KR101679777B1 - Patch type electrochemical biosensor and method of manufacturing the same - Google Patents

Abstract

The present invention relates to a patch-type electrochemical biosensor and a manufacturing method thereof. A patch type electrochemical biosensor includes a substrate, an electrode portion, and a micro needle array. The electrode portion is patterned on the substrate. The microneedle array includes a plurality of microneedles. Each micro needle has a support, a biocompatible membrane formed around the periphery of the support, a catalyst electrode formed on the top of the support, and a biodegradable tip surrounding the catalyst electrode. A plurality of micro-needles are arranged standing on the electrode portion and connected through respective supports.

Description

[0001] The present invention relates to a patch type electrochemical biosensor and a manufacturing method thereof,

The present invention relates to a micro-TAS (Micro Total Analysis System) field for analyzing biological signals using a micro / nano structure, and a patch type micro analyzer for use in a continuous bio-signal monitoring field for continuously measuring bio- To an electrochemical biosensor.

Conventional commercially available needles for drug injection purposes have a diameter of several hundred micrometers to several millimeters, which can cause a patient to feel rejection and hemorrhage can occur. However, since the needles directly inject drugs into the body, there is an advantage that they are more effective than patients taking the drugs. Therefore, the needles are still universally used.

Recently, a patch type micro needle has appeared to overcome the above-described disadvantages. The micro needle is a needle having a small diameter like the mouth of a mosquito, and has a merit that it can reduce the burden on the user. In addition, the drug delivery device using the patch type micro needle is small and light, so that the user can comfortably use the drug. This drug delivery mechanism is one of the best techniques for patients who need medication through needles in a small African country where there are few doctors.

On the other hand, since the conventional blood sampling method has a disadvantage that it can not be continuously monitored and has a disadvantage of being one-time, the micro needle can be considered to overcome the above-mentioned drawbacks. However, the existing patch type micro needle is being commercialized only for drug delivery, and the research is actively performed in the field of drug delivery system.

Recently, a continuous bio-signal monitoring system capable of continuously measuring biological information such as blood glucose, cholesterol, and lactic acid, which requires continuous monitoring, has appeared. However, recent commercialized systems have the disadvantage that they need to be pierced to the patient's skin to a certain depth using a needle, which can cause a psychological burden on the user and bleeding.

The present invention provides a patch-type electrochemical biosensor capable of real-time monitoring by measuring biometric information while minimizing anxiety and pain of a patient, and a method of manufacturing the same.

According to an aspect of the present invention, there is provided a patch type electrochemical biosensor comprising a substrate, an electrode unit, and a micro needle array. The electrode portion is patterned on the substrate. The microneedle array includes a plurality of microneedles. Each micro needle has a support, a biocompatible membrane formed around the periphery of the support, a catalyst electrode formed on the top of the support, and a biodegradable tip surrounding the catalyst electrode. A plurality of micro-needles are arranged standing on the electrode portion and connected through respective supports.

In the method of manufacturing a patch-type electrochemical biosensor according to the present invention, a substrate having at least an upper surface portion of an insulating property is provided. Then, the electrode portion is patterned with a conductive material on the substrate. Then, supports are formed of a conductive material on the electrode portion. A biocompatible membrane is then formed around the perimeter of each support except for the top of each. A biodegradable tip is then formed to enclose each top portion of the supports.

In the method of manufacturing a patch-type electrochemical biosensor according to the present invention, a substrate is first prepared. The substrate is then cut into a plurality of support body bodies, and then the incised support body bodies are vertically erected. Next, an electrode portion is patterned with a conductive material on the substrate, and electrode supporting conductors are formed from conductive materials so as to be connected to the electrode portions on each surface of the support body bodies, thereby forming supports. A biocompatible membrane is then formed around the perimeter of each support except for the top of each. A biodegradable tip is then formed to enclose each top portion of the supports.

