阅读说明：本技术 原位微型去污平台及其在电化学传感器芯片表面清洁中的应用 (In-situ micro decontamination platform and application thereof in surface cleaning of electrochemical sensor chip ) 是由 牛鹏飞 王小荷 庞慰 刘亦叶 佘祥 于 2020-11-26 设计创作，主要内容包括：本发明公开了一种原位微型去污平台及其在电化学传感器芯片表面清洁中的应用,原位微型去污平台包括：平行设置的微流道组件和支撑衬底,电化学传感器芯片、微流道组件和支撑衬底从上至下依次设置,其中,支撑衬底的顶面设置有一微型超声器件,微流道组件上形成有通孔,通孔的孔壁围成一顶端和底端均敞口的腔体,腔体与原位微型去污平台外相通,以使能够向该腔体排入和排出液体,腔体内的液体能够与电化学传感器芯片的三电极和微型超声器件的振动区域接触。本发明基于超声在液体中传播会产生声流现象,利用微型超声器件发射的超声波可原位去除电化学传感器芯片的表面结垢,不会对电化学传感器芯片表面产生损伤。(The invention discloses an in-situ micro decontamination platform and application thereof in surface cleaning of an electrochemical sensor chip, wherein the in-situ micro decontamination platform comprises: the micro-channel assembly and the supporting substrate are arranged in parallel, the electrochemical sensor chip, the micro-channel assembly and the supporting substrate are sequentially arranged from top to bottom, a micro ultrasonic device is arranged on the top surface of the supporting substrate, a through hole is formed in the micro-channel assembly, a cavity with an open top end and an open bottom end is defined by the hole wall of the through hole, the cavity is communicated with the outside of the in-situ micro decontamination platform, so that liquid can be discharged into and discharged out of the cavity, and the liquid in the cavity can be in contact with three electrodes of the electrochemical sensor chip and a vibration area of the micro ultrasonic device. The invention is based on the phenomenon that the ultrasonic wave is transmitted in the liquid to generate the acoustic current, and the ultrasonic wave emitted by the miniature ultrasonic device can be used for removing the surface scale of the electrochemical sensor chip in situ without damaging the surface of the electrochemical sensor chip.)

1. An in-situ micro decontamination platform for an electrochemical sensor chip, comprising: the micro-channel assembly comprises a micro-channel assembly (4) and a supporting substrate (2) which are arranged in parallel, wherein the electrochemical sensor chip (6), the micro-channel assembly (4) and the supporting substrate (2) are sequentially arranged from top to bottom, a micro ultrasonic device (2-1) is arranged on the top surface of the supporting substrate (2), a through hole is formed in the micro-channel assembly (4), a cavity (4-3) with an open top end and an open bottom end is defined by the hole wall of the through hole, the cavity (4-3) is communicated with the outside of an in-situ micro decontamination platform so that liquid can be discharged into and out of the cavity (4-3), and the liquid in the cavity (4-3) can be in contact with three electrodes of the electrochemical sensor chip (6) and a vibration area of the micro ultrasonic device (2-1).

2. The in-situ micro decontamination platform according to claim 1, wherein a liquid inlet chamber (4-1) and a liquid outlet chamber (4-2) are formed in the micro flow channel assembly (4), the liquid inlet chamber (4-1) is communicated with the chamber (4-3) through a first channel (4-4), the liquid outlet chamber (4-2) is communicated with the chamber (4-3) through a second channel (4-5), and the chamber (4-3) is communicated with the outside of the in-situ micro decontamination platform through the liquid inlet chamber (4-1) and the liquid outlet chamber (4-2);

the number of the liquid inlet cavities (4-1) is 1 or more, and the number of the liquid outlet cavities (4-2) is 1 or more;

the miniature ultrasonic device (2-1) is manufactured by an MEMS (micro electro mechanical systems) process, and the miniature ultrasonic device (2-1) is a film bulk acoustic resonator, a micro-mechanical ultrasonic transducer or a piezoelectric ultrasonic transducer;

the height of the through hole is 10 mu m-20 mm, and the width of the through hole is 0.1 mm-30 mm;

the liquid inlet cavity (4-1), the liquid outlet cavity (4-2), the cavity (4-3), the first channel (4-4) and the second channel (4-5) jointly form a micro-flow channel, the widths of the first channel (4-4) and the second channel (4-5) are respectively 10 mu m-5 mm, the lengths of the first channel (4-4) and the second channel (4-5) are respectively 1mm-5cm, the liquid inlet cavity (4-1) and the liquid outlet cavity (4-2) are positioned on two sides or the same side of the cavity (4-3), and the widths of the liquid inlet cavity (4-1) and the liquid outlet cavity (4-2) are 0.1 mm-10 mm;

the length of the electrochemical sensor chip (6) is 1mm-5 cm;

the micro-channel component (4) is polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene glycol terephthalate PET;

the length of the micro ultrasonic device (2-1) is 100 mu m-3 cm, and the length of the vibration region of the micro ultrasonic device (2-1) is 5 mu m-2 cm.

3. The in situ micro decontamination platform of claim 1, further comprising: an electrochemical sensor area defining component (5) parallel to the micro flow channel component (4), wherein a first opening (5-1) is formed on the electrochemical sensor area defining component (5), the electrochemical sensor chip (6) and the micro ultrasonic device (2-1) are arranged in parallel or in non-parallel, and when the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel, the liquid can contact with the sensing area of the three electrodes through the first opening (5-1); when arranged non-parallel, the electrochemical sensor chip (6) is in contact with the liquid through the first opening (5-1).

4. The in-situ micro decontamination platform according to claim 3, wherein when said electrochemical sensor chip (6) and said micro ultrasound device (2-1) are in a non-parallel arrangement, said electrochemical sensor chip (6) is fixed on said electrochemical sensor area defining assembly (5) and a sensing area of a three electrode of said electrochemical sensor chip (6) passes through said first opening (5-1) and is capable of contacting with said liquid.

