TWI706132B - Sensor and detection device applying the same sensor - Google Patents

Abstract

A sensor includes: an ultrasonic element comprising a first electrode, a second electrode, an insulating layer disposed on the second electrode, and a diaphragm disposed between the first electrode and the insulating layer, the insulating layer and the diaphragm enclosing a sealed cavity, and the first electrode is carried on the diaphragm, when the first electrode and the forming a potential difference between the second electrodes, the diaphragm vibrating to form an ultrasonic wave of a predetermined frequency range; and a combination body disposed on the surface of the first electrode away from the second electrode for binding to a target analyte in the analyte, and changes the load-bearing weight of the vibration film when the combination is combined with the target detector, thereby changing the frequency range of the ultrasonic waves, thereby changing the frequency range of the ultrasonic wave. The present invention also provides a detecting device to which the above sensor is applied. The sensor has a simple structure and can quickly determine whether a target test object is combined with the combined body.

Description

Sensor and detection device using the sensor

The invention belongs to the technical field of microfluid detection, and relates to a sensor and a detection device using the sensor.

In the prior art, the binding conditions are usually created for the receptor or adsorbent and the target detection substance in the test object, and the two are combined to determine whether the target detection substance is contained in the test object. However, simply creating binding conditions cannot detect whether the receptor or adsorbent binds to the target analyte. Other methods are needed to detect whether the receptor or adsorbent binds to the target analyte.

In the first aspect of the present invention, the present invention provides a sensor including: an ultrasonic element, which includes a first electrode, a second electrode, and an insulating layer provided on the second electrode that are relatively spaced apart and electrically insulated from each other , And a diaphragm arranged between the first electrode and the insulating layer, the insulating layer and the diaphragm enclosing to form a sealed cavity, and the first electrode is carried on the diaphragm Above, when a potential difference is formed between the first electrode and the second electrode, the diaphragm vibrates to form an ultrasonic wave of a predetermined frequency range; and the combination is arranged on the first electrode away from the second electrode The surface is used to combine with the target detection object in the object to be tested, and when the combined body is combined with the target detection object, the load-bearing weight of the diaphragm is changed, thereby changing the frequency range of the ultrasonic wave. In a second aspect, the present invention provides a detection device for detecting a target detection object in an object to be tested, comprising: a hollow tube, the hollow tube is open at both ends, and the inner wall of the hollow tube is provided with the sensor provided in the first aspect . The third aspect The invention provides a DNA detection device, including: a liquid inlet; a liquid outlet; a screening area, which is connected to the liquid inlet, and is used to predict the lysis of the cell fluid to be detected entering from the liquid inlet DNA fragments; and a detection zone, which is provided between the screening zone and the liquid outlet and communicates with the two, and the detection zone is provided with the sensor provided in the first aspect for detecting The predicted DNA fragments in the lysed cell sap in the screening zone.

The structure of the above-mentioned sensor is simple, and the frequency of the ultrasonic wave can be changed by the vibration change of the diaphragm, so as to quickly determine whether the target detection object is combined with the binding body. The detection device provided with the above-mentioned sensor has a simple structure. When the detection device is used to detect the object to be tested, the operation of the detection process is very convenient, the detection efficiency is obviously improved, and it is positively helpful for detecting the tiny object to be tested.

When a biochemical reaction occurs when the receptor or adsorbent binds to the target analyte, the by-products produced by the biochemical reaction can be detected; or when the pH value changes when the receptor or adsorbent binds to the target analyte, the PH value can be passed The color of the value is judged; or when the quality of the test object changes locally when the receptor or adsorbent binds to the target test object, the quality of the test object can be detected to determine whether the target test object and the receptor or The adsorbent is combined to determine whether the test object contains the target test object.

10, 20, 30: detection device

11: Catheter

100: sensor

110: Combination

130: target detection object

120: Ultrasonic components

121: first electrode

125: insulating layer

123: diaphragm

122: second electrode

124: Cavity

21: Suction ball

31: Liquid inlet

34: Liquid outlet

32: Screening area

310: first layer

320: second layer

330: hydrophobic layer

340: Channel

350: first electrode layer

360: first shell

380: second shell

370: Thin film transistor array layer

391: Thin Film Transistor

391a: Source

33: detection area

a: Frequency-conductivity diagram before the binding body and the target detection substance are combined

b: Frequency-conductivity diagram after the binding body and the target detection substance are combined

Fig. 1 is a schematic plan view of the sensor in the first embodiment of the present invention.

