110 is uniform around all sides of the layered structure 101. However, in other embodiments, the thickness of the encapsulation 110 is not uniform around all sides of the layered structure 101. For example, in one embodiment, the thickness of the encapsulation 110 at the tip of the layered structure axis 124 is thinner than the thickness of the encapsulation 110 on the top and bottom sides.

[0149] In some embodiments, the shape and thickness of the encapsulation portion 110 can vary along the layered structure 101. Specifically, the shape and thickness of the encapsulation portion 110 along the axis 124 and the tip 130 of the layered structure 101 are determined by many factors, including, for example, the size of the layered structure tip 130, the properties of the encapsulation material, the method of applying the encapsulation portion 110 to the layered structure 101, etc. Three requirements for the encapsulation of the layered structure tip 130 include: 1) the encapsulation portion will not significantly increase the size of the layered structure tip 130, allowing for painless insertion into the skin; 2) the encapsulation portion will adhere securely to the layered structure tip 130; and 3) the encapsulation material will not generate debris near the layered structure tip 130 during handling, insertion, or use (i.e., the encapsulation material will not peel, crack, tear, or break).

[0150] In some embodiments, the envelope 110 decreases in thickness as it approaches the tip of the axis 124 of the layered structure 101, as depicted in FIG17 . Thus, at the distal end 132 of the layered structure's tip 130, the envelope converges with the shape of the ductile layer 104. In another embodiment, the thickness of the envelope 110 is uniform along the axis 124 of the layered structure 101 and extends beyond the distal end 132 of the tip 130. Specifically, the envelope 110 extends beyond and encapsulates the tip 130 of the layered structure 101, as depicted in FIG18 . In another embodiment, the thickness of the envelope 110 again decreases along the axis 124 as it approaches the tip 130 of the layered structure 101. However, rather than extending to the distal end 132 of the tip 130 of the layered structure 101, the envelope 110 converges proximally with the tip 130 of the distal end 132, as depicted in FIG19 . In another embodiment, the thickness of the envelope 110 is uniform along a portion of the axis 124 of the layered structure 101 and terminates proximally at the layered structure tip 130 with a square profile, as depicted in FIG. 20 .

[0151] In some embodiments, where the encapsulation portion includes more than one encapsulation material, a first encapsulation material 110a is disposed along a proximal portion of the shaft 124 and / or tip 130, and a second encapsulation material 110b is disposed along a distal portion of the shaft 124 and / or tip 130, e.g. Figure 21 Depicted in.

[0152] In some embodiments, the distance M between adjacent microprobes 100 is D (like Figure 1A In some embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 3.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 2.5 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 2.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 1.5 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 1.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.1 mm to 0.5 mm.

[0153] In some embodiments, the distance between adjacent microprobes 100 is 0.5 mm to 3.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 1.0 mm to 3.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 1.5 mm to 3.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 2.0 mm to 3.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 2.5 mm to 3.0 mm.

[0154] In some embodiments, the distance between adjacent microprobes 100 is 0.5 mm to 2.5 mm. In other embodiments, the distance between adjacent microprobes 100 is 1.0 mm to 2.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 1.5 mm to 2.5 mm. In other embodiments, the distance between adjacent microprobes 100 is 0.5 mm to 1.0 mm. In other embodiments, the distance between adjacent microprobes 100 is 2.0 mm to 2.5 mm.

[0155] As previously mentioned, the smaller the sensor system, the less pain is felt during insertion and use. Therefore, it is an object of the present invention to minimize the size of the disclosed sensor system 10. Due to the novel structure of the sensor system 10 of the present embodiment, its size has been minimized relative to conventional microprobe systems.

[0156] For example, in some embodiments, the length L of the sensing system 10 is L (like Figure 1A In other embodiments, the length of the sensing system 10 is 2 mm to 8 mm. In other embodiments, the length of the sensing system 10 is 2 mm to 6 mm. In other embodiments, the length of the sensing system 10 is 2 mm to 4 mm.

[0157] In some embodiments, the sensing system 10 has a length of 4 mm to 10 mm. In other embodiments, the sensing system 10 has a length of 6 mm to 10 mm. In other embodiments, the sensing system 10 has a length of 8 mm to 10 mm.

[0158] In other embodiments, the sensing system 10 has a length of 4 mm to 8 mm. In some embodiments, the sensing system 10 has a length of 4 mm to 6 mm. In other embodiments, the sensing system 10 has a length of 6 mm to 8 mm.

[0159] In some embodiments, the width W of the sensing system 10 L (like Figure 1A In other embodiments, the width of the sensing system 10 is from 0.5 to 5 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 4.5 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 4.0 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 3.5 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 3.0 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 2.5 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 2.0 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 1.5 mm. In other embodiments, the width of the sensing system 10 is from 0.5 to 1.0 mm.

