Sensor assembly and measurement device

Abstract

This invention relates to a sensor assembly comprising a first substrate, a second substrate, and a sensor. The first substrate includes at least one or more capillary holes defining a fluid path. The fluid path extends from a top side through the first substrate to a fluid channel on a bottom side of the first substrate. The second substrate is configured to be connected to the first substrate, and the fluid channel of the first substrate is in fluid communication with a first metallized via and a second metallized via formed in the second substrate. This allows the fluid path to extend through the first metallized via and the second metallized via. The sensor includes a first electrode and a second electrode. The first electrode and the second electrode are disposed on the second substrate, and the second substrate is in fluid communication with the fluid channel of the first substrate. The first electrode is in electrical contact with the first metallized via, and the second electrode is in electrical contact with the second metallized via.

Description

Technical Field

[0001] This invention generally relates to a sensor assembly for sampling bodily fluids. More particularly, it relates to a sensor assembly disposed on a first substrate having at least one capillary pore and a second substrate having two metallized vias and a sensor. The invention also relates to a sensor assembly wherein the first substrate has a plurality of microneedles, wherein the capillary pores extend through the plurality of microneedles. Prior Technology

[0002] There are numerous ways to sample bodily fluids, such as using syringes. This is cumbersome, and there are improved alternatives, such as using microneedles. Although microneedles have many applications, the vast majority of publicly available microneedles involve various forms of drug delivery.

[0003] For example, the concept of miniaturized needle arrays for drug delivery purposes dates back to U.S. Patent No. 3,964,482 from the 1970s. One of the earliest reported microneedles in the scientific literature was an out-of-plane silicon needle array, characterized by 100 needles 1.5 mm long on an area of ​​4.2 mm × 4.2 mm, as described in Campbell et al., “A silicon-based, three-dimensional neural interface: manufacturing processes for an intercortical electrode array,” IEEE Trans Biomed Eng, August 1991; 38(8):758-68. Ultimately, just as the second half of the 20th century belonged to microelectronics, the 21st century will belong to biosensing technology.

[0004] Integrated circuits (ICs) have a profound impact on our daily lives today, and leveraging the same miniaturization and cost benefits of mass-producing biosensors could move clinical diagnostics and health monitoring from expensive laboratories to small, handheld consumer devices. Sampling of the analyte to be measured is a prerequisite for biosensing. Many designs described in scientific papers are intended for the extraction of bodily fluids, such as blood or interstitial fluid (ISF). Different bodily fluids require various solutions; for example, blood has been successfully extracted using the natural "overpressure" in the vascular system, while successful extraction of ISF without negative pressure via diffusion or other mechanisms such as capillary forces is rare or even nonexistent. The terms "negative pressure" and "sub-pressure" are used as equivalents in this invention.

[0005] Regardless of the sampling method, samples must be delivered to the sensing device in a controlled manner. To further improve usability and prevent errors, this is better implemented in an integrated unit. Summary of the Invention

[0006] The objective of this invention is to set aside the defects and disadvantages of previously known sensor components mentioned above and to provide an improved solution for bodily fluid sampling.

[0007] To improve the extraction of fluids such as ISF, negative pressure can be applied. However, this is difficult to combine with readings collected by self-integrating sensors. It has been recognized that extending the fluid path through the sensor assembly is beneficial. Furthermore, in order to have an operational sensor, the included electrodes need to be communicatively connected to external parts of the sensor assembly.

[0008] The objective of this invention is to provide an improved sensor assembly having an integrated operational sensor that extends through the assembly and allows for easy sampling of bodily fluids such as interstitial fluid (ISF).

[0009] The objective of this invention is satisfied in a sensor assembly as defined in the appended claims.

[0010] In a first embodiment, the present invention relates to a sensor assembly comprising a first substrate, a second substrate, and a sensor. The first substrate includes at least one capillary aperture defining a fluid path. The fluid path extends from a top side through the first substrate to a fluid channel on a bottom side of the first substrate. The second substrate is configured to be connected to the first substrate, and the fluid channel of the first substrate is in fluid communication with a first metallized via and a second metallized via formed in the second substrate. This allows the fluid path to extend through the first metallized via and the second metallized via. The sensor includes a first electrode and a second electrode. The first electrode and the second electrode are disposed on the second substrate, which is in fluid communication with the fluid channel of the first substrate. The first electrode is in electrical contact with the first metallized via, and the second electrode is in electrical contact with the second metallized via.

[0011] In one embodiment, the first substrate may include a plurality of holes.

