Sensor and preparation method and application thereof

Abstract

The invention provides a sensor and a preparation method and application thereof, and belongs to the technical field of bioelectronics and flexible wearable medical equipment. According to the sensor provided by the invention, the low noise characteristic of an oxide semiconductor (such as an amorphous indium gallium zinc oxide a-IGZO) thin film transistor can be combined with the enzyme specificity of the microneedle sensor, so that high-gain amplification of a weak biological signal is realized, and the sensor has higher sensitivity and detection limit. The microneedle array is in direct contact with interstitial fluid by penetrating through the skin cuticle, compared with a traditional surface electrode for sweat detection, the physiological marker level of the microneedle array is closer to the actual level, the signal attenuation problem can be avoided, the contact area with target molecules can be remarkably increased through the large surface area of the microneedle array, and the electrochemical reaction efficiency is improved.

Description

Technical Field

[0001] The present invention belongs to the technical fields of bioelectronics and flexible wearable medical devices, and particularly relates to a sensor, a preparation method thereof, and an application thereof. Background Art

[0002] Currently, blood glucose detection mainly relies on finger-prick blood sampling and electrochemical test strips, which have problems such as high invasiveness, cumbersome operation, and the need to frequently replace test strips. In addition, the sensitivity of traditional enzyme electrode sensors is limited by the electrode material and the noise suppression level of the signal amplification circuit, making it difficult to achieve accurate detection of low-concentration biomarkers.

[0003] In recent years, microneedle technology has been widely used in transdermal detection due to its minimally invasive and painless characteristics. However, its application still faces the following problems: the tiny contact area of microneedles results in low electrochemical signal intensity, requiring support from a high-performance amplifier; insufficient integration: existing microneedle sensors mostly rely on external bulky signal processing devices, making it difficult to achieve miniaturization and wearability. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a sensor, a preparation method thereof, and an application thereof. The sensor provided by the present invention can achieve high-gain amplification of weak biological signals, has higher sensitivity and detection limit, and can achieve wearability.

[0005] To achieve the above purpose, the present invention provides the following solutions:

[0006] The present invention provides a sensor, comprising a single-stage amplifier and a microneedle array sensor; the single-stage amplifier includes a metal oxide thin-film transistor;

[0007] The microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array, a first Ag layer coated on the surface of the microneedles, and an enzyme immobilization layer; the reference electrode includes a second microneedle array, a second Ag layer coated on the surface of the microneedles, and an AgCl layer;

[0008] The single-stage amplifier is connected to the working electrode through a wire.

[0009] Preferably, the metal oxide thin-film transistor includes a substrate, a core layer, and a passivation layer stacked in sequence from bottom to top;

[0010] The core layer includes a bottom gate electrode layer, a gate insulating layer, and an active layer stacked in sequence from bottom to top, a source electrode layer and a drain electrode layer covering a part of the upper surface of the active layer, and an etching stop layer covering the exposed part of the active layer;

[0011] The bottom gate electrode layer includes a first bottom gate electrode layer and a second bottom gate electrode layer which are arranged at intervals; the active layer includes a first active layer and a second active layer which are arranged at intervals; the source electrode layer includes a first source electrode layer and a second source electrode layer which are arranged at intervals; the drain electrode layer includes a first drain electrode layer and a second drain electrode layer which are arranged at intervals;

[0012] The first drain electrode layer is connected to the second source electrode layer, the first source electrode layer is grounded, and the first bottom gate electrode layer is the signal input terminal; the second bottom gate electrode layer is short - circuited with the second drain electrode layer.

[0013] Preferably, the active layer includes an N - type metal oxide thin film.

[0014] Preferably, the N - type metal oxide thin film includes an a - IGZO thin film, and the thickness of the active layer is 10 - 50 nm.

[0015] Preferably, the first bottom gate electrode layer, the first source electrode layer, the first drain electrode layer, the second bottom gate electrode layer, the second source electrode layer and the second drain electrode layer independently include a metal layer, and the thickness is independently 100 - 200 nm; the gate insulating layer includes a first non - metal oxide layer and a non - metal nitride layer, and the total thickness is 50 - 250 nm; the etching stop layer includes a second non - metal oxide layer, and the thickness is 100 - 200 nm; the passivation layer includes a third non - metal oxide layer, and the thickness is 100 - 200 nm.

[0016] Preferably, the first micro - needle array and the second micro - needle array independently include a plurality of conical micro - needles. The height of the needle body of the conical micro - needle is 600 - 1000 μm, the bottom diameter is 50 - 300 μm, the interval between the conical micro - needles is 100 - 300 μm, and the top diameter is 10 - 30 μm.

[0017] Preferably, the metal layer includes a molybdenum layer, an aluminum layer or a copper layer; the first non - metal oxide layer, the second non - metal oxide layer and the third non - metal oxide layer independently include a silicon dioxide layer; the non - metal nitride layer includes a silicon nitride layer.

[0018] The present invention provides a preparation method of the sensor described in the above - mentioned scheme, including the following steps:

[0019] Connect the metal - oxide thin - film transistor in the single - pole amplifier to the working electrode of the micro - needle array sensor through a wire to obtain the sensor;

[0020] The micro - needle array sensor includes a reference electrode and a working electrode; the working electrode includes a first micro - needle array and a first Ag layer and an enzyme - immobilized layer coated on the surface of the micro - needles; the reference electrode includes a second micro - needle array and a second Ag layer and an AgCl layer coated on the surface of the micro - needles.

[0021] Preferably, the thicknesses of the first Ag layer and the second Ag layer are independently 50 to 200 nm.