According to the present invention, since the microneedle array is inserted into the skin layer outermost of the skin and biometric information is measured through the catalytic electrode of the microneedles, the patient's anxiety and pain due to the insertion of the microneedles into the skin can be minimized . In addition, it is possible for the patient to insert the micro needle array into the skin through an auxiliary instrument or the like without direct feeling of discomfort. The user can monitor the biological information measured from the micro needle array inserted into the skin through a smart phone, a tablet PC, a smart watch, or the like in real time.

According to the present invention, in a continuous bio-information measuring and recording apparatus, it is possible to accurately confirm biometric information characteristics in a body and necessity of injection of a drug, and to monitor such information in real time to transmit data to a facility such as a hospital It is possible to build a possible integrated system.

1 is a perspective view of a patch-type electrochemical biosensor according to an embodiment of the present invention.
Fig. 2 is a plan view of Fig. 1. Fig.
Fig. 3 is a cross-sectional view of the microneedles in Fig. 1;
FIG. 4 is a view for explaining an example of use of the patch-type electrochemical biosensor shown in FIG.
5 is a cross-sectional view showing a microneedle including another example of a support.
6 to 8 are plan views respectively showing other examples of the shapes of the working electrode and the auxiliary electrode.
9 is a plan view showing a patch-type electrochemical biosensor having electrode portions of another example.
FIGS. 10A to 10E are views for explaining a method of manufacturing a patch-type electrochemical biosensor according to an embodiment of the present invention.
11A to 11D are views for explaining a method of manufacturing a patch-type electrochemical biosensor according to another embodiment of the present invention.

The present invention will now be described in detail with reference to the accompanying drawings. Here, the same reference numerals are used for the same components, and a detailed description of known functions and configurations that may unnecessarily obscure the gist of the present invention will be omitted. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art. Accordingly, the shapes and sizes of the elements in the drawings and the like can be exaggerated for clarity.

1 is a perspective view of a patch-type electrochemical biosensor according to an embodiment of the present invention. Fig. 2 is a plan view of Fig. 1. Fig. Fig. 3 is a cross-sectional view of the microneedles in Fig. 1;

1 to 3, a patch-type electrochemical biosensor 100 includes a substrate 110, an electrode unit 120, and a micro needle array 130.

The substrate 110 may be configured such that at least the upper surface portion is insulating. The substrate 110 may be an insulating substrate whose entire portion is made of nonconductive material. The electrode portion 120 is pattern-formed on the substrate 110. The electrode unit 120 may be made of a conductive material such as nickel, gold, or the like.

For example, the electrode unit 120 includes a working electrode 121 and an auxiliary electrode 122. That is, the electrode unit 120 is composed of two electrodes. In the measurement of a biological signal, a potential is applied to the working electrode 121 with reference to the auxiliary electrode 122. (+) Potential or (-) potential may be applied to the working electrode 121. [ Then, the living body signal of the current type can be measured through the working electrode 121 and the auxiliary electrode 122.

The working electrode 121 and the auxiliary electrode 122 may be respectively disposed in the form of a longitudinal comb. The shape of the comb having the vertical comb is in the form of a comb in which a plurality of combs are arranged vertically with respect to the comb body. The comb body 121a of the working electrode 121 may be disposed on one edge of the substrate 110 and the comb body 122a of the auxiliary electrode 122 may be disposed on the opposite edge of the substrate 110. [ The vertical comb 121b of the working electrode 121 may be alternately arranged with the vertical comb 122b of the auxiliary electrode 122. [

The micro needle array 130 includes a plurality of micro needles 131. Each micro needle 131 has a support 132, a biocompatible membrane 133, a catalytic electrode 134, and a biodegradable tip 135. These microneedles 131 are arranged on the electrode part 120 in plural numbers and are connected through the respective supporting parts 132. When the electrode unit 120 is composed of the working electrode 121 and the auxiliary electrode 122, a plurality of micro needles 131 may be arranged in the working electrode 121 and the auxiliary electrode 122, respectively.

