Detection device and detection method therefor, sensor, and detection chip

Abstract

The present invention relates to the technical field of biological detection, and provides a detection device, a detection method, a sensor, and a detection chip. The detection device comprises a dielectric layer, a source electrode, a drain electrode, and a gate electrode. The dielectric layer comprises a sample testing region, in which a sample to be tested is disposed and causes a change in an electrical signal of the dielectric layer. The source electrode and the drain electrode are located on two sides of the dielectric layer in a normal direction of the dielectric layer, and the orthographic projections of the source electrode and the drain electrode on the dielectric layer overlap. One of the source electrode and the drain electrode and at least a portion of the gate electrode are arranged on the same side of the dielectric layer, and the orthographic projection of the gate electrode on the dielectric layer does not overlap the orthographic projections of the source electrode and the drain electrode on the dielectric layer. An electrical signal intensity of the dielectric layer in the normal direction is less than or equal to one-thousandth of an electrical signal intensity of the dielectric layer in the plane. The detection device exhibits high selectivity and high detection sensitivity for a target biomarker in said sample.

Description

Detection devices and their detection methods, sensors and detection chips Technical Field

[0001] This application relates to the field of biological detection technology, and in particular to a detection device and its detection method, sensor and detection chip. Background Technology

[0002] With the development of biosensor technology, biosensors based on field-effect transistors (FETs) have gradually become important components in biological detection technology.

[0003] However, current FET-based biosensors still suffer from poor integration and poor selectivity of FETs for target biomarkers. Furthermore, in order to adapt to modern biological detection applications, the response speed and sensitivity of biosensors need to be further improved. Summary of the Invention

[0004] The embodiments of this application adopt the following technical solutions:

[0005] In a first aspect, embodiments of this application provide a detection device for detecting a target biomarker, comprising:

[0006] A medium layer includes a sample testing area, which is configured to place a sample to be tested and cause a change in the electrical signal of the medium layer, wherein the sample to be tested may or may not contain a target biomarker.

[0007] The source electrode and the drain electrode are located on opposite sides of the dielectric layer along the normal direction of the dielectric layer, and the orthographic projections of the source electrode and the drain electrode on the dielectric layer overlap.

[0008] A gate electrode, wherein at least a portion of the source electrode and the drain electrode are disposed on the same side of the dielectric layer, and the orthographic projections of the gate electrode and the source electrode and the drain electrode onto the dielectric layer do not overlap;

[0009] Wherein, the electrical signal strength of the dielectric layer along the normal direction is less than or equal to one-thousandth of the electrical signal strength of the dielectric layer in the plane.

[0010] In some implementations, the detection device further includes a surface modification layer and a detector, wherein the surface modification layer at least covers the portion of the dielectric layer located in the sample testing area, the surface modification layer is configured to form a covalent bond with the detector, and the detector is configured to cause a change in the electrical signal of the dielectric layer after reacting with the sample to be tested.

[0011] In some implementations, the orthographic projection of the gate electrode onto the dielectric layer partially overlaps with the sample test area.

[0012] In some implementations, a portion of the gate electrode and the source electrode are disposed on the same side of the dielectric layer, and a portion of the gate electrode is disposed on the side of the dielectric layer parallel to the normal direction of the dielectric layer.

[0013] In some implementations, the detection device further includes a first detection electrode and a second detection electrode disposed in the sample testing area, wherein the first detection electrode and the second detection electrode are respectively located on both sides of the dielectric layer.

[0014] In some implementations, the orthographic projections of the first detection electrode and the second detection electrode onto the dielectric layer overlap.

[0015] In some implementations, the material of the dielectric layer is graphene.

[0016] In some implementations, the dielectric layer is made of molybdenum disulfide.

[0017] In some implementations, the detection device further includes an adjustment section configured to improve the in-plane charge transport speed and charge distribution uniformity in the dielectric layer.

[0018] In some implementations, the dielectric layer is made of a two-dimensional ferromagnetic material.

[0019] In some implementations, the adjustment unit includes a magnet and a support, the magnet being fixed to the support and configured to rotate around the support and provide a magnetic field, and the dielectric layer being configured to be disposed in the area covered by the magnetic field.

[0020] In some implementations, the magnetic induction intensity of the magnetic field ranges from 0.1T to 1T, and the rotation frequency of the magnet ranges from 10Hz to 100Hz.

[0021] In some implementations, the dielectric layer is made of a piezoelectric semiconductor material.

[0022] In some implementations, the adjustment unit includes a radio frequency (RF) signal generation structure configured to generate an RF signal, wherein electrons in the piezoelectric semiconductor material are configured to migrate and generate periodic electrical signals under the influence of the RF signal.

[0023] In some implementations, the radio frequency signal generation structure includes an interdigitated electrode pair, one of the source electrode and the drain electrode being disposed on the same side of the dielectric layer as the interdigitated electrode pair, and the interdigitated electrode pair not overlapping with the orthographic projections of the source electrode, the drain electrode and the gate electrode on the dielectric layer.

[0024] In some implementations, the interdigital electrode pair includes a plurality of first interdigital electrodes and a plurality of second interdigital electrodes, wherein the first interdigital electrodes and the second interdigital electrodes are alternately arranged;

[0025] The frequency range of the signals applied to the first interdigital electrode and the second interdigital electrode is 5MHz to 10MHz, and the intensity range of the signals applied to the first interdigital electrode and the second interdigital electrode is 24dBm to 33dBm.

[0026] In some implementations, the first interdigital electrode and the second interdigital electrode are configured to apply the same signal.

[0027] In some implementations, the detection device further includes a hydrophobic layer covering a portion of the dielectric layer located in the sample testing area; the surface modification layer is located on the side of the hydrophobic layer away from the dielectric layer.

[0028] In some implementations, the detection device further includes a groove disposed on the portion of the dielectric layer located in the sample testing area, and the surface modification layer covers the bottom and sidewalls of the groove.

[0029] In some implementations, the surface modification layer includes thiol groups and / or carboxyl groups, and the detector is attached to the sample test area via the thiol groups and / or carboxyl groups.

[0030] Secondly, embodiments of this application provide a sensor comprising an array of multiple detection devices as described in any one of the first aspects.

[0031] Thirdly, embodiments of this application provide a detection chip, which includes a sensor as described in the second aspect, and a controller electrically connected to the sensor, the controller being configured to perform concentration analysis of a target biomarker in the sample to be detected based on an electrical signal in the detection device.