[0022] The present invention provides an application of the sensor described in the above solution or the sensor prepared by the preparation method described in the above solution in the preparation of a wearable device.

[0023] The present invention provides a sensor, comprising a unipolar amplifier and a microneedle array sensor; the unipolar amplifier includes a metal oxide thin film transistor; the microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array and a first Ag layer and an enzyme immobilization layer coated on the surface of the microneedles; the reference electrode includes a second microneedle array and a second Ag layer and an AgCl layer coated on the surface of the microneedles; the unipolar amplifier is connected to the working electrode through a wire. The sensor provided by the present invention can utilize the low-noise characteristics of an oxide semiconductor (such as amorphous indium gallium zinc oxide a-IGZO) thin film transistor and the enzyme-specific binding of the microneedle sensor to achieve high-gain amplification of weak biological signals, having higher sensitivity and detection limit. The microneedle array directly contacts the interstitial fluid by penetrating the stratum corneum of the skin. Compared with the traditional surface electrode for detecting sweat, the physiological marker level is closer to the actual level, and the problem of signal attenuation can be avoided. Its large surface area can significantly increase the contact area with the target molecule and improve the electro-chemical reaction efficiency.

[0024] Furthermore, the oxide semiconductor (such as a-IGZO) has a high carrier mobility (>10 cm 2 / V·s) and a low defect state density, and the noise of the oxide semiconductor thin film transistor (TFT) is 1 to 2 orders of magnitude lower than that of the traditional silicon-based device. This enables the amplifier prepared by this TFT to effectively suppress noise and retain the details of the original signal. For the unipolar amplifier composed of a diode load, its driving part (denoted as M1) and load part (denoted as M2) cooperate. M1 serves as the amplifying transistor, and its first bottom gate electrode layer receives the input signal of the microneedle array sensor; the second bottom gate electrode layer is short-circuited with the second drain electrode layer to form the diode load part, providing a non-linear impedance. When the input signal changes, the transconductance of M1 and the dynamic impedance of M2 act together to achieve a voltage gain (typical value >20 dB), and at the same time, better input impedance matching can reduce signal transmission loss. The present invention combines the unipolar amplifier of the metal oxide thin film transistor and the microneedle array sensor, and the minimum current detection limit of the system can reach 1 nM, and the linear range is 0.1 to 20 mM. The microneedle array sensor and the unipolar amplifier are directly integrated on the substrate through metal interconnection, and the signal transmission path is shortened to the millimeter level, avoiding the electromagnetic interference and parasitic capacitance effect introduced by long wires. The response time after signal amplification is <10 seconds (traditional system >30 seconds), meeting the real-time monitoring requirements. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0026] Figure 1 Schematic diagram of the structure of the metal oxide thin film transistor unipolar amplifier prepared in Example 1;

[0027] Figure 2 Schematic diagram of the preparation process of the metal oxide thin film transistor unipolar amplifier in Example 1;

[0028] Figure 3 Schematic diagram of the preparation process of the microneedle array sensor in Example 1;

[0029] Figure 4 Physical diagram of the PDMS mold in Example 1;

[0030] Figure 5 Schematic diagram of the structure of the microneedle array sensor in Example 1;

[0031] Figure 6 Schematic diagram of the structure of the sensor in Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0032] The present invention provides a sensor, including a unipolar amplifier and a microneedle array sensor; the unipolar amplifier includes a metal oxide thin film transistor; the microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array, a first Ag layer and an enzyme immobilization layer coated on the surface of the microneedles; the reference electrode includes a second microneedle array, a second Ag layer and an AgCl layer coated on the surface of the microneedles; the unipolar amplifier is connected to the working electrode through a wire.

[0033] Unless otherwise specified, the materials and equipment used in the present invention are all commercially available products.

[0034] In the present invention, the metal oxide thin film transistor preferably includes a substrate, a core layer and a passivation layer stacked in sequence from bottom to top;

[0035] The core layer includes a bottom gate electrode layer, a gate insulating layer and an active layer stacked in sequence from bottom to top, a source electrode layer and a drain electrode layer covering a part of the upper surface of the active layer, and an etching stop layer covering the exposed part of the active layer;

[0036] The bottom gate electrode layer includes a first bottom gate electrode layer and a second bottom gate electrode layer which are arranged at intervals; the active layer includes a first active layer and a second active layer which are arranged at intervals; the source electrode layer includes a first source electrode layer and a second source electrode layer which are arranged at intervals; the drain electrode layer includes a first drain electrode layer and a second drain electrode layer which are arranged at intervals;

[0037] The first drain electrode layer is connected to the second source electrode layer, the first source electrode layer is grounded, and the first bottom gate electrode layer is a signal input end; the second bottom gate electrode layer is short - circuited with the second drain electrode layer.

[0038] Preferably, in the present invention, the metal - oxide thin - film transistor is divided into two parts with the same structure along the center line, serving as a driving part and a load part respectively; the core layer of the driving part preferably includes a first bottom gate electrode layer, a gate insulating layer, a first active layer, a first source electrode layer, a first drain electrode layer, and an etching stop layer; the core layer of the load part preferably includes a second bottom gate electrode layer, a gate insulating layer, a second active layer, a second source electrode layer, a second drain electrode layer, and an etching stop layer.

[0039] In the present invention, the first source electrode layer and the first drain electrode layer preferably overlap and are arranged at intervals on the left and right sides above the first active layer respectively, and the interval region forms a first channel; the second source electrode layer and the second drain electrode layer preferably overlap and are arranged at intervals on the left and right sides above the second active layer respectively, and the interval region forms a second channel. In the present invention, the lengths of the first channel and the second channel are preferably independently 50 μm.

