A biosensor, a biochip and a method of use

Abstract

The application discloses a biological detection sensor, a biological detection chip and a use method, wherein the biological detection sensor of one embodiment comprises a tunneling field effect transistor, a carbon nanotube field effect transistor and a detection electrode, the tunneling field effect transistor is provided with a modified antibody, is used for causing band-to-band tunneling and generating a tunneling current when charges generated by specific combination of a sample to be detected and the modified antibody occur; the carbon nanotube field effect transistor is used for amplifying the tunneling current; and the detection electrode is used for forming a corresponding detection voltage according to the amplified tunneling current. The embodiment provided by the application can improve the detection precision of the biological detection sensor, meet the detection of positive charges and negative charges, and effectively improve the use range of the biological detection sensor by using the tunneling field effect transistor with low subthreshold swing and amplifying the tunneling current generated by the tunneling field effect transistor by using the bipolarity of the carbon nanotube field effect transistor.

Description

Technical Field

[0001] This invention relates to the field of biological detection technology, and in particular to a biological detection sensor, a biological detection chip, and a method of using it. Background Technology

[0002] Field-effect transistor (FET) biosensors possess significant advantages such as high sensitivity, rapid response, and label-free detection, showing great potential in point-of-care testing (POCT). Thin-film semiconductor transistors, in particular, offer advantages like good process compatibility and excellent gate control characteristics, making them highly anticipated for biosensor applications. When the subthreshold region of a transistor is used for sensing, a smaller subthreshold swing (SS) makes the sensing signal easier to detect. Common transistor subthresholds are approximately 200-300 mV / dec, meaning a minimum voltage change of 200 mV is required for a change in current of one order of magnitude. However, voltage changes caused by electrode modification are often only around tens of mV, failing to reach the 200 mV detection threshold and hindering the detection of characteristic signals. Furthermore, current POCT detection methods require first identifying the charge polarity of the modified biomolecules and then selecting P-type or N-type transistor devices accordingly, complicating the detection process and limiting the choice of transistor device type.

[0003] Improving the signal detection rate of biological detection, simplifying detection steps, and improving detection accuracy have become technical problems that urgently need to be solved by those skilled in the art. Summary of the Invention

[0004] To address at least one of the aforementioned problems, a first embodiment of the present invention provides a biosensor based on a tunneling field-effect transistor, comprising a tunneling field-effect transistor, a carbon nanotube field-effect transistor, and a detection electrode, wherein...

[0005] The tunneling field-effect transistor is equipped with a modified antibody, which is used to induce band tunneling and generate a tunneling current based on the charge generated when the sample to be detected undergoes a specific binding reaction with the modified antibody.

[0006] The carbon nanotube transistor is used to amplify the tunneling current;

[0007] The detection electrode is used to generate a corresponding detection voltage based on the amplified tunneling current.

[0008] For example, in some embodiments of the biosensor provided in this application, the biosensor further includes a first capacitor and a second capacitor.

[0009] The tunneling field-effect transistor includes a first gate, a first source, and a first drain; the carbon nanotube transistor includes a second gate, a second source, and a second drain; the first capacitor includes a first terminal and a second terminal; and the second capacitor includes a third terminal and a fourth terminal.

[0010] The modified antibody is disposed on the first gate, the first source, the second source, and the second terminal are connected to the first node, the first node is connected to the first power signal, and the first drain, the first terminal, and the second gate are connected to the second node.

[0011] The second drain, the third terminal, and the detection electrode are connected to the third node;

[0012] The fourth terminal is connected to the second power signal.

[0013] For example, in some embodiments of the biosensor provided in this application, the biosensor includes a substrate, a first active layer disposed on the substrate, a gate insulating layer covering the first active layer, a gate layer disposed on the gate insulating layer, an interlayer insulating layer covering the gate layer and the exposed gate insulating layer, a first electrode layer and a second active layer disposed on the interlayer insulating layer, a passivation layer covering the first electrode layer and the second active layer, and a second electrode layer disposed on the passivation layer, wherein...

[0014] The first active layer includes the first active structure of the tunneling field-effect transistor. The first active structure includes a first active portion, a first channel, and a second active portion arranged sequentially along a first direction. The first active portion includes a first doping type, and the second active portion includes a second doping type. The first doping type is different from the second doping type.

[0015] The gate layer includes a first gate of the tunneling field-effect transistor and a second gate of the carbon nanotube field-effect transistor disposed in the same layer.

[0016] The first electrode layer includes a first source and a first drain of the tunneling field-effect transistor and a second source and a second drain of the carbon nanotube field-effect transistor disposed in the same layer. The orthographic projection of the first source on the substrate does not overlap with the orthographic projection of the first drain on the substrate, and the orthographic projection of the second source on the substrate does not overlap with the orthographic projection of the second drain on the substrate. The first source is connected to the first active part through a via penetrating the interlayer insulating layer and the gate insulating layer, and the first drain is connected to the second active part through a via penetrating the interlayer insulating layer and the gate insulating layer.

[0017] The second active layer includes the second active structure of the carbon nanotube field-effect transistor. One end of the second active structure is connected to the second source and the other end is connected to the second drain. The orthographic projection of the second active structure on the substrate overlaps with the orthographic projection of the second source on the substrate. The orthographic projection of the second active structure on the substrate overlaps with the orthographic projection of the second drain on the substrate.