[0032] Fourthly, this application provides a detection method in its embodiments, comprising the detection device as described in some embodiments of the first aspect, the detection method comprising:

[0033] A first voltage signal is applied to one of the source electrode or the drain electrode using a first probe;

[0034] A second voltage signal is applied to the gate electrode using a second probe;

[0035] The third probe is used to detect the reference channel current value through another of the source or drain electrodes;

[0036] The sample test area of ​​the dielectric layer is surface-modified to obtain a surface-modified layer;

[0037] The detection body is connected using the surface modification layer;

[0038] Add the sample to be tested;

[0039] The first voltage signal is applied to one of the source electrode or the drain electrode using the first probe;

[0040] The second voltage signal is applied to the gate electrode using the second probe;

[0041] The target channel current value is detected by using a third probe through another of the source or drain electrodes;

[0042] The concentration of the target biomarker in the sample to be tested is determined based on the difference between the reference channel current value and the target channel current value.

[0043] The probe station includes the first probe, the second probe, and the third probe.

[0044] Fifthly, this application provides a detection method in its embodiments, comprising the detection device as described in some embodiments of the first aspect, the detection method comprising:

[0045] A first voltage signal is applied between the source electrode and the drain electrode using a first probe and a third probe;

[0046] A second voltage signal is applied to the gate electrode using a second probe;

[0047] The reference channel current value is detected between the first detection electrode and the second detection electrode using the fourth and fifth probes;

[0048] The sample test area of ​​the dielectric layer is surface-modified to obtain a surface-modified layer;

[0049] The detection body is connected using the surface modification layer;

[0050] Add the sample to be tested;

[0051] The first voltage signal is applied between the source electrode and the drain electrode using the first probe and the third probe;

[0052] The second voltage signal is applied to the gate electrode using the second probe;

[0053] The target channel current value is detected between the first detection electrode and the second detection electrode using the fourth probe and the fifth probe;

[0054] The concentration of the target biomarker in the sample to be tested is determined based on the difference between the reference channel current value and the target channel current value.

[0055] The probe station includes the first probe, the second probe, the third probe, the fourth probe, and the fifth probe.

[0056] The above description is only an overview of the technical solution of this application. In order to better understand the technical means of this application and to implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this application more obvious and understandable, the following are specific embodiments of this application. Attached Figure Description

[0057] To more clearly illustrate the technical solutions in the embodiments of this application or related technologies, the drawings used in the description of the embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0058] Figures 1 to 4, 9, 12 and 14 are schematic cross-sectional views of seven detection devices provided in the embodiments of this application;

[0059] Figures 5-8, 10 and 13 are top view structural schematic diagrams of six detection devices provided in the embodiments of this application;

[0060] Figure 11 is a simplified illustration of the binding between a surface modification layer, a detector, and an antigen provided in an embodiment of this application;

[0061] Figure 15 is a top view of an interdigitated electrode pair provided in an embodiment of this application;

[0062] Figure 16 is a schematic cross-sectional view of another detection device provided in an embodiment of this application;

[0063] Figure 17 is a top view of another detection device provided in an embodiment of this application. Specific Implementation

[0064] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0065] In the embodiments of this application, the terms "first", "second", "third", "fourth" are used to distinguish the same or similar items with essentially the same function and effect, only for the purpose of clearly describing the technical solution of the embodiments of this application, and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated.

[0066] In the embodiments of this application, the terms "upper" and "lower" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0067] In the description of this specification, the terms "one embodiment," "some embodiments," "exemplary embodiment," "example," "specific example," or "some examples," etc., are intended to indicate that a particular feature, structure, material, or characteristic associated with that embodiment or example is included in at least one embodiment or example of this application. The illustrative representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics mentioned may be included in any suitable manner in any one or more embodiments or examples.

[0068] In the embodiments of this application, "multiple" means two or more, and "at least one" means one or more, unless otherwise explicitly defined.

[0069] The features such as "parallel," "perpendicular," and "identical" used in the embodiments of this application include features in the strict sense of "parallel," "perpendicular," and "identical," as well as cases where "approximately parallel," "approximately perpendicular," and "approximately identical" include certain tolerances. Taking into account the measurement and the tolerances associated with the measurement of a specific quantity (e.g., limitations of the measurement system), they represent the acceptable deviation range for a specific value as determined by a person skilled in the art. For example, "approximately" can mean within one or more standard deviations, or within 10% or 5% of said value.

[0070] Unless the context otherwise requires, throughout the specification and claims, the term “comprising” is interpreted as open and encompassing, that is, “including, but not limited to”.

[0071] In this application, "same layer" refers to the relationship between multiple film layers formed from the same material after undergoing the same step (e.g., a patterning process). "Same layer" here does not always mean that multiple film layers have the same thickness or the same height in a cross-sectional view. The polygons used in this specification are not strictly defined; they can be approximate triangles, parallelograms, trapezoids, pentagons, or hexagons, and may have minor deformations due to tolerances.

[0072] It should be noted that all biological samples and testing processes involved in this application were obtained and conducted with the permission of the individual or their guardian and in accordance with laws and regulations.

[0073] As human lifespan increases, the prevalence of neurodegenerative diseases is also rising annually. Neurodegenerative diseases are a group of chronic diseases characterized by neuronal dysfunction and death. Among them, Alzheimer's disease (AD) is the most common neurodegenerative disease, accounting for 60-70% of all dementia cases, followed by Parkinson's disease (PD), affecting more than 6 million people worldwide. Therefore, exploring biomarkers for neurodegenerative diseases and improving clinical examination and diagnosis is essential.

[0074] With the development of biosensor technology, biosensors based on field-effect transistors (FETs) have attracted much attention due to their high sensitivity, real-time monitoring capabilities, and miniaturization. These sensors utilize changes in the electrical properties of semiconductor materials to detect the binding of biomolecules, thereby enabling the detection of specific target biomarkers, such as the detection of the concentration of specific biomolecules in a sample.

[0075] Biomarkers are biochemical indicators that can mark changes or potential changes in the structure or function of systems, organs, tissues, cells, and subcellular structures, and have a very wide range of applications. Among them, neurodegenerative biomarkers are those used to detect and assess neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease). These biomarkers can be detected through cerebrospinal fluid or blood, aiding in early diagnosis and monitoring disease progression.

[0076] However, taking the current application of FET-based biosensors in detecting neurodegenerative markers in blood as an example, FET-based biosensors face corresponding challenges in several aspects.

[0077] First, the FETs currently used in biosensors are mainly planar FETs. However, planar FETs have limitations in integration density, which makes it difficult to apply FETs to biosensors with high-density biosensor arrays.