Fig. 2 is a schematic cross-sectional view of the sensor in the first embodiment.

3 is a schematic cross-sectional view of the combination of the sensor and the target object under test in the first embodiment of the present invention.

4 is a graph of frequency-conductance curves before and after the combination of the sensor and the target object under test in the first embodiment of the present invention.

5 is a schematic cross-sectional structure diagram of a gas detection device provided by a second embodiment of the present invention.

6 is a schematic cross-sectional structure diagram of a liquid detection device provided by a third embodiment of the present invention.

Fig. 7 is a schematic cross-sectional structure diagram of a DNA detection device provided by a fourth embodiment of the present invention.

In order to be able to understand the above objectives, features and advantages of the present invention more clearly, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments. It should be noted that in the following description, many specific details are set forth in order to fully understand the present invention, and the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field of the present invention. The terms used in the description of the present invention herein are only for the purpose of describing specific embodiments, and are not intended to limit the present invention.

Please refer to FIGS. 1 and 2. In the first embodiment of the present invention, the sensor 100 includes an ultrasonic element 120 and a combined body 110 disposed on the ultrasonic element 120. The ultrasonic element 120 is a Capacitive Micromachined Ultrasonic Transducer (CMUT), which includes a first electrode 121, a second electrode 122, and a second electrode 122 that are spaced apart and electrically insulated from each other. The upper insulating layer 125 and the diaphragm 123 disposed between the first electrode 121 and the insulating layer 125. The first electrode 121 is carried on the diaphragm 123, and the insulating layer 125 and the diaphragm 123 enclose a sealed cavity 124.

When the sensor 100 is working, a DC voltage is applied to the first electrode 121 and the second electrode 122, a strong electrostatic field will be formed between the first electrode 121 and the second electrode 122; The electric field force in the electrostatic field will pull the part of the diaphragm 123 on the side of the first electrode 121 toward the cavity 124; then, on the basis of a direct current voltage, the first electrode 121 and the The two electrodes 122 are applied with an alternating voltage, and the changing electric field generated under the alternating voltage causes the diaphragm 123 to oscillate up and down. Through the physical oscillation of the diaphragm 123, the ultrasonic element 120 generates ultrasonic waves in a predetermined frequency range. The combined body 110 is arranged on the side of the first electrode 121 of the ultrasonic element 120 away from the diaphragm 123.

Please refer to FIG. 3, the combination body 110 is used to combine with the target detection object 130 in the test object, and the test object may be liquid, gas, or solid. When the object to be tested contains the target detection object 130, the combination of the target detection object 130 and the binding body 110 on the first electrode 121 will cause the weight carried by the diaphragm 123 to change, so Affects the physical oscillation amplitude of the diaphragm 123, which in turn affects the frequency range of the ultrasonic wave of the ultrasonic element 120, and changes the frequency range of the ultrasonic wave.

Please refer to FIG. 4, which shows the change of the conductance of the ultrasonic element 120 with the frequency of the ultrasonic wave measured by the impedance analyzer, wherein the curve a represents the ultrasonic element 120 before the combination body 110 is combined with the target detection object 130 The frequency-conductivity relationship of the curve b represents the frequency-conductance relationship of the ultrasonic element 120 after the combination 110 and the target detection object 130 are combined. It can be seen from curve a and curve b that when the combined body 110 is not combined with the target detection object 130 in the test object and when combined with the target detection object 130, the ultrasonic frequency range emitted by the ultrasonic element 120 is significantly different. Moreover, it can be seen from curve a that when the binding body 110 does not bind to the target detection substance 130 in the test object, the conductance has a maximum value at a frequency of 12 MHz. It can be seen from the curve b that when the combined body 110 is combined with the target detection object 130 in the test object, the conductance has a maximum value when the frequency of the ultrasonic wave is between 11.999 MHz and 12 MHz (about 11.9995 MHz). That is, when the combined body 110 is combined with the target detection object 130, when the conductance of the ultrasonic element 120 has a maximum value, the frequency of the corresponding ultrasonic wave is different from that the combined body 110 is not combined with the target detection object 130 The maximum value of conductance corresponds to the frequency of ultrasound. In this embodiment, when the combined body 110 is combined with the target detection object 130, the corresponding frequency when the conductance of the ultrasonic element 120 has a maximum value is compared with that when the combined body 110 is not combined with the target detection object. 130 is reduced when combined. Therefore, when the relationship between the frequency of the ultrasonic element 120 and its conductance changes to a certain extent, it can be inferred that the combined body 110 has been combined with the target detection object 130, and then it can be determined that the object to be tested contains the Target detection object 130. These changes can be detected by ultrasonic frequency detection equipment (for example, impedance analyzer).