The support base 132 serves to support the micro needle 131. The support part 132 may be made of a conductive metal such as gold, platinum, or the like. The support 132 may be in the form of a cylinder having a micro-scale diameter, such as the mouth of a mosquito. Although not shown, the supporter 132 may serve as a passage for moving the drug when the drug is injected.

The biocompatible membrane 133 is formed around the periphery of the top 132 of the support 132. The biocompatible membrane 133 may be made of a biocompatible polymer material such as parylene. The biocompatible membrane 133 serves to electrically isolate the supporter 132 of the conductive metal from the tissue fluid in the body and to protect the micro needle 131.

The catalytic electrode 134 is formed at the upper end of the supporter 132. The catalytic electrode 134 facilitates the oxidation reaction of glucose contained in a living body such as blood, thereby enabling a bio-signal related to blood glucose to be electrochemically measured. Also, the catalytic electrode 134 may electrochemically measure bio-signals related to biometric information such as cholesterol, lactic acid, and the like. The catalytic electrode 134 may be an enzyme-based catalytic electrode. In this case, the catalytic electrode 134 may be formed by immobilizing enzyme such as gold or platinum. As another example, the catalytic electrode 134 may be a catalytic electrode based on an inert gas. In this case, the catalyst electrode 134 may be made of platinum or the like. The catalytic electrode 134 has a nanoporous structure to increase the surface area, thereby maximizing the oxidation reaction of glucose. When the entire portion of the support member 132 is made of gold or platinum or the like as the catalyst electrode 134, the catalyst electrode 134 may be omitted.

The biodegradable tip 135 surrounds the catalyst electrode 134. The biodegradable tip 135 protects the catalyst electrode 134 before the micro needle 131 is inserted into the skin and serves to pierce the skin when inserted into the skin. The biodegradable tip 135 may have a pointed shape that facilitates skin insertion. When the biodegradable tip 135 is inserted into the skin, it naturally melts inside the body to expose the catalytic electrode 134. Therefore, the catalytic electrode 134 is capable of electrochemically measuring the biological signal. The biodegradable tip 135 may be made of a biodegradable polymer material such as PLGA made of polylactic acid (PLA), polyglycolic acid (PGA), or a co-polymer thereof.

The patch type electrochemical biosensor 100 described above has flexibility in that the micro needles 131 of the micro needle array 130 are formed in a microscale shape so that the user can easily grasp the skin 1 of the body, It is easy to paste and use. The micro needle 131 is inserted into the epidermis at a depth of 500 탆 or less of the skin 1 and can measure biological information such as blood glucose, cholesterol, and lactic acid through blood or an interstitial fluid (ISF). The measured biometric information is transmitted to the monitoring device 3 such as a smart phone, a tablet PC, a smart watch or the like via the wireless communication module 2 such as a Bluetooth or an RF module, Information can be conveniently and continuously monitored.

5 is a cross-sectional view showing a microneedle including another example of the supporter 232. Fig. 5, in the micro needle 231, the support table 232 is formed of a material such as stainless steel or the like, and the insulating plate 232b and the electrode connection wire 232b are formed around the support table body 232a. (232c) may be sequentially formed. The biocompatible membrane 233 is formed at the perimeter of each of the supports 232 except for the upper end. The catalytic electrode 234 is formed at each upper end of the supports 232. The biodegradable tip 235 is formed to surround the catalytic electrode 234.

6 is a view showing another example of the working electrode and the auxiliary electrode. As shown in FIG. 6, the working electrode 321 and the auxiliary electrode 322 may be in the form of a diagonal comb. The shape of a comb having a diagonal comb is a comb shape in which a plurality of combs are arranged at an angle to the comb body. The comb body 321a of the working electrode 321 may be disposed on one edge of the substrate 110 and the comb body 322a of the auxiliary electrode 322 may be disposed on the opposite edge of the substrate 110. [ The diagonal comb teeth 321b of the working electrode 321 may be alternately arranged with the diagonal comb teeth 322b of the auxiliary electrode 322. [

As another example, as shown in Fig. 7, the working electrode 421 and the auxiliary electrode 422 may be arranged on the substrate 110 in a rectangular shape. As another example, as shown in Fig. 8, the working electrode 521 and the auxiliary electrode 522 may be disposed on the substrate 110 in a spiral form. In this case, the working electrode 521 and the auxiliary electrode 522 can be arranged side by side along the spiral direction.