[0012] In one embodiment, the sensor assembly may further include a component for applying secondary pressure to the fluid path to draw fluid from the capillary orifice toward the second substrate.

[0013] In one embodiment, the sensor assembly may further include a plurality of microneedles integrally formed on a first substrate. Each microneedle may include an elongated body extending along a longitudinal axis from a distal end to a proximal end on the first substrate. Each microneedle may further have a bevel at its distal end. Capillary pores may extend longitudinally through the elongated body and further define a fluid path. The proximal end may be integrally formed with the first substrate, and the fluid path may be in fluid communication with a fluid channel of the first substrate.

[0014] In one embodiment, the second substrate may be configured to be connected to the first substrate on one side opposite to the plurality of microneedles.

[0015] In one embodiment, the first electrode may be shaped into a spiral and the second electrode may be shaped into a spiral, wherein the spiral shapes of the first and second electrodes are nested.

[0016] In one embodiment, the sensor is located on one side of the second substrate facing the first substrate.

[0017] In one embodiment, the sensor may be located at least partially on one side of the second substrate facing the first substrate.

[0018] In one implementation, the sensor may be located at least partially within the via.

[0019] In one embodiment, the via may further include a signal path that extends through the second substrate, and the sensor may be configured to be electrically connected to the signal path.

[0020] In one embodiment, the through-hole may be hollow, thereby providing fluid communication between two opposite sides of the second substrate.

[0021] In embodiments, the sensor may be an electrochemical sensor. Electrochemical sensors are known in this art. One known type of electrochemical glucose sensor is the Clark biosensor. This sensor is based on a thin layer of glucose oxidase (GOx) on an oxygen electrode. The reading is the amount of oxygen consumed by GOx during its reaction with the matrix glucose enzyme. A more detailed description of biosensors such as the Clark type can be found in Anthony PF Turner: Biosensors: sense and sensibility, Chem. Soc. Rev., Vol. 42, No. 8, April 21, 2013, pp. 3175-3648. The described sensor is applicable to the present invention. In such embodiments, at least one electrode of the sensor is coated with an enzyme, such as a oxidoreductase. Enzymes suitable for the present invention are oxidoreductases that act on electron donors with oxygen as an acceptor. In the Unified Nomenclature of Enzymes of the International Union of Biochemistry and Molecular Biology, such enzymes are generally classified as EC 1.XXX. A preferred enzyme is glucose oxidase (EC 1.1.3.4).

[0022] In one embodiment, the side of the through-hole may further contain a material having a specified surface energy. Thus, the flow behavior of the fluid can be controlled by its interaction with the specified surface energy.

[0023] In an embodiment, the wall surface of the through hole can be further made hydrophobic, such as by coating it with a hydrophobic substance.

[0024] In an embodiment, the wall surface of the through hole can be further made hydrophilic, such as by coating it with a hydrophilic substance.

[0025] In this embodiment, the cross-sectional area of ​​the capillary pore in the distal end may be larger than that in the proximal end.

[0026] In an embodiment, the fluid channel may further include a reduced cross-sectional area to further enhance fluid flow within the fluid channel.

[0027] The term cross-sectional area refers to the area of ​​a cross section of an object. A cross section is the area where an object intersects with a plane. When comparing different cross-sectional areas, it should be understood that, unless otherwise stated, the intersecting planes are parallel.

[0028] In one embodiment, the first substrate may further include a frame located on the same side as the plurality of microneedles, wherein the frame at least partially surrounds a region on the first substrate having the plurality of microneedles.

[0029] In one embodiment, the frame may have a height equal to or greater than the height of a plurality of microneedles in the direction extending from the substrate.

[0030] In this embodiment, the cross-sectional area of ​​the capillary pores of the microneedle can gradually decrease longitudinally from the distal end to the proximal end. This helps to enhance fluid flow through the capillary pores by means of capillary forces acting in the capillary pores.

[0031] In one embodiment, the cross-section of the capillary orifice (intersecting the longitudinal direction) may further include at least one rounded corner. This facilitates the wetting of the capillary orifice, which has a positive effect on fluid flow.

[0032] In embodiments, the capillary orifice may have a triangular cross-section. Triangular cross-sections have been shown to provide excellent fluid flow in capillary orifices. The triangular cross-section in this application encompasses a cross-section having a substantially triangular shape, i.e., having convex or concave or straight edges, acute or obtuse corners, and rounded corners.

[0033] In one embodiment, the walls of the capillary pores may include a hydrophilic surface, which enhances fluid flow within the capillary pores.