[0018] The second electrode layer includes a first electrode portion and a second electrode portion. The first electrode portion is the first electrode plate of the first capacitor. The second electrode portion is multiplexed as the first electrode plate of the second capacitor and the detection electrode of the biosensor. The first drain of the tunneling field-effect transistor is multiplexed as the second electrode plate of the first capacitor. The orthographic projection of the first electrode plate on the substrate and the orthographic projection of the first drain on the substrate at least partially overlap. The second drain of the carbon nanotube field-effect transistor is multiplexed as the second electrode plate of the second capacitor. The orthographic projection of the second electrode plate on the substrate and the orthographic projection of the second drain on the substrate at least partially overlap.

[0019] For example, in some embodiments of the biosensor provided in this application,

[0020] The orthographic projection of the first channel onto the substrate falls into the orthographic projection of the first gate onto the substrate;

[0021] The orthographic projection of the second gate onto the substrate falls into the orthographic projection of the second active structure onto the substrate.

[0022] For example, in some embodiments of the biosensor provided in this application,

[0023] The orthographic projection of the first gate onto the substrate overlaps with the orthographic projection of the first active portion onto the substrate.

[0024] The orthographic projection of the first gate onto the substrate overlaps with the orthographic projection of the second active portion onto the substrate.

[0025] For example, in some embodiments of the biosensor provided in this application, the biosensor further includes a reset transistor, which includes a third gate, a third source, and a third drain.

[0026] The third gate is connected to a reset signal, the third source is connected to a third node, and the third drain is connected to the second power supply signal.

[0027] For example, in some embodiments of the biosensor provided in this application,

[0028] The first active layer further includes a third active structure of the reset transistor, the third active structure including a third active portion, a second channel and a fourth active portion arranged sequentially along a first direction, the third active portion and the fourth active portion including the same doping type;

[0029] The gate layer further includes a third gate, wherein the orthographic projection of the second channel on the substrate and the orthographic projection of the third gate on the substrate at least partially overlap;

[0030] The first electrode layer further includes a third source and a third drain of the reset transistor. The orthographic projection of the third source on the substrate and the orthographic projection of the third drain on the substrate do not overlap. The third source is connected to the third active portion through a via penetrating the interlayer insulating layer and the gate insulating layer. The third drain is connected to the fourth active portion through a via penetrating the interlayer insulating layer and the gate insulating layer.

[0031] For example, in some embodiments of the biosensor provided in this application, the aspect ratio of the second channel is greater than or equal to 20.

[0032] A second embodiment of the present invention provides a biological detection chip, including at least one biological detection sensor as described in the first embodiment.

[0033] For example, in some embodiments of this application, the biodetection chip includes m*n biodetection sensors arranged in M ​​rows and N columns, a scan signal line, a reset signal line and a second power signal line connecting the tunneling field-effect transistors of each row of biodetection sensors, and a first power signal line connecting each column of biodetection sensors, where m≥1 and n≥1.

[0034] Each biosensor responds to signal gating via the connected scan signal line and the first power signal line.

[0035] A third embodiment of the present invention provides a method of using the biological detection sensor described in the first embodiment, comprising:

[0036] The sample to be tested undergoes a specific binding reaction with a modified antibody disposed on a tunneling field-effect transistor of a biosensor, and the tunneling field-effect transistor undergoes band tunneling and generates a tunneling current.

[0037] The carbon nanotube transistors of the biosensor amplify the tunneling current.

[0038] The detection electrode of the biosensor generates a corresponding detection voltage based on the amplified tunneling current.

[0039] The beneficial effects of this invention are as follows:

[0040] This invention addresses existing problems by developing a biological detection sensor, a biological detection chip, and a method of use. It involves placing a modified antibody on the gate of a tunneling field-effect transistor (TFPTT) with a low subthreshold swing. The charge generated when the sample to be detected specifically binds to the modified antibody induces band tunneling and generates a tunneling current. Simultaneously, the bipolar characteristics of a carbon nanotube TFPTT amplify the tunneling current generated by the TFPTT. This improves the detection accuracy of the biological detection sensor while also enabling the detection of both positive and negative charges. It overcomes the problems existing in current technologies, thereby increasing the signal detection rate of biological detection, simplifying the detection process, and effectively expanding the application range of the biological detection sensor. Attached Figure Description

[0041] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0042] Figure 1 A circuit diagram of a biological detection sensor according to an embodiment of the present invention is shown;

[0043] Figure 2 A schematic diagram of the layer structure of a biological detection sensor according to an embodiment of the present invention is shown;

[0044] Figure 3 A circuit diagram of the biosensor according to another embodiment of the present invention is shown;

[0045] Figure 4 A schematic diagram of the layer structure of the reset transistor according to an embodiment of the present invention is shown;

[0046] Figure 5 A schematic diagram of the circuit board of a biological detection sensor according to an embodiment of the present invention is shown;

[0047] Figure 6 A schematic diagram of the circuit board fabrication of the biodetection chip according to an embodiment of the present invention is shown;

[0048] Figure 7 A flowchart illustrating the usage method of one embodiment of the present invention is shown. Detailed Implementation

[0049] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further explains the invention. Similar components in the drawings are indicated by the same reference numerals. Those skilled in the art should understand that the specific description below is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0050] It should be noted that the terms "on," "formed on," and "set on" used in this document can indicate that one layer is directly formed or set on another layer, or that one layer is indirectly formed or set on another layer, meaning that there are other layers between the two layers. In this document, unless otherwise stated, the term "located on the same layer" means that two layers, components, elements, or parts can be formed through the same patterning process, and that these two layers, components, elements, or parts are generally formed of the same material. In this document, unless otherwise stated, the description of "patterning process" generally includes steps such as photoresist coating, exposure, development, etching, and photoresist stripping. The description of "one-time patterning process" refers to a process that uses a single photomask to form patterned layers, components, elements, etc.

