Method for manufacturing a glucose sensor and use thereof

Abstract

The application relates to a preparation method and application of a glucose sensor, which comprises the following steps: introducing an ionic liquid [EMIM][PF6] and DBSA into PEDOT:PSS simultaneously, promoting the phase separation of the ionic liquid in the PEDOT:PSS by the DBSA, forming high-conductivity ionic liquid domains, and preparing a semiconductor channel material with effective electron and ion transmission performance. Further, an interdigital electrode is used to control the semiconductor channel length to prepare an OECT device with super-high transconductance. The obtained super-high transconductance OECT has sensitive detection capability for glucose. The research result provides a simple and effective strategy for preparing the OECT with super-high transconductance, and can be used for highly sensitive chemical and biological detection in the near future.

Description

TECHNICAL FIELD

[0001] The present application relates to a glucose sensor, in particular to a preparation method and application of a glucose sensor. BACKGROUND

[0002] Organic electrochemical transistors (OECTs) can convert and amplify chemical / biological signals into high-sensitivity electrical signals, and have been used as sensors for various analytes, such as ions, lactate, glucose, dopamine, DNA, bacteria, proteins, and cells, etc.

[0003] Transconductance is one of the most important parameters that determine the ability of OECTs to amplify chemical / biological signals. Generally, the larger the transconductance, the higher the detection sensitivity of the OECT-based sensor. Improving the transconductance is the core of designing and preparing OECT devices. It is known that the transconductance of OECTs in the saturation state is g m =(W / L)·d·μ·C * ·(V Th -V G ), where W, L, and d are the width, length, and thickness of the channel, respectively; μ and C* are the carrier mobility and bulk capacitance of the channel, respectively; V Th and V G are the threshold voltage and gate voltage, respectively. This equation shows that the transconductance of OECTs is linearly related to the geometric shape of the channel (g m ∝Wd / L) and electrical and ionic properties (g m ∝μC * ). Therefore, geometric size control, side chain engineering, and channel doping are common strategies to improve the transconductance of OECTs.

[0004] However, the transconductance reported so far is not sufficient for high-sensitivity analyte detection. Therefore, the present application prepares OECT devices with ultra-high transconductance for high-sensitivity, high-selectivity glucose detection. SUMMARY

[0005] To solve the problems of the prior art, the present application aims to provide a preparation method and application of a glucose sensor, an electrochemical transistor (OECT) with high transconductance, which has a sensitive detection ability and high stability for glucose.

[0006] In order to solve the technical problems of the present application, the present application adopts the following technical solution: a preparation method of a glucose sensor, the sensor comprising a source electrode, a drain electrode, a semiconductor channel, and a gate electrode; the source electrode and the drain electrode are gold interdigital electrodes; the semiconductor channel material comprises 1-butyl-3-methyl-hexafluorophosphate ([EMIM][PF6]) and dodecylbenzenesulfonic acid (DBSA) co-doped poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS); and the gate electrode is a platinum gate electrode modified by glucose oxidase (GOx) and Nafion.

[0007] The preparation method of the glucose sensor comprises the following steps:

[0008] S1, sputtering a platinum gate electrode and source and drain electrodes on a substrate with the aid of a mask plate; the spacing of the interdigital electrodes is 3 μm;

[0009] S2, using [EMIM][PF6] and DBSA co-doped PEDOT:PSS as a semiconductor channel material; the channel length is 3 μm, and the channel thickness is 200 nm;

[0010] S3, using a platinum electrode modified by GOx and Nafion as a platinum gate electrode to prepare a glucose sensor;

[0011] The preparation method of the semiconductor channel in step S2 comprises the following steps:

[0012] A1, mixing a 20 wt% [EMIM][PF6] solution (1.3 wt% diluted in deionized water) and a 4 wt% DBSA solution into a PEDOT:PSS solution, stirring vigorously for 10 min, adding a 0.5 vol.% (methacryloyloxy)propyltrimethoxysilane (GOP S) solution, and stirring for 2 h to prepare a semiconductor solution;

[0013] A2, spin coating 100 μL of the semiconductor solution at a rotation speed of 900 rpm for 60 s, and then annealing at 120°C for 1 h to obtain a 200 nm semiconductor channel thin film;

[0014] A3, in order to improve the stability of the device during testing, dropping 2 μL of a 5 wt% Nafion solution on the semiconductor thin film to form a Nafion film.

[0015] Preferably, the size of the sensor is 4 mm x 7 mm.

[0016] Preferably, the substrate in step S1 is polyethylene terephthalate (PET) or glass or polyimide (PI).