[0034] In an embodiment, the fluid channel can be configured to provide a negative pressure relative to atmospheric pressure to the capillary orifice, thereby enhancing fluid flow through the capillary orifice. The negative pressure can be generated, for example, by a syringe connected to the fluid channel. The negative pressure can also be generated by a suction coating device connected to the fluid channel as described in WO2019 / 020327, which is incorporated herein by reference.

[0035] In one embodiment, the second substrate can be operatively connected to the first substrate by means of an anode or direct bonding, which provides a strong and fluid-tight seal without the risk of adhesive clogging the fluid channels.

[0036] In the second embodiment, the present invention relates to a measuring device comprising a sensor assembly according to the present invention, further comprising a suction device configured to be connected to the sensor assembly on a side opposite to one or more microneedles and in fluid communication with a first via and a second via of a second substrate, thereby providing a pressure difference through the via and fluid channel of the wafer.

[0037] In one embodiment, one or more microneedles integrally formed on a first substrate may comprise an elongated body extending along a longitudinal axis from a distal end having a bevel to a proximal end on the substrate. The elongated body may include capillary pores extending longitudinally therein and defining a fluid path. The proximal end may be integrally connected to the substrate, and the capillary pores may be in fluid communication with a fluid channel of the first substrate. Furthermore, the cross-sectional area of ​​the capillary pores in the distal end may be larger than the cross-sectional area of ​​the capillary pores in the proximal end.

[0038] The inclined plane is referred to as the inclined surface relative to the longitudinal axis of the capillary pore.

[0039] In a third embodiment, the present invention relates to a chip comprising a sensor assembly, the sensor assembly comprising a first substrate, a second substrate, and a sensor. The first substrate includes at least one capillary aperture defining a fluid path. The fluid path extends from a top side through the first substrate to a fluid channel on a bottom side of the first substrate. The second substrate is configured to be connected to the first substrate, and the fluid channel of the first substrate is in fluid communication with a first metallized via and a second metallized via formed in the second substrate. This allows the fluid path to extend through the first metallized via and the second metallized via. The sensor includes a first electrode and a second electrode. The first electrode and the second electrode are disposed on the second substrate, the second substrate being in fluid communication with the fluid channel of the first substrate. The first electrode is in electrical contact with the first metallized via, and the second electrode is in electrical contact with the second metallized via.

[0040] In one embodiment, the first substrate may include a plurality of holes.

[0041] In one embodiment, the sensor assembly may further include a plurality of microneedles integrally formed on a first substrate of the sensor assembly. Each microneedle may include an elongated body extending along a longitudinal axis from a distal end to a proximal end on the first substrate. Each microneedle may further have a bevel at its distal end. Capillary pores may extend longitudinally through the elongated body and further define a fluid path. The proximal end may be integrally formed with the first substrate, and the fluid path may be in fluid communication with a fluid channel of the first substrate.

[0042] In one embodiment, each microneedle of the wafer may include an elongated body extending along a longitudinal axis from a distal end having a bevel to a proximal end on a first substrate. The elongated body may include capillary apertures extending longitudinally therein and defining a fluid path. The cross-sectional area of ​​the capillary apertures in the distal end may be larger than the cross-sectional area of ​​the capillary apertures in the proximal end. The proximal end may be integrally formed with the first substrate, and the first fluid path may be in fluid communication with a fluid channel of the first substrate. The first substrate may have fluid channels forming the fluid path.

[0043] In this implementation, the width of the fluid channel may be greater than the depth of the fluid channel.

[0044] In one embodiment, at least a portion of the wall of the capillary orifice may form part of the wall of the fluid channel, thereby enhancing fluid flow.

[0045] In one embodiment, the fluid channel of the wafer may include an angle of less than 90 degrees. The direction of change. By avoiding sharp bends in the fluid channel, fluid flow is enhanced.

[0046] In one embodiment, the wafer may further include a substrate having a fluid orifice in fluid communication with a fluid channel and open in the back side of the substrate. This provides an access point for the sampling fluid, which can be connected to a second substrate layer, a sensor element, or other fluid channel.

[0047] In one embodiment, the fluid orifice may include an enlarged region extending longitudinally toward the back of the substrate or second substrate. This improvement allows for close fluid connection with other fluid channels such as tubes or syringes.

[0048] In one implementation, the substrate can be operably connected to the substrate by means of anodizing / direct bonding, which provides a strong and fluid-tight seal without the risk of adhesive clogging the fluid channels.