5. The in-situ micro decontamination platform according to claim 4, wherein said first opening (5-1) is a slit when said electrochemical sensor chip (6) and said micro ultrasound device (2-1) are disposed non-parallel; when the electrochemical sensor chip (6) and the micro ultrasonic device (2-1) are arranged in parallel, the size of the first opening (5-1) is larger than or equal to that of a sensing area of the three electrodes and smaller than or equal to that of the cross section of the through hole.

6. The in situ micro decontamination platform of claim 4, further comprising: the top cover (7) is positioned above the electrochemical sensor chip (6), a first through hole (7-1) for inputting liquid into the liquid inlet cavity (4-1) and a second through hole (7-2) for discharging the liquid in the liquid inlet cavity (4-2) are formed in the top cover (7), and when the electrochemical sensor chip (6) and the micro ultrasonic device (2-1) are arranged in a non-parallel mode, a third opening (7-3) is formed in the top cover (7) and used for penetrating through the electrochemical sensor chip (6).

7. The in-situ micro decontamination platform according to claim 4, wherein when said electrochemical sensor chip (6) and said micro ultrasound device (2-1) are in a parallel arrangement, a hole is formed at a position of said electrochemical sensor chip (6) and/or electrochemical sensor area defining assembly (5) opposite to said first through hole (7-1) and second through hole (7-2); when the electrochemical sensor chip (6) and the micro ultrasonic device (2-1) are arranged in a non-parallel mode, holes are formed in the positions, opposite to the first through hole (7-1) and the second through hole (7-2), of the electrochemical sensor area limiting assembly (5), so that the first through hole (7-1) can be communicated with the liquid inlet cavity (4-1) and the second through hole (7-2) can be communicated with the liquid outlet cavity (4-2).

8. The in situ micro decontamination platform of claim 4, further comprising: the micro-channel lower bottom plate (3) is arranged between the micro-channel assembly (4) and the supporting substrate (2), a second opening (3-1) is formed in the micro-channel lower bottom plate (3), the liquid can be in contact with a vibration area of the micro-ultrasonic device (2-1) through the second opening (3-1), and the bottom surfaces of the liquid inlet cavity (4-1), the first channel (4-4), the liquid outlet cavity (4-2) and the second channel (4-5) are open and sealed by the top surface of the micro-channel lower bottom plate (3);

further comprising: a bottom cover (1) located below the support substrate (2);

the thickness of the supporting substrate (2) is 0.1 mm-10 mm;

the thickness of the lower bottom plate (3) of the micro-channel is 0.0125 mm-5 mm;

the thickness of the electrochemical sensor area limiting assembly (5) is 0.0125 mm-5 mm;

the in-situ micro decontamination platform realizes fastening and adhesive bonding or magnetic attraction in a bolt mode;

the lower surface of the electrochemical sensor area defining component (5) has adhesive property;

the upper surface of the lower micro-channel bottom plate (3) has adhesiveness;

the upper surface of the electrochemical sensor area limiting component (5) has adhesive property;

the lower surface of the lower micro-channel bottom plate (3) has adhesiveness;

the material of the electrochemical sensor area limiting component (5) is polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene terephthalate PET;

the length of the electrochemical sensor area limiting assembly (5) is 1 mm-10 cm;

the size of the second opening (3-1) is larger than or equal to that of a vibration area of the micro ultrasonic device (2-1) and smaller than or equal to that of the cross section of the through hole.

9. Use of the in situ micro decontamination platform of claim 1 for ultrasonic decontamination of electrochemical sensor chips.

10. The application of the ultrasonic decontamination method according to claim 9, wherein in the ultrasonic decontamination, liquid is introduced into the cavity (4-3) to enable the micro ultrasonic device (2-1) to work for 0.1-30 min;

the frequency of ultrasonic waves emitted by the micro ultrasonic device (2-1) is 1 MHz-10 GHz;

the working power of the miniature ultrasonic device (2-1) is 0.01-10W.

Technical Field

The invention belongs to the technical field of electrochemical sensor chip decontamination, and particularly relates to an in-situ micro decontamination platform and application thereof in surface cleaning of an electrochemical sensor chip.

Background

The electrochemical sensor chip is widely applied to the fields of industrial analysis, gas detection, biological medicine and the like, has the advantages of low manufacturing cost, small volume, low energy consumption, high detection speed, high sensitivity, good selectivity, easy integration and the like, and is widely applied to biological sample detection capable of reflecting the physiological health condition of human bodies. However, in the detection of biological samples, the surface of the electrode of the electrochemical sensor chip often adsorbs various pollutants to form a scaling phenomenon, which affects even blocks the detection performance, and further affects continuous detection. Scientists have sought solutions in the electrochemical electrode materials themselves (i.e., anti-fouling) and in electrode cleaning strategies (i.e., decontamination). The anti-fouling means of the electrode is usually to coat the surface of the electrode with a barrier layer to prevent contaminants from reaching the surface of the electrode. For example, in the field of wearable sweat sensing, professor Gao Wei of university of California, professor Ali Javey of Berkeley division of university of California and the like coat the surface of a micro-nano gold electrode with an ion selective film Nafion to realize limited anti-fouling of the electrode in sweat, and detect heavy metal ions, therapeutic drugs methylxanthine, levodopa and the like in the sweat. (GAO W, NYEIN H Y Y, SHAHPAR Z, et al, 2016. week Microsensor Array for multiple Heavy Metal Monitoring of Body fluids. ACS Sensors [ J ],1:866-874.TAI L C, GAO W, CHAO M, et al, 2018.methyl alkaline Drug Monitoring with week switch substrates [ J ],30: e1707442.TAI L C, LIAW T S, LIN Y, et al, 2019. week switch Band for Noninditional Monitoring. Nano lenses [ J ],19: 6346. Nafion is desirable to note that the properties of the thermoplastic ion exchange membrane, including its ability to undergo mechanical stretching, mechanical strain, and the like, can be altered over time. At the electrode Cleaning level, commonly used Cleaning methods are plasma treatment, UV irradiation, Laser heating, Electrochemical Cleaning, etc. (Sun, T., Blanchard, P.Y., Mirkin, M.V., Cleaning nanoelectors with air plant, Analytical Chemistry,2015,87:4092-4095.Pifferi, V., Soliveri, G., Panzaara, G., Ardizzone, S., Cappeletti, G., Meroni, D.Falciola, L.Sensors Cleaning by light, a promoter of treatment for on-site applications, coatings systems, monitor additives, 5: 71210-78, sample, moisture, S.A. slurry, S.A. filtration, moisture, S.A. filtration, etc., moisture, biological analysis, S.A. slurry, moisture, S.A. and S.A. filtration, biological analysis, S.A. 1, biological analysis, sample, biological analysis, 3-7178, sample, biological analysis, sample, biological analysis, S. 242, biological analysis, 2010,26:682- & 688.), however, the methods all need large-scale laboratory analysis test equipment and cannot realize integrated manufacturing to realize the in-situ decontamination effect on the microfluidic electrochemical sheet.