[0051] To address the issues of low signal detection rate and complex detection steps in related technologies for biological detection, such as... Figure 1 As shown, one embodiment of the present invention provides a biosensor based on a tunneling field-effect transistor, comprising a tunneling field-effect transistor T1, a carbon nanotube field-effect transistor T2, and a detection electrode D, wherein,

[0052] The tunneling field-effect transistor T1 is equipped with a modified antibody A, which is used to induce band tunneling and generate a tunneling current based on the charge generated when the sample to be detected undergoes a specific binding reaction with the modified antibody A.

[0053] The carbon nanotube transistor T2 is used to amplify the tunneling current;

[0054] The detection electrode D is used to generate a corresponding detection voltage based on the amplified tunneling current.

[0055] In this embodiment, by placing a modified antibody on the gate of a tunneling field-effect transistor with a low subthreshold swing, the charge generated when the sample to be detected specifically binds to the modified antibody induces band tunneling and generates a tunneling current. Simultaneously, the bipolar characteristics of the carbon nanotube field-effect transistor amplify the tunneling current generated by the tunneling field-effect transistor. This improves the detection accuracy of the biosensor while also enabling the detection of both positive and negative charges. It overcomes the problems existing in the prior art, thereby improving the signal detection rate of biosensors, simplifying the detection steps, and effectively expanding the application range of biosensors.

[0056] Specifically, this embodiment utilizes the transport mechanism of tunneling field-effect transistors (TFPTs) and the characteristic that the source-drain current strongly depends on changes in gate voltage. By using the charge generated from the specific binding reaction between the modified antibody and the sample to be tested on the gate of the TFPT to induce band tunneling, a tunneling current is generated to detect changes in charge. Since the subthreshold swing of the TFPT is less than 60 mV / dec, the antigen concentration in the sample is more easily detected, thereby improving the detection accuracy of the charge signal. Simultaneously, utilizing the characteristics of carbon nanotube field-effect transistors (CNTs), on the one hand, the drain current of the TFPT, i.e., the tunneling current, is output to the gate of the CNT to further amplify the current signal; on the other hand, utilizing the bipolar characteristics of the CNT, it exhibits N-type or P-type conductivity depending on the gate voltage applied to the CNT. This eliminates the need to determine the positive or negative charge polarity of the biomolecules in the sample before detection, thus simultaneously satisfying the detection of both positive and negative charges and expanding the application range of biosensors.

[0057] In a specific example, such as Figure 1 and Figure 5 As shown, the biosensor includes a tunneling field-effect transistor T1, a first capacitor C1, a carbon nanotube field-effect transistor T2, a second capacitor C2, and a detection electrode D;

[0058] The tunneling field-effect transistor T1 includes a first gate G1, a first source S1 and a first drain D1, the carbon nanotube transistor T2 includes a second gate G2, a second source S2 and a second drain D2, the first capacitor C1 includes a first terminal 1 and a second terminal 2, and the second capacitor C2 includes a third terminal 3 and a fourth terminal 4.

[0059] The modified antibody A is disposed on the first gate G1, the first source S1, the second source S2 and the second terminal 2 are connected to the first node N1, the first node N1 is connected to the first power supply signal V1, and the first drain D1, the first terminal 1 and the second gate G2 are connected to the second node N2.

[0060] The second drain D2, the third terminal 3, and the detection electrode D are connected to the third node N3;

[0061] The fourth terminal 4 is connected to the second power signal GND.

[0062] In this embodiment, a modified antibody A is disposed on the gate G1 of the tunneling field-effect transistor T1. The charge generated by the specific binding reaction between the sample to be tested and the modified antibody is loaded onto the gate G1, causing the tunneling field-effect transistor T1 to conduct. The tunneling current is generated according to the change in charge to realize the detection of the antigen concentration in the sample to be tested. Simultaneously, the first capacitor C1 is charged to control the voltage signal applied to the gate of the carbon nanotube field-effect transistor. When the biomolecules of the sample to be detected are positively charged and a positive voltage signal is applied to the gate of the tunneling field-effect transistor T1, tunneling occurs between the N-type doped region and the channel contact region. When the biomolecules of the sample to be detected are negatively charged and a negative voltage signal is applied to the gate of the tunneling field-effect transistor T1, tunneling occurs between the P-type doped region and the channel contact region. Furthermore, due to the bipolar characteristics of the carbon nanotube field-effect transistor, both electrons and holes can pass through the channel. Regardless of whether the gate of T2 accumulates a positive or negative bias voltage, the channel can generate a gate-controlled current, thus simultaneously satisfying the detection of both positive and negative charges, effectively simplifying the detection steps and expanding the application range of the biosensor. Based on the input first power signal V1, after the carbon nanotube field-effect transistor is turned on, the tunneling current is amplified. The detection voltage on the detection electrode D is adjusted through the second capacitor C2, thereby characterizing the antigen concentration of the sample to be detected through the detection voltage Vd of the detection electrode D, thus realizing the biosensor detection of the sample.

[0063] To further illustrate the specific implementation of this embodiment, in an optional embodiment, such as Figure 2 As shown, the biosensor includes a substrate 10, a first active layer disposed on the substrate 10, a gate insulating layer 12 covering the first active layer, a gate layer disposed on the gate insulating layer 12, an interlayer insulating layer 14 covering the gate layer and the exposed gate insulating layer 12, a first electrode layer and a second active layer disposed on the interlayer insulating layer 14, a passivation layer 16 covering the first electrode layer and the second active layer, and a second electrode layer disposed on the passivation layer 16.

