WO2018099437A1

WO2018099437A1 - Microneedle array chip

Info

Publication number: WO2018099437A1
Application number: PCT/CN2017/114062
Authority: WO
Inventors: Sin-Ger HUANG
Original assignee: Huang Sin Ger
Priority date: 2016-12-01
Filing date: 2017-11-30
Publication date: 2018-06-07

Abstract

An out-of-plane microneedle array chip (100) with controllable puncturing depth comprises: a first substrate (120), a second substrate (130) opposite to the first substrate (120), a driving unit (180) positioned between the first substrate (120) and the second substrate (130), a microneedle array (132) coupled to the second substrate (130), and a controller (140) coupled to the first substrate (120), and connected with the driving unit (180).

Description

MICRONEEDLE ARRAY CHIP

Field of the Invention

The present invention relates to medical and cosmeticapparatus, andparticularly to anout-of-planemicroneedle array chip with controllable puncturing depth.

Background

The sensing electrode used by a conventional physiological inspection system. Such the sensing electrode is apt to be affected by the inferior electric conductivity of the corneum, the improvement of the overall detection capability is very limited. The microneedles can penetrate the corneum and enter the epidermis which is composed of living cells and has a superior electric conductivity. It has replaced the conventional sensing electrode and been extensively used in physiological inspection systems.

On other hand, many situations requiring the extraction of fluids, e.g., blood-glucose monitoring, required the use of sharp instruments such as lancets that pierce the skin. Such devices arerelatively painful to use and may pose a risk of inadvertent piercing of skin. Unlike the existing needles, the microneedles pass through skin without pain and do not leave an external injury.

However, since the thicknesses and elasticity of skins differ according to individuals, and skin regions, a method for controlling adepth of insertion of the microneedles is required.

Summary

It is anobject of the present invention to provide anout-of-planemicroneedle array chip that the puncturing depthof the puncturing needle is accurately controlledto overcome the defects in the prior art, is used for rapidly pushing the microneedle array chip to a specific positionadjusted according to personal needs. The thickness of the skinsurface of a limb or any other part of a human bodycan be easily and quickly detected by an external detecting device while the microneedle array chip is contacting the skin surface of the limb or any other part of the human body.

The invention relates to anout-of-plane microneedle array chip with controllable puncturing depth, which comprises a bottom substrate, a movable substrateopposing to the bottom substrate, a micro-controller arranged on the bottom substrate, a driving unitarranged between the bottom substrate and the movable substrate which connected to the micro-controllerunit, amicroneedle array comprising conductive structurearranged on the removable substrate, wherein the driving unitcan controlthe movement of the movable substrate according toa position control signalfrom the micro-controller to adjust the distance between the bottom substrate and the movable substrate. The conductive structure comprises one or more micro-channels and the microneedle array chipcomprises one or more protrusion structures, wherein the protrusion structure may penetrate theskin surface of the subject to obtain a body fluid of the subject and delivery the body fluid by the micro-channels.

The driving unit comprises one or more mechanical transmissioncomponentsconnected to the removable substrate. The mechanical transmission componentcauses a relative movement between the bottom substrate and the movable substrate to move any one of them away from another thereof or move them closer to each other while receiving a position control signal form the micro-controller.

The microneedle array chip also includes a communication unit arranged on the same plate as the micro-controller for receiving physical signals of thesubject and transmitting to the micro-controller or receiving the physiological signals or detecting signals and transmitting to an external electronic apparatus.

Themicroneedle array chip also includes a detecting unit connected to the conductive structure for detecting the body fluid of the subject, generating a data signal and transmitting the data signal to the communication unit.

In another embodiment of the present invention, the protrusion structureis consisted of electrode structure for contacting or penetrating the body of the subject to detect the physiological signal of the body of the subject. The conductive structure is consisted of one or more electrically conductive unitsthat can transmit the physiological signal of the body of the subject. The conductive unit is directly connected to the micro-controller or the communication unit to transmit the physiological signal of the body of the subject to the micro-controller or the communication unit.