[0017] Preferably, the preparation of the electrodes in step S1 is:

[0018] The gold source electrode, the drain electrode and the platinum gate electrode are prepared by mask plate assisted ion sputtering, the electrode spacing of the interdigital electrode is 3 microns, and the semiconductor channel length is 3 microns and the width is 2 mm.

[0019] Preferably, the preparation method of the GOx / Nafion / platinum gate electrode in the step S3 is as follows:

[0020] B1, 10 microliters of GOx solution (20 mg / L) are uniformly dropped on the surface of the platinum gate electrode, and dried at 37 DEG C; -1

[0021] B2, 5 microliters of 5wt% Nafion solution are uniformly dropped on the GOx / platinum gate electrode for fixing the GOx film, and dried at 37 DEG C;

[0022] B3, the prepared glucose sensor is washed with deionized water and stored at 37 DEG C for use.

[0023] In order to solve another technical problem of the present application, the technical scheme is as follows: the application of any glucose sensor for high-sensitivity glucose detection.

[0024] A glucose sensor includes an electrochemical transistor (OECT) having a high transconductance.

[0025] The present application has the advantages of:

[0026] The glucose sensor of the present application is prepared by introducing ionic liquid [EMIM][PF6] and dodecyl benzene sulfonic acid (DBSA) into poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) as a semiconductor channel at the same time, an electrochemical transistor (OECT) device with ultra-high transconductance is prepared, and the platinum gate electrode of the OECT device is modified by using perfluorosulfonic acid (Nafion) and glucose oxidase (GOx), a glucose sensor with high sensitivity is prepared. Compared with the OECT based on pure PEDOT:PSS, the transconductance of the OECT based on co-doped PEDOT:PSS is significantly enhanced from 1.85 mS to 180 mS, which is attributed to the bulk capacitance (55.6 F cm -3 ) and conductivity (1015 S cm -1 ​The increase of the concentration of DBSA and the decrease of the channel length (3 μm). Since DBSA promotes the phase separation of the ionic liquid in PEDOT:PSS, the ionic liquid forms conductive domains in PEDOT:PSS, preparing a semiconductor channel with effective electron and ion transport performance. The sensor based on the OECT with ultra-high transconductance has higher sensitivity (10 nM) and good selectivity to glucose, and the detection limit is improved by two orders of magnitude compared with the device based on pure PEDOT:PSS.

[0027] The glucose sensor of the application uses a GOx and Nafion modified platinum electrode for high sensitivity and high selectivity glucose detection.

[0028] The glucose sensor of the application improves the stability and life of the sensor by preparing a thin Nafion layer on the surface of the semiconductor channel. The transconductance of the device only decreases by about 3% after 120 days of storage in ambient air.

[0029] The glucose sensor of the application co-dopes PEDOT:PSS with [EMIM][PF6] and DBSA in a series of proportions. The transconductance of the prepared OECT device is highly related to the co-doping concentration of [EMIM][PF6] and DBSA in the PEDOT:PSS channel. The higher or lower the concentration of [EMIM][PF6] and / or DBSA, the smaller the transconductance. In particular, when 20wt% [EMIM][PF6] and 4wt% DBSA are co-doped in the PEDOT:PSS thin film, the maximum transconductance reaches 22.7 mS.

[0030] The glucose sensor of the application further improves the transconductance to 180 mS when using interdigital electrodes with an electrode spacing of 3 μm as the source and drain electrodes. To our knowledge, this transconductance value is the highest among the reported OECT devices.

[0031] The glucose sensor of the application has the advantages of simple structure, low preparation cost, high sensitivity, good selectivity, and can accurately and effectively detect glucose. The glucose sensor shows obvious response (drain current reduction) to the addition of 10 nM glucose, and good linear response in the range of 1-100 nM and 1 μM-10 mM, which covers the normal glucose level of the human body.

[0032] It can be used in cooperation with other medical devices, paving the way for a multifunctional biological detection platform, effectively promoting the development of health field electronic products, and has strong practicality and wide applicability. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 It is a schematic diagram of the structure of the glucose sensor.

[0034] Figure 2 Current response of glucose sensor to glucose solutions of different concentrations.

[0035] Figure 3 Selectivity test of glucose sensor to solutions of different compositions.

[0036] Figure 4 Variation of transconductance of OECT device co-doped with different concentrations of [EMIM][PF6] and DBSA.

[0037] Figure 5 Transfer characteristics of PEDOT:PSS device co-doped with 20 wt% [EMIM][PF6] and 4 wt% DBSA.