[0064] It is worth noting that, Figure 2 This is a schematic diagram of the layered structure of a biosensor, not a schematic diagram of a cross-section of the biosensor. Figure 2 Only the specific structures of tunneling field-effect transistor T1 and carbon nanotube field-effect transistor T2 are shown, indicating that they are not on the same cross section. The specific layer structures are shown below:

[0065] The first active layer includes the first active structure 11 of the tunneling field-effect transistor T1. The first active structure 11 includes a first active portion 112, a first channel 111 and a second active portion 113 arranged sequentially along a first direction. The first active portion 112 includes a first doping type and the second active portion 113 includes a second doping type. The first doping type is different from the second doping type.

[0066] In this embodiment, one of the first doping type and the second doping type is heavily N-type doped and the other is heavily P-type doped. For example, or, the first doping type is heavily P-type doped and the second doping type is heavily N-type doped. Furthermore, the design of the tunneling field-effect transistor (TFPT) in this embodiment facilitates the reconfigurable characteristics of the TFPT. For instance, when the antigen in the sample to be detected undergoes a specific binding reaction with the modified antibody, positive or negative charges are formed, causing a change in the gate voltage. That is, the positive or negative voltage formed at the gate of the TFPT can achieve P / N type switching, meaning the TFPT can provide greater flexibility and adaptability.

[0067] The gate layer includes a first gate 131 of the tunneling field-effect transistor T1 and a second gate 132 of the carbon nanotube field-effect transistor T2, both disposed on the same layer. To ensure the generation of tunneling current, the orthographic projection of the first channel 111 onto the substrate 10 falls within the orthographic projection of the first gate 131 onto the substrate 10, meaning the electrode width of the first gate 131 is greater than the width of the first channel 111. The orthographic projection of the first gate 131 onto the substrate 10 partially overlaps with the orthographic projection of the first active portion 112 onto the substrate 10; the orthographic projection of the first gate 131 onto the substrate 10 partially overlaps with the orthographic projection of the second active portion 113 onto the substrate 10.

[0068] In this embodiment, the tunneling field-effect transistor T1 has a top-gate structure, and the carbon nanotube field-effect transistor T2 has a bottom-gate structure. The gates of both are formed in the same fabrication step.

[0069] The first electrode layer includes a first source 141 and a first drain 142 of the tunneling field-effect transistor T1 and a second source 143 and a second drain 144 of the carbon nanotube field-effect transistor T2, which are disposed in the same layer. The orthographic projection of the first source 141 on the substrate 10 does not overlap with the orthographic projection of the first drain 142 on the substrate 10, and the orthographic projection of the second source 143 on the substrate 10 does not overlap with the orthographic projection of the second drain 144 on the substrate 10. The first source 141 is connected to the first active portion 112 through a via penetrating the interlayer insulating layer 14 and the gate insulating layer 12, and the first drain 142 is connected to the second active portion 113 through a via penetrating the interlayer insulating layer 14 and the gate insulating layer 12.

[0070] The second active layer includes the second active structure 15 of the carbon nanotube field-effect transistor T2. One end of the second active structure 15 is connected to the second source 143 and the other end is connected to the second drain 144. The orthographic projection of the second active structure 15 on the substrate 10 overlaps with the orthographic projection of the second source 143 on the substrate 10, and the orthographic projection of the second active structure 15 on the substrate 10 overlaps with the orthographic projection of the second drain 144 on the substrate 10.

[0071] In this embodiment, the orthogonal projection of the second gate 132 onto the substrate 10 falls within the orthogonal projection of the second active structure 15 onto the substrate 10. The active structure of the carbon nanotube field-effect transistor is made of carbon nanotubes, which possess properties such as high carrier mobility, good conductivity, and stability. The carbon nanotube field-effect transistor exhibits N-type or P-type conductivity depending on the voltage applied to the gate, eliminating the need to determine the positive or negative charge polarity of the biomolecules in the sample before detection. This allows for the simultaneous detection of both positive and negative charges, amplifying the tunneling current and expanding the application range of biosensors.

[0072] The second electrode layer includes a first electrode portion 171 and a second electrode portion 172. The first electrode portion 171 is the first electrode plate of the first capacitor, and the second electrode portion 172 is multiplexed as the first electrode plate of the second capacitor and the detection electrode of the biosensor. The first drain 142 of the tunneling field-effect transistor T1 is multiplexed as the second electrode plate of the first capacitor. The orthographic projection of the first electrode plate 171 on the substrate 10 and the orthographic projection of the first drain 142 on the substrate 10 at least partially overlap. The second drain 144 of the carbon nanotube field-effect transistor T2 is multiplexed as the second electrode plate of the second capacitor. The orthographic projection of the second electrode plate 172 on the substrate 10 and the orthographic projection of the second drain 144 on the substrate 10 at least partially overlap.

[0073] To further illustrate the specific structure of this embodiment, the following steps are used as an example to illustrate the fabrication of a biosensor:

[0074] The first step is to deposit a Si3N4+SiO2 buffer layer on substrate 10, then deposit amorphous silicon and form a pattern by photolithography etching, and then crystallize to form an LTPS film layer, which is the channel region of the first active structure.

[0075] The second step is to fabricate a gate insulating layer 12 on top of the LTPS film. The gate insulating layer is made of a stack of SiO2 and Si3N4 and the thickness of the gate insulating layer is less than 100nm.

[0076] The third step is to form an N-doped region and a P-doped region on both sides of the channel region, respectively, to form the first active structure of the tunneling field-effect transistor T1, such as a first active part 112 with an N-doped region, a first channel 111 and a second active part 113 with a P-doped region.