9, the electrode unit 620 may include a working electrode 621, an auxiliary electrode 622, and a reference electrode 623. That is, the electrode unit 620 may be formed of three electrodes. A potential is applied to the working electrode 621 on the basis of the reference electrode 623. (+) Potential or (-) potential may be applied to the working electrode 621. [ Then, a living body signal in the form of a current can be measured through the working electrode 621 and the auxiliary electrode 622. A phenomenon that the potential applied to the working electrode 621 in the electrochemical reaction is shaken by the chemical reaction in the electrolyte may be generated. In order to correct this phenomenon, the reference electrode 623 is used.

The working electrode 621 and the auxiliary electrode 622 may be in the form of a comb having a vertical comb. The reference electrode 623 may be disposed on the substrate 110 in strip form along one edge of the substrate 110. As another example, the working electrode and the auxiliary electrode may be arranged on the substrate in the form of a comb having a diagonal comb, a rectangular shape, a spiral shape or the like, as in the above-described example.

A method of manufacturing a patch-type electrochemical biosensor according to an embodiment of the present invention will be described with reference to FIGS. 10A to 10E. Here, a method of manufacturing the patch-type electrochemical biosensor shown in Figs. 1 to 3 will be exemplified.

First, a substrate 110 having an insulating property at least on the upper surface portion is provided. The substrate 110 may be provided with an insulating substrate whose entire portion is nonconductive. Then, as shown in Fig. 10A, the electrode portion 120 is patterned with a conductive material on the substrate 110. Then, as shown in Fig. At this time, the working electrode 121 and the auxiliary electrode 122 may be pattern-formed on the substrate 110 by vapor deposition or the like. The working electrode 121 and the auxiliary electrode 122 can be formed in the form of a comb having vertical combs. Of course, the working electrode 121 and the auxiliary electrode 122 may be formed in different forms as described above.

Then, the supporting members 132 are formed of a conductive material on the electrode unit 120. [ 10B, a mold 10 having a plurality of holes 11 corresponding to the respective shapes of the supporting members 132 is used and the supporting member 132 is mounted on the electrode unit 120 by electroplating or the like, Lt; / RTI >

Next, as shown in FIG. 10C, a biocompatible film 133 is formed on the periphery of each of the supports 132 except for the upper end portions. At this time, the periphery of the supporting members 132 may be coated with a biocompatible polymer material, and then the top portion of the biocompatible film 133 may be etched using a shadow mask.

Then, as shown in FIG. 10D, a catalyst electrode 134 is formed at each upper end portion of the supports 132. Next, as shown in FIG. 10E, a biodegradable tip 135 is formed to surround the catalyst electrode 134. It is also possible to form the biodegradable tip 135 so as to surround each upper end portion of the supporters 132 without forming the catalyst electrode 134. After the above-described process, a plurality of micro needles 131 are arranged on the electrode unit 120 to form the micro needle array 130.

A method of manufacturing a patch-type electrochemical biosensor according to another embodiment of the present invention will be described with reference to FIGS. 11A to 11D. Here, a method of manufacturing a patch-type electrochemical biosensor including the micro-needles shown in FIG. 5 will be described.

First, a substrate 210 is provided. At this time, the substrate 210 may be formed of a conductive material such as stainless steel or the like. Then, as shown in FIG. 11A, the substrate 210 is cut into a plurality of support base bodies 232a, and then the cut support base bodies 232a are set up vertically, as shown in FIG. 11B. At this time, a plurality of support base bodies 232a can be cut by lancing the substrate 210 by cutting, laser cutting, etching, or the like. Next, an insulating film 232b is formed on the upper surface of the substrate 210 and each surface of the supporting body 232a. When the substrate 210 is formed of an insulating substrate, the process of forming the insulating film 232b may be omitted.