[0040] In the present invention, the active layer preferably includes an N - type metal - oxide thin film. In the present invention, the N - type metal - oxide thin film preferably includes an a - IGZO thin film, and the thickness is preferably 10 - 50 nm. In the embodiments of the present invention, it can specifically be 10 nm, 20 nm, 30 nm, 40 nm, or 50 nm.

[0041] In the present invention, the first bottom gate electrode layer, the first source electrode layer, the first drain electrode layer, the second bottom gate electrode layer, the second source electrode layer, and the second drain electrode layer preferably independently comprise a metal layer, and the metal layer preferably comprises a molybdenum layer, an aluminum layer, or a copper layer; the thickness is independently 100 - 200 nm, and in the embodiments of the present invention, it can specifically be 100 nm, 120 nm, 140 nm, 150 nm, 160 nm, 180 nm, or 200 nm; in the present invention, the gate insulating layer preferably comprises a first non-metal oxide layer and a non-metal nitride layer, the first non-metal oxide layer preferably comprises a silicon dioxide layer, and the non-metal nitride layer preferably comprises a silicon nitride layer; the total thickness is preferably 50 - 250 nm, and in the embodiments of the present invention, the thickness of the first non-metal oxide layer can be 50 nm, and the thickness of the non-metal nitride layer can be 200 nm.

[0042] In the present invention, the etching stop layer preferably comprises a second non-metal oxide layer, the second non-metal oxide layer preferably comprises a silicon dioxide layer, and the thickness is preferably 100 - 200 nm, and in the embodiments of the present invention, it can specifically be 100 nm, 120 nm, 140 nm, 160 nm, 180 nm, or 200 nm. In the present invention, the passivation layer preferably comprises a third non-metal oxide layer, the third non-metal oxide layer preferably comprises a silicon dioxide layer, and the thickness is preferably 100 - 200 nm, and in the embodiments of the present invention, it can specifically be 100 nm, 120 nm, 140 nm, 160 nm, 180 nm, or 200 nm.

[0043] In the present invention, the first micro-needle array and the second micro-needle array preferably independently comprise a plurality of conical micro-needles, and in the embodiments of the present invention, the number of each group of micro-needle arrays can be 10×10 (the total number is 100).

[0044] In the present invention, the height of the body of the conical micro-needle is preferably 600 - 1000 μm, and in the embodiments of the present invention, it can specifically be 600 μm, 700 μm, 800 μm, 900 μm, or 1000 μm; the bottom diameter is preferably 50 - 300 μm, and in the embodiments of the present invention, it can specifically be 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, or 300 μm; the interval between the conical micro-needles is preferably 100 - 300 μm, and in the embodiments of the present invention, it can specifically be 100 μm, 120 μm, 140 μm, 160 μm, 200 μm, 220 μm, 250 μm, 280 μm, or 300 μm, and the top diameter is preferably 10 - 30 μm, and in the embodiments of the present invention, it can specifically be 10 μm, 15 μm, 20 μm, 25 μm, or 30 μm.

[0045] The sensor provided by the present invention can utilize the low-noise characteristics of oxide semiconductor (such as amorphous indium gallium zinc oxide a-IGZO) thin-film transistors and the enzyme specificity of the microneedle sensor to achieve high-gain amplification of weak biological signals, with higher sensitivity and detection limit. The microneedle array directly contacts the interstitial fluid by penetrating the stratum corneum of the skin. Compared with the traditional surface electrodes for detecting sweat, the physiological marker level is closer to the actual level, and the signal attenuation problem can be avoided. Its large surface area can significantly increase the contact area with the target molecules and improve the electro-chemical reaction efficiency.

[0046] In addition, oxide semiconductors (such as a-IGZO) have high carrier mobility (>10 cm 2 / V·s) and low defect state density. The noise of oxide semiconductor thin-film transistors (TFTs) is 1-2 orders of magnitude lower than that of traditional silicon-based devices. This enables the amplifier fabricated with this TFT to effectively suppress noise and retain the details of the original signal. For the unipolar amplifier composed of a diode load, its driving part (denoted as M1) and load part (denoted as M2) act synergistically. M1 serves as the amplifying transistor, and its first bottom gate electrode layer receives the input signal from the microneedle array sensor; the second bottom gate electrode layer is short-circuited with the second drain electrode layer to form the diode load part, providing a non-linear impedance. When the input signal changes, the transconductance of M1 and the dynamic impedance of M2 act together to achieve a voltage gain (typical value >20 dB). At the same time, better input impedance matching can reduce signal transmission loss. The present invention combines the unipolar amplifier composed of metal oxide thin-film transistors and the microneedle array sensor. The lowest current detection limit of the system can reach 1 nM, and the linear range is 0.1-20 mM. The microneedle array sensor and the unipolar amplifier are directly integrated on the substrate through metal interconnection. The signal transmission path is shortened to the millimeter level, avoiding the electromagnetic interference and parasitic capacitance effects introduced by long wires. The response time after signal amplification is <10 seconds (traditional system >30 seconds), meeting the requirements of real-time monitoring.

[0047] The present invention provides a preparation method for the sensor described in the above solution, including the following steps:

[0048] Connect the metal oxide thin-film transistor in the unipolar amplifier to the working electrode of the microneedle array sensor through a wire to obtain the sensor;

[0049] The microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array, a first Ag layer coated on the surface of the microneedles, and an enzyme immobilization layer; the reference electrode includes a second microneedle array, a second Ag layer coated on the surface of the microneedles, and an AgCl layer.