[0160] In some embodiments, the width of the sensing system 10 is between 1.0 mm and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 1.5 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 2.0 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 2.5 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 3.0 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 3.5 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 4.0 and 5.0 mm. In other embodiments, the width of the sensing system 10 is between 4.5 and 5.0 mm.

[0161] In some embodiments, the width of the sensing system 10 is from 1.0 mm to 4.5 mm.

[0162] In other embodiments, the width of the sensing system 10 is 1.5 to 4.0 mm. In other embodiments, the width of the sensing system 10 is 3.5 to 4.0 mm. In other embodiments, the width of the sensing system 10 is 2.0 to 3.5 mm. In other embodiments, the width of the sensing system 10 is 4.0 to 4.5 mm.

[0163] In some embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.4 mm.

[0164] In other embodiments, the thickness of the sensing system 10 is between 0.1 mm and 0.4 mm. In other embodiments, the thickness of the sensing system 10 is between 0.15 mm and 0.4 mm. In other embodiments, the thickness of the sensing system 10 is between 0.2 mm and 0.4 mm. In other embodiments, the thickness of the sensing system 10 is between 0.25 mm and 0.4 mm. In other embodiments, the thickness of the sensing system 10 is between 0.3 mm and 0.4 mm. In other embodiments, the thickness of the sensing system 10 is between 0.35 mm and 0.4 mm.

[0165] In some embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.35 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.3 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.25 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.2 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.15 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.1 mm.

[0166] In some embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.35 mm. In other embodiments, the thickness of the sensing system 10 is between 0.1 mm and 0.15 mm. In other embodiments, the thickness of the sensing system 10 is between 0.15 mm and 0.25 mm. In other embodiments, the thickness of the sensing system 10 is between 0.2 mm and 0.3 mm. In other embodiments, the thickness of the sensing system 10 is between 0.05 mm and 0.35 mm. In other embodiments, the thickness of the sensing system 10 is between 0.3 mm and 0.35 mm. In other embodiments, the thickness of the sensing system 10 is between 0.5 mm and 0.1 mm.

[0167] It should be understood that certain features of the disclosure described in the context of separate embodiments for the sake of clarity may also be provided in a single embodiment. Conversely, various features of the disclosure described in the context of a single embodiment for the sake of brevity may also be provided individually or in any suitable subcombination or as appropriate in any other described embodiment of the disclosure. Certain features described in the context of individual embodiments are not considered essential features of those embodiments, unless the embodiment is inoperable without those elements.

Claims

1. A sensing system comprising: At least one micro The probe, wherein the microprobe comprises: A hierarchical structure, comprising: a sensing unit, the sensing unit comprising at least one sensor, wherein the at least one sensor comprises a working electrode, wherein when viewed along the layered direction of the layered structure, the sensing unit has a first perimeter, wherein the sensing unit comprises a first material having a first material toughness, and wherein the sensing unit comprises a first side and an opposite second side; a deformable layer positioned on said first side of said sensing unit, wherein the deformable layer is configured to deform under stress; a stretchable layer positioned on the deformable layer opposite to the sensing unit, wherein the extensible layer has a second perimeter when viewed along a layering direction of the layered structure, wherein the first perimeter is entirely within the second perimeter, wherein the ductile layer comprises a second material having a second material toughness greater than the toughness of the first material; a sensor interface layer positioned on the second side of the sensing unit; and at least one encapsulation, wherein the at least one encapsulating portion at least partially encapsulates the layered structure, and wherein the at least one encapsulation is configured to mechanically isolate the layered structure from a surrounding environment, The thickness of the encapsulation portion is in a range from 100 nanometers to 200 micrometers. 2 . The sensing system of claim 1 , wherein the encapsulation is configured to contain debris originating from at least one of the first material, the second material, the deformable layer material, or the sensor interface material. The sensing system of claim 1 , wherein the encapsulation is chemically inert. The sensing system of claim 1 , wherein the encapsulation is further configured to electrically isolate the layered structure from the surrounding environment. The sensing system of claim 1 , wherein the encapsulation includes an opening to the sensor interface layer.

6. The sensing system of claim 5, wherein the opening comprises a hydrogel configured to increase in volume when in contact with a liquid. The sensing system according to claim 1 , wherein the encapsulation portion completely encapsulates the layered structure. The sensing system according to claim 1 , wherein at least a portion of the tip of the sensing unit is not encapsulated. 9 . The sensing system according to claim 1 , wherein the encapsulation portion comprises polyamide, parylene, polyurethane, or a combination thereof.