The ultrasonic cleaning technology is widely applied to cleaning, has the advantages of high cleaning speed, good cleaning effect, easy automatic control, no limitation of complex shapes of the surfaces of cleaning pieces, environmental protection, no pollution, lower cost and the like, and is widely applied to the fields of large-scale equipment, precise instruments, electronic equipment, medical instruments and the like. The ultrasonic cleaning technology is applied to the cleaning of the electrodes of the electrochemical sensor, so that the electrochemical sensor can realize the effective continuous detection of the biological sample.

A common mechanism of action for ultrasonic cleaning is ultrasonic cavitation. When ultrasonic waves act on liquid, tensile stress locally appears in the liquid to form negative pressure, and when the ultrasonic negative pressure reaches a certain critical value (cavitation threshold value), gas originally dissolved in the liquid is supersaturated due to the reduction of pressure, and the gas escapes from the liquid to form small bubbles. The bubbles will oscillate, grow, shrink and collapse with the vibration of the surrounding medium, and the extreme shock wave generated in this process will act strongly on the electrode surface to remove the contaminants attached thereon, so as to clean the electrode surface (KLIMA J2011 Application of ultrasounds in electrochemistry and design of experimental arrangement. ultrasounds [ J ],51: 202).

The current ultrasonic cleaning technology mainly adopts a mode of applying ultrasonic waves to liquid through an ultrasonic bath or an amplitude rod to clean an object immersed in the liquid. In U.S. Pat. No. 8,097,148, ultrasonic energy is applied to a liquid through an ultrasonic horn for removing the electrode functional layer with attached contaminants and contaminants attached thereto.

It is noted that the above-mentioned ultrasonic cleaning using the ultrasonic cavitation mechanism, where the pressure at the bubble Collapse reaches thousands of pascals, causes a high-speed flow of liquid up to 200m/s, is extremely aggressive, and causes a great damage to the electrode surface (COMPTON R G, EKLUND J C, marker F, et al, 1997, dual activation: coupling ultrasound to electrochemical-an overview. electrochemical Acta [ J ],42:2919-2927.PLESSET M S, CHAPMAN R B1971. colloid of inorganic particulate vacuum in the neighbor bone of a solid bone. The cavitation effect causes the corrosion of the electrode surface which must be avoided because the uneven electrode is more difficult to electroplate and clean after being used, and the damage of the electrode causes the change of the electrode detection performance, and under the same condition, the detection signal is inconsistent, which affects the sensitivity and accuracy of the working platform. In this way, in continuous detection, the electrode surface cannot be kept in a stable state, and it is difficult to reproduce the same result for the same detection object, and it is difficult to realize multiple, accurate, and stable measurements. Particularly, in the detection of biological samples, various functional substances can be modified on the surface of the electrode, and the high temperature and high pressure caused by cavitation are not favorable for the stable adhesion of the functional layer on the surface of the electrode, and can also influence the experimental result. That is, the functional layer needs to be grown again on the surface of the electrode after the ultrasonic treatment in the above patent (U.S. Pat. No. 8,097,148), which is not suitable for the electrochemical sensor with complicated electrode functionalization process, and the number of times of electrode reuse is limited. In addition, the ultrasonic bath and the ultrasonic amplitude rod are bulky, have high power consumption and are not beneficial to integration.

In summary, at present, there is no in-situ electrochemical electrode surface scaling removal platform which integrates an ultrasonic emission device and does not damage the electrode surface, and a related solution is needed.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide an in-situ micro decontamination platform, wherein a micro ultrasonic device in the in-situ micro decontamination platform emits ultrasonic waves, the ultrasonic waves are propagated and attenuated in liquid to cause high-speed and violent fluid motion of the liquid in a cavity, the fluid motion is repeatedly washed in the surface area of a working electrode of an electrochemical sensor chip, and the generated shearing force can take away dirt accumulated on the surface of the working electrode of the electrochemical sensor chip, so that the aim of cleaning the electrochemical sensor chip is fulfilled.

The invention also aims to provide application of the in-situ micro decontamination platform to ultrasonic decontamination of the electrochemical sensor chip.

The purpose of the invention is realized by the following technical scheme.

An in-situ micro decontamination platform for an electrochemical sensor chip, comprising: the micro-channel assembly and the supporting substrate are arranged in parallel, the electrochemical sensor chip, the micro-channel assembly and the supporting substrate are sequentially arranged from top to bottom, wherein a micro ultrasonic device is arranged on the top surface of the supporting substrate, a through hole is formed in the micro-channel assembly, a cavity with an open top end and an open bottom end is formed by surrounding the hole wall of the through hole, the cavity is communicated with the outside of the in-situ micro decontamination platform, so that liquid can be discharged into and out of the cavity, and the liquid in the cavity can be in contact with three electrodes of the electrochemical sensor chip and the vibration area of the micro ultrasonic device.

In the technical scheme, a liquid inlet cavity and a liquid outlet cavity are formed in the micro-channel assembly, the liquid inlet cavity is communicated with the cavity through a first channel, the liquid outlet cavity is communicated with the cavity through a second channel, and the cavity is communicated with the outside of the in-situ micro decontamination platform through the liquid inlet cavity and the liquid outlet cavity.

In the above technical scheme, the number of the liquid inlet cavities is 1 or more, and the number of the liquid outlet cavities is 1 or more.