[0078] Secondly, in the early stages of neurodegenerative diseases, the concentration of neurodegenerative markers in cerebrospinal fluid or blood is low. Due to the complexity of cerebrospinal fluid or blood samples, FET-based biosensors have difficulty selecting neurodegenerative markers from complex samples. In this process, FETs often bind to non-specific markers, thereby reducing detection accuracy.

[0079] In addition, to adapt to modern biological detection applications, the response speed and sensitivity of biosensors need to be further improved.

[0080] Based on this, this application provides a detection device, detection method, sensor, and detection chip. The detection device includes a dielectric layer, a source electrode, a drain electrode, and a gate electrode. The dielectric layer includes a sample testing area, where a sample to be detected is placed and causes a change in the electrical signal of the dielectric layer. The sample to be detected may or may not contain a target biomarker. The source electrode and the drain electrode are located on opposite sides of the dielectric layer along the normal direction of the dielectric layer, and their orthographic projections on the dielectric layer overlap. At least a portion of the area of ​​one of the source electrode and the drain electrode is located on the same side of the dielectric layer as at least a portion of the area of ​​the gate electrode. The gate electrode does not overlap with the orthographic projections of the source electrode and the drain electrode on the dielectric layer. The sample testing area is located in the channel region of the detection device, and the electrical signal intensity of the dielectric layer along the normal direction is less than or equal to one-thousandth of the electrical signal intensity of the dielectric layer in the plane.

[0081] The detection device provided in the embodiments of this application uses a field-effect transistor with a vertical structure as the detection device. The source electrode and the drain electrode are located on both sides of the dielectric layer along the normal direction of the dielectric layer. At least a portion of the source electrode and the drain electrode are located on the same side of the dielectric layer. The gate electrode does not overlap with the orthographic projections of the source electrode and the drain electrode on the dielectric layer. At this time, the direction of current flow in the channel region intersects with the plane of the dielectric layer (for example, the direction of current flow in the channel region is perpendicular to the plane of the dielectric layer).

[0082] Thus, when detecting target biomarkers in a sample, the binding of the target biomarker to groups in the sample test area causes changes in the electrical signal (e.g., electrons) in the dielectric layer. On the one hand, by setting the electrical signal intensity along the normal direction of the dielectric layer to be less than or equal to one-thousandth of the electrical signal intensity in the plane, the dielectric layer has a stronger anti-interference ability due to its larger electrical signal intensity in the plane. Electrons in the dielectric layer can migrate to the channel region quickly and almost without noise interference in the plane, causing changes in the channel current. On the other hand, since the channel region length (approximately the distance between the source and drain electrodes) is shorter when the source and drain electrodes are conducting, the channel current loss during transmission is lower, improving transmission efficiency and facilitating accurate detection of changes in the channel current. Considering these two factors, when detecting low concentrations of target biomarkers, the small changes in electrical signals generated by biomolecule binding can be effectively transmitted in the dielectric layer plane and cause changes in the channel current, thereby improving the detection sensitivity and response speed of the detection device.

[0083] The detection device provided in the embodiments of this application will now be described and explained in detail with reference to the accompanying drawings.

[0084] An embodiment of this application provides a detection device for detecting target biomarkers, as shown in Figures 1 to 4. The detection device includes:

[0085] The medium layer 1 includes a sample testing area 1A, which is configured to set a sample to be tested (sample S in Figure 11) and cause a change in the electrical signal of the medium layer 1. The sample S may or may not contain a target biomarker.

[0086] Source electrode 2 and drain electrode 3 are located on both sides of dielectric layer 1 along the normal direction of dielectric layer 1, and the orthogonal projections of source electrode 2 and drain electrode 3 on dielectric layer 1 overlap.

[0087] One of the gate electrode 4, the source electrode 2, and the drain electrode 3 is disposed on the same side of the dielectric layer 1 as at least a portion of the gate electrode 4, and the orthographic projections of the gate electrode 4 and the source electrode 2 and the drain electrode 3 on the dielectric layer 1 do not overlap.

[0088] Wherein, the electrical signal intensity of dielectric layer 1 along the normal direction is less than or equal to one-thousandth of the electrical signal intensity of dielectric layer 1 in the plane.

[0089] In the embodiments of this application, the dielectric layer 1 is a material with semiconductor properties, and the conductivity of the dielectric layer 1 in the plane is greater than the conductivity of the dielectric layer 1 along the normal direction.

[0090] It should be noted that the electrical signal strength of dielectric layer 1 along the normal direction being less than or equal to one-thousandth of the electrical signal strength of dielectric layer 1 in the plane can be interpreted in several ways:

[0091] First, based on the intrinsic properties of the material, the carrier mobility of dielectric layer 1 along the normal direction is less than or equal to one-thousandth of the carrier mobility of dielectric layer 1 in the plane.

[0092] Second, based on the intrinsic properties of the material, the conductivity of dielectric layer 1 along the normal direction is less than or equal to one-thousandth of the conductivity of dielectric layer 1 in the plane.

[0093] Third, under detection conditions, the current value of dielectric layer 1 along the normal direction is less than or equal to one-thousandth of the current value of dielectric layer 1 in the plane. Specifically, the current value of dielectric layer 1 along the normal direction is the channel current, and the current value of dielectric layer 1 in the plane is the current generated by the migration of electrons within the dielectric layer plane due to the binding of biomolecules. When electrons migrate from the dielectric layer plane to the channel region, these electrons cause changes in the channel current, thereby enabling the detection of the concentration of the target biomarker.

[0094] Specifically, the carrier mobility of dielectric layer 1 along the normal direction and the carrier mobility of dielectric layer 1 in the plane need to be the average value obtained by multi-point measurement under the same measurement method and test conditions; the conductivity of dielectric layer 1 along the normal direction and the conductivity of dielectric layer 1 in the plane need to be the average value obtained by multi-point measurement under the same measurement method and test conditions; the current value of dielectric layer 1 along the normal direction and the current value of dielectric layer 1 in the plane need to be the average value obtained by multi-point measurement under the same measurement method and test conditions.

[0095] For example, the material of the dielectric layer 1 can be a two-dimensional material.

[0096] Two-dimensional materials refer to materials in which electrons can move freely in two dimensions at a non-nanoscale scale (i.e., in-plane movement). Therefore, in this application, the electrical signal intensity of the dielectric layer 1 along the normal direction is limited to less than or equal to one-thousandth of the electrical signal intensity of the dielectric layer 1 in the plane. In this way, the dielectric layer 1 has extremely high carrier mobility in the plane, thereby greatly improving the control capability of the gate electrode 4 over the channel current.