[0038] Figure 6 Variation of conductivity of PEDOT:PSS film doped with different concentrations of [EMIM][PF6].

[0039] Figure 7 SEM image of PEDOT:PSS co-doped with 20 wt% [EMIM][PF6] and 4 wt% DBSA.

[0040] Figure 8 EDS image of PEDOT:PSS co-doped with 20 wt% [EMIM][PF6] and 4 wt% DBSA.

[0041] Figure 9 SEM image of PEDOT:PSS doped with 20 wt% [EMIM][PF6].

[0042] Figure 10 AFM image of PEDOT:PSS co-doped after selective washing out of [EMIM][PF6].

[0043] Figure 11 UV-vis-NIR spectra of various semiconductor thin films.

[0044] Figure 12 Schematic diagram of glucose sensor of the present application. DETAILED DESCRIPTION

[0045] The present application will be described in detail below with reference to the accompanying drawings and specific examples.

[0046] Example 1: Preparation of semiconductor thin film. 30 μL of [EMIM][PF6] solution (1.3 wt%) and 5 μL of DBSA (90%) solution were mixed into 2 mL of PEDOT:PSS solution (1.5 wt%). After the mixed solution was stirred for 10 min, 10 μL of GOPS solution was added into the mixed solution and stirred for 2 h. 100 μL of semiconductor solution was spin-coated at 900 rpm for 60 s to obtain a semiconductor thin film with a thickness of about 200 nm, which contained 20 wt% of [EMIM][PF6] and 4 wt% of DBSA. By adjusting the doping ratio of [EMIM][PF6] and DBSA solution, PEDOT:PSS thin films with different doping concentrations of [EMIM][PF6] were prepared. By replacing the mixed semiconductor solution with a PEDOT:PSS solution to which 0.5 vol% of GOPS was added, a pure PEDOT:PSS thin film was also spin-coated;

[0047] Preparation of OECT device: Gold source and drain electrodes were deposited on the substrate surface by mask-assisted ion sputtering, and then platinum gate electrode was deposited in a similar way. The channel length and width of the device were controlled at 200 μm and 2 mm, respectively. Further, OECT devices with ultra-high transconductance were prepared by using interdigital electrodes with a pitch of 3 μm as source and drain electrodes. After the substrate was cleaned with oxygen plasma, the semiconductor thin film was spin-coated on the electrode surface, and then annealed at 120 °C for 1 h. A layer of Nafion thin film was formed on the annealed semiconductor thin film by dropping 2 μL of 5 wt% Nafion solution to improve the stability and life of the device.

[0048] Preparation of glucose sensor based on OECT device: Modification of the gate of the OECT device: 10 μL of GOx solution (20 mg L -1 ) was first dropped on the gate area, and after drying at 37 °C, 5 μL of Nafion solution (5 wt%) was dropped. After drying at 37 °C, it was thoroughly rinsed with deionized water.

[0049] The reagents in the present application are all commercially available, wherein: [EMIM][PF6] is an ionic liquid, DBSA is dodecylbenzenesulfonic acid, PEDOT:PSS is poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, and GOPS is (methacryloyloxy)propyltrimethoxysilane.

[0050] The glucose sensor is as shown in Fig. 1. Figure 1As shown, the preparation method: gold source and drain electrode through mask assisted ion sputtering deposition on the substrate surface, and then deposited platinum gate electrode by similar method. The channel length and width of the device are controlled at 200 μm and 2 mm respectively. Further, the OECT device with ultra-high transconductance is prepared by using interdigital electrode with a pitch of 3 μm as source and drain electrode. After the substrate is cleaned by oxygen plasma, the semiconductor thin film is spin-coated on the surface of the electrode, and then annealed at 120℃ for 1h, and then 2 μL of 5wt% Nafion solution is drop-coated on the semiconductor thin film after annealing to form a Nafion film, so as to improve the stability and service life of the device.

[0051] Preparation of glucose sensor based on OECT device: modification of the gate of OECT device: first drop 10 μL of GOx solution (20 mg L -1 ) on the gate area, dry at 37℃, then drop 5 μL of Nafion solution (5wt%). After drying at 37℃, rinse thoroughly with deionized water. As Figure 2 shown: the glucose sensor shows obvious response (leakage current decreases) to the addition of 10 nM glucose, and good linear response in the range of 1-100 nM and 1 μM-10 mM, which covers the normal glucose level of human body.