[0050] In the present invention, the preparation of the metal oxide thin-film crystal preferably includes the following steps:

[0051] The substrate is subjected to first magnetron sputtering using a first metal target to obtain a first metal thin film, and then the first metal thin film is subjected to first patterning to form a bottom gate electrode layer on the substrate; the bottom gate electrode layer includes a first bottom gate electrode layer and a second bottom gate electrode layer which are arranged at intervals.

[0052] In the present invention, the substrate preferably includes a rigid glass substrate or a flexible material substrate. The present invention has no requirements for the size and shape of the substrate, and it can be selected according to the size and shape acceptable by the sputtering equipment.

[0053] In the present invention, the conditions for the first magnetron sputtering preferably include: the gas flow ratio of argon to oxygen is 60:0.1, the sputtering power is 500 W DC, and the sputtering time is 420 s.

[0054] In the present invention, the first patterning preferably includes spin coating, exposure, development, and etching carried out in sequence. The present invention selects a corresponding developer according to the spin-coated photoresist. In the present invention, the exposure time is preferably 1 - 2 s, and in the embodiments of the present invention, it can specifically be 1 s or 2 s; the development time is preferably 30 - 45 s, and in the embodiments of the present invention, it can specifically be 30 s, 32 s, 35 s, 40 s, 42 s, or 45 s; the present invention preferably uses an aluminum etchant for etching.

[0055] After obtaining the bottom gate electrode layer, the present invention sequentially deposits a first non-metal oxide layer and a non-metal nitride layer on the bottom gate electrode layer to form a gate insulating layer on the bottom gate electrode layer.

[0056] In the present invention, the deposition conditions for the first non-metal oxide layer preferably include: the reaction gases are SiF4 and N2O, and the sputtering temperature is 220 °C; the deposition conditions for the non-metal nitride layer preferably include: the reaction gases are SiF4 and NH3, and the sputtering temperature is 350 °C. The present invention can ensure the density of the thin film by performing high-temperature sputtering at 350 °C.

[0057] After obtaining the gate insulating layer, the present invention performs second magnetron sputtering on the gate insulating layer using a metal oxide target to obtain a metal oxide thin film, and then the metal oxide thin film is sequentially subjected to second patterning and first annealing to form an active layer on the gate insulating layer; the active layer preferably includes a first active layer and a second active layer which are arranged at intervals.

[0058] In the present invention, the conditions for the second magnetron sputtering preferably include: the gas flow ratio of argon to oxygen is 60:7.5, the sputtering time is 390 s, and the power is 300 W.

[0059] In the present invention, the first patterning preferably includes spin coating, exposure, development, and etching performed in sequence; the spin coating, exposure, and development in the second patterning step are preferably the same as those in the first patterning, which will not be elaborated here; the etching in the second patterning step preferably uses oxalic acid.

[0060] In the present invention, the temperature of the first annealing is preferably 200 - 350 °C. In the embodiments of the present invention, it can specifically be 200 °C, 220 °C, 250 °C, 300 °C, 320 °C, 340 °C, or 350 °C, and the time is preferably 1 - 2 h. In the embodiments of the present invention, it can specifically be 1 h, 1.5 h, or 2 h. The present invention improves the defect states of the active layer material through the first annealing.

[0061] After obtaining the active layer, the present invention deposits a second non-metal oxide layer on the active layer, and performs third patterning on the second non-metal oxide layer in sequence to obtain an etch stop layer.

[0062] In the present invention, the preparation of the second non-metal oxide layer is preferably the same as that of the first non-metal oxide layer described above, which will not be elaborated here.

[0063] In the present invention, the third patterning preferably includes spin coating, exposure, development, and etching performed in sequence; the spin coating, exposure, and development in the third patterning step are preferably the same as those in the first patterning, which will not be elaborated here; the etching in the third patterning step preferably uses reactive ion etching.

[0064] After obtaining the etch stop layer, the present invention performs third magnetron sputtering on the etch stop layer using a second metal target to obtain a second metal thin film, and then performs fourth patterning on the second metal thin film to obtain a source electrode layer and a drain electrode layer, forming a core layer on the substrate; the source electrode layer preferably includes a first source electrode layer and a second source electrode layer arranged at intervals; the drain electrode layer preferably includes a first drain electrode layer and a second drain electrode layer arranged at intervals.

[0065] In the present invention, the third magnetron sputtering and the fourth patterning are respectively the same as the first magnetron sputtering and the first patterning described above, which will not be elaborated here.

[0066] In the present invention, the first source electrode layer and the first drain electrode layer are preferably stacked on the left and right sides above the first active layer respectively and arranged at intervals, and the interval region forms a first channel; the second source electrode layer and the second drain electrode layer are preferably stacked on the left and right sides above the second active layer respectively and arranged at intervals, and the interval region forms a second channel.

[0067] After the preparation of the core layer, the present invention preferably performs a second annealing on the obtained device; in the present invention, the temperature of the second annealing is preferably 350 °C, and the time is preferably 90 min.

[0068] After the annealing is completed, the present invention preferably connects the first drain electrode layer and the second source electrode layer, shorts the second bottom gate electrode layer and the second drain electrode layer, and then prepares a passivation layer.

[0069] The present invention preferably deposits a third non-metal oxide layer on the core layer for a fifth patterning to form a passivation layer, thereby obtaining the metal oxide thin film transistor.

[0070] In the present invention, the third deposition is the same as the first deposition, which will not be elaborated herein. In the present invention, the fifth patterning is preferably the same as the third patterning, which will not be elaborated herein.