[0097] Two-dimensional materials, also known as two-dimensional atomic crystal materials, were proposed in 2004 following the successful isolation of a single-atom-layer graphene material by Geim's group at the University of Manchester.

[0098] For example, the two-dimensional material can be graphene, boron nitride (BN), molybdenum disulfide (MoS2), tungsten disulfide (WS2), molybdenum diselenide (MoSe2), tungsten diselenide (WSe2), or MXene.

[0099] It should be understood that the above-mentioned detection device is a vertical field-effect transistor (VFET). A vertical field-effect transistor (VFET) is a transistor design in which the current flow direction is perpendicular to the surface of the dielectric layer, rather than the horizontal direction in a traditional planar field-effect transistor (FET).

[0100] Taking the structure shown in Figure 1 as an example, since the source electrode 2 and the drain electrode 3 are located on both sides of the dielectric layer 1 along the normal direction of the dielectric layer 1, and the source electrode 2 and the gate electrode 4 are disposed on the same side of the dielectric layer 1, when a control signal (a voltage signal) is applied to the gate electrode 4 and an input signal (a voltage signal) is applied to the source electrode 2, the carriers in the dielectric layer 1 between the source electrode 2 and the drain electrode 3 move (i.e., the carriers in the channel region of the transistor move, generating channel current), and the flow direction of the channel current of the transistor is almost perpendicular to the plane direction of the dielectric layer 1, that is, the flow direction of the channel current is almost vertical.

[0101] In an exemplary embodiment, the orthographic projections of the source electrode 2 and the drain electrode 3 onto the dielectric layer 1 do not overlap with the sample detection area 1A.

[0102] In this application, the sample testing area 1A is disposed on the dielectric layer 1. To facilitate the addition of the sample to be tested (e.g., the solution to be tested) during testing, the orthogonal projections of the source electrode 2 and the drain electrode 3 on the dielectric layer 1 do not overlap with the sample testing area 1A. This allows for a larger contact area between the sample to be tested and the dielectric layer 1, which is beneficial for the binding of biomolecules during the detection reaction. For example, changes in electrons caused by the attachment of target biomarkers to the dielectric layer 1 are sensed by the dielectric layer 1, leading to charge migration within the dielectric layer 1.

[0103] The sample to be tested contains the target biomarker, which can be a neurodegenerative biomarker.

[0104] Common neurodegenerative markers include:

[0105] 1. β-Amyloid (Aβ): One of the main pathological features of Alzheimer's disease. Decreased Aβ42 levels or changes in the Aβ42 / Aβ40 ratio are associated with the disease.

[0106] 2. Tau protein: including total Tau protein and phosphorylated Tau protein (p-Tau). Abnormalities in Tau protein are closely related to diseases such as Alzheimer's disease.

[0107] 3. α-synuclein: a marker of diseases such as Parkinson's disease and multiple system atrophy, and its abnormal aggregation is one of the pathological features.

[0108] In some possible embodiments, the source electrode 2 and the drain electrode 3 described above comprise materials containing at least one of the following elements: Au, Al, Mo, etc.

[0109] In the embodiments of this application, when the detection device detects a target biomarker in the sample to be tested, the binding of the target biomarker to a specific group in the sample test area 1A causes a change in the electrical signal (e.g., electrons) in the dielectric layer 1. On the one hand, by setting the electrical signal intensity of the dielectric layer along the normal direction to be less than or equal to one-thousandth of the electrical signal intensity of the dielectric layer in the plane, since the electrical signal intensity in the plane of the dielectric layer is relatively large, its anti-interference ability is strong, and the electrons in the dielectric layer... The current can migrate rapidly to the channel region in the plane with almost no noise interference, causing changes in the channel current. On the other hand, since the source and drain electrodes are conducting, the length of the channel region (approximately the distance between the source and drain electrodes) is short, resulting in lower channel current loss during transmission and improved transmission efficiency. This is beneficial for accurately detecting changes in the channel current. Considering these two factors, when detecting low-concentration target biomarkers, the small changes in electrical signals generated by biomolecule binding can be effectively transmitted in the dielectric layer plane and cause changes in the channel current, thereby improving the detection sensitivity and response speed of the detection device.

[0110] It should be noted that, as explained above, when the sample to be tested contains the target biomarker, the binding of the target biomarker to a specific group in the sample test area will cause a change in the electrical signal (e.g., electrons) in dielectric layer 1. However, when the sample to be tested does not contain the target biomarker, since no biomolecule binding occurs, there is almost no change or migration of electrons in the dielectric layer, and therefore almost no change in the channel current. It is important to emphasize that although the sample to be tested does not contain the target biomarker, because the sample also contains other biomolecules, in some cases, other non-biological or biological binding changes may occur between the sample and the detection device, resulting in a very small change in the channel current. However, this change in channel current is very small (less than the change in channel current caused by the binding of the target biomarker to a specific group in the sample test area). Thus, the detection device can still be used to identify whether the sample to be tested contains the target biomarker.

[0111] In addition, since the current flows vertically in the above-mentioned detection devices, the devices occupy a smaller area, which is more conducive to high-density integration and can be applied in high-density biological detection arrays.

[0112] In some implementations, as shown in Figure 11, the detection device further includes a surface modification layer K and a detector a. The surface modification layer K covers at least the portion of the dielectric layer 1 located in the sample test area 1A. The surface modification layer K is configured to form a covalent bond with the detector a. The detector a is configured to cause a change in the electrons of the dielectric layer 1 after reacting with the sample to be detected.

[0113] The aforementioned "covalent bond" is a type of chemical bond in which two or more atoms share their outer electrons, ideally reaching an electron saturation state, thereby forming a relatively stable chemical structure. Such a strong interaction formed by several adjacent atoms through the sharing of electrons is called a covalent bond.

[0114] The surface modification layer K can be obtained by surface treatment of a local area of ​​the detection device (e.g., sample test area 1A). The surface modification layer K can improve the adhesion of the detector to the medium layer 1, thereby improving the efficiency of the detector in capturing antigens (target biomarkers).

[0115] For example, the surface modification layer K can be obtained by surface treatment of the sample test area 1A with thiol, as shown in Figure 11. After surface treatment, at least one functional group selected from mercapto (-SH), hydroxyl (-OH) or carboxyl (-COOH) can be attached to the surface of the medium layer 1 in the sample test area 1A.