[0049] In one embodiment, a plurality of microneedles on the wafer may be surrounded by an edge that is flush with or closely below the distal end of the microneedles. This serves to tension the membrane (e.g., skin) of the test subject during engagement with the distal end of the microneedles. Furthermore, the membrane, combined with the surrounding edge, forms a chamber in which the only opening is through one or more capillary pores of the first substrate. The enhanced sealing provided by the membrane and the edge, combined with the pressure, increases the effective penetration depth of the microneedles into the membrane as the membrane moves toward the substrate of the wafer.

[0050] In one embodiment, a plurality of microneedles on the wafer may be surrounded by an edge that extends beyond the distal ends of the microneedles. Thus, the edge extends further from the first substrate than the distal ends of the microneedles. This serves the purpose of tensioning the membrane of the test specimen during engagement with the distal ends of the microneedles. Simple Explanation of the Diagram

[0051] A more thorough understanding of the above and other features and advantages of the present invention will become apparent from the following detailed description of the embodiments, which are accompanied by the accompanying drawings:

[0052] [Figure 1] is a schematic cross-sectional view of the sensor assembly.

[0053] [Figure 2a] is a schematic perspective view of a sensor assembly with a plurality of microneedles shown from above.

[0054] [Figure 2b] is a schematic perspective view of the sensor assembly shown from below.

[0055] [Figure 3] is a schematic perspective view of the cross-section of a sensor assembly with a plurality of microneedles.

[0056] [Figure 4] is a cross-sectional view of a sensor assembly with microneedles.

[0057] [Figure 5a] is a cross-sectional view along the longitudinal axis of the microneedle according to the embodiment.

[0058] [Figure 5b] is a cross-sectional view along the longitudinal axis of the microneedle according to the embodiment.

[0059] [Figure 5c] is a cross-sectional view along the longitudinal axis of the microneedle according to the embodiment.

[0060] [Figure 6] is a bottom view of the wafer.

[0061] [Figure 7] is a three-dimensional top view of the second substrate with through holes and sensors.

[0062] [Figure 8] is a schematic cross-sectional view of a sensor assembly with multiple holes and a plurality of microneedles. Implementation

[0063] This invention is based on the insights revealed. Upon close examination, it becomes clear that sensor components in prior art for bodily fluid sampling either cannot apply negative pressure or cannot be provided in the form of an integrated unit. Solutions capable of applying negative pressure rely on the transfer of the sample to the sensing device. Similarly, solutions that can provide an integrated unit cannot provide negative pressure. Negative pressure improves sampling or is even necessary for some sampling methods.

[0064] An improved sensor assembly is described in order to combine the improved extraction of fluids such as ISF by using the applied negative pressure and the improved uses provided by the integrated unit.

[0065] To enhance understanding, some diagrams depict the substrates of the sensor assembly as spaced apart. It should be understood that substrates depicted as spaced apart are typically joined. For example, the substrates can be joined by anodic / direct bonding, which provides a strong and fluid-tight seal without the risk of adhesive clogging fluid channels. Other methods of joining substrates are conceivable, such as clamping or by adhesive.

[0066] Figure 1 is a schematic cross-sectional view of a sensor assembly 100 according to an embodiment of the present invention, the sensor assembly having a first substrate 110, a second substrate 120 and a sensor 130.

[0067] The first substrate 110 has capillary holes 111 that define a fluid path 112 extending from the top side 113 through the first substrate 110 to the bottom side 115 of the first substrate 110.

[0068] The second substrate 120 is configured to be connected to the first substrate 110, so that the fluid channel 114 of the first substrate is in fluid communication with the first metallized via 121 and the second metallized via 122 formed in the second substrate 120, thereby allowing the fluid path 112 to extend through the first metallized via 121 and the second metallized via 122.

[0069] A sensor 130, including a first electrode and a second electrode, is disposed on a second substrate 120 in fluid communication with a fluid channel 114 of a first substrate 110. The first electrode is in electrical contact with a first metallized via 121, and the second electrode is in electrical contact with a second metallized via 122.

[0070] The first metallized via 121 and the second metallized via 122 may be hollow, thereby providing fluid communication between two opposite sides of the second substrate 120.

[0071] The side of the through-hole may further contain a material with a specified surface energy. Thus, the flow behavior of the fluid can be controlled by its interaction with the specified surface energy. For example, the side of the through-hole may contain a hydrophobic or hydrophilic material.

[0072] The internal dimensions and geometry of the orifice can also be designed to allow capillary forces to act on the liquid, partially or entirely, through the fluid channels of the sensor assembly 100. These capillary forces can be used in conjunction with the applied negative pressure.