In another embodiment of the present invention, eachprotrusion structure of the microneedle array ischaracterized ina flat-topped columnarshape. The conductive structure may delivery conducting liquids or conducting gels to wet the top of the protrusion structure, an external detecting device may detect the existence of the skin surface, and the driving unit may push the removable substrate to make the top of the protrusion structure contact the skin surface for detecting the physiological signal of the body of the subject.

In another embodiment of the present invention, the driving unit comprises magnetic componentshaving a first magnetic component installed on the bottom substrate and a second magnetic component installed on the removable substrate opposing to the first magnetic component. The distance between the bottom substrate and the removable substrate is adjusted by utilizing the magnetic force between the first magnetic component and the second magnetic component.

In another embodiment of the present invention, the driving unit comprises a heating component installed between the removable substrate and the bottom substrate. A confined space is consisted of the removable substrate, a protective covering and the bottom substrate. The driving unit heats a filling material inside the confined space that expands the volume size of the filling materialto adjust the distance between the removable substrate and the bottom substrate when the driving unit has receiveda position control sign from the micro-controller.

Description of Figures

Figure 1 is a schematic view of themicroneedle array chip in accordance with the presentof the first embodiment.

Figure 2 is an exploded view of themicroneedle array chip in accordance with the presentof the first embodiment.

Figure 3 is a functional view of themicroneedle array chip in accordance with the presentof the first embodiment.

Figure 4 a-b are cross-section views of the microneedle array chip along the line A-A’of Figure 1.

Figure 5 is a schematic view of themicroneedle array chip in accordance with the presentof the second embodiment.

Figure 6 is a schematic view of themicroneedle array chip in accordance with the presentof the third embodiment.

Figure 7 is a schematic view of themicroneedle array chip in accordance with the presentof the forth embodiment.

Embodiment

Figure 1 is a schematic view of themicroneedle array chip 100 in accordance with the presentof the first embodiment. The microneedle array chip 100 includes a protective covering 110, a bottom substrate 120, and a movable substrate 130 having a microneedle array 132. The protective covering 110 may completely or partially cover the bottom substrate 120 and surround the removable substrate 130 to form an opening corresponding to the microneedle array 132. In a normal state, the microneedle array 132 is located inside the protective covering 110 and the top portion of the microneedle array 132 is less than the height of the plane of the protective covering 110 and the opening. The top portion of the microneedle array 132 protrudes out of the plane parallel to the protective covering 110 and the opening while the removable substrate 130under a force used for pushing ittoward to the direction away from the bottom substrate 120.

The bottom substrate 120 is arranged opposing to the removable substrate 130, in the first embodiment, the surface area of the removable substrate 130 is less than the surface area of the bottom substrate 120 that the extra surface area covering by the protective covering 110 forms a gripping surface for convenient to use. In another embodiment, the surface area of the removable substrate 130 is equal to the surface area of the bottom substrate 120 that the protective covering 110 surrounds both the side walls of the bottom substrate 120 and the removable substrate 130 and the surface of the bottom substrate 120 away from the removable substrate 130. The side walls of the bottom substrate 120 and the removable substrate 130 covering by the protective covering 110 forms a gripping surface or the surface of the bottom substrate 120 away from the removable substrate 130 forms a gripping surface.

The microneedle array 132 includes one or more protrusion structures 1322 arranged on the surface of the microneedlearray 132 away from the bottom substrate 120. The protrusion structure 1322 is designed to contact subjects for extracting body fluids or the physiological signals of subjects. In the first embodiment, the microneedle array 132, the protrusion structure 1322 and the removable substrate 130 are integrated into a whole and cannot be disassembled and assembled. In another embodiment, the microneedle array 132 and the removable substrate 130 could be disassembled and assembled. The microneedle array 132 is fixed to the removable substrate 130 by a fixing mechanism, such as fastener structure, magnetic attraction-type structure or slot-type structure, for conveniently replacingthe microneedle array 132. The shape of the protrusion structure 1322 includes but not limited tocone, tetrahedron or cylinder structure. In another embodiment, the protrusion structure 1322 includes a flat portion of the top of the protrusion structure 1322. The protrusion structure 1322 can be made ofstainless steel, silicon, nickel, polydimethylsiloxane (PDMS) or epoxy.