[0071] In the present invention, the preparation of the microneedle array preferably includes the following steps:

[0072] Inject a photoresist solution into a mold, after vacuum degassing, perform ultraviolet curing on the obtained mold containing the photoresist solution, and obtain the microneedle array after baking.

[0073] In the present invention, the photoresist solution preferably includes an SU-8 photoresist solution; the mold is preferably a PDMS mold, and the surface of the PDMS mold has a negative mold structure corresponding to the shape of the target microneedles.

[0074] In the present invention, the degree of vacuum for the vacuum degassing is preferably 1×10 - 3 Pa to 1×10 - 2 Pa. In the examples of the present invention, it can specifically be 1×10 - 3 Pa or 1×10 -2 Pa; the time for the vacuum degassing is preferably 5 to 10 min. In the examples of the present invention, it can specifically be 5 min, 8 min, or 10 min.

[0075] In the present invention, the wavelength of the ultraviolet light for the ultraviolet curing is preferably 365 nm, and the irradiation intensity is preferably 10 to 50 mW / cm 2 , in the examples of the present invention, it can specifically be 10 mW / cm 2 , 20 mW / cm 2 , 30 mW / cm 2 , 40 mW / cm 2 or 50 mW / cm 2; The time is preferably 1 to 5 minutes. In the embodiments of the present invention, it can specifically be 1 minute, 2 minutes, 3 minutes, 4 minutes, or 5 minutes.

[0076] In the present invention, the baking temperature is preferably 90 °C, and the time is preferably 0.5 to 1 hour. In the embodiments of the present invention, it can specifically be 0.5 hour, 0.6 hour, 0.8 hour, or 1 hour.

[0077] In the present invention, ultraviolet light cures the photosensitive components in SU-8, and under the action of baking, microneedles with sufficient hardness to pierce the skin are obtained.

[0078] In the present invention, the preparation of the working electrode preferably includes the following steps:

[0079] Evaporate and deposit an Ag layer on the surface of the microneedles in the microneedle array and coat with an enzyme solution to form a laminated first Ag layer and enzyme immobilization layer on the surface of the microneedles, thereby obtaining the working electrode.

[0080] In the present invention, the first evaporation and deposition uses a vacuum coating system, and the vacuum degree is preferably 5×10 -4 Pa, and the evaporation rate is preferably 0.2 to 0.5 nm / s.

[0081] In the present invention, the concentration of the enzyme solution is preferably 10 mg / mL; the enzyme in the enzyme solution preferably includes glucose oxidase or lactate dehydrogenase; the enzyme solution is preferably obtained by dissolving the enzyme in a chitosan-acetic acid solution; the mass concentration of chitosan in the chitosan-acetic acid solution is preferably 0.5%; the chitosan-acetic acid solution is preferably obtained by dissolving chitosan in a 1 wt% acetic acid aqueous solution.

[0082] The present invention has no special requirements for the coating, and a well-known method in the art can be used.

[0083] The present invention preferably drops 10 to 15 μL of the enzyme solution onto a microneedle array with an area of 1 cm × 1 cm (each group of microneedle arrays has 10 × 10 microneedles), and the enzyme is fixed to the surface of the first Ag layer through refrigeration to form an enzyme immobilization layer.

[0084] In the present invention, the refrigeration temperature is preferably 4 °C, and the time is preferably 1 to 3 hours. In the embodiments of the present invention, it can specifically be 1 hour, 2 hours, or 3 hours.

[0085] In the present invention, for the microneedle working electrode after immobilization of glucose oxidase, when it contacts glucose, an oxidation-reduction reaction occurs, generating a weak current signal proportional to the concentration, and its signal will be higher than that of a traditional surface electrode.

[0086] In the present invention, the preparation of the reference electrode preferably includes the following steps:

[0087] In the present invention, a second Ag layer is secondarily deposited on the surface of the microneedles in the microneedle array and then chlorinated to form a stacked second Ag layer and AgCl layer on the surface of the microneedles, thereby obtaining a reference electrode.

[0088] In the present invention, the conditions for the second deposition are preferably the same as those for the first deposition described above, and will not be elaborated herein.

[0089] In the present invention, the chlorination preferably includes: immersing the second Ag layer in a KCl solution, applying a voltage to form an Ag / AgCl layer.

[0090] In the present invention, the concentration of the KCl solution is preferably 0.1 - 1 M, and in the examples of the present invention, it can specifically be 0.1 M, 0.2 M, 0.4 M, 0.6 M, 0.8 M, or 1 M; the voltage is preferably 0.5 - 1.5 V, and in the examples of the present invention, it can specifically be 0.5 V, 0.8 V, 1.0 V, 1.2 V, 1.4 V, or 1.5 V; the time for applying the voltage is preferably 10 - 30 min, and in the examples of the present invention, it can specifically be 10 min, 15 min, 20 min, 25 min, or 30 min.

[0091] In the present invention, the thicknesses of the first Ag layer and the second Ag layer are preferably independently 50 - 200 nm, and in the examples of the present invention, they can specifically be 50 nm, 80 nm, 100 nm, 120 nm, 150 nm, 180 nm, or 200 nm.

[0092] After obtaining the working electrode and the reference electrode, the present invention preferably integrates the working electrode and the reference electrode on the same substrate and connects them to a signal processing circuit through wires to obtain a microneedle array sensor.

[0093] The present invention preferably connects the first bottom gate electrode layer as a signal input terminal to the working electrode, connects the reference electrode to a bias voltage, connects the second bottom gate electrode layer to a power supply voltage, and grounds the first source electrode layer.