[0116] The detector can form covalent bonds with the functional groups in the surface modification layer K, thus creating numerous capture sites (i.e., detectors) on the dielectric layer 1. Each capture site (detector) can biobind to the antigen (target biomarker). This biobinding process causes electronic changes in the dielectric layer 1, resulting in changes in the electrical signal (i.e., changes in the channel current). The changes in the channel current can then be detected using the source electrode 2 and the drain electrode 3 to analyze and calculate the concentration of the target biomarker.

[0117] For example, the detection agent may include one of an antibody, a probe, or an aptamer.

[0118] This instruction manual uses antibodies as an example for the detection subject.

[0119] Antibodies are protective proteins produced by the body in response to antigen stimulation. (Immunoglobulins are not limited to antibodies.) They are large, Y-shaped proteins secreted by plasma cells (effector B cells) and used by the immune system to identify and neutralize foreign substances such as bacteria and viruses. Antibodies recognize a unique characteristic of a specific foreign substance, which is called an antigen.

[0120] In an exemplary embodiment, a thiol solution can be coated on the surface of the dielectric layer 1 to form a surface modification layer K on a local surface of the dielectric layer 1; or, one end of the detection device can be immersed in the thiol solution to form a surface modification layer K on a local part of the dielectric layer 1 and on the gate electrode 4.

[0121] For example, further, the sample is placed at approximately 4°C (±2°C) for 20-28 hours (e.g., 24 hours); then washed with PBS buffer of different concentrations (e.g., 10× and 1× PBS buffer); and then washed with water (e.g., distilled or deionized water). The antibody corresponding to the target biomarker is dispersed in a 1:1 EDC and NHS solution, and the mixed solution is dropped into the sample detection area 1A, and then washed with water (e.g., distilled or deionized water) to successfully attach the antibody to the medium layer 1.

[0122] Among them, PBS buffer is one of the most widely used buffers in biochemical research. Its main components are Na2HPO4, KH2PO4, NaCl, and KCl. It is generally used as a solvent to dissolve and protect reagents. EDC is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, abbreviated as EDC hydrochloride. NHS is N-hydroxysuccinimide.

[0123] If a thiol molecule contains a mercapto group (-SH) at one end and a carboxylic acid group (-COOH) at the other end, a thiol solution can be coated onto the surface of medium layer 1. Then, it can be activated by using a mixture of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxythiosuccinimide (S-NHS) to form a surface modification layer K with a carboxyl group (-COOH) on the surface of medium layer 1. Further processing can then link the surface modification layer K to the antibody, thereby successfully linking the antibody to medium layer 1.

[0124] In some implementations, as shown in Figures 3 and 4, the orthographic projection of the gate electrode 4 onto the dielectric layer 1 overlaps with a portion of the sample test area 1A.

[0125] It is understandable that the gate electrode 4 extends into the sample test area 1A.

[0126] When the orthographic projection of the gate electrode 4 on the dielectric layer 1 partially overlaps with the sample test area 1A, as shown in Figure 11, the surface modification layer K can cover a portion of the gate electrode 4. The surface of a portion of the gate electrode 4 can be coated with at least one functional group selected from thiol (-SH), hydroxyl (-OH), or carboxyl (-COOH). After surface treatment of the sample test area 1A with thiol, the surface of the gate electrode 4 can be coated with thiol (-SH). The antibody can form covalent bonds with the functional groups in the surface modification layer K. Thus, both the dielectric layer 1 and the gate electrode 4 have multiple capture sites (i.e., antibodies). Each capture site (antibody) can biobind with the antigen (target biomarker). This biobinding process causes changes in the charge in the dielectric layer 1 and the charge in the gate electrode 4, thereby causing changes in the channel current in the dielectric layer 1 and the voltage on the gate electrode 4.

[0127] In some implementations, as shown in Figures 2 and 4, a portion of the gate electrode 4 is disposed on the same side of the source electrode 2 as the dielectric layer 1, and a portion of the gate electrode 4 is disposed on the side of the dielectric layer 1 parallel to the normal direction of the dielectric layer 1.

[0128] In the embodiments of this application, by setting a portion of the gate electrode 4 and the source electrode 2 on the same side of the dielectric layer 1, and setting a portion of the gate electrode 4 parallel to the normal direction of the dielectric layer 1 on the side of the dielectric layer 1, the coverage of the electric field formed by the gate electrode 4 on the channel region in the dielectric layer 1 is increased, which can significantly increase the control capability of the gate electrode 4 over the detection device (transistor).

[0129] Figures 5 to 8 provide four top-view structural diagrams of the detection device. In Figures 5 and 6, the orthographic projection of the gate electrode 4 onto the dielectric layer 1 does not overlap with the sample detection area 1A. In Figures 7 and 8, the orthographic projection of the gate electrode 4 onto the dielectric layer 1 partially overlaps with the sample detection area 1A. In Figures 6 and 8, the gate electrode 4 and the source electrode 2 are disposed on the same side of the dielectric layer 1. In Figures 5 and 7, a portion of the gate electrode 4 and the source electrode 2 are disposed on the same side of the dielectric layer 1, and a portion of the gate electrode 4 is disposed on the side of the dielectric layer 1 parallel to the normal direction of the dielectric layer 1.

[0130] In some implementations, as shown in Figure 9, the detection device further includes a first detection electrode J1 and a second detection electrode J2 disposed in the sample test area 1A, with the first detection electrode J1 and the second detection electrode J2 located on both sides of the dielectric layer 1, respectively.

[0131] When the first detection electrode J1 and the second detection electrode J2 are located on opposite sides of the dielectric layer 1, it is not required that the first detection electrode J1 and the second detection electrode J2 overlap. This can be determined according to the design space. The channel current can also be detected even if the first detection electrode J1 and the second detection electrode J2 do not overlap.

[0132] Compared to detecting channel current changes through the source electrode 2 and drain electrode 3, detecting channel current changes through the first detection electrode J1 and the second detection electrode J2 avoids signal interference from the input signal between the source electrode 2 and drain electrode 3 when the channel current changes. This is especially beneficial when detecting low-concentration target biomarkers, as the change in charge in the dielectric layer 1 caused by biobinding is relatively small, resulting in a smaller change in the channel current (i.e., the electrical response signal of low-concentration samples is smaller). Detecting channel current changes through the first detection electrode J1 and the second detection electrode J2 allows for more accurate detection of low-concentration samples, improving the detection sensitivity of the device. The detection process of the device can be further explained in the detection method section below.

[0133] In some implementations, as shown in Figure 9, the orthographic projections of the first detection electrode J1 and the second detection electrode J2 on the dielectric layer 1 overlap.

[0134] The existence of overlap should be understood as "at least partially overlapping", that is, including both partial and complete overlap.