[0073] Additionally, the sensor assembly may further include components for applying negative pressure to the fluid path to draw fluid from the capillary aperture toward the second substrate. The negative pressure may be generated, for example, by a syringe connected to the fluid channel.

[0074] Figure 2a is a schematic perspective view of the sensor assembly 200 shown from above. The sensor assembly 200 includes a first substrate 210, a second substrate 220, and a sensor 230.

[0075] The first substrate 210 has capillary apertures 211, as shown here on the microneedles, defining a fluid path extending from the top side 213 through the first substrate 210 to a fluid channel 214 on the bottom side of the first substrate 210. The first substrate is shown here having a plurality of microneedles. In other embodiments, the first substrate 210 may not have microneedles, and the capillary apertures 211 may then be located on the top side 213.

[0076] A second substrate 220 is drawn at a distance from the first substrate 210, such that the fluid channel of the first substrate is in fluid communication with the first metallized via 221 and the second metallized via 222 formed in the second substrate 220, thereby allowing the fluid path to extend through the first metallized via 221 and the second metallized via 222.

[0077] A sensor 230, including a first electrode 231 and a second electrode 232, is disposed on a second substrate 220 which is in fluid communication with a fluid channel of a first substrate 210. The first electrode 231 is in electrical contact with a first metallized via 221, and the second electrode 232 is in electrical contact with a second metallized via 222.

[0078] The sensor assembly 200 may have one or more microneedles. The microneedles may be integrally formed on the first substrate 210. Each microneedle may include an elongated body extending along a longitudinal axis from a distal end to a proximal end on the top side 213 of the first substrate 210. Each microneedle may further have a bevel at its distal end. Capillary apertures may extend longitudinally through the elongated body and further define a fluid path. The proximal end may be integrally formed with the first substrate 210, and the fluid path may be in fluid communication with a fluid channel 214 of the first substrate 210.

[0079] Sensor 230 is illustrated herein on one side of the second substrate 220 facing the first substrate 210. In other embodiments, the sensor may be an elongated portion extending in a via in the second substrate 220. For example, the sensor may be an electrochemical sensor.

[0080] Each via may further include a signal path that extends through the second substrate 220. The sensor 230 may be configured to be electrically connected to the signal path.

[0081] The first electrode 231 can be formed into a spiral shape and the second electrode 232 can be formed into a spiral shape, wherein the spiral shapes of the first and second electrodes are nested.

[0082] Figure 2b is a schematic perspective view of the sensor assembly 200 shown from below. The sensor assembly 200 includes a first substrate 210, a second substrate 220, and a sensor.

[0083] The first substrate 210 has capillary holes that define a fluid path extending from the top side through the first substrate 210 to a fluid channel 214 (shown here as extending above the surface) on the bottom side 215 of the first substrate 210.

[0084] A second substrate 220 is drawn at a distance from the first substrate 210, such that the fluid channel 214 of the first substrate is in fluid communication with the first metallized via 221 and the second metallized via 222 formed in the second substrate 220, thereby allowing the fluid path to extend through the first metallized via 221 and the second metallized via 222.

[0085] A sensor including a first electrode and a second electrode is disposed on a second substrate 220 in fluid communication with a fluid channel 214 of a first substrate 210. The first electrode is in electrical contact with a first metallized via 221, and the second electrode is in electrical contact with a second metallized via 222.

[0086] A fluid channel 214 is shown on the back side of a first substrate 210 in the figure. At least one fluid channel orifice on the back side of the first substrate 210 is connected between a fluid path through the first substrate and the at least one fluid channel 214, thereby fluidly connecting at least one capillary orifice to the fluid channel 214. The at least one fluid channel 214 may be, for example, a network of interconnecting channels. The width of the fluid channel 214 may be greater than the depth of the fluid channel 214.

[0087] Figure 3 is a schematic perspective view of a cross-section of a sensor assembly 300 having a plurality of microneedles showing the fluid path of the sensor assembly. The sensor assembly 300 includes a first substrate 310, a second substrate 320, and a sensor.

[0088] The first substrate 310 has a plurality of capillary holes 311, shown here as passing through a plurality of microneedles, which define a fluid path extending from the top side 313 through the first substrate 310 to a fluid channel 314 on the bottom side of the first substrate 310. In this figure, a cross-section of the fluid channel 314 can be seen.

[0089] The second substrate 320 and the sensor are configured according to the previously presented pattern.