10. The sensing system of claim 1, wherein the sensor interface layer is chemically inert.

11. The sensing system of claim 1, wherein the sensor interface layer has a thickness in the range of 10 nanometers to 200 micrometers.

12. The sensing system of claim 1, wherein the deformable layer is an adhesive.

13. The sensing system of claim 1, wherein the deformable layer comprises polyurethane, silicone, polyacrylate, polyamide, SU-8, polymethyl methacrylate, parylene, epoxy, polydimethylsiloxane, or a combination thereof.

14. The sensing system of claim 1, wherein the deformable layer is reinforced with aluminum oxide, silicon oxide, silicon oxynitride, or a combination thereof.

15. The sensing system of claim 1, wherein the thickness of the deformable layer is in the range of 1 micron to 100 microns. 16 . The sensing system of claim 1 , wherein the sensing unit is adhered to the extensible layer by a layered structure comprising a first adhesive, a deformable material, and a second adhesive. 17 . The sensing system of claim 1 , wherein a thickness of the deformable layer is greater than a surface roughness of each of the sensing unit and the ductile layer.

18. The sensing system of claim 1, wherein the deformable layer electrically isolates the sensing unit from the stretchable layer.

19. The sensing system of claim 1, wherein at least one of the sensing unit and the ductile layer is encapsulated by: an oxide, a polymer, or a combination thereof.

20. The sensing system of claim 1, wherein at least one of the sensing unit and the ductile layer is encapsulated by: an oxide, a primer, or a combination thereof.

21. The sensing system of claim 19 or 20, wherein the oxide is a metal oxide.

22. The sensing system of claim 19 or 20, wherein the oxide is a native oxide.

23. The sensing system of claim 1, wherein the ductile layer comprises stainless steel.

24. The sensing system of claim 1, wherein the ductile layer comprises a recess in a surface adjacent to the sensing unit, wherein the sensing unit is received within and at least partially surrounded by the recess. 25 . The sensing system of claim 24 , wherein a depth of the recess is equal to a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite to the first side. 26 . The sensing system of claim 24 , wherein a depth of the recess is greater than a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite to the first side. 27 . The sensing system of claim 24 , wherein a depth of the recess is smaller than a dimension between a first side of the sensing unit adjacent to the ductile layer and a second side of the sensing unit opposite to the first side.

28. The sensing system of claim 1, wherein the sensing unit comprises a shaft and a tip.

29. The sensing system of claim 28, wherein the ductile layer comprises a shaft and a tip.

30. The sensing system of claim 29, wherein the tip of the ductile layer extends distally beyond the tip of the sensing unit such that the ductile layer is configured to absorb axial insertion forces applied thereto during use.

31. The sensing system of claim 1, wherein the encapsulation is biocompatible.

32. The sensing system of claim 1, wherein the encapsulation is biodegradable.

33. The sensing system of claim 1, wherein the enclosure is anti-fouling.

34. The sensing system of claim 1, wherein the encapsulation is hydrophobic.

35. The sensing system of claim 1, wherein the encapsulation is hydrophilic.

36. The sensing system of claim 1, wherein the sensor interface layer is biocompatible.

37. The sensing system of claim 1, wherein the sensor interface layer is biodegradable.

38. The sensing system of claim 1, wherein the sensor interface layer is anti-fouling.

39. The sensing system of claim 1, wherein the sensor interface layer is hydrophobic.

40. The sensing system of claim 1, wherein the sensor interface layer is hydrophilic.

41. A microprobe comprising: A hierarchical structure, comprising: a sensing unit, the sensing unit comprising at least one sensor, wherein the at least one sensor comprises a working electrode, wherein when viewed along the layered direction of the layered structure, the sensing unit has a first perimeter, wherein the sensing unit comprises a first material having a first material toughness, and wherein the sensing unit comprises a first side and an opposite second side; a deformable layer positioned on said first side of said sensing unit, wherein the deformable layer is configured to deform under stress; a stretchable layer positioned on the deformable layer opposite to the sensing unit, wherein the extensible layer has a second perimeter when viewed along the layering direction of the layered structure, wherein the first perimeter is completely within the second perimeter, wherein the ductile layer comprises a second material having a second material toughness greater than the toughness of the first material; and a sensor interface layer positioned on the second side of the sensing unit; and at least one encapsulation, wherein the at least one encapsulating portion at least partially encapsulates the layered structure, and wherein the at least one encapsulation is configured to mechanically isolate the layered structure from a surrounding environment, The thickness of the encapsulation portion is in a range from 100 nanometers to 200 micrometers.

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