[0052] The selectivity of the OECT-based glucose sensor is the key to practical application. Human body fluid is a complex biological system, which contains many interference factors, and may produce obvious false signals in glucose detection. The response of the sensor to glucose is much larger than that to common interference (UA, AA, DA) Figure 3 ), indicating that the OECT-based sensor has good selectivity to glucose.

[0053] The concentration of the semiconductor channel layer of the OECT device of the application is optimized by co-doping [EMIM][PF6] and DBSA, as shown in Figure 4 .

[0054] When 20wt% [EMIM][PF6] and 4wt% DBSA are co-doped in the PEDOT:PSS thin film, the maximum transconductance reaches 22.7 mS. The higher or lower the concentration of [EMIM][PF6] and / or DBSA is, the smaller the transconductance is. In the absence of DBSA, when the concentration of [EMIM][PF6] is controlled at 20wt%, the maximum transconductance is only 8.9 mS. In the absence of [EMIM][PF6], the maximum transconductance is only 2.9 mS, while the transconductance is as high as 22.7 mS when [EMIM][PF6] is introduced at the same time.

[0055] The transfer characteristic curve of the PEDOT:PSS co-doped with 20wt% [EMIM][PF6] and 4wt% DBSA, using interdigital electrodes with an electrode spacing of 3 μm as source and drain electrodes, is shown in Figure 5 .

[0056] The OECT device works in depletion mode and obtains an ultra-high transconductance of 180 mS.

[0057] The doping amount of [EMIM][PF6] was regulated, and the conductivity of the co-doped PEDOT:PSS film was tested, as shown in Figure 6 .

[0058] In general, the [EMIM][PF6]-doped PEDOT:PSS film shows higher conductivity. In particular, when doped with 20wt% [EMIM][PF6], the conductivity of the film is about 1015S cm -1 , which is almost three orders of magnitude higher than the conductivity of the pure PEDOT:PSS film (1S cm -1 ).

[0059] The morphology characterization of the PEDOT:PSS co-doped with 20wt% [EMIM][PF6] and 4wt% DBSA is shown in Figure 7 . It is observed that one phase is embedded in another phase.

[0060] In order to identify the type of phase, the element mapping of the surface of the [EMIM][PF6] and DBSA co-doped film was studied using an energy dispersive spectrometer (EDS), as shown in Figure 8 .

[0061] Because F is an element unique to [EMIM][PF6], the F element distribution is consistent with the position of the embedded phase in Figure 6 , proving that the [EMIM][PF6] phase undergoes phase separation and is embedded in the PEDOT:PSS phase.

[0062] In order to determine the role of DBSA, the morphology of the [EMIM][PF6] film doped with and without DBSA was compared, as shown in Figure 9 .

[0063] With the addition of DBSA, the phase separation of the [EMIM][PF6] doped film is more uniform, and the size is reduced to the order of microns, indicating that DBSA can promote the phase separation of the [EMIM][PF6] co-doped film.

[0064] In order to determine the degree of phase separation of [EMIM][PF6] in the PEDOT:PSS film, [EMIM][PF6] was selectively washed away using an ethanol solution, and the film was characterized by AFM, as shown inFigure 10

[0065] Holes with a few microns in diameter were observed in the co-doped thin film, which were generated by the removed [EMIM][PF6] phase. This is the evidence of [EMIM][PF6]-induced PEDOT:PSS molecular aggregation and large phase separation. The maximum hole diameter is only about 4 μm. In addition, the depth of the hole is close to the thickness of the film, indicating that the [EMIM][PF6] phase almost completely embeds into the film, forming [EMIM][PF6] domains.

[0066] The interaction between PEDOT:PSS, [EMIM][PF6] and DBSA is reflected in the UV-vis-NIR spectra of the thin films: Figure 11

[0067] The pure PEDOT:PSS thin film shows weak apparent absorption in the whole spectral range. Compared with the pure PEDOT:PSS thin film, the absorption of the thin film doped with 20% [EMIM][PF6] and 4 wt% DBSA is significantly increased in the whole spectral range. The increased absorption is due to the increased doping level and carrier concentration caused by the introduction of [EMIM][PF6] and DBSA. A new strong peak appears in the ultraviolet range of ~345 nm in the co-doped PEDOT:PSS thin film, which may be from the aromatic ring of the EMIM cation. Another notable feature is that the absorption intensity of the thin film increases with the addition of DBSA or [EMIM][PF6], and reaches a maximum when DBSA and [EMIM][PF6] are co-doped. This result indicates that [EMIM][PF6] and DBSA have a strong synergistic effect in the PEDOT:PSS thin film.