[0090] The sensor assembly may also have a frame structure sized to support the tip of a finger, the tip of which is constructed as a longitudinal protrusion along the microneedle and preferably has a diameter of less than 15 mm.

[0091] In some instances, the sensor assembly may be at least partially surrounded by a frame structure sized to support the fingertip. This supports and tensions the skin at the fingertip to facilitate the penetration of at least one microneedle into the skin.

[0092] The sensor assembly can also be protected by a protective structure that protrudes to at least the same plane as the tip of the needle, thereby enabling the wafer to be handled in the MEMS fabrication conditions of the wafer set described herein.

[0093] The sensor assembly may also have a protective structure that extends the skin before being penetrated by the aforementioned plurality of needles.

[0094] Figure 3 also shows an example of the enclosure frame structure 340 on the top side of the first substrate 310.

[0095] Figure 4 is a cross-sectional view of a schematic sensor assembly 400 having microneedles 416. The sensor assembly 400 has a first substrate 410, a second substrate 420, and a sensor 430.

[0096] The first substrate 410 has a capillary hole 411 that defines a fluid path 412 extending from a microneedle 416 on the top side 413 through the first substrate 410 to a fluid channel 414 on the bottom side 415 of the first substrate 410.

[0097] The second substrate 420 and the sensor 430 are configured according to the previously presented diagram. Thus, the fluid path 412 extends at least through the microneedle 416, the fluid channel 414, and the metallized vias 421 and 422. Thus, fluid in the fluid path 412 can pass through the sensor 430 while passing through the first substrate 410 and the second substrate 420.

[0098] Microneedles 416 may have sharp tips defined by crystalline planes. For example, microneedles may have a slope of 111 planes defined for each needle or several needles.

[0099] Each microneedle 416 may include a capillary pore 411, such as a single capillary pore. Thus, body fluids can be extracted by capillary aspiration through the microneedle 416.

[0100] The microneedle 416 may have a cap at its distal end to protect the capillary pore from blockage, thereby at least one opening of the capillary pore is provided in the lateral direction of the microneedle perpendicular to the axial or longitudinal extension of the microneedle.

[0101] Each microneedle's capillary pore can have a hydrophilic surface. This can facilitate the capillary flow of body fluids.

[0102] Microneedles may contain a plurality of cutting elements extending longitudinally along the microneedle. This allows the skin to be cut and opened to facilitate the extraction of bodily fluids.

[0103] The periphery of the hole in each microneedle projected onto the bevel of the needle can be located at a distance from the tip, with the tip outside the periphery.

[0104] The length of the microneedle 416 can be from 200 μm to 1000 μm, preferably from 400 μm to 900 μm, and more preferably from 300 μm to 600 μm, and the length of its outer circumference can be from 400 μm to 800 μm. Thus, the microneedle 416 has a size suitable for penetrating the skin and extracting body fluids.

[0105] If the portion of the hole projected onto the side containing the capillary system can be connected to the outside of the capillary, a maximum wall surface with minimized surface tension can be generated.

[0106] The connection between the orifice and the capillary can be designed, for example, to have a minimized contact angle, thereby enabling tension-driven flow.

[0107] Each needle's shaft can be either shanked or shankless.

[0108] Vertical orifices can be filled with materials that are selective and specific to certain molecules, thereby creating an integrated extraction and sensing chip assembly. The filling material can be, for example, glucose oxidase and toner, thus creating a glucose-specific extraction and sensing chip assembly.

[0109] Multiple openings may be arranged laterally around the outer periphery of the microneedle 416. At least one opening may be arranged around the central channel along the longitudinal extension of the microneedle 416. This facilitates the extraction of bodily fluids and further reduces the risk of blockage.

[0110] The orifice, with its hollow structure, can serve as an inlet for sampling bodily fluids. Thus, bodily fluids such as interstitial fluid (ISF) can be extracted and introduced into the sensor 430 with minimal discomfort to the patient.

[0111] The sensor 430 can have a capillary collection network with different patterns, and its advantage is that it can collect and store liquids without evaporation problems. Therefore, the chip can both sample and analyze.

[0112] The sensor 430 may have an interface between a vertical orifice and a collection capillary, which is laterally misaligned to allow liquid to wet the wall and thus fill the collection channel on the back side by capillary action.

[0113] Microneedles 416 may have bevels oriented in the crystallization direction or preferably in the same direction.

[0114] Figure 5a is a cross-sectional view along the longitudinal axis of the microneedle 516 according to an embodiment. In this figure, a circular cross-section of the capillary orifice 511 is shown.