Figure 2 is an exploded view of themicroneedle array chip 100 in accordance with the presentof the first embodiment. The microneedle array chip 100 also includes a micro-controller 140, a communication unit 150, a storage unit 160, a detecting unit 170 and a driving unit 180. The removable substrate 130 also includes a conductive structure 134 which is connected to microneedle array 132. The conductive structure 134 is used to deliver body fluids or the physiological signals obtained from subjects. In the first embodiment, the protrusion structure 1322 is designed as an acicular structure. The conductive structure 134 comprises one or more micro-channels and the microneedle array comprises one or more protrusion structures, wherein the protrusion structure may penetrate the skin surface of the subject to obtain body fluids of the subject and delivery the body fluids by the micro-channels. The microneedle array chip 100 also includes a detecting device 190 connected to the conductive structure 134. The detecting device190 is used for detecting body fluids of subjects, generating data signals corresponding to the body fluids of the subjects and transmitting the data signals to the micro-controller 140 or the communication unit 150 as well. In another embodiment, the microneedle array chip 100 will not include the detecting device190 because the conductive structure 134 can be connected to an external detecting unit or storage unit through to the opening of the protective covering 110 for detecting body fluids of subjects.

In another embodiment, the protrusion structure 1322 is consisted of electrode structure for contacting or penetrating the body of the subject to detect the physiological signal of the body of the subject. The conductive structure 134 is consisted of one or more electrically conductive units that transmits the physiological signal of the body of the subject. The conductive unit is directly connected to the micro-controller or the communication unit to transmit the physiological signal of the body of the subject to the micro-controller or the communication unit. Therefore, the microneedle array 100 maybe not include the detecting device190 because the conductive structure 134 can be directly electrically connected and transmitted the physiological signal of the body of the subject to the micro-controller 140 or the communication unit 150. In another embodiment, the microneedle array 132 and the removable substrate 132 could be disassembled and assembled. The microneedle array 132 is fixed to the removable substrate 130 by a slot-type structurefor conveniently replacingthe microneedle array 132. The removable structure 130 has a concave structure for receiving and fixing the conductive structure 134 as well. The conductive structure 134 can be connected to the detecting device 190 of the microneedle array 130 or the external detecting unit /storage unit.

The micro-controller 140 is connected to the communication unit 150 and the driving unit 180 for receiving physical signal, physiological signals or detecting signals, and generating a position control signal to the driving unit 180 or transmitting physical signals, physiological signals or detecting signals to the communication unit 150. In another embodiment, the micro-controller 140 is arranged on surface of the removable substrate 130 closed to the bottom substrate120. In another embodiment, the micro-controller 140 is arranged on surface of the bottom substrate 120 away from the removable substrate130. The position control signal could be but not limited to current signal or voltage signal.

The communication unit 150 is arranged in the same plate as the micro-controller 140 for receiving the physical signals of the subject and transmitting to the micro-controller 140 or receiving the physiological signals or detecting signals and transmitting to an external electronic apparatus. The external electronic apparatus could be but not limited toa server, a cloud storage apparatus, a computer or an electronic apparatus with display unit.

The storage unit 160 is connected to the micro-controller 140 for storing the physical signals, physiological signals or detecting signal of the subject, wherein the physical signalincludes but not limited to thethickness of the surface layer of human’s skin or thethickness of the stratum corneum layer of human’s skin and, the physiological signals or detecting signals include but not limited to the electroencephalograph (EEG) or electrocardiogram (ECG) .