[0077] The fourth step is to form a first gate 131 and a second gate 132 on the gate insulating layer. In order to ensure the generation of tunneling current, the orthogonal projection of the first channel on the substrate falls into the orthogonal projection of the first gate on the substrate, that is, the electrode width of the first gate is greater than the width of the first channel.

[0078] The fifth step is to deposit an interlayer insulating layer 14, which also serves as the gate insulating layer of the carbon nanotube field-effect transistor T2. The interlayer insulating layer material is SiO2, and the thickness of the interlayer insulating layer is greater than or equal to 100 nm.

[0079] The sixth step is to form the source and drain electrodes of the tunneling field-effect transistor T1 and the carbon nanotube field-effect transistor T2 on the interlayer insulating layer 14. The source and drain electrodes are made of Mo or Al.

[0080] Step 7: Deposit passivation layer 16.

[0081] Step 8: A first electrode portion 171 and a second electrode portion 172 are formed on the passivation layer 16. The first electrode portion 171 is the first electrode plate of the first capacitor, and the second electrode portion 172 is reused as the first electrode plate of the second capacitor and the detection electrode of the biosensor.

[0082] This completes the fabrication of the biological detection sensor.

[0083] In actual use, such as Figure 5As shown, firstly, the scan signal line transmits the pulse signal Vgate1 to the gate of the tunneling field-effect transistor T1. In order to maximize the difference in signal before and after detection, the voltage of the pulse signal Vgate1 is set to the critical voltage at which the tunneling current is about to occur. That is, the conduction band at the channel of the tunneling field-effect transistor T1 can be aligned with the valence band at the source (N-type doped). This critical voltage is related to the gate capacitance. The larger the gate capacitance, the smaller the critical voltage. The critical voltage is less than or equal to 30V, otherwise gate breakdown is likely to occur. For example, if the gate insulating layer is a stack of silicon oxide and silicon nitride, such as SiO2 / Si3N4 = 20 / 30nm, the absolute value of the critical voltage is 10V. When the charge polarity generated after the antigen and antibody bind is positive, Vgate1 is set to 10V. When the charge polarity generated after the antigen and antibody bind is negative, Vgate1 is set to -10V. The first power supply signal V1 is transmitted to the source of the tunneling field-effect transistor. The first power supply signal V1 is set to reduce the barrier width at the connection between the source and drain of the tunneling field-effect transistor and the channel in order to increase the tunneling probability. The magnitude of the first power supply signal V1 is inversely related to the doping concentration. In this example, the doping concentration is 1e18 / cm3 and V1 is set to 5V. Before the sample to be tested is loaded onto the modified antibody, the voltage applied to the channel by the gate of the tunneling field-effect transistor is vgate1, for example, 10V. At this time, the tunneling probability of the tunneling field-effect transistor is almost zero. When the sample to be tested is loaded onto the modified antibody, after the antigen of the sample to be tested binds to the modified antibody, a voltage increment ΔVgate1 is generated at the channel. The magnitude is positively correlated with the antigen concentration, for example, tens of mV. The voltage increment ΔVgate1 causes the generation of tunneling current, which charges the first capacitor C1 through the drain of the tunneling field-effect transistor. The first capacitor C1 is 5-15fF. If the first capacitor C1 is too small, the voltage holding time of the gate of the carbon nanotube field-effect transistor will be too low, which is not conducive to signal detection. If the first capacitor C1 is too large, the detection accuracy will be reduced. The channel material of the carbon nanotube field-effect transistor is carbon nanotube. As a two-dimensional material, its channel is relatively sensitive. Furthermore, due to its bipolar characteristics after passivation, the channel switching of the carbon nanotube field-effect transistor is only affected by the absolute value of the gate voltage and is independent of its polarity. As the first capacitor C1 is charged, the carbon nanotube field-effect transistor is turned on, and the first power supply signal V1 charges the second capacitor C2 through the carbon nanotube field-effect transistor, thereby causing a change in the detection voltage Vdetect of the detection electrode.In other words, firstly, the sample to be detected undergoes a specific binding reaction with the modified antibody disposed on the tunneling field-effect transistor of the biosensor. The tunneling field-effect transistor undergoes band tunneling and generates a tunneling current, which charges the first capacitor C1. Then, the carbon nanotube transistor T2 of the biosensor turns on in response to the gate applied voltage, amplifying the tunneling current. The first power signal V1 charges the second capacitor C2 through the carbon nanotube transistor T2. Finally, the detection electrode of the biosensor forms a corresponding detection voltage based on the amplified tunneling current and the second capacitor.

[0084] The biosensor of this embodiment uses a modified antibody on the gate of a tunneling field-effect transistor with a low subthreshold swing. The charge generated when the sample to be detected specifically binds to the modified antibody causes band tunneling and generates a tunneling current. At the same time, the bipolar characteristics of the carbon nanotube field-effect transistor amplify the tunneling current generated by the tunneling field-effect transistor. This improves the detection accuracy of the biosensor and also meets the requirements for detecting both positive and negative charges. It can overcome the problems existing in the prior art, thereby improving the signal detection rate of biosensors, simplifying the detection steps, and effectively expanding the application range of biosensors.

[0085] To further improve the stability of the biosensor, in one optional embodiment, such as Figure 3 As shown, the biosensor further includes a reset transistor T3, which comprises a third gate G3, a third source S3, and a third drain D3.

[0086] The third gate G3 is connected to the reset signal, the third source S3 is connected to the third node N3, and the third drain D3 is connected to the second power supply signal GND.

[0087] In this embodiment, by setting a reset transistor T3, when the third gate G3 is turned on in response to an externally input reset signal, the second capacitor is discharged, and the entire biosensor is reset and initialized, so that the biosensor is in an initial state consistent with the reference. For example, the reset transistor in this embodiment is an N-channel transistor.