In the above technical solution, the micro ultrasonic device is manufactured by an MEMS process, and the micro ultrasonic device is a film bulk acoustic resonator, a micro mechanical ultrasonic transducer, or a piezoelectric ultrasonic transducer.

In the technical scheme, the height of the through hole is 10 mu m-20 mm, and the width of the through hole is 0.1 mm-30 mm.

In the technical scheme, the liquid inlet cavity, the liquid outlet cavity, the first channel and the second channel form a micro-channel together, the width of the first channel and the width of the second channel are respectively 10 μm-5 mm, the length of the first channel and the length of the second channel are respectively 1mm-5cm, the liquid inlet cavity and the liquid outlet cavity are positioned at two sides or the same side of the cavity, and the width of the liquid inlet cavity and the width of the liquid outlet cavity are 0.1 mm-10 mm.

In the technical scheme, the liquid inlet cavity and the liquid outlet cavity are consistent in structure, the first channel and the second channel are consistent in structure, and the sum of the lengths of the liquid inlet cavity and the first channel is 1mm-5 cm.

In the technical scheme, the length of the electrochemical sensor chip is 1mm-5 cm.

In the technical scheme, the micro-channel component is polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene terephthalate PET.

In the technical scheme, the length of the micro ultrasonic device is 100 micrometers-3 cm, and the length of the vibration region of the micro ultrasonic device is 5 micrometers-2 cm.

In the above technical solution, the method further comprises: an electrochemical sensor area defining component parallel to the micro flow channel component, wherein a first opening is formed on the electrochemical sensor area defining component, the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel or in non-parallel, and when the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel, the liquid can contact with the sensing area of the three electrodes through the first opening; when in a non-parallel arrangement, the electrochemical sensor chip is in contact with the liquid through the first opening.

In the above technical solution, when the electrochemical sensor chip and the micro ultrasonic device are disposed in a non-parallel manner, the electrochemical sensor chip is fixed on the electrochemical sensor area defining component, and the sensing area of the three electrodes of the electrochemical sensor chip passes through the first opening and can be in contact with the liquid.

In the above technical solution, when the electrochemical sensor chip and the micro ultrasonic device are disposed in a non-parallel manner, the first opening is a slit; when the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel, the size of the first opening is larger than or equal to that of the sensing area of the three electrodes and smaller than or equal to that of the cross section of the through hole.

In the above technical solution, the method further comprises: the top cover is positioned above the electrochemical sensor chip, a first through hole for inputting liquid into the liquid inlet cavity and a second through hole for discharging liquid out of the liquid outlet cavity are formed in the top cover, and when the electrochemical sensor chip and the miniature ultrasonic device are arranged in a non-parallel mode, a third opening is further formed in the top cover and used for penetrating through the electrochemical sensor chip.

In the above technical solution, when the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel, holes are formed at positions of the electrochemical sensor chip and/or the electrochemical sensor area defining component opposite to the first through hole and the second through hole; when the electrochemical sensor chip and the micro ultrasonic device are arranged in a non-parallel mode, holes are formed in the positions, opposite to the first through holes and the second through holes, of the electrochemical sensor area limiting assembly, so that the first through holes can be communicated with the liquid inlet cavity, and the second through holes can be communicated with the liquid outlet cavity.

In the above technical solution, the method further comprises: the micro-channel lower base plate is arranged between the micro-channel assembly and the supporting substrate, a second opening is formed in the micro-channel lower base plate, liquid can pass through the second opening to be in contact with the vibration area of the micro-ultrasonic device, and the bottom surfaces of the liquid inlet cavity, the first channel, the liquid outlet cavity and the second channel are open and sealed by the top surface of the micro-channel lower base plate.

In the above technical solution, the method further comprises: a bottom cover positioned below the support substrate.

In the above technical solution, the thickness of the support substrate is 0.1mm to 10 mm.

In the technical scheme, the thickness of the lower bottom plate of the micro-channel is 0.0125 mm-5 mm.

In the technical scheme, the thickness of the electrochemical sensor area limiting assembly is 0.0125 mm-5 mm.

In the technical scheme, the in-situ micro decontamination platform realizes fastening and adhesive bonding in a bolt mode or magnetic attraction.

In the above technical solution, the lower surface of the electrochemical sensor area defining component has adhesiveness.

In the above technical solution, the upper surface of the lower plate of the microchannel has adhesiveness.

In the above technical solution, the upper surface of the electrochemical sensor area defining component has adhesive properties.

In the above technical solution, the lower surface of the lower plate of the micro flow channel has adhesiveness.

In the technical scheme, the material of the electrochemical sensor area limiting component is polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene terephthalate PET.

In the technical scheme, the length of the electrochemical sensor area limiting component is 1 mm-10 cm.

In the above technical solution, the size of the second opening is greater than or equal to the size of the vibration region of the micro ultrasonic device and is less than or equal to the size of the cross section of the through hole.

An application of an in-situ micro decontamination platform to ultrasonic decontamination of an electrochemical sensor chip.

In the technical scheme, when ultrasonic decontamination is carried out, liquid is introduced into the cavity, so that the micro ultrasonic device works for 0.1-30 min.

In the technical scheme, the frequency of the ultrasonic wave emitted by the miniature ultrasonic device is 1 MHz-10 GHz.

In the technical scheme, the working power of the miniature ultrasonic device is 0.01-10W.

The invention has the beneficial effects that:

1. the invention is based on the phenomenon that ultrasonic waves are transmitted in liquid to generate acoustic flow, the invention can remove the surface scale of the chip of the electrochemical sensor in situ by utilizing the ultrasonic waves emitted by the miniature ultrasonic device, the horizontal flow rate of the liquid is greatly reduced when the liquid reaches the surface of the working electrode, the sharp reduction of the horizontal flow rate of the liquid can form larger shearing force on the surface of the working electrode, therefore, the organic matters adsorbed on the surface of the working electrode and other substances capable of blocking electrochemical reaction can be removed, the electron transfer process in the electrochemical reaction process is recovered, thereby achieving the effect of activating the working electrode, greatly prolonging the service life of the working electrode, and not damaging the surface of the chip of the electrochemical sensor, the method can realize repeated use of a single electrochemical sensor chip in a complex sample under various scenes, and maintain the stable performance consistent with the initial state.