The detecting unit 170 is connected to the micro-controller 140 for detecting the distance between the bottom substrate 120 and the removable substrate 130. The detecting unit 170 could be but not limited togyroscope, accelerator, magnetic inductor, capacitance sensing technology or a combination thereof. In the first embodiment, the detecting 170 is an accelerator arranged inside the protective covering 110, and on the same side as the bottom substrate 120 and the removable substrate 130. In another embodiment, the detecting 170 is a gyroscope for replacing the accelerator as well. In another embodiment, the detecting unit 170 includes two electrically conductive units and one measuring unit. One of the electrically conductive units is arranged on the bottom substrate 120 and the other electrically conductive unit is arranged on the removable substrate 130 opposing to the electrically conductive unit arranged on the bottom substrate 120. The detecting unit is used to detect the magnitude of capacitance for obtaining the distance between the bottom substrate 120 and the removable substrate 130.

The driving unit 180 is arranged between the bottom substrate 120 and the removable substrate 130 forreceiving the position control signal form the micro-controller 140and adjusting the distance between the bottom substrate 120 and the movable substrate 130. In the first embodiment, the driving unit 180 comprises one or more mechanical transmissioncomponent 182 connected to the removable substrate 130. For more details, the mechanical transmissioncomponent 182 includes one carrying body and one actuator. The carrying body completely or partially covers the peripheral region of the removable substrate 130 that surrounds the outer region of the microneedle array 132. The actuator could be but not limited to a stepper motor, a vcm voice coil motor, aultrasonic motor or a piezo motor. The mechanical transmission component 182causes a relative movement between the bottom substrate 120 and the movable substrate 130 to move any one of them away from another thereof or move them closer to each other while receiving a position control signal form the micro-controller 140.

Figure 3 is a functional view of themicroneedle array chip 100 in accordance with the presentof the first embodiment. In an unused state, the microneedle array 132 is located inside the protective covering 110 and the height of the top portion of the microneedle array 132 is less than the height of the plane of the opening. The thickness of the skin surface102 of a limb or any other part of a human bodycan be easily and quickly detected by an external detecting device 106 while the microneedle array chip 100 is contacting the skin surface of the limb or any other part of a human body. The externaldetecting device 160 generates physical signals and transmitsto the communication unit 150 of the microneedle array 100. The skin surface 102 could be but not limited to a stratum corneum or a cuticular layer and the physical signal of the subject is the thickness of surface skin 102. The external detecting device 106 could be but not limited to Raman Spectra apparatus.

In another embodiment, the microneedle array chip 100 also includes at least twoneedle-shapedelectrically conductive elements and one resistance measuring element (not shown) . The needle-shapedelectrically conductive element is arranged on the surface of removable substrate 130 away from the bottom substrate 120. The resistance measuring element is used for measuring the magnitude of resistance of the needle-shapedelectrically conductive elements. The needle-shapedelectrically conductive element may penetrate intoa body of a subject. The magnitude of resistance between the two needle-shapedelectrically conductive elements could be measured by the resistance measuring element. The magnitude of resistance between the two needle-shaped electrically conductive elements will become higher because of the skin surface without blood vessels or body fluids. If the needle-shaped electrically conductive elementspenetrate into the dermis layer of the subject, the magnitude of resistance between the two needle-shaped electrically conductive elements will be lower at the moment when the needle-shaped electrically conductive element is attained to the dermis layer.

Figure 4 a-b are cross-section views of the microneedle array chip 100 along the line A-A’of Figure 1. In the first embodiment, Figure 4a shows the initial condition while the microneedle array chip 100 is contacting the skin surface 102 of a limb of a subject. The communication unit 150 of the microneedle array chip 100receives and transmits physical signals of the subject to the micro-controller 140. The micro-controller 140 analyzes the physical signals and generates position control signals. The driving unit 180 receives the position control signals and drives the removable substrate 130 to move along the direction toward to the skin surface 102 of the subject. The displacement distanceof the removable substrate 130 is dependent on the physical signals of the subject.