[0068] The above results show that by simultaneously introducing ionic liquid [EMIM][PF6] and DBSA into PEDOT:PSS, using DBSA-promoted phase separation of ionic liquid in PEDOT:PSS, high-conductivity ionic liquid domains are formed, and a semiconductor channel material with effective electron and ion transport performance is prepared.

[0069] Comparative Example 1:

[0070] OECT glucose sensor based on pure PEDOT:PSS detects glucose: the detection limit is 1 μM, and a good linear response is obtained in the range of 10 μM to 10 mM.

[0071] ​​The OECT device was prepared using pure PEDOT:PSS as the semiconductor channel material, and the transconductance value was 1.85 mS. In general, the [EMIM][PF6] doped PEDOT:PSS thin film showed higher conductivity. In particular, when doped with 20wt% [EMIM][PF6], the conductivity of the thin film was about 1015S cm -1 , almost three orders of magnitude higher than the conductivity of the pure PEDOT:PSS thin film (1 Scm -1 ).

[0072] The small and light glucose sensor of the present application can be used for high sensitivity and high selectivity detection of glucose. The basic principles, main features and advantages of the present application are shown and described above. Those skilled in the art should understand that the above examples do not limit the present application in any form, and any technical solutions obtained by equivalent replacement or equivalent transformation fall within the protection scope of the present application.

[0073] The present application is not limited to the specific technical solutions described in the above embodiments, and any technical solution formed by equivalent replacement falls within the protection scope required by the present application.

Claims

1. A method of preparing a glucose sensor, characterized by, The sensor comprises a source electrode, a drain electrode, a semiconductor channel, and a gate electrode; the source electrode and the drain electrode are gold interdigital electrodes; the semiconductor channel material comprises 1-butyl-3-methyl-hexafluorophosphate ([EMIM][PF6]) and dodecylbenzenesulfonic acid (DBSA) co-doped poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS); and the gate electrode is a glucose oxidase (GOx) and Nafion modified platinum gate electrode. The preparation method of the glucose sensor comprises the following steps: S1. Sputtering a platinum gate electrode and gold source and drain electrodes on a substrate with the aid of a mask plate; the interdigital electrode spacing is 3 μm; S2. Using [EMIM][PF6] and DBSA co-doped PEDOT:PSS as the semiconductor channel material; the channel length is 3 μm and the channel thickness is 200 nm; S3. Using a GOx and Nafion modified platinum electrode as the platinum gate electrode to prepare a glucose sensor; The preparation method of the semiconductor channel in step S2 comprises the following steps: A1. Mixing a 20 wt% [EMIM][PF6] solution and a 4 wt% DBSA solution into a PEDOT:PSS solution, stirring vigorously for 10 min, adding a 0.5 vol.% methacryloxypropyltrimethoxysilane (GOP S) solution, and stirring for 2 h to prepare a semiconductor solution; A2. Spinning 100 μL of the semiconductor solution at a rotation speed of 900 rpm for 60 s, and then annealing at 120 °C for 1 h to obtain a 200 nm semiconductor channel thin film; A3. To improve the stability of the device during testing, 2 μL of a 5 wt% Nafion solution is drop-coated on the semiconductor thin film to form a Nafion film.

2. The method of claim 1, wherein the glucose sensor is prepared by the steps of: The size of the sensor is 4 mm x 7 mm.

3. The method of claim 1, wherein the glucose sensor is prepared by the steps of: The substrate in step S1 is polyethylene terephthalate (PET) or glass or polyimide (PI).

4. The method of claim 1, wherein the glucose sensor is prepared by the steps of: The preparation of the electrodes in step S1 is as follows: The gold source and drain electrodes and the platinum gate electrode are prepared by mask-assisted ion sputtering, with an electrode spacing of 3 μm and a width of 2 mm.

5. The method of claim 1, wherein the glucose sensor is prepared by the steps of: The preparation method of the GOx / Nafion / platinum gate electrode in step S3 is as follows: B1, 10 μL of 20 mg L -1 of GOx solution was uniformly dropped on the surface of the platinum grid electrode and dried at 37 ℃; B2. Uniformly drop-coating 5 μL of a 5 wt% Nafion solution on the GOx / platinum gate electrode to immobilize the GOx film, and drying at 37 °C; B3. Washing the prepared glucose sensor with deionized water and storing it at 37 °C for use.

6. Use of a glucose sensor prepared according to any one of the methods of claims 1-5, characterized in that, For high-sensitivity glucose detection.

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