The conjugate 110 can be a chemical adsorbent, for example, including organic polymers (polymer), porous materials, nanoparticles, metal films, etc.; it can also be a biological receptor, for example, including antibodies, Derivatives such as catalyst, protein or DNA, RNA, cDNA. In other words, the sensor 100 provided in this embodiment can be applied as a biological sensor or a chemical sensor.

When the combined body 110 (limited to the solid combined body 110) can be mixed with liquid, the combined body 110 can be printed on the first electrode by ink-jet printing (IJP) 121 is away from the side surface of the diaphragm 123. According to the different types of the target detection 130 objects, the corresponding combination body 110 capable of reacting with it is used, and the combination body 110 is printed on the surface of the first electrode 121.

As shown in the following table:

When the target analyte 130 is a sulfide, ketone, alcohol or olefin, the conjugate 110 may include a corresponding polymerizable polymer. When the target analyte 130 is an antigen, the The conjugate 110 may include a corresponding antibody. When the target analyte 130 is DNA, the conjugate 110 may include a restriction enzyme (restriction enzyme). According to the different categories selected by the target object 130 and the combination 110, the sensor 100 provided in this embodiment can be applied to human volatile organic compounds (Volatile Organic Compounds, VOC) testing, environmental VOC testing, pesticide testing, food safety testing and other application areas. When the detection device provided with the sensor 100 is used to detect the object to be tested, the operation of the detection process is simple, which is positively helpful for detecting the tiny object to be tested.

Second embodiment

Referring to FIG. 5, a second embodiment of the present invention provides a detection device 10 that can be used to detect whether a target object 130 is contained in a gas. The detection device 10 includes the sensor 100 and also includes a hollow tube 11. The hollow tube 11 is open at both ends and is made of corrosion-resistant material, such as glass. The sensor 100 is arranged on the inner wall of the hollow tube 11.

When the gas to be detected enters through an opening at one end of the hollow tube 11, and the airflow flows through the plurality of sensors 120 on the inner wall of the hollow tube 11, if the gas to be detected contains the target The detection object 130, the target detection object 130 will be combined with the combination body 110 on the sensor 120, which causes the frequency of the ultrasonic element 120 to change. In other words, if the frequency of the ultrasonic wave changes, it means that the target side object 130 is contained in the gas to be measured. By detecting the amount of change in the ultrasonic frequency, the content of the target detection substance 130 in the gas to be measured can be calculated. The detection device 10 of this embodiment can be applied to the VOC detection of the exhaled human body. For example, to detect whether the exhaled gas contains the target detection substance 130, you only need to exhale from one end of the hollow tube 11, and then The change of the sensor 100 can quickly know the result, and the detection process is time-saving and efficient.

The third embodiment

Please refer to FIG. 6, the third embodiment of the present invention provides another detection device 20 that can be used to detect whether a target detection substance 130 is contained in a liquid to be tested. The main difference between the detection device 20 in this embodiment and the second embodiment is that the detection device 20 in this embodiment includes a hollow tube 11 as in the second embodiment and a suction set at one end of the hollow tube 11 Ball 21. The suction ball 21 communicates with one end of the hollow tube 11. The suction ball 21 may be made of extrudable rubber material.

By squeezing the suction ball 21, the liquid to be tested is sucked from the other end of the hollow tube 11. The liquid to be measured flows through the hollow tube 11, and if the liquid to be measured contains the target object 130, the The target object 130 will be combined with the combined body 110 on the sensor 100 unit. Then, by detecting whether the frequency of the ultrasonic wave changes, it is determined whether the liquid to be measured contains the target object 130, and finally the liquid to be measured flows into the inside of the suction ball 21. In this embodiment, the suction ball 21 is made of rubber. In other embodiments, the suction ball 21 may also be made of other elastic materials. The detection device 20 of this embodiment can be applied to the detection of VOC in drinking water or surface water, for example. The detection process is extremely convenient. First, the suction ball 21 is squeezed, and then one end of the hollow tube 11 is mixed with water or other liquids. When the test object touches, the suction ball 21 is finally released. According to the change of the sensor 100, it can be known whether the liquid test object contains the target detection object 130. The detection process is simple and convenient, and the detection results are accurate and efficient.