[0094] The present invention provides the application of the sensor described in the above solution or the sensor prepared by the preparation method described in the above solution in the preparation of wearable devices.

[0095] The specific application scenarios of the sensor provided by the present invention include detecting the concentrations of glucose solution and lactic acid.

[0096] To further illustrate the present invention, the following will describe in detail a sensor and its preparation method and application provided by the present invention with reference to the accompanying drawings and examples, but they should not be construed as limiting the protection scope of the present invention.

[0097] Example 1

[0098] Preparation of Unipolar Amplifier:

[0099] Structural Composition

[0100] As Figure 1 shown, this embodiment provides a unipolar amplifier composed of metal-oxide thin-film transistors for amplifying electrochemical signals. The composition of the metal-oxide thin-film transistors is as follows: a rigid glass substrate, a core layer, and a passivation layer formed of a silicon dioxide thin film, which are stacked in sequence from bottom to top. The core layer includes a bottom gate electrode layer, a gate insulating layer, and an active layer, which are stacked in sequence from bottom to top, a source electrode layer and a drain electrode layer covering a part of the upper surface of the active layer, and an etch stop layer covering the exposed part of the active layer.

[0101] The metal-oxide thin-film transistor is divided into a driving part (i.e., M1 in Figure 1 ) and a load part (i.e., M2 in Figure 1 ) along the center line. The core layer composition of the driving part is as follows: a first bottom gate electrode layer, a gate insulating layer formed of a silicon dioxide and silicon nitride thin film, a first active layer formed of an N-type metal-oxide thin film a-IGZO, a first source-drain electrode layer formed of a metal material thin film (referring to the first source electrode layer and the first drain electrode layer), and an etch stop layer formed of a silicon dioxide thin film (i.e., the M1 etch stop layer in Figure 1 ). The first bottom gate electrode layer, the first gate insulating layer, and the first active layer are stacked in sequence from bottom to top. The first source electrode layer and the first drain electrode layer are respectively stacked on the left and right sides above the first active layer and are spaced apart. The spaced area forms a first channel with a length of 50 μm. The etch stop layer covers the first channel and the exposed part of the first active layer.

[0102] The first bottom gate electrode layer covers the middle area of the driving part substrate. The gate insulating layer of the driving part covers the first bottom gate electrode layer and other areas of the driving part substrate except the first bottom gate electrode layer. The first active layer covers the middle area of the gate insulating layer.

[0103] The core layer of the load part is the same as that of the driving part. Among them, the first drain electrode layer is connected to the second source electrode layer. The first source electrode layer is grounded. The first bottom gate electrode layer serves as a signal input terminal. The second bottom gate electrode layer is short-circuited with the second drain electrode layer to form a diode load part.

[0104] The thin-film transistor in this unipolar amplifier is a bottom-gate etch-stop type structure. The preparation process is simple, which can reduce the complexity of the process and the device has good performance.

[0105] Figure 1The M1 bottom gate electrode layer is the first bottom gate electrode layer, the M1 active layer is the first active layer, the M1 source electrode layer is the first source electrode layer, and the M1 drain electrode layer is the first drain electrode layer; the M2 bottom gate electrode layer is the second bottom gate electrode layer, the M2 active layer is the second active layer, the M2 source electrode layer is the second source electrode layer, and the M2 drain electrode layer is the second drain electrode layer.

[0106] Preparation method

[0107] Such as Figure 2 , S1: Sputter a metal thin film on the substrate and pattern it to form a bottom gate electrode layer, which is divided into a first bottom gate electrode layer and a second bottom gate electrode layer;

[0108] The bottom gate electrode layer is composed of a metal thin film sputtered by a magnetron sputtering device. The metal thin film is molybdenum (Mo), the gas flow ratio of argon to oxygen is 60:0.1, the sputtering power is 500 W DC, the sputtering time is 420 s, the film thickness is 150 nm, and the bottom gate electrode layer is formed through patterning. The patterning is carried out in sequence of coating photoresist, exposure, development, and etching. Select the corresponding developer according to the coated photoresist. The specific photoresist is a positive photoresist, with the model AZ SFP-1400, the developer is tetramethylammonium hydroxide (TMAH), the exposure time is 1 s, the development time is 40 s, and aluminum etchant is used for etching.

[0109] S2: Deposit a silicon dioxide thin film and a silicon nitride thin film on the bottom gate electrode layer in sequence to form a gate insulating layer;

[0110] The gate insulating layer is formed by depositing a 200-nm silicon nitride thin film and a 50-nm silicon dioxide thin film respectively by a chemical vapor deposition device. The reaction gases for the silicon nitride thin film are SiF4 and NH3, the sputtering temperature is 350 °C, the reaction gases for the silicon dioxide thin film are SiF4 and N2O, the sputtering temperature is 220 °C, and the high-temperature sputtering at 350 °C can ensure the density of the film.

[0111] S3: Sputter an N-type metal oxide thin film on the gate insulating layer, and perform patterning treatment and annealing treatment on the N-type metal oxide thin film to form an active layer, which is divided into a first active layer and a second active layer.