As shown in the Figure 4b, the top portion of the protrusion structure 1322 of the microneedle array 132 gradually inserts into the skin surface 102 of the limb of the subject while the removable substrate 130 is moving, and the driving unit 180 will stop removing the removable substrate 130 until the top portion of the protrusion structure 1322 of the microneedle array 132 has been entered into the limb of the subject for extracting the body fluid of the subject, such as blood or enchyma. The conductive structure 134 of the microneedle array 132 transmits the body fluid of the subject to the detecting device190 for collecting the body fluid of the subject. When the previous process has completed, the height of the top portion of the protrusion structure 1322 of the microneedle array 132 will be adjusted to less or equal than the height of the plate of the opening of the microneedle array chip 100. The detecting device 190 generates a detecting signal and transmits to the communication unit 150, and the communication unit 150 transmits the detecting signal to the external electronic apparatus for outputting the detection result.

Figure 5 is a schematic view of themicroneedle array chip 200 in accordance with the presentof the second embodiment. The second embodiment is substantiallysimilar to the first embodiment, with the primary difference being that the driving unit 280 is a magnetic unit including a first magnetic element 282 arranged on the bottom substrate 220 and a second magnetic element 284 arranged on the removable substrate 230 opposing to the first magnetic element 282. The first magnetic element 282 and thesecond magnetic element 284 are wound with conducting coils. A magnetic repelling force is formed between the first magnetic element 282 and the second magnetic element 284 to push or pull the removable substrate 230 toward to the skin surface 202 of a limb of a subject while the driving unit 280 receives a position control signal from the micro-controller 240. The top portion of the microneedle array 232 of the removable substrate 230 gradually inserts into the skin surface 202 of the limb of the subject until the top portion of the protrusion structure 2322 of the microneedle array 232 is contacting or inside the skin tissue layer 204. The magnetic repelling force formed between the first magnetic element 282 and the second magnetic element 284 will gradually decrease while the top portion of the microneedle 232 is more closed to the skin tissue layer 204. The protrusion structure 2322 may penetrate the skin surface of the subject to obtain the body fluid of the subject and the physical signal of the subject while the magnetic repelling force is equal to the drag of inserting the microneedle array 232 into the skin surface 202when the removable substrate 230is undertheforce balanced status. When the previousprocess has completed, the height of the top portion of the protrusion structure 2322 of the microneedle array 232 will be adjusted to less or equal than the height of the plate of the opening of the microneedle array chip 200 by the magnetic force provided from the driving unit 280 to push or pull the removable substrate 230. In the second embodiment, the detecting unit 270 is consisted of a magnetic sensor for detecting the distance between the removable substrate 230 and the bottom substrate 220.

Figure 6 is a schematic view of themicroneedle array chip 300 in accordance with the presentof the third embodiment. The third embodiment is substantiallysimilar to the first embodiment, with the primary difference being that the driving unit 380 is a heating unit arranged between the bottom substrate 320 and the removable substrate 330. A confined space is consisted of the removable substrate 330, a protecting covering 310 and the bottom substrate 320. The driving unit 380 heats the filling material inside the confined space that expands the volume size of the filling materialto push or pull the removable substrate 330 toward to the direction of the skin surface 302 of a limb of a subject. The temperature of the filling material inside the confined space will be fixed for stabilizing the position of the removable substrate 330 when the top portion of the protrusion structure 3322 of the microneedle array 332 contacts or enters into the limb of the subject for stablyextractingthe body fluid or the physical signal of the subject. When the previous process has completed, the microneedle array chip 300 provides athermal convection, a thermal conduction, a water-cooling or a wind-cooling mean fordecreasing the temperature of the air of the confined space to move the position of the removable substrate 330. The top portion of the protrusion structure 3322 of the microneedle array 332 will be less than the height of the plane of the opening of the microneedle array chip 300. It is another mean to decrease the temperature by directly removing the microneedle array chip 300 when the previous process has completed. The filling material of the present embodiment could be but not limited to gaseous mediums or gel materials, wherein the gaseous mediums could be but not limited nitrogen, oxygen, carbon dioxide, inert gas or a combination thereof.