[0115] Figure 5b is a cross-sectional view along the longitudinal axis of the microneedle 516 according to an embodiment. This figure shows the uneven cross-section of the capillary orifice 511. The microneedle 516 shown has two rounded corners. Other designs are also possible, such as one or three rounded corners. The corners can have the same or different radii of curvature. Alternatively, the triangle can be described as having six corners, with three sides significantly larger than the other three sides.

[0116] Figure 5c is a cross-sectional view along the longitudinal axis of the microneedle 516 according to an embodiment. In this figure, a triangular cross-section of the capillary pore 511 is shown.

[0117] In this application, a triangular cross-section should encompass a shape having three edges connected to corresponding corners. The edges can be straight, curved, convex, or concave. The corners can be sharp, blunt, or circular with different or the same radii. Therefore, in this application, a cross-section having an egg or heart shape is considered triangular. This reasoning also applies to the shape of holes, such as those relating to microneedles.

[0118] For example, the triangular shape of the capillary pore 511 can be substantially triangular, in which the convex substrate is connected to the straight section via a curved corner. This shape of the capillary pore has been proven effective for extracting interstitial fluid from the fingers of human test subjects.

[0119] For example, the cross-sectional area of ​​the capillary pores in the distal end can be larger than that in the proximal end. Furthermore, the fluid channel can further include a reduced cross-sectional area to further enhance fluid flow within the channel. The cross-sectional area of ​​the capillary pores of the microneedle can, for example, gradually decrease along the longitudinal direction from the distal end to the proximal end.

[0120] Figure 6 is a schematic bottom view of a chip with a sensor assembly according to an embodiment of the present invention. A first substrate 610 and a second substrate 620 are shown. The second substrate 620 has a first metallized via 621 and a second metallized via 622. The metallized vias are used to transmit readings from sensors on opposite sides of the second substrate 620 and to make electrical contact with extended pads. The extended pads are used to further simplify the readings from the sensors.

[0121] Figure 7 is a top view of the second substrate 720 having through holes and sensors. The view is a perspective view, so there may be some distortion in the figure.

[0122] A first metallized via 721 and a second metallized via 722 are formed on the second substrate 720. The second substrate further includes a sensor having a first electrode 731 and a second electrode 732, which can be considered as spirals in the figures. The first electrode 731 is in electrical contact with the first metallized via 721, and the second electrode 732 is in electrical contact with the second metallized via 722. Thus, readings from the electrodes can be transmitted through the second substrate 720 via the first metallized via 721 and the second metallized via 722.

[0123] The sensor assembly may also have a plurality of needles organized in an array or matrix at a minimum distance of 100 micrometers but not more than 1 mm apart. The plurality of needles have sharp tips in the same plane or slightly below the enclosure structure, and the tips may have a 54.7-degree bevel and the needles have hollow holes with capillary dimensions that allow extraction without clogging and an axis longer than 200 micrometers.

[0124] Figure 8 is a schematic cross-sectional view of a sensor assembly having multiple holes 812 from a plurality of microneedles 816. The sensor assembly 800 has a first substrate 810 and a second substrate 820.

[0125] The first substrate 810 has a plurality of capillary pores that define a fluid path 812 extending from a plurality of microneedles 816 on the top side 813 through the first substrate 810 to a fluid channel 814 on the bottom side 815 of the first substrate 810. The figures are illustrated to show capillary pores in two of the plurality of microneedles 816; however, it should be understood that some of the plurality of microneedles 816 may have capillary pores, and each of these capillary pores may be connected to the fluid channel 814.

[0126] Each capillary aperture can extend from the top side 813 of the first substrate 810 to the fluid channel aperture on the bottom side 815 of the first substrate 810. If the sensor assembly has microneedles, the capillary aperture can extend from the tip of the microneedles to the fluid channel aperture on the bottom side 815 of the first substrate 810.

[0127] The second substrate 820 includes a sensor 830 configured according to the previously presented pattern. At least therefore, a fluid path 812 extends through a plurality of microneedles 816, a fluid channel 814, and metallized vias 821, 822. Thus, fluid in the fluid path 812 can pass through the sensor 830 while passing through the first substrate 810 and the second substrate 820.

[0128] Microneedles 816 can be positioned, for example, at a minimum distance of 200 micrometers from each other, in order to avoid the bed of nails effect.

[0129] The microneedle 816 enables orientation in a manner that allows for the connection of at least a subset of microneedles using integrated (e.g., etched) capillaries.