2. The in-situ micro decontamination platform adopts a layered structure, has small volume, light weight, low power consumption, is convenient for integrated manufacture, has the potential of integration, portability and productization, and has wide application prospect.

Drawings

FIG. 1 is a schematic structural diagram of an in-situ micro decontamination platform according to the present invention (with an electrochemical sensor chip disposed in parallel with a micro ultrasonic device);

FIG. 2 is a schematic structural diagram of an in-situ micro decontamination platform according to the present invention (with an electrochemical sensor chip disposed non-parallel to a micro ultrasound device);

FIG. 3 is a schematic view showing the structure of a microchannel according to the present invention;

FIG. 4 is a schematic structural diagram of a micro ultrasonic device, wherein a is a schematic cross-sectional structural diagram of the micro ultrasonic device, b is a shape of a vibration region of the micro ultrasonic device, and c is a top view of the micro ultrasonic device;

FIG. 5 is a schematic structural diagram of an electrochemical sensor chip, wherein a is a sensing region configuration of the electrochemical sensor chip, b is a sensing region configuration of the electrochemical sensor chip, c is a sensing region configuration of the electrochemical sensor chip, and d is an overall structure of the electrochemical sensor chip;

FIG. 6 is a schematic structural diagram of an electrochemical sensor region defining assembly, wherein a is a top view of the electrochemical sensor region defining assembly, b is the shape of the first opening, and c is a schematic view of the first opening projected onto the electrochemical sensor chip;

FIG. 7 is a schematic structural diagram of a micro channel and a cavity of the present invention, wherein a is the micro channel, b is the micro channel, c is the micro channel, d is the micro channel, and e is the cross-sectional shape of the cavity;

FIG. 8 is a cyclic voltammogram of the pristine electrode, sweat contaminated electrode, acoustically cleaned electrode (1.5W working power);

FIG. 9 is a cyclic voltammogram of the original electrode and acoustically cleaned electrode (0.5W and 1.0W operating power);

fig. 10 is a scanning electron microscope image of (a) a primary electrode (b) a sweat fouling electrode (c) an acoustic cleaning electrode;

fig. 11 is an atomic force microscope image of (a) a prime electrode, (b) a sweat smudge electrode, (c) an acoustically clean electrode, with 256 × 256 scan points, 10 μm × 10 μm scan area;

FIG. 12 is a cyclic voltammogram of the original electrode and acoustically cleaned electrode in test 2;

figure 13 is a cyclic voltammogram of the pristine and acoustically cleaned electrodes of structure 1, structure 3 and structure 4 in test 3.

Wherein

1: bottom cover, 2: support substrate, 2-1: micro ultrasonic device, 3: micro-channel lower base plate, 3-1: second opening, 4: micro flow channel assembly, 4-1: liquid inlet cavity, 4-2: liquid outlet cavity, 4-3: cavity, 4-4: first channel, 4-5: second passage, 5: electrochemical sensor area defining assembly, 5-1: first opening, 6: electrochemical sensor chip, 7: top cover, 7-1: first via hole, 7-2: second via, 7-3: a third opening.

Detailed Description

The technical scheme of the invention is further explained by combining specific examples.

Example 1

As shown in fig. 1 and 2, an in situ micro decontamination platform comprises: the micro-channel assembly 4 and the supporting substrate 2 are arranged in parallel, the electrochemical sensor chip 6, the micro-channel assembly 4 and the supporting substrate 2 are sequentially arranged from top to bottom, wherein a micro ultrasonic device 2-1 is arranged on the top surface of the supporting substrate 2, a through hole is formed in the micro-channel assembly 4, a cavity 4-3 with an open top end and an open bottom end is defined by the hole wall of the through hole, the cavity 4-3 is communicated with the outside of the in-situ micro decontamination platform so that liquid can be discharged into and out of the cavity 4-3, and the liquid in the cavity 4-3 can be in contact with three electrodes of the electrochemical sensor chip 6 and a vibration area of the micro ultrasonic device 2-1.

Example 2

As shown in FIG. 3, on the basis of embodiment 1, a liquid inlet chamber 4-1 and a liquid outlet chamber 4-2 are formed in the microchannel module 4, wherein the number of the liquid inlet chambers is 1 or more, and the number of the liquid outlet chambers is 1 or more. Each liquid inlet cavity 4-1 is communicated with the cavity 4-3 through a first channel 4-4, each liquid outlet cavity 4-2 is communicated with the cavity 4-3 through a second channel 4-5, and the cavity 4-3 is communicated with the outside of the in-situ micro decontamination platform through the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2. The cross-section of the cavity 4-3 may be circular, square, oval or profiled, as shown in fig. 7 e.

The liquid inlet cavity 4-1, the liquid outlet cavity 4-2, the cavity 4-3, the first channel 4-4 and the second channel 4-5 jointly form a micro-flow channel, the width of the first channel 4-4 and the width of the second channel 4-5 are respectively 10 mu m-5 mm, the length of the first channel 4-4 and the length of the second channel 4-5 are respectively 1mm-5cm, as shown in figures 7 a-d, the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are positioned at two sides or the same side of the cavity 4-3, the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are both cylindrical, and the diameter of the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 is 0.1 mm-10 mm.

The height of the through hole is 10 mu m-20 mm, and the width of the through hole is 0.1 mm-30 mm.

Preferably, the structures of the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are consistent, the structures of the first channel 4-4 and the second channel 4-5 are consistent, and the sum of the lengths of the liquid inlet cavity 4-1 and the first channel 4-4 is 1mm-5 cm.

The micro flow channel assembly 4 is made of polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene terephthalate PET.

Preferably, the thickness of the support substrate 2 is 0.1mm to 10 mm.