[0088] During operation, firstly, the reset signal Vreset is a 10V positive voltage, and the reset transistor is turned on to reset the entire circuit. After reset, before loading the sample to be tested, the reset signal Vreset is set to 0, and the scan signal Vgate1 is a 10V pulse signal (<5µs; the longer the pulse time, the higher the requirement for the detection signal reading speed; the shorter the pulse time, the higher the requirement for detection accuracy and the leakage current level of the first capacitor C1). The first power supply signal V1 is 5V, and the tunneling field-effect transistor T1 is in the almost-on state during the pulse time, while the carbon nanotube field-effect transistor T2 is turned off, and the detection voltage Vdetect1 of the detection electrode is read. The sample to be tested, containing modified antigen molecules (e.g., a sample solution containing antigen molecules is dropped into the modified electrode connected to the gate of the tunneling field-effect transistor T1), is loaded onto the modified electrode. The scan signal Vgate1 is a 10V pulse signal (<5µs), and the tunneling field-effect transistor T1... During the pulse time, the transistor is turned on to charge the first capacitor C1. Subsequently, the carbon nanotube field-effect transistor T2 is turned on to charge the second capacitor C2. To ensure the smooth detection of the detection signal, the second capacitor C2 is set to be large enough to prevent saturation, for example, a few tenths of a pF. After the tunneling field-effect transistor T1 is turned off, as the leakage current of the first capacitor C1 decreases, the carbon nanotube field-effect transistor T2 gradually disconnects, and the voltage of the second capacitor C2 no longer increases. At this time, the detection voltage Vdetect2 of the detection electrode is read. By calculating the difference between the two detection voltages, the antigen concentration in the sample to be detected can be characterized. That is, the antigen concentration in the sample to be detected affects the scanning signal Vgate1 voltage, which in turn affects the magnitude of the tunneling current of the tunneling field-effect transistor T1. The larger the current, the more completely the channel of the carbon nanotube field-effect transistor T2 is opened, that is, the smaller the resistance and the longer the turn-on time, thus the more charge is delivered to the second capacitor C2, and the greater the change in the voltage of the second capacitor C2. Because the subthreshold swing SS of the tunneling field-effect transistor (TST) is relatively small (theoretically <60 mV / dec), compared to conventional transistors, the current generated by the TST T1 after the specific binding reaction is larger within the same pulse time. This increases the voltage acting on the carbon nanotube field-effect transistor T2, leading to a greater change in the second capacitance C2, thus making the signal characterizing antigen concentration easier to detect. When the subthreshold swing SS of the TST is 50 mV / dec, the detection accuracy of the biosensor in this embodiment can be improved by at least 4 times compared to conventional transistors.Furthermore, the carbon nanotube field-effect transistor that amplifies the tunneling current signal has bipolar characteristics. Therefore, it is not necessary to consider the positive or negative charge polarity of biomolecules in the sample to be detected. It is only necessary to change the bias voltage of the scanning signal Vgate1 according to the polarity. When the biomolecules in the sample to be detected exhibit negative charge, the voltage of the scanning signal Vgate1 is set to a negative voltage, and tunneling occurs in the P / I contact region. When the biomolecules in the sample to be detected exhibit positive charge, the voltage of the scanning signal Vgate1 is set to a positive voltage, and tunneling occurs in the N / I contact region. Therefore, the biosensor of this embodiment can simultaneously detect positively charged / negatively charged antigens and obtain the antigen concentration of the sample to be detected.

[0089] To further illustrate the specific implementation of this embodiment, in an optional embodiment, such as Figure 4 As shown, the first active layer also includes a third active structure 18 of the reset transistor T3. The third active structure 18 includes a third active portion 182, a second channel 181 and a fourth active portion 183 arranged sequentially along a first direction. The third active portion 182 and the fourth active portion 183 include the same doping type.

[0090] The gate layer further includes a third gate 133, wherein the orthographic projection of the second channel 181 on the substrate 10 at least partially overlaps with the orthographic projection of the third gate 133 on the substrate 10;

[0091] The first electrode layer further includes a third source 145 and a third drain 146 of the reset transistor. The orthographic projection of the third source 145 on the substrate 10 and the orthographic projection of the third drain 146 on the substrate 10 do not overlap. The third source 145 is connected to the third active portion 182 through a via penetrating the interlayer insulating layer 14 and the gate insulating layer 12. The third drain 146 is connected to the fourth active portion 183 through a via penetrating the interlayer insulating layer 14 and the gate insulating layer 12.

[0092] In this embodiment, the third active portion 182 and the fourth active portion 183 have the same doping type, for example, both are heavily N-type doped or both are heavily P-type doped. The doping type of the reset transistor determines the polarity of the reset signal Vreset. The reset signal Vreset corresponding to N-type doping is a positive voltage, and the reset signal Vreset corresponding to P-type doping is a negative voltage. The third active portion of the reset transistor is formed in the same step as the first active portion of the tunneling field-effect transistor. The reset transistor has a top-gate structure, and the third gate of the reset transistor is disposed on the same layer as the first gate of the tunneling field-effect transistor. The third source and third drain of the reset transistor are disposed on the same layer as the first source and first drain of the tunneling field-effect transistor. The fabrication steps of the reset transistor are the same as those of the tunneling field-effect transistor.

[0093] It is worth noting that the reset transistor can be a conventional transistor. In this embodiment, the manufacturing process of a tunneling field-effect transistor is used, and a reset transistor similar to that of a tunneling field-effect transistor is employed. Those skilled in the art should select an appropriate reset transistor according to the actual application requirements, which will not be elaborated here.