Fourth embodiment

Referring to FIG. 7, this embodiment provides a DNA detection device 30. The DNA detection device 30 includes a liquid inlet 31, a screening area 32, a detection area 33, and a liquid outlet 34 that are connected in sequence. Sensor 100 in area 33.

The liquid inlet 31 is used to allow the cell liquid to be detected to flow into the screening area 32, and the liquid outlet 34 is used to allow the cell liquid to be detected in the detection area 33 to flow out. The DNA detection device 30 includes a first layer 310 and a second layer 320 that are spaced apart and opposed to each other, and a channel 340 formed between the first layer 310 and the second layer 320 for the circulation of cell fluid. The first layer 310 includes a hydrophobic layer 330, a first electrode layer 350, and a first shell 360 stacked in sequence, wherein the hydrophobic layer 330 is closest to the channel 340. The second layer 320 includes a hydrophobic layer 330, a thin film transistor array layer 370, and a second housing 380 stacked in sequence, wherein the hydrophobic layer 330 is closest to the channel 340. The channel 340 penetrates the liquid inlet 31 and the liquid outlet 34.

The sensor 100 is the sensor 100 described in the first embodiment, and is disposed on the inner wall of the channel 340 of the detection area 33. In this embodiment, the sensor 100 is disposed on the surface of the hydrophobic layer 330 of the first layer 310. The detection area 33 is used for detecting cells that are lysed when passing through the channel 340 and passing through the screening area 32 after passing through the liquid inlet 31. The first housing 360 and the second housing 380 are both insulated, which are used to protect the DNA detection device 30.

As shown in FIG. 7, the hydrophobic layer 330 of the first layer 310 and the hydrophobic layer 330 of the second layer 320 constitute the inner wall of the channel 340. The thin film transistor array layer 370 includes a plurality of thin film transistors 391 arranged in an array. Among them, each thin film transistor 391 is a conventional low temperature polysilicon (LTPS) thin film transistor in the art, and includes a source electrode 391a. Different voltages are applied to the first electrode layer 350 and the source electrode 391a of the thin film transistor 391 to form an electric field inside the channel 340, and by adjusting the first electrode layer 350 and the source electrode 391a The voltage between the thin film transistor array layers 370 can adjust the wetting performance of the cell fluid on the hydrophobic layer 330, thereby controlling the flow rate of the cell fluid in the channel 340.

Further referring to FIG. 7, when the DNA detection device 30 of this embodiment is used for predictive DNA detection, the cell liquid used for detection is first separated by a centrifuge, and the separated cell liquid is removed from the liquid inlet 31 It is introduced into the DNA detection device 30. The purpose of the cell fluid flowing through the screening area 32 through the channel 340 is to obtain a predetermined DNA fragment for detection. Therefore, in the screening area 32, after the cell fluid is introduced into the channel 340, in order to completely separate the DNA from the cell membrane, a membrane dissolving agent can be added to the channel 340 to dissolve the cell membrane and release the DNA. The inner cell material inside. Since DNA is a negatively charged substance, DNA in the solution can be adsorbed on the hydrophobic layer 330 of the second layer 320 under the action of an electrostatic field. At the same time, a restriction enzyme (restriction enzyme) solution is added to the channel 340 flowing through the screening area 32. When the DNA contains the predicted DNA fragment, the restriction enzyme can cut the desired predicted DNA fragment ( That is, the target analyte), when the DNA does not contain the predicted DNA fragment, the restriction enzyme cannot extract the required predicted DNA fragment. Afterwards, the voltage between the first electrode layer 350 and the thin film transistor 391 layer is adjusted so that the cell sap containing the restriction enzyme solution (which may or may not contain the predicted DNA fragment) flows forward, Enter the detection area 33.