Example 3

In example 2, the length of the electrochemical sensor chip 6 was 1mm to 5 cm. The electrochemical sensor chip 6 is an integrated working electrode, reference electrode and counter electrode on one substrate. The substrate can be hard substrates such as glass, silicon wafers and the like, and can also be flexible materials such as PI, PET and the like. The electrochemical sensor chip 6 that can be cleaned by the present invention not only can be used for cleaning a large number of commercial electrochemical sensor chips on the market, but also can be used for cleaning electrochemical sensor chips that are designed by itself according to the rules of electrochemical sensors by means of evaporation, photolithography, etc., and can be but is not limited to the structures shown in a, b, c, and d in fig. 5. The working electrode and the counter electrode can be made of carbon, gold, platinum and the like, and the reference electrode can be made of the same material as the working electrode and the counter electrode, or can be made of Ag/AgCl and other classical reference electrodes. The total working area of the electrochemical sensor chip is between 10 mu m and 10 mm.

Example 4

On the basis of the embodiment 3, the frequency of ultrasonic waves emitted by the micro ultrasonic device 2-1 is 1 MHz-10 GHz, the micro ultrasonic device 2-1 is manufactured by an MEMS (micro electro mechanical systems) process, and the micro ultrasonic device 2-1 is a film bulk acoustic resonator, a micro mechanical ultrasonic transducer or a piezoelectric ultrasonic transducer.

The length of the micro ultrasonic device 2-1 is 100 mu m-3 cm, and the length of the vibration region of the micro ultrasonic device 2-1 is 5 mu m-2 cm.

Further comprising: an electrochemical sensor area defining component 5 parallel to the micro flow channel component 4, wherein a first opening 5-1 is formed on the electrochemical sensor area defining component 5, and the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in parallel or in non-parallel, wherein when the electrochemical sensor chip and the micro ultrasonic device are arranged in parallel, liquid can pass through the first opening 5-1 to be in contact with a sensing area of the three electrodes; when arranged non-parallel, the electrochemical sensor chip 6 is in contact with the liquid through the first opening 5-1.

Preferably, the electrochemical sensor region defining assembly 5 has a thickness of 0.0125mm to 5 mm.

Preferably, the material of the electrochemical sensor region defining component 5 is polydimethylsiloxane PDMS, polymethyl methacrylate PMMA or polyethylene terephthalate PET.

Preferably, the electrochemical sensor area defining member 5 has a length of 1mm to 10 cm.

As shown in a of fig. 4, the micro-ultrasonic device 2-1 has a sandwich structure of electrode/piezoelectric layer/electrode, the upper side of the electrode contains a protective layer to prevent the electrode surface from being corroded or oxidized, the lower side of the electrode contains an acoustic reflection mirror, and the main structure is placed on a support substrate (such as a silicon substrate, a polyimide film substrate, etc.). Based on the inverse piezoelectric effect, when an alternating signal is applied to the miniature ultrasonic device, the piezoelectric layer generates mechanical vibration and emits ultrasonic waves. The piezoelectric layer can be made of aluminum nitride, zinc oxide, piezoelectric ceramics PZT, lithium niobate, quartz crystal, organic flexible material polyvinylidene fluoride PVDF and the like. The vibration region of the micro-ultrasonic device, i.e. the piezoelectric layer and the electrodes, can be in various shapes such as a circle, an ellipse, a quadrangle, a pentagon, a hexagon and the like, as shown in b and c in fig. 4, the vibration region can contain one vibration source or an array of a plurality of vibration sources, and the vibration region of the micro-ultrasonic device 2-1 containing a plurality of vibration sources contains the interval regions between different vibration sources; the micro ultrasonic device 2-1 is generally rectangular or square, and comprises a signal connecting line and a supporting pad, wherein the signal connecting line can be very long, and leads signals out of a micro channel to be conveniently connected with an external circuit.

Example 5

As shown in fig. 2, based on example 4, when the electrochemical sensor chip 6 and the micro-ultrasonic device 2-1 are disposed in a non-parallel manner, the electrochemical sensor chip 6 is fixed on the electrochemical sensor area defining member 5 and the sensing area of the three electrodes of the electrochemical sensor chip 6 passes through the first opening 5-1 and can be in contact with the liquid.

Preferably, the first opening 5-1 is a slit.

Example 6

As shown in fig. 1, on the basis of embodiment 4, when the electrochemical sensor chip 6 and the micro-ultrasonic device 2-1 are disposed in parallel, the size of the first opening 5-1 is equal to or larger than the size of the sensing area of the three electrodes and equal to or smaller than the size of the cross section of the through hole. The shape of the first opening 5-1 may be circular, pentagonal, hexagonal, or irregularly shaped as shown in fig. 6.

Example 7

On the basis of embodiment 5 or 6, the method further comprises the following steps: the micro-channel lower bottom plate 3 is arranged between the micro-channel assembly 4 and the supporting substrate 2, a second opening 3-1 is formed on the micro-channel lower bottom plate 3, liquid can be contacted with a vibration area of the micro-ultrasonic device 2-1 through the second opening 3-1, and the bottom surfaces of the liquid inlet cavity 4-1, the first channel 4-4, the liquid outlet cavity 4-2 and the second channel 4-5 are open and are sealed by the top surface of the micro-channel lower bottom plate 3.

Preferably, the thickness of the lower plate 3 of the micro flow channel is 0.0125mm to 5 mm.

Preferably, the size of the second opening 3-1 is equal to or larger than the size of the vibration region of the micro-ultrasonic device 2-1 and equal to or smaller than the size of the cross section of the through hole.

Example 8

On the basis of the embodiment 7, the in-situ micro decontamination platform realizes fastening and adhesive bonding or magnetic attraction in a bolt mode.

Example 9

Based on the embodiment 8, the lower surface of the electrochemical sensor area defining component 5 has adhesiveness, the upper surface of the microchannel lower plate 3 has adhesiveness, the upper surface of the electrochemical sensor area defining component 5 has adhesiveness, and the lower surface of the microchannel lower plate 3 has adhesiveness, so as to improve the sealing performance of the in-situ micro decontamination platform and reduce the volume of the in-situ micro decontamination platform.

Example 10

On the basis of embodiment 9, the method further comprises the following steps: a bottom cover 1 positioned below the support substrate 2.