[0135] Since the channel current of the transistor flows almost perpendicular to the plane of dielectric layer 1, that is, the channel current flows almost vertically, by setting the first detection electrode J1 and the second detection electrode J2 on both sides of dielectric layer 1 respectively, and the orthogonal projections of the first detection electrode J1 and the second detection electrode J2 on dielectric layer 1 overlap, the setting direction of the first detection electrode J1 and the second detection electrode J2 is closer to the channel current flow direction, which further reduces the loss in electrical signal transmission and improves the sensitivity and accuracy of channel current detection.

[0136] Figure 10 provides a top view of a detection device with a first detection electrode J1 and a second detection electrode J2.

[0137] In some implementations, the material of the dielectric layer 1 is graphene.

[0138] For example, the material of the dielectric layer 1 can be few-layer graphene, multi-layer graphene, or graphite sheets with greater thickness.

[0139] Few-layer graphene (FLG) refers to a two-dimensional material composed of 3 to 10 layers of graphene stacked together. In other words, few-layer graphene refers to a two-dimensional carbon material composed of 3 to 10 layers of carbon atoms periodically and closely packed in a benzene ring structure (i.e., a hexagonal honeycomb structure) in different stacking patterns (including ABC stacking, ABA stacking, etc.).

[0140] Multilayer graphene is a two-dimensional carbon material composed of carbon atoms in a periodically densely packed benzene ring structure (i.e., hexagonal honeycomb structure) with a thickness of more than 10 layers and less than 10 nm. It is stacked in different ways (including ABC stacking, ABA stacking, etc.) and its properties are closer to those of bulk graphite, but it still retains certain two-dimensional characteristics.

[0141] Among them, the layers of few-layer graphene and multi-layer graphene are bonded by van der Waals forces, with an interlayer spacing of approximately 0.335 nm.

[0142] Graphite (graphite sheets, graphene with more layers, such as 10nm–250nm) is an allotrope of carbon, best known for its layered structure, and is referred to as graphene in a broader sense. In each layer, carbon atoms are arranged in sp... 2 Hybridization results in a hexagonal honeycomb arrangement, with layers interacting through relatively weak van der Waals forces. The electrical conductivity of graphite primarily stems from the electronic structure of the carbon atoms within its layers.

[0143] For example, when the material of the dielectric layer 1 is graphene, its thickness is 5 to 50 layers of graphene, specifically ranging from 2.5 nm to 250 nm.

[0144] For example, its thickness can be 3nm, 5nm, 8nm, 16nm, 20nm, 30nm, 35nm, 40nm, 50nm, 80nm, 100nm, 120nm, 150nm, 180nm, 200nm, 220nm or 230nm.

[0145] In the embodiments of this application, graphene has extremely high carrier mobility (up to 200,000 cm⁻¹ at room temperature). 2 The graphene VFET (with a current density of / V·s) is far higher than that of traditional semiconductor materials such as silicon. In vertically structured transistors, charge carriers are transported along the vertical direction, which can fully utilize the high mobility of graphene to achieve high-speed electron transport. The vertical structure of graphene VFET can effectively suppress short-channel effects because the channel length is determined by the thickness in the vertical direction, rather than the lateral dimension, thus supporting smaller device sizes. The vertical design of graphene VFET allows for a larger current density to pass through the device, improving the current driving capability. In addition, the high conductivity and fast switching characteristics of graphene result in less energy loss during the switching process, reducing the power consumption of the detection device.

[0146] It should also be noted that, due to the high conductivity of graphene in the plane, when the charge change in the dielectric layer 1 is caused by the bio-binding process, electrons can quickly achieve uniform distribution in the plane, which significantly improves the signal transmission efficiency and reliability. This helps to reduce signal attenuation and distortion during transmission, and improve the detection accuracy and sensitivity of the detection signal.

[0147] In some implementations, the material of dielectric layer 1 is molybdenum disulfide (MoS2).

[0148] For example, molybdenum disulfide (MoS2) has properties similar to graphene, enabling it to exhibit semiconductor characteristics between the source electrode 2 and the drain electrode 3, and two-dimensional material characteristics in the horizontal direction.

[0149] Between the source electrode 2 and the drain electrode 3, the inherent obstruction to electron transport allows the voltage Vg of the gate electrode 4 to regulate the current. At the same time, the short thickness and electron transport distance between the source electrode 2 and the drain electrode 3 significantly reduce the energy loss of electrons during transport when the device is turned on. This is crucial for achieving high sensitivity and accurate detection of low-concentration protein samples.

[0150] For example, the thickness of molybdenum disulfide (MoS2) is 3 to 50 layers, with a thickness range of 1.8 nm to 300 nm.

[0151] For example, its thickness can be 3nm, 5nm, 8nm, 16nm, 20nm, 30nm, 35nm, 40nm, 50nm, 80nm, 100nm, 120nm, 150nm, 180nm, 200nm, 220nm, 250nm, 280nm or 290nm.

[0152] Similar to the two-dimensional properties of graphene, molybdenum disulfide (MoS2) has high conductivity in the plane. When the charge change in the dielectric layer 1 is caused by the bio-binding process, electrons can quickly achieve uniform distribution in the plane, which significantly improves the signal transmission efficiency and reliability. This helps to reduce signal attenuation and distortion during transmission, and improve the detection accuracy and sensitivity of the detection signal.

[0153] In some implementations, the detection device further includes an adjustment unit configured to improve the charge transport speed and charge distribution uniformity in the plane of the dielectric layer 1.

[0154] By setting an adjustment unit, the charge (e.g., electrons) in the dielectric layer 1 of the transistor can be externally controlled, enabling the charge (e.g., electrons) in the dielectric layer 1 to migrate rapidly in the planar direction. This improves the charge transport speed and charge distribution uniformity in the planar direction of the dielectric layer 1, greatly reduces the transmission resistance of channel current in the channel region, improves signal transmission efficiency, helps reduce signal attenuation and distortion during transmission, improves the detection accuracy and sensitivity of the detection signal, and is beneficial for the detection of low-concentration samples with small electrical response signals.

[0155] In some implementations, the material of dielectric layer 1 is a two-dimensional magnetic material.

[0156] For example, the material of dielectric layer 1 is a two-dimensional ferromagnetic material.

[0157] Two-dimensional magnetic materials are characterized by existing in a layered form, stacked together by van der Waals forces, i.e., intermolecular forces, with atoms within the layers connected by chemical bonds.

[0158] Two-dimensional magnetic materials can be mainly divided into two categories: two-dimensional ferromagnetic (FM) materials and two-dimensional antiferromagnetic (AFM) materials.