The cell fluid containing the restriction enzyme solution after passing through the screening zone 32 then flows through the detection zone 33, and the detection zone 33 detects whether the cell fluid contains the predicted DNA fragment. The detection area 33 is provided with the aforementioned sensor 100, and the first electrode 121 of the sensor 100 is provided with a binding body 110 for binding the predicted DNA fragment. The ultrasonic wave emitted by the sensor 100 The frequency range determines whether the binding body 110 on the sensor 100 binds to the predicted DNA fragment, and then determines whether the cell contains the predicted DNA fragment. When the DNA contains the predicted DNA fragment, when the cell fluid containing the restriction enzyme solution flows through the detection zone 33, the predicted DNA fragment will combine with the In combination with 110, the frequency range of the ultrasonic wave emitted by the sensor 100 changes, thereby determining that the cell contains a predetermined DNA fragment; otherwise, it is determined that the cell does not contain a predetermined DNA fragment. After that, the cell solution is discharged from the DNA detection device 30 from the liquid outlet 34. Under the premise of ensuring the accuracy of the structure, the detection process is simple and convenient.

The detection device 30 may be square or tubular as a whole.

For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be Modifications or equivalent replacements are made without departing from the scope of the technical proposal of the present invention.

120: Ultrasonic components

121: first electrode

122: second electrode

125: insulating layer

123: diaphragm

124: Cavity

110: Combination

130: target detection object

Claims (10)

A sensor is improved in that it includes: an ultrasonic element, which includes a first electrode, a second electrode, an insulating layer provided on the second electrode, and an ultrasonic element that are spaced apart and electrically insulated from each other. The diaphragm between the first electrode and the insulating layer, the insulating layer and the diaphragm are enclosed to form a sealed cavity, and the first electrode is carried on the diaphragm, when the first electrode A potential difference is formed between an electrode and the second electrode, and the diaphragm vibrates to form an ultrasonic wave in a predetermined frequency range; and a combined body is arranged on the surface of the first electrode away from the second electrode and used to interact with The target detection object in the test object is combined, and when the combination is combined with the target detection object, the bearing weight of the diaphragm is changed, so that the frequency range of the ultrasonic wave is changed. The sensor according to claim 1, wherein: when the combined body is combined with the target detection object, when the conductance of the ultrasonic element has a maximum value, the frequency of the corresponding ultrasonic wave is different from that of the combined body not detected with the target The maximum value of conductance corresponding to the frequency of ultrasound when the substance is combined. The sensor according to claim 1, wherein: the object to be measured is gas, liquid or solid. A detection device for detecting a target detection object in an object to be tested. The improvement is that it includes a hollow tube, the hollow tube is open at both ends, and the inner wall of the hollow tube is provided with any one of claims 1-3 Sensor. The detection device according to claim 4, wherein a suction ball is communicated with an opening at one end of the hollow tube, and the suction ball is used for sucking the test object into the hollow tube when being squeezed. The detection device according to claim 5, wherein: the suction ball is made of rubber. A DNA detection device, which is improved in that it comprises: a liquid inlet; a liquid outlet; a screening area, which is connected to the liquid inlet, and is used to dissolve the cell fluid to be detected entering from the liquid inlet Predict DNA fragments; and The detection zone is arranged between the screening zone and the liquid outlet and communicates with the two, and the detection zone is provided with the sensor according to any one of claim items 1-3 for detecting The predicted DNA fragment in the lysed cell fluid in the screening area. The DNA detection device according to claim 7, wherein: the liquid inlet is used to allow the cell fluid to flow into the screening area, and the liquid outlet is used to allow the cell fluid detected in the detection area to flow out. The DNA detection device according to claim 7, wherein: the DNA detection device includes a first layer and a second layer that are spaced apart and opposed to each other, and cells are formed between the first layer and the second layer A channel for liquid circulation, the first layer includes a hydrophobic layer and a first electrode layer stacked in sequence, and the second layer includes a hydrophobic layer and a thin film transistor array layer stacked in sequence, wherein the hydrophobic layer of the first layer The hydrophobic layer of the layer and the second layer constitute the inner wall of the channel. The DNA detection device according to claim 9, wherein: the thin film transistor array layer includes a plurality of thin film transistors arranged in an array, wherein each thin film transistor includes a source, and the first electrode layer and Different voltages are applied to the source of the thin film transistor to form an electric field inside the channel, and the cell sap on the hydrophobic layer is adjusted by adjusting the voltage between the first electrode layer and the thin film transistor array layer. The wettability of the upper surface, thereby controlling the flow of the cell fluid in the channel.

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