[0130] The microneedle 816 can be fully integrated with capillary systems that enable capillary flow to a fluid outlet.

[0131] The second substrate can be attached to the first substrate by wafer bonding or other means, but it can also be connected by capillary or equivalent flow system.

[0132] The sensor can also be configured to detect glucose levels in bodily fluids, i.e., a glucose sensor. This provides a sensor for quickly and accurately detecting glucose levels in bodily fluids.

[0133] The sensor can be configured to detect the concentration or presence of lactate, carbon dioxide, or other molecules in bodily fluids. This provides a sensor for rapidly and accurately detecting the levels of the aforementioned molecules or other molecules, ions, or biomarkers in bodily fluids.

[0134] While specific embodiments have been described, those skilled in the art will understand that various modifications and alterations can be contemplated within the scope defined in the appended claims. All prior art documents cited herein are expressly incorporated herein by reference in their entirety.

[0135] none

Claims

1. A sensor assembly (100, 200, 300, 400, 800) comprising: a first substrate (110, 210, 310, 410, 610, 810) including at least one capillary aperture (111, 211, 311, 411, 511, 811) defining a fluid path (112, 212, 312, 412, 812) extending from a top side (113, 313, 413, 813) through the first substrate to a fluid channel (114, 214, 414, 814) on a bottom side (115, 215, 415, 815) of the first substrate; A second substrate (120, 220, 320, 420, 620, 720, 820) is configured to be connected to the first substrate. The fluid channel of the first substrate is in fluid communication with a first metallized via (121, 221, 421, 621, 721, 821) and a second metallized via (122, 222, 422, 622, 722, 822) formed in the second substrate, thereby allowing the fluid path to extend through the first metallized via and the second metallized via. A sensor (130, 230, 430, 830) is sandwiched between a first substrate and a second substrate in a sealed manner, so that the sensor is not exposed to the outside of the first substrate and the second substrate. The sensor includes a first electrode (231, 731) and a second electrode (232, 732). The first electrode and the second electrode are disposed on the second substrate in fluid communication with the fluid channel of the first substrate. The first electrode is in electrical contact with the first metallized via, and the second electrode is in electrical contact with the second metallized via.

2. The sensor assembly of claim 1, wherein the first substrate includes a plurality of holes.

3. The sensor assembly of claim 1 or 2, further comprising: a component for applying a secondary pressure to the fluid path to draw fluid from the capillary pores toward the second substrate.

4. The sensor assembly of claim 1 or 2, further comprising: a plurality of microneedles integrally formed on the first substrate, wherein each microneedle comprises: an elongated body extending along a longitudinal axis on the first substrate from a distal end of the elongated body having a bevel to a proximal end; wherein the capillary pores extend longitudinally through the elongated body and further define the fluid path; wherein the proximal end is integrally formed with the first substrate, and the fluid path is in fluid communication with the fluid channel of the first substrate.

5. The sensor assembly of claim 4, wherein the second substrate is configured to be connected to the first substrate on a side opposite to the plurality of micropins.

6. The sensor assembly of claim 1 or 2, wherein the first electrode is shaped into a helical shape and the second electrode is shaped into a helical shape, and wherein the helical shapes of the first electrode and the second electrode are nested.

7. The sensor assembly of claim 1 or 2, wherein the sensor is located on the side of the second substrate facing the first substrate.

8. The sensor assembly of claim 1 or 2, wherein the sensor is at least partially located on the side of the second substrate facing the first substrate.

9. The sensor assembly of claim 1 or 2, wherein the sensor is at least partially located in the first metallized via and the second metallized via.

10. The sensor assembly of claim 1 or 2, wherein the first metallized via and the second metallized via further include a signal path extending through the second substrate, and the sensor is configured to be electrically connected to the signal path.

11. The sensor assembly of claim 1 or 2, wherein the first metallized via and the second metallized via are hollow, thereby providing fluid communication between two opposite sides of the second substrate.

12. The sensor assembly of claim 1 or 2, wherein the sensor is an electrochemical sensor.

13. The sensor assembly of claim 1 or 2, wherein the wall surfaces of the first metallized via and the second metallized via are hydrophilic.

14. A measuring apparatus comprising a sensor assembly as claimed in any one of claims 1 to 13, further comprising a secondary pressure device configured to be connected to the sensor assembly on a side opposite to at least one of a plurality of microneedles and in fluid communication with the first metallized via and the second metallized via of the second substrate, thereby providing secondary pressure through the first metallized via and the second metallized via of the wafer and the fluid channel.

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