[0112] The active layer is composed of an N-type metal oxide thin film sputtered by a magnetron sputtering device. The N-type metal oxide thin film is an a-IGZO thin film, the gas flow ratio of argon to oxygen is 60:7.5, the sputtering time is 390 s, the power is 300 W, the thickness is 30 nm, and the active layer is formed through patterning. The patterning steps are the same as those for preparing the bottom gate electrode, except that oxalic acid is used for etching; finally, annealing is carried out to improve the defect states of the active layer material. The annealing temperature is 220 °C, and the annealing time is 90 min;

[0113] S4: Deposit a layer of silicon dioxide film on the active layer and pattern the silicon dioxide film to form an etch stop layer;

[0114] Similar to S2, the etch stop layer deposits a layer of silicon dioxide film by chemical vapor deposition equipment. The growth method is the same as S2, with a thickness of 200 nm. After coating, exposure, development, and etching, a patterned etch stop layer is formed. Select the corresponding developer according to the coated photoresist. The specific photoresist is a positive photoresist, model AZ SFP-1400, the developer is tetramethylammonium hydroxide (TMAH), the exposure time is 1 s, the development time is 40 s, and reactive ion etching is used.

[0115] S5: Sputter a metal film on the etch stop layer and pattern it to form source electrode layers and drain electrode layers, namely the first source electrode layer, the first drain electrode layer, the second source electrode layer, and the second drain electrode layer;

[0116] The formation steps of the source and drain electrode layers are the same as those of the bottom gate electrode layer;

[0117] After completing the above steps, anneal the entire device to improve the performance of the device. The annealing temperature is 350 °C and the annealing time is 90 min;

[0118] S6: Short-circuit the second bottom gate electrode layer and the second drain electrode layer through metal interconnection, and connect the first drain electrode layer and the second source electrode layer;

[0119] S7: Deposit a layer of silicon dioxide film on the core layer with a thickness of 200 nm and pattern the silicon dioxide film to form a passivation layer (the position of the passivation layer is the same as that of the etch stop layer and is deposited above the etch stop layer).

[0120] Similar to S4, the passivation layer deposits a layer of silicon dioxide film by chemical vapor deposition equipment. After coating, exposure, development, and etching, a passivation layer is formed. Select the corresponding developer according to the coated photoresist. The specific photoresist is a positive photoresist, model AZ SFP-1400, the developer is tetramethylammonium hydroxide (TMAH), the exposure time is 1 s, the development time is 40 s, and reactive ion etching is used. The passivation layer protects the device from corrosion by water and oxygen.

[0121] Preparation of the microneedle array sensor:

[0122] Structural composition

[0123] The microneedle array sensor consists of a reference electrode and a working electrode. The working electrode is composed of a first microneedle array, a first Ag layer coated on the surface of the microneedles, and an enzyme immobilization layer. The reference electrode is composed of a second microneedle array, a second Ag layer coated on the surface of the microneedles, and an AgCl layer. The first microneedle array and the second microneedle array are composed of a plurality of conical microneedles. The height of the needle body of the conical microneedle is 1000 μm, the bottom diameter is 300 μm, the interval between the conical microneedles is 200 μm, and the top diameter is 15 μm.

[0124] The microneedle array sensor is used to detect the target biological signal and convert it into an electrochemical signal.

[0125] Preparation method

[0126] Such as Figure 3 , S1: Provide a PDMS mold (as shown in Figure 4 ), the surface of the PDMS mold has a negative mold structure corresponding to the shape of the target microneedle; Inject the SU-8 photoresist solution into the PDMS mold, and remove the air bubbles inside the solution by vacuum treatment. The vacuum degree is 1×10 - 2 Pa, and the vacuum time is 5 min to ensure that there are no air bubbles;

[0127] S2: Ultraviolet light cure the PDMS mold injected with the SU-8 photoresist solution. The wavelength of the ultraviolet light is 365 nm, the irradiation intensity is 10 mW / cm 2 , the curing time is 2 min, and bake at 90 °C for 1 h. The ultraviolet light cures the photosensitive components in the SU-8, and under the action of baking, microneedles with sufficient hardness to pierce the skin are obtained;

[0128] S3: As shown in Figure 5 , demold to obtain a microneedle array made of SU-8. The height of the needle body of the microneedle is 1000 μm, the bottom diameter is 300 μm, the interval is 200 μm, and the top diameter is 15 μm;

[0129] S4: Prepare two groups of microneedle arrays by the above method, which are used as the working electrode and the reference electrode respectively; Evaporate an Ag thin film on the surface of the microneedles in the two groups of microneedle arrays by physical vapor deposition. Use a vacuum coating system, the vacuum degree is 5×10 -4 Pa, the evaporation rate is 0.5 nm / s, and the film thickness is 100 nm; This film provides electrical conductivity for the microneedles and is used to transmit electrical signals;

[0130] S5: Functionalize the surface of the Ag thin film of the microneedle array forming the working electrode: Mix 0.5 wt% chitosan-acetic acid solution (as an adhesive, formed by dissolving chitosan in 1 wt% aqueous acetic acid solution to make the mass concentration of chitosan 0.5%) with solid glucose oxidase so that the final concentration of glucose oxidase is 10 mg / mL to form a mixed solution; coat the mixed solution on the surface of the Ag thin film. Specifically, drop 15 μL of the mixed solution on a microneedle array with an area of 1 cm × 1 cm (each group of microneedle arrays has 10 × 10 microneedles), and refrigerate for 3 hours under the condition of 4°C to fix the glucose oxidase to the Ag surface and form an enzyme immobilization layer;

[0131] S6: Chlorinate the surface of the Ag thin film of the microneedle array forming the reference electrode: Immerse the Ag thin film in 0.1 M KCl solution, apply a voltage of 0.5 for 10 min to form an Ag / AgCl layer;

[0132] S7: Integrate the working electrode and the reference electrode on the same substrate and connect them to the signal processing circuit through wires (that is, connect the working electrode to the first bottom gate electrode layer through wires);