Further comprising: a top cover 7 positioned above the electrochemical sensor chip 6, a first through hole 7-1 for inputting liquid into the liquid inlet cavity 4-1 and a second through hole 7-2 for discharging the liquid in the liquid cavity 4-2 are formed on the top cover 7, and when the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in a non-parallel way, a third opening 7-3 for passing through the electrochemical sensor chip 6 is also formed on the top cover 7.

When the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in parallel, holes are formed at positions of the electrochemical sensor chip 6 and/or the electrochemical sensor area defining component 5 opposite to the first through hole 7-1 and the second through hole 7-2;

when the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in a non-parallel manner, holes are formed at positions of the electrochemical sensor area limiting assembly 5 opposite to the first through hole 7-1 and the second through hole 7-2, so that the first through hole 7-1 can be communicated with the liquid inlet cavity 4-1, and the second through hole 7-2 can be communicated with the liquid outlet cavity 4-2.

The following tests were performed on the electrochemical sensor chip ultrasonic decontamination based on the in-situ micro decontamination platform, all of the following tests were performed using the in-situ micro decontamination platform obtained in example 10, and the specific structure was as follows:

structure 1:

in-situ micro decontamination platform parameters:

the widths of the first channel 4-4 and the second channel 4-5 are respectively 1.5mm, the lengths of the first channel 4-4 and the second channel 4-5 are respectively 5mm, the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are positioned at two sides of the cavity 4-3, and the diameters of the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are 2 mm.

The height of the through hole is 3mm, and the width of the through hole is 10.2 mm.

The feed liquor chamber is 1, and it is 1 to go out the liquid chamber.

The structures of the liquid inlet cavity 4-1 and the liquid outlet cavity 4-2 are consistent, the structures of the first channel 4-4 and the second channel 4-5 are consistent, and the sum of the lengths of the liquid inlet cavity 4-1 and the first channel 4-4 is 7 mm.

The micro flow channel assembly 4 is polymethyl methacrylate (PMMA).

The thickness of the support substrate 2 was 3 mm.

The length of the electrochemical sensor chip 6 is 15 mm. The working electrode of the electrochemical sensor chip 6 is gold, which has a length of 10mm and a width of 2 mm.

The frequency of ultrasonic waves emitted by the micro ultrasonic device 2-1 is 1 MHz-10 GHz, and the details are shown in the following tests, wherein the micro ultrasonic device 2-1 is manufactured by an MEMS (micro electro mechanical System) process, and the micro ultrasonic device 2-1 is a film bulk acoustic resonator.

The length of the micro ultrasonic device 2-1 is 2cm, and the length of the vibration region of the micro ultrasonic device 2-1 is 5 mm.

The electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in parallel.

The electrochemical sensor area defining member 5 has a thickness of 3 mm.

The material of the electrochemical sensor area limiting component 5 is polymethyl methacrylate (PMMA).

The electrochemical sensor area defining member 5 has a length of 3 cm.

The thickness of the lower plate 3 of the microchannel is 3 mm.

Structure 2:

structure 2 is substantially the same as structure 1 except that: the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in a non-parallel mode.

Structure 3

Structure 3 is substantially the same as structure 1 except that: the height of the through hole is 5 mm.

Structure 4

Structure 4 is substantially the same as structure 1 except that: the height of the through hole is 1 cm.

Test 1. the structure 1 is adopted to research the decontamination effect of the ultrasonic stimulation under different powers on the surface of the electrochemical sensor chip polluted by sweat. The micro ultrasonic device 2-1 is a film bulk acoustic resonator, a working electrode of an electrochemical sensor chip adopts a gold electrode, a test solution is firstly introduced into the cavity 4-3, the test solution is a 50mM potassium ferricyanide aqueous solution, the working electrode is an original electrode at the moment, and a cyclic voltammetry curve obtained by testing is marked as the original electrode, as shown in the original electrode in figures 8 and 9. And then sweat serving as biological liquid is introduced into the cavity 4-3 (at this time, the test liquid is ejected out of the in-situ micro decontamination platform by the biological liquid through the liquid outlet cavity), so that the surface of the gold electrode of the electrochemical sensor chip 6 is polluted, the electrode is a sweat polluted electrode at this time, and a cyclic voltammetry curve of the electrode is recorded as a sweat polluted electrode as shown in fig. 8. And then, introducing a cleaning solution into the cavity 4-3, wherein the cleaning solution is deionized water, and applying working powers of 0.5W, 1W and 1.5W to the micro ultrasonic device 2-1 at the working frequency of 2.58GHz for two minutes. And then introducing a test solution into the cavity 4-3 (at the moment, the cleaning solution is ejected out of the in-situ micro decontamination platform by the test solution through the liquid outlet cavity), measuring a cyclic voltammetry curve in the test solution, and recording the working electrode as an acoustic cleaning electrode at the moment. The peak value of the oxidation-reduction current in the cyclic voltammogram is in positive correlation with the surface cleanliness of the working electrode. Acoustic cleaning electrode with applied working power of 1.5W as shown in fig. 8, the micro-ultrasonic device 2-1 can remove almost all sweat organic residues at working power of 1.5W and restore the oxidation-reduction current peak of the gold electrode to be close to the original electrode peak, which can be used as a cleaning standard. The redox peak of the acoustic cleaning electrode after applying the working power of 1W can recover about 0.65 of the peak value of the original electrode, the redox peak of the acoustic cleaning electrode after applying the working power of 0.5W can recover about 0.45 of the peak value of the original electrode, and the cyclic voltammetry curves of the acoustic cleaning electrode after applying the working power of 1W and 0.5W are shown in fig. 9. Scanning electron microscopy and atomic force microscopy were used to characterize the changes in surface topography of the gold electrodes of the original electrode, sweat contaminated electrode and acoustically cleaned electrode at 1.5W working power. The test result of the scanning electron microscope is shown in fig. 10, and the experimental result shows that after the ultrasonic cleaning is carried out for 2min at the working power of 1.5W, the pollutants on the surface of the gold electrode are obviously removed. The gold electrode surface morphology in fig. 10 was characterized using an atomic force microscope, fig. 11 is a test result showing that the surface roughness of the original electrode was about 5.8nm and that the sweat contaminating electrode increased to about 20.6 nm. The surface roughness of the gold electrode can be recovered to about 7.4nm by using the acoustic cleaning electrode obtained after the 2.58GHz and 1.5W miniature ultrasonic device 2-1 is used for cleaning the electrode for 2min, namely, the surface roughness of the gold electrode is reduced to be close to the roughness of the original electrode state.