Next, as shown in FIG. 11C, the electrode unit 220 is patterned on the substrate 210 with a conductive material. At this time, the working electrode 221 and the auxiliary electrode 222 can be pattern-formed. An electrode connection wire 232c is formed of a conductive material so as to be connected to the electrode unit 220 on the support base bodies 232a to form supports 232. When the insulating film 232b is formed on the support body 232a, an electrode connecting lead 232c is formed on the surface of the insulating film 232b. The working electrode 221, the auxiliary electrode 222, and the electrode connecting wire 232c may be patterned by vapor deposition or the like.

Then, as shown in FIG. 11D, a biocompatible film 233 is formed at a peripheral portion excluding the upper end portions of the support rods 232. At this time, the periphery of the support may be coated with a biocompatible polymer material, and then the top portion of the biocompatible film may be etched using a shadow mask.

Then, a catalyst electrode 234 is formed on each upper end of the support bars 232, and a biodegradable tip 235 is formed to surround the catalyst electrode 234, as in the above-described embodiment. It is also possible to form the biodegradable tip 235 so as to surround each upper end portion of the supporter 232 without forming the catalyst electrode 234.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is clearly understood that the same is by way of illustration and example only and is not to be taken by way of limitation and that those skilled in the art will recognize that various modifications and equivalent arrangements may be made therein. It will be possible. Accordingly, the true scope of protection of the present invention should be determined only by the appended claims.

110, 210. Substrate 120, 220, 620. Electrode
130 .. Micro needle array 131, 231 .. Micro needle
132, 232 .. support 1 33, 233 .. biocompatible membrane
134, 234. Catalytic electrode 135, 235. Biodegradable membrane

Claims (9)

delete delete Board;
An electrode part patterned on the substrate; And
A plurality of micro needles each having a biocompatible membrane formed around a support and a top portion of the support, a plurality of micro needles each having a catalyst electrode formed on an upper end of the support and a biodegradable tip surrounding the catalyst electrode, And a micro needle array connected through each support,
Wherein the electrode portion comprises a working electrode and an auxiliary electrode;
The working electrode and the auxiliary electrode may be arranged in any one of a rectangular shape, a longitudinal comb shape, a diagonal comb shape, and a spiral shape, A patch type electrochemical biosensor.
Board;
An electrode part patterned on the substrate; And
A plurality of micro needles each having a biocompatible membrane formed around a support and a top portion of the support, a plurality of micro needles each having a catalyst electrode formed on an upper end of the support and a biodegradable tip surrounding the catalyst electrode, And a micro needle array connected through each support,
Wherein the electrode portion comprises a working electrode, an auxiliary electrode, and a reference electrode;
The working electrode and the auxiliary electrode may be arranged in any one of a rectangular shape, a longitudinal comb shape, a diagonal comb shape, and a spiral shape, A patch type electrochemical biosensor.
The method according to claim 3 or 4,
Wherein the catalyst electrode comprises any one of an enzyme-based catalyst electrode and a reactive-based catalyst electrode.
delete Providing a substrate;
Cutting the substrate into a plurality of support base bodies, and then vertically erecting the support base bodies;
Patterning the electrode portion with a conductive material on the substrate;
Forming electrode supports on the surface of each of the support members by forming an electrode connection conductor with a conductive material so as to be connected to the electrode unit;
Forming a biocompatible membrane around the perimeter of each of the supports; And
Forming a biodegradable tip around each upper end of the support;
The method comprising the steps of:
8. The method of claim 7,
Prior to forming the biodegradable tip on each upper portion of the supports,
Further comprising the step of forming a catalyst electrode on each upper end portion of the supporter.
8. The method of claim 7,
When the substrate is provided as a conductor,
Before the step of patterning the electrode part with a conductive material on the substrate,
Further comprising forming an insulating layer on the upper surface of the substrate and each surface of the supporting body bodies.

Images