[0159] Two-dimensional ferromagnetic materials mainly include transition metal halides, transition metal sulfides, transition metal carbonitrides, transition metal phosphorus sulfides, and the Mn-Bi-Te family. These materials possess intrinsic long-range magnetic order, and their magnetism is significantly dependent on the number of layers. When the system thickness is reduced to the single-layer limit, they typically exhibit magnetic behavior that is significantly different from that of bulk and few-layer samples.

[0160] Taking two-dimensional ferromagnetic materials such as transition metal phosphorus-sulfur compounds as the dielectric layer as an example, they can be FePS3, NiPS3, and MnPS3.

[0161] In some implementations, as shown in Figure 12, the adjustment unit includes a magnet C and a support Z. The magnet C is fixed on the support Z and is configured to rotate around the support Z and provide a magnetic field. The dielectric layer 1 is configured to be disposed in the area covered by the magnetic field.

[0162] In an exemplary embodiment, at least a portion of the dielectric layer 1 is located in a horizontal magnetic field provided by the rotating magnetic field.

[0163] In some implementations, the magnetic induction intensity of the magnetic field ranges from 0.1T to 1T, and the rotation frequency of the magnet ranges from 10Hz to 100Hz.

[0164] For example, the thickness of the dielectric layer 1 (two-dimensional ferromagnetic material) ranges from 30 nm to 200 nm.

[0165] For example, its thickness can be 35nm, 40nm, 50nm, 80nm, 100nm, 120nm, 150nm, 180nm or 190nm.

[0166] For example, two-dimensional ferromagnetic materials can be prepared using a chemical vapor deposition (CVD) method.

[0167] It should be noted that, without the application of a magnetic field, taking the material of dielectric layer 1 as a transition metal phosphorus sulfide as an example, when the detector on the surface of dielectric layer 1 binds to the target biomarker, it will cause a change in the charge on the surface of dielectric layer 1. The electrons in dielectric layer 1 will arrange themselves under the influence of the carrier concentration and carrier mobility of the dielectric layer 1 material itself. When a magnetic field is applied and the transistor is turned on, on the one hand, the electrons in dielectric layer 1 will be affected by the channel current in the vertical direction and will be transported in the vertical direction. On the other hand, under the action of the external rotating magnetic field in the horizontal direction, the electrons in dielectric layer 1 can be uniformly distributed in the plane direction of dielectric layer 1, which helps to stabilize the transmission of smaller signals, improves the signal transmission efficiency, and thus is beneficial for the detection of low-concentration samples with small electrical response signals.

[0168] In practical applications, a rotating magnetic field needs to be applied before testing the sample, and the dielectric layer 1 must always be within the area covered by the magnetic field throughout the entire test.

[0169] In some implementations, the material of dielectric layer 1 is a piezoelectric semiconductor material.

[0170] For example, piezoelectric semiconductor materials include aluminum nitride (AlN) or zinc oxide (ZnO).

[0171] Aluminum nitride (AlN) is a novel inorganic non-metallic material belonging to the third generation of semiconductor materials. It is a covalent compound with a diamond-like nitride crystal structure, belonging to the hexagonal crystal system, and is white or grayish-white in color.

[0172] In this application, a dielectric layer (e.g., aluminum nitride) can be prepared on the drain electrode using magnetron sputtering. The preparation conditions for magnetron sputtering are as follows: high-purity Al target and N2 are used as the reactive gas; during sputtering, the quality and performance of the film are affected by adjusting the N2 gas pressure; the sputtering power range is 11 kW to 215 kW; the preparation temperature range is 75 °C to 521 °C; and the preparation gas pressure is 0.5 Pa. This allows for the preparation of AlN films with preferred c-axis orientation, achieving a crystallinity of over 96%. Magnetron sputtering is a type of physical vapor deposition (PVD).

[0173] Zinc oxide (ZnO) is an oxide semiconductor material and also belongs to piezoelectric semiconductors. Compared with elemental semiconductor materials, it is mostly ionic crystal in structure, with a generally larger band gap and lower mobility.

[0174] In some implementations, as shown in Figure 13, the adjustment unit includes a radio frequency signal generation structure 6, which is configured to generate a radio frequency signal. Electrons in the piezoelectric semiconductor material are configured to migrate under the action of the radio frequency signal and generate periodic electrical signals.

[0175] In Figure 13, to avoid the diagram being unclear due to too many interdigitated electrode pairs, only 3 pairs of interdigitated electrode pairs are drawn. The actual number will be based on the description of interdigitated electrode pairs in the following text.

[0176] For piezoelectric semiconductor materials, their semiconductor properties allow them to exist as insulating materials between the source electrode 2 and the drain electrode 3. At the same time, under the action of an applied radio frequency signal, the piezoelectric semiconductor material can achieve electron localization on the surface of the dielectric layer 1, and allow electrons to migrate in a region on the surface of the dielectric layer 1, thereby generating a stable periodic signal. This periodic electrical signal is easy to detect, which is beneficial for detecting low-concentration samples with small electrical response signals, and improves the detection accuracy and sensitivity of the detection device.

[0177] In some implementations, as shown in Figure 13, the radio frequency signal generation structure 6 includes an interdigitated electrode pair, one of the source electrode 2 and the drain electrode 3 is disposed on the same side of the dielectric layer 1 as the interdigitated electrode pair, and the interdigitated electrode pair does not overlap with the orthographic projections of the source electrode 2, the drain electrode 3 and the gate electrode 4 on the dielectric layer 1.

[0178] In an exemplary embodiment, as shown in FIG13, when interdigitated electrode pairs are provided in the detection device, the gate electrode 4 can be disposed in the region between the interdigitated electrode pairs and the source electrode 2, and the sample detection region 1A can also be disposed in the region between the interdigitated electrode pairs and the source electrode 2.

[0179] Of course, if the interdigitated electrode pairs do not overlap with the orthographic projections of the source electrode 2, drain electrode 3, and gate electrode 4 on the dielectric layer 1, the positions of the interdigitated electrode pairs can be adjusted according to the design space, and no specific limitation is made here.

[0180] Figure 14 provides a schematic diagram of the cross-sectional structure of a detection device, wherein Figure 14 is a schematic diagram of the cross-sectional structure of Figure 13 along the M1M2 direction.

[0181] In some implementations, as shown in Figures 13 and 15, the interdigital electrode pair includes a plurality of first interdigital electrodes 62 and a plurality of second interdigital electrodes 62, with the first interdigital electrodes 61 and the second interdigital electrodes 62 being alternately arranged.