Figure 7 is a schematic view of themicroneedlearray chip 400 in accordance with the presentof the forth embodiment. The forth embodiment is substantiallysimilar to the first embodiment, with the primary difference being that the top portion of each protrusion structure 4322 of the microneedle array chip 432 is a flat-topped columnarshape. The conductive structure 434 may delivery conducting liquids or conducting gels to wet the top of the protrusion structure 4322, an external detecting device 406 is used to detect the existence of the skin surface 302, and the driving unit 480 is used to push or pull the removable substrate 430 to make the top of the protrusion structure 4322 contact the skin surface 402 for detecting the physiological signals of the body of the subject. The conducting liquids or conducting gelsare made of one or more materials such as water, alcohol, sodium chloride orhydrophilic polymer or a combination there of.

Although the present invention has been described in connection with certain specific embodiments for instructional purposes, the present invention is not limited thereto. Accordingly, various modifications, adaptations, and combinations of various features of the described embodiments can be practiced without departing from the scope of the invention as set forth in the claims.

Claims

A microneedle array chip comprising:

a first substrate;

a second substrate opposite to the first substrate;

a driving unit positioned between the first substrate and the second substrate;

a microneedle array coupled to the second substrate; and

a controller coupled to the first substrate and connected with the driving unit.
The microneedle array chip as claimed in claim 1, the microneedle array includes a conductive structure.
The microneedle array chip as claimed in claim 1, the microneedle array includes one or more protrusion structures arranged on a surface of the microneedle array away from the first substrate.
The microneedle array chip as claimed in claim 1, the microneedle array includes one or more protrusion structure that is consisted of electrode structure.
The microneedle array chip as claimed in claim 1, the microneedle array includes one or more protrusion structures, each one protrusion structureis characterized in a flat-topped columnarshape.
The microneedle array chip as claimed in claim 1, the driving unit includes a mechanical transmission component coupled to the second substrate.
The microneedle array chip as claimed in claim 1, the microneedle array chip includes a communication unit positioned on the first substrate.
The microneedle array chip as claimed in claim 1, the driving unit includes a heating component installed between the first substrate and the second substrate.
The microneedle array chip as claimed in claim 1, the driving unit is a magnetic unit included a first magnetic element arranged on the first substrate and a second magnetic element arranged on the second substrate opposing to the first magnetic element.
The microneedle array chip as claimed in claim 1, the microneedle array chip includes a detecting unit connected to the controller for detectinga distance between the first substrate and the second substrate.
The microneedle array chip as claimed in claim 1, the microneedle array chip includes at least two needle-shapedelectrically conductive elements and one resistance measuring element, both of the needle-shapedelectrically conductive elements are coupled to the second substrate.
The microneedle array chip as claimed in claim 2, the conductive structurecomprises one or more micro-channels.
The microneedle array chip as claimed in claim 2, the conductive structureis consisted of one or more electrically conductive units.
The microneedle array chip as claimed in claim 2, the microneedle array chip includes a detecting device connected to the conductive structure.
The microneedle array chip as claimed in claim 10, the detecting unit includes two electrically conductive units and one measuring unit, one of the electrically conductive units is arranged on the first substrate and the other electrically conductive unit is arranged on the second substrate opposing to the electrically conductive unit arranged on the first substrate.
A microneedle array chip comprising:

a first substrate;

a second substrate opposite to the first substrate;

a driving unit positioned between the first substrate and the second substrate;

a microneedle array coupled to the second substrate; and

a controller coupled to the second substrate, and connected with the driving unit.
The microneedle array chip as claimed in claim 16, the microneedle array chip includes a detecting unit connected to the controller for detectinga distance between the first substrate and the second substrate.
The microneedle array chip as claimed in claim 16, the microneedle array includes one or more protrusion structures, each one protrusion structureis characterized in a flat-topped columnarshape.