[0094] In actual use, such as Figure 5 As shown, firstly, the reset signal Vreset is transmitted to the gate of the reset transistor, which turns on to reset the entire circuit. Then, the scan signal line transmits the pulse signal Vgate1 to the gate of the tunneling field-effect transistor T1 and the first power supply signal V1 to the source of the tunneling field-effect transistor. The sample to be detected undergoes a specific binding reaction with the modified antibody disposed on the tunneling field-effect transistor of the biosensor. The tunneling field-effect transistor undergoes band tunneling and generates a tunneling current, which charges the first capacitor C1. Then, the carbon nanotube transistor T2 of the biosensor turns on in response to the gate applied voltage, amplifying the tunneling current. The first power supply signal V1 charges the second capacitor C2 through the carbon nanotube transistor T2. Finally, the detection electrode of the biosensor forms a corresponding detection voltage based on the amplified tunneling current and the second capacitor.

[0095] To further improve the reset speed of the biosensor, in an optional embodiment, the aspect ratio of the second channel is greater than or equal to 20.

[0096] In this embodiment, the width of the second channel of the reset transistor is 100μm and the length is 5μm. When the width-to-length ratio of the second channel is greater than or equal to 20, the larger the width-to-length ratio, the faster the discharge speed of the second capacitor, thereby accelerating the reset speed.

[0097] Based on the biological detection sensors of the above embodiments, one embodiment of the present invention also provides a biological detection chip, including multiple biological detection sensors of the above embodiments.

[0098] In an optional embodiment, the biosensor chip includes m*n biosensors arranged in M ​​rows and N columns, a scan signal line, a reset signal line, and a second power signal line connecting the tunneling field-effect transistors of each row of biosensors, and a first power signal line connecting each column of biosensors, where m≥1 and n≥1.

[0099] Each biosensor responds to signal gating via the connected scan signal line and the first power signal line.

[0100] In this embodiment, high-throughput detection is achieved by arranging multiple biological sensors in an array on a biological detection chip. Specifically, as shown... Figure 6The diagram shows four biosensors, U1, U2, U3, and U4, arranged in a 2x2 array. During operation, the initial voltage is first tested by setting the Vreset signals (Vreset1 and Vreset2) on the reset signal lines connected to all biosensors to a high level, turning on the reset transistors and resetting the circuit. Then, the Vreset signal is set to 0, and a pulse signal is applied to the scan signal Vgate1 transmitted via the scan signal line. Simultaneously, the first power signal V1 transmitted via the first power signal line is powered on, and the detection voltage Vdetect11 of the detection electrode of biosensor U1 is read. Next, Vreset1 is set high again for reset, and the scan signal Vgate1 is again loaded with a pulse signal. Simultaneously, the second power signal V2 is transmitted via the second power signal line, and the detection voltage Vdetect12 of the detection electrode of biosensor U2 is read. That is, the initial detection voltages Vdetect11 and Vdetect12 are obtained sequentially using the left and right biosensors in the first row. Vdetect12; Similarly, the same operation is performed using the left and right biosensors in the second row to obtain the initial detection voltages Vdetect21 and Vdetect22, that is, to read the detection voltages of the detection electrodes of biosensors U3 and U4 respectively; then the sample to be tested is loaded onto the modified antibody of each biosensor, for example, the sample solution to be tested is dropped onto the modified antibody to carry out a specific binding reaction, and the above detection voltage reading operation is repeated to obtain the detection voltages Vdetect11', Vdetect12', Vdetect21' and Vdetect22' of the four biosensors U1, U2, U3 and U4 after the reaction. In this embodiment, the scanning signal Vgate is kept to be the same before and after the reaction. The antigen concentration in the sample to be tested can be obtained by comparing the voltage difference before and after the reaction. The larger the voltage difference before and after the reaction, the higher the antigen concentration.

[0101] Based on the above-mentioned biological detection sensors, such as Figure 7 As shown, one embodiment of the present invention also provides a method of using the above-described biosensor, comprising:

[0102] The sample to be tested undergoes a specific binding reaction with a modified antibody disposed on a tunneling field-effect transistor of a biosensor, and the tunneling field-effect transistor undergoes band tunneling and generates a tunneling current.

[0103] The carbon nanotube transistors of the biosensor amplify the tunneling current.

[0104] The detection electrode of the biosensor generates a corresponding detection voltage based on the amplified tunneling current.

[0105] In this embodiment, a modified antibody is placed on the gate of a tunneling field-effect transistor with a low subthreshold swing. The charge generated when the sample to be detected specifically binds to the modified antibody induces band tunneling and generates a tunneling current. Simultaneously, the bipolar characteristics of a carbon nanotube field-effect transistor amplify the tunneling current generated by the transistor. This improves the detection accuracy of the biosensor while also enabling the detection of both positive and negative charges, overcoming problems in existing technologies. This improves the signal detection rate of biosensors, simplifies the detection process, and effectively expands the application range of biosensors. Specific implementation details of this embodiment are found in the foregoing embodiments and will not be repeated here.

[0106] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A biosensor based on a tunneling field-effect transistor, characterized in that, This includes tunneling field-effect transistors, carbon nanotube field-effect transistors, and detection electrodes, among which... The tunneling field-effect transistor is equipped with a modified antibody, which is used to induce band tunneling and generate a tunneling current based on the charge generated when the sample to be detected undergoes a specific binding reaction with the modified antibody. The carbon nanotube transistor is used to amplify the tunneling current; The detection electrode is used to generate a corresponding detection voltage based on the amplified tunneling current.

2. The biological detection sensor according to claim 1, characterized in that, The biosensor also includes a first capacitor and a second capacitor. The tunneling field-effect transistor includes a first gate, a first source, and a first drain; the carbon nanotube transistor includes a second gate, a second source, and a second drain; the first capacitor includes a first terminal and a second terminal; and the second capacitor includes a third terminal and a fourth terminal. The modified antibody is disposed on the first gate, the first source, the second source, and the second terminal are connected to the first node, the first node is connected to the first power signal, and the first drain, the first terminal, and the second gate are connected to the second node. The second drain, the third terminal, and the detection electrode are connected to the third node; The fourth terminal is connected to the second power signal.

3. The biosensor according to claim 2, characterized in that, The biosensor includes a substrate, a first active layer disposed on the substrate, a gate insulating layer covering the first active layer, a gate layer disposed on the gate insulating layer, an interlayer insulating layer covering the gate layer and the exposed gate insulating layer, a first electrode layer and a second active layer disposed on the interlayer insulating layer, a passivation layer covering the first electrode layer and the second active layer, and a second electrode layer disposed on the passivation layer. The first active layer includes the first active structure of the tunneling field-effect transistor. The first active structure includes a first active portion, a first channel, and a second active portion arranged sequentially along a first direction. The first active portion includes a first doping type, and the second active portion includes a second doping type. The first doping type is different from the second doping type. The gate layer includes a first gate of the tunneling field-effect transistor and a second gate of the carbon nanotube field-effect transistor disposed in the same layer. The first electrode layer includes a first source and a first drain of the tunneling field-effect transistor and a second source and a second drain of the carbon nanotube field-effect transistor disposed in the same layer. The orthographic projection of the first source on the substrate does not overlap with the orthographic projection of the first drain on the substrate, and the orthographic projection of the second source on the substrate does not overlap with the orthographic projection of the second drain on the substrate. The first source is connected to the first active part through a via penetrating the interlayer insulating layer and the gate insulating layer, and the first drain is connected to the second active part through a via penetrating the interlayer insulating layer and the gate insulating layer. The second active layer includes the second active structure of the carbon nanotube field-effect transistor. One end of the second active structure is connected to the second source and the other end is connected to the second drain. The orthographic projection of the second active structure on the substrate overlaps with the orthographic projection of the second source on the substrate, and the orthographic projection of the second active structure on the substrate overlaps with the orthographic projection of the second drain on the substrate. The second electrode layer includes a first electrode portion and a second electrode portion. The first electrode portion is the first electrode plate of the first capacitor. The second electrode portion is multiplexed as the first electrode plate of the second capacitor and the detection electrode of the biosensor. The first drain of the tunneling field-effect transistor is multiplexed as the second electrode plate of the first capacitor. The orthographic projection of the first electrode plate on the substrate and the orthographic projection of the first drain on the substrate at least partially overlap. The second drain of the carbon nanotube field-effect transistor is multiplexed as the second electrode plate of the second capacitor. The orthographic projection of the second electrode plate on the substrate and the orthographic projection of the second drain on the substrate at least partially overlap.

4. The biosensor according to claim 3, characterized in that, The orthographic projection of the first channel onto the substrate falls into the orthographic projection of the first gate onto the substrate; The orthographic projection of the second gate onto the substrate falls into the orthographic projection of the second active structure onto the substrate.

5. The biosensor according to claim 4, characterized in that, The orthographic projection of the first gate onto the substrate overlaps with the orthographic projection of the first active portion onto the substrate. The orthographic projection of the first gate onto the substrate overlaps with the orthographic projection of the second active portion onto the substrate.

6. The biosensor according to claim 3, characterized in that, The biosensor further includes a reset transistor, which comprises a third gate, a third source, and a third drain. The third gate is connected to a reset signal, the third source is connected to a third node, and the third drain is connected to the second power supply signal.

7. The biosensor according to claim 6, characterized in that, The first active layer further includes a third active structure of the reset transistor, the third active structure including a third active portion, a second channel and a fourth active portion arranged sequentially along a first direction, the third active portion and the fourth active portion including the same doping type; The gate layer further includes a third gate, wherein the orthographic projection of the second channel on the substrate and the orthographic projection of the third gate on the substrate at least partially overlap; The first electrode layer further includes a third source and a third drain of the reset transistor. The orthographic projection of the third source on the substrate and the orthographic projection of the third drain on the substrate do not overlap. The third source is connected to the third active portion through a via penetrating the interlayer insulating layer and the gate insulating layer. The third drain is connected to the fourth active portion through a via penetrating the interlayer insulating layer and the gate insulating layer.

8. The biosensor according to claim 7, characterized in that, The width-to-length ratio of the second channel is greater than or equal to 20.

9. A bio-detection chip, characterized in that, It includes at least one biosensor as described in any one of claims 1-8.

10. The biodetection chip according to claim 9, characterized in that it comprises m*n biodetection sensors in M ​​rows and N columns, a scan signal line, a reset signal line and a second power signal line connecting the tunneling field-effect transistors of each row of biodetection sensors, and a first power signal line connecting each column of biodetection sensors, where m≥1 and n≥1. Each biosensor responds to signal gating via the connected scan signal line and the first power signal line.

11. A method of using a biosensor as described in any one of claims 1-8, characterized in that, include: The sample to be tested undergoes a specific binding reaction with a modified antibody disposed on a tunneling field-effect transistor of a biosensor, and the tunneling field-effect transistor undergoes band tunneling and generates a tunneling current. The carbon nanotube transistors of the biosensor amplify the tunneling current. The detection electrode of the biosensor generates a corresponding detection voltage based on the amplified tunneling current.

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