[0133] Preparation of the sensor:

[0134] Structural composition

[0135] As Figure 6 ( Figure 6 in which the substrate is the base plate and VOUT represents the output voltage), the sensor consists of a unipolar amplifier composed of metal oxide thin film transistors and a microneedle array sensor. The microneedle sensor is used to detect the target biological signal and convert it into an electrochemical signal. The unipolar amplifier is used to amplify the electrochemical signal. The working electrode of the microneedle sensor is connected to the first bottom gate electrode layer of the unipolar amplifier through a wire. The reference electrode of the microneedle sensor is connected to the bias voltage (VIN), and the second bottom gate electrode layer of the unipolar amplifier is connected to the power supply voltage (VDD); the first source electrode layer of the unipolar amplifier is connected to the ground terminal (GND). The sensor provided in this embodiment is used to detect glucose solution.

[0136] In this embodiment, by directly connecting the microneedle array sensor to the input end of the unipolar amplifier based on a-IGZO thin film transistors, in-situ amplification of weak electrochemical signals is realized, and noise interference is reduced; the microneedle array and the amplification circuit are integrally packaged to meet the miniaturization and comfort requirements of wearable devices; the microneedles directly contact body fluids, and the detection response time is shortened to within 10 seconds, which has great advantages compared with the traditional response time of 20 seconds.

[0137] The present invention provides a unipolar amplifier. Compared with a single thin-film transistor, the diode load part provided by the present invention can increase the output impedance and bring greater gain, thus greatly enhancing the performance of the sensor. In an embodiment, a single transistor combined with a microneedle sensor can achieve a sensitivity of 0.55 μA / mM and a linear detection range of 1 to 10 mM. Greater gain can bring a greater improvement in sensitivity.

[0138] Although the above embodiments have made a detailed description of the present invention, they are only a part of the embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A sensor, characterized in that, It includes a unipolar amplifier and a microneedle array sensor; the unipolar amplifier includes a metal oxide thin film transistor; The microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array, a first Ag layer coated on the surface of the microneedles, and an enzyme immobilization layer; the reference electrode includes a second microneedle array, a second Ag layer coated on the surface of the microneedles, and an AgCl layer; The unipolar amplifier is connected to the working electrode through a wire.

2. The sensor according to claim 1, wherein The metal oxide thin film transistor includes a substrate, a core layer, and a passivation layer stacked in sequence from bottom to top; The core layer includes a bottom gate electrode layer, a gate insulating layer, and an active layer stacked in sequence from bottom to top, a source electrode layer and a drain electrode layer covering a part of the upper surface of the active layer, and an etching stop layer covering the exposed part of the active layer; The bottom gate electrode layer includes a first bottom gate electrode layer and a second bottom gate electrode layer arranged at intervals; the active layer includes a first active layer and a second active layer arranged at intervals; the source electrode layer includes a first source electrode layer and a second source electrode layer arranged at intervals; the drain electrode layer includes a first drain electrode layer and a second drain electrode layer arranged at intervals; The first drain electrode layer is connected to the second source electrode layer, the first source electrode layer is grounded, the first bottom gate electrode layer is the signal input terminal; the second bottom gate electrode layer is short-circuited with the second drain electrode layer.

3. The sensor according to claim 2, wherein The active layer includes an N-type metal oxide thin film.

4. The sensor according to claim 3, characterized in that, The N-type metal oxide thin film includes an a-IGZO thin film, and the thickness of the active layer is 10 - 50 nm.

5. The sensor according to claim 2 or 3, characterized in that, The first bottom gate electrode layer, the first source electrode layer, the first drain electrode layer, the second bottom gate electrode layer, the second source electrode layer, and the second drain electrode layer independently include a metal layer, and the thickness is independently 100 - 200 nm; the gate insulating layer includes a first non-metal oxide layer and a non-metal nitride layer, and the total thickness is 50 - 250 nm; the etching stop layer includes a second non-metal oxide layer, and the thickness is 100 - 200 nm; the passivation layer includes a third non-metal oxide layer, and the thickness is 100 - 200 nm.

6. The sensor according to claim 1 or 2, characterized in that The first microneedle array and the second microneedle array independently include a plurality of conical microneedles, the height of the needle body of the conical microneedles is 600 - 1000 μm, the bottom diameter is 50 - 300 μm, the interval between the conical microneedles is 100 - 300 μm, and the top diameter is 10 - 30 μm.

7. The sensor according to claim 5, wherein The metal layer includes a molybdenum layer, an aluminum layer, or a copper layer; the first non-metal oxide layer, the second non-metal oxide layer, and the third non-metal oxide layer independently include a silicon dioxide layer; the non-metal nitride layer includes a silicon nitride layer.

8. The preparation method of the sensor according to any one of claims 1 to 7, characterized in that, It includes the following steps: Connect the metal oxide thin film transistor in the unipolar amplifier to the working electrode of the microneedle array sensor through a wire to obtain the sensor; The microneedle array sensor includes a reference electrode and a working electrode; the working electrode includes a first microneedle array, a first Ag layer coated on the surface of the microneedles, and an enzyme immobilization layer; the reference electrode includes a second microneedle array, a second Ag layer coated on the surface of the microneedles, and an AgCl layer.

9. The preparation method according to claim 8, characterized in that, The thicknesses of the first Ag layer and the second Ag layer are independently 50 to 200 nm.

10. Use of the sensor according to any one of claims 1 to 7 or the sensor prepared by the preparation method according to any one of claims 8 to 9 in the preparation of a wearable device.

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