[0182] The frequency range of the signal applied to the first interdigital electrode 61 and the second interdigital electrode 62 is 5MHz to 10MHz, and the intensity range of the signal applied to the first interdigital electrode 61 and the second interdigital electrode 62 is 24dBm to 33dBm.

[0183] For example, the surface sound velocity of dielectric layer 1 is 5000 to 15000 m / s.

[0184] In the application of biosensors, the propagation speed of surface acoustic waves may be altered by the binding or adsorption of biomolecules. This change can be captured by the sensor and converted into an electrical signal for analysis.

[0185] A higher surface acoustic velocity (SAV) may mean that sound waves propagate faster on the surface of the dielectric layer, thereby improving the response speed of the detection device. At the same time, the stability and consistency of the SAV are also crucial to ensuring the accuracy and reliability of the detection device.

[0186] It is understandable that when the surface sound velocity is high, the faster the external radio frequency signal propagates on the surface of the dielectric layer, the more favorable it is for electrons to migrate in a region on the surface of dielectric layer 1, thereby generating a stable periodically changing signal. This periodic electrical signal is easy to detect, which in turn is beneficial for detecting low-concentration samples with small electrical response signals, thus improving the detection accuracy and sensitivity of the detection device.

[0187] In an exemplary embodiment, as shown in FIG15, the interdigital electrode pair further includes a first connecting electrode and a second connecting electrode, wherein the first connecting electrode connects all the first interdigital electrodes 61 together, and the second connecting electrode connects all the second interdigital electrodes 62 together.

[0188] The widths of the first interdigital electrode 61 and the second interdigital electrode 62 are both in the range of 110 μm to 220 μm. For example, the widths of the first interdigital electrode 61 and the second interdigital electrode 62 can be 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, or 200 μm.

[0189] For example, the first interdigital electrode 61 and the second interdigital electrode 62 have the same width.

[0190] The first interdigital electrode 61 and the second interdigital electrode 62 extend in the same direction, and the first connecting electrode and the second connecting electrode extend in the same direction, and the extension directions of the first connecting electrode and the second connecting electrode intersect with the extension directions of the first interdigital electrode 61 and the second interdigital electrode 62. In Figure 15, it is drawn as an example where the extension directions of the first connecting electrode and the second connecting electrode are perpendicular to the extension directions of the first interdigital electrode 61 and the second interdigital electrode 62.

[0191] The number of interdigital electrode pairs is 20 to 50, that is, the number of the first interdigital electrode 61 and the second interdigital electrode 62 is both 20 to 50, and the number of the first interdigital electrode 61 and the second interdigital electrode 62 is the same.

[0192] The spacing between two adjacent first interdigital electrodes 61 and second interdigital electrodes 62 ranges from 110μm to 220μm.

[0193] For example, the spacing between the first interdigital electrode 61 and the second interdigital electrode 62 can be 120μm, 130μm, 140μm, 150μm, 160μm, 170μm, 180μm, 190μm or 200μm.

[0194] For example, the first interdigital electrode 61 and the second interdigital electrode 62 are alternately arranged, and the first interdigital electrode 61 and the second interdigital electrode 62 are arranged at equal intervals.

[0195] In the embodiments of this application, by setting the spacing between two adjacent first interdigital electrodes 61 and second interdigital electrodes 62 to be in the range of 110μm to 220μm, and taking aluminum nitride (AlN) as the material of the dielectric layer 1, a surface sound velocity of 11000m / s can be achieved.

[0196] For example, the power range of the signal applied to the first interdigital electrode 61 and the second interdigital electrode 62 is 24 to 33 dBm.

[0197] In some implementations, the first interdigital electrode 61 and the second interdigital electrode 62 are configured to apply the same signal.

[0198] For example, the power, voltage, and frequency of the signals applied to the first interdigital electrode 61 and the second interdigital electrode 62 are the same.

[0199] In some implementations, the detection device also includes a hydrophobic layer that covers a portion of the dielectric layer 1 located in the sample test area 1A; the surface modification layer K is located on the side of the hydrophobic layer away from the dielectric layer 1.

[0200] It is understandable that before performing surface treatment on the dielectric layer 1 to obtain the surface modification layer K, a hydrophobic treatment can be performed first. Since the sample to be tested is usually a hydrophilic water solution, by performing a hydrophobic treatment on the surface of the dielectric layer 1, the hydrophobic layer is placed between 21 and the surface modification layer K. This avoids the detection solution from flowing to other areas during the detection process, thereby increasing the contact time between the sample to be tested and the surface modification layer K, which helps the functional groups in the surface modification layer K to connect with the detector.

[0201] For example, when the orthogonal projection of the gate electrode 4 onto the dielectric layer overlaps with the sample test area 1A, the hydrophobic layer covers a portion of the gate electrode 4.

[0202] In some implementations, the detection device also includes a groove disposed in the portion of the dielectric layer 1 located in the sample test area 1A, and the surface modification layer K covers the bottom and sidewalls of the groove.

[0203] For example, when the orthographic projection of the gate electrode 4 on the dielectric layer overlaps with the sample test area 1A, a portion of the gate electrode 4 can extend into the area where the groove is located.

[0204] By setting the groove in the portion of the medium layer 1 located in the sample test area 1A, and the surface modification layer K covering the bottom and sidewalls of the groove, the detection solution is prevented from flowing to other areas during the detection process, thereby increasing the contact time between the sample to be tested and the surface modification layer K, which helps the functional groups in the surface modification layer K to connect with the detector.

[0205] In some implementations, the surface modification layer K includes thiol and / or carboxyl groups, and the detector is attached to a portion of the medium layer located in the sample test area 1A via the thiol and / or carboxyl groups.

[0206] It should be noted that in the actual detection process, when an input signal is applied to the source electrode, the gate electrode controls the detection device to turn on, and an initial current I0 is generated in the channel region of the detection device. The initial current I0 can be detected by the source electrode and the drain electrode.

[0207] When a protein biomarker (target biomarker) reacts with the detector and generates a current, the current value flowing through the channel region changes. The detection current I can be detected by the source and drain electrodes (the change in current is the detection current I minus the initial current I0). The concentration of the corresponding target biomarker can be calculated based on the change in current.

[0208] In some embodiments, when a first detection electrode J1 and a second detection electrode J2 are provided in the detection device, the initial current I0 and the detection current I can be detected by the first detection electrode J1 and the second detection electrode J2.

[0209] In some implementations, a triode vacuum tube can be used as a detection device to detect the concentration of the target marker in the sample.

[0210] For example