Test 2. the effect of ultrasonic cleaning on the ultrasonic cleaning effect in the case of sweat was investigated using structure 1. Test 2 is essentially the same as test 1, except that test 2 does not introduce cleaning fluid into chambers 4-3 (i.e. to keep the sweat still within the chambers) and has a working power of 1.5W. Fig. 12 shows the experimental result, and the micro-ultrasonic device 2-1 can recover the redox current peak of the acoustic cleaning electrode to about 0.7 of the original electrode peak after ultrasonic decontamination is performed for 2min at the working power of 1.5W and the working frequency of 2.58GHz under the condition of sweat.

Test 3. the effect of via height on the ultrasonic cleaning effect was studied using structure 1, structure 3 and structure 4. The method of testing structures 1, 3 and 4 was essentially the same as test 1, except that the operating power was 1.5W. The cyclic voltammograms of the original electrodes of structure 1, structure 3 and structure 4 were identical, and the cyclic voltammograms of the original electrode of structure 1 and the acoustic cleaning electrodes of structure 1, structure 3 and structure 4 as shown in fig. 13, the redox current peaks of the acoustic cleaning electrodes in the through holes of 3mm, 5mm and 1cm height could be returned to about the peak of the original gold electrode.

And 4, researching the influence of the working time of the miniature ultrasonic device 2-1 on the ultrasonic cleaning effect by using the structure 1. Test 4 is essentially the same as test 1, except that the micro-ultrasonic device 2-1 is applied with a working power of 1.5W and is operated for 30s, 1min, 2min and 5min, respectively. The experimental result shows that the peak value of the redox current of the electrode after being cleaned for 30s is recovered to about 0.37 of the peak value of the redox current of the original electrode, the peak value of the redox current of the electrode after being cleaned for 1min is recovered to about 0.6 of the peak value of the redox current of the original electrode, the peak value of the redox current of the electrode after being cleaned for 2min is recovered to be close to the peak value of the redox current of the original electrode, and the peak value of the redox current of the electrode after being cleaned for 5min is also recovered to be close to the peak value of the redox current of the.

And 5, researching the influence of the micro ultrasonic device 2-1 in different frequency bands on the ultrasonic cleaning effect by using the structure 1. Test 5 is essentially the same as test 1, except that the micro-ultrasonic device 2-1 applies 1.5W of operating power and has an operating frequency of 10 MHz. The result shows that after the miniature ultrasonic device with the working power of 1.5W and the working frequency of 10MHz works for 2-1 min, the oxidation-reduction current peak value of the acoustic cleaning electrode can be recovered to about 0.68 of the original electrode peak value.

And 6, researching the influence of different types of electrochemical sensor chips on the ultrasonic cleaning effect by using the structure 1. Test 6 is essentially the same as test 1, the only difference being that the miniature ultrasound device 2-1 is applied with a working power of 1.5W and the working electrodes of the electrochemical sensor chip used in test 6 are glassy carbon and graphitic carbon, respectively. The results show that the redox current peak values of sweat-polluted electrodes of which the working electrodes are respectively a glassy carbon electrode and a graphite carbon electrochemical sensor chip are respectively about 0.2 time and 0.3 time of the corresponding original electrodes, and the performance of the working electrodes is reduced due to serious surface pollution. And the oxidation-reduction current peak values of the acoustic cleaning electrodes of the two electrochemical sensor chips are respectively restored to be close to the peak values of the corresponding original electrodes.

And 7, researching the influence of the arrangement mode of the miniature ultrasonic device on the ultrasonic cleaning effect by using the structure 2. Test 7 is essentially the same as test 1, except that the micro-ultrasonic device 2-1 applies 1.5W of operating power and employs an in-situ micro-desmear platform of structure 2. The result shows that under the condition that the electrochemical sensor chip 6 and the micro ultrasonic device 2-1 are arranged in a non-parallel mode, the redox current peak value of the acoustic cleaning electrode can be recovered to be close to the original electrode current peak value after the micro ultrasonic device 2-1 with the working power of 1.5W and the working frequency of 2.58GHz works for 2 min.

And 8, researching the decontamination effect of the ultrasonic stimulation on the surface of the electrochemical sensor chip polluted by the blood by using the structure 1. Test 8 is essentially the same as test 1, the only difference being that the biological fluid is blood. The experimental result shows that the electrochemical sensor chip can restore the peak value of the oxidation-reduction current of the acoustic cleaning electrode to be close to the original electrode peak value under the working power of 1.5W, namely almost all organic residues and pollutants in blood can be removed, and the electrochemical sensor chip can be used as a cleaning standard. The oxidation-reduction peak of the acoustic cleaning electrode after 1W of working power can recover about 0.5 of the peak value of the original electrode, and the oxidation-reduction peak of the acoustic cleaning electrode after 0.5W of power can recover about 0.32 of the peak value of the original electrode. Scanning electron microscopy and atomic force microscopy were used to characterize the changes in surface topography of the gold electrodes of the original electrode, sweat contaminated electrode and acoustically cleaned electrode at 1.5W working power. The test result of the scanning electron microscope shows that after the ultrasonic cleaning is carried out for 2min at the working power of 1.5W, the pollutants on the surface of the gold electrode are obviously removed. The surface morphology of the gold electrode after ultrasonic stimulation was characterized using an atomic force microscope and the experimental results showed that the surface roughness of the original electrode was about 6.8nm and that the value of the blood contaminated electrode (equivalent to the sweat contaminated electrode in test 1) increased to about 23.5 nm. The roughness of the acoustic cleaning electrode at the working power of 1.5W is restored to about 7.9nm, that is, the surface roughness of the acoustic cleaning electrode is reduced to be near the roughness of the original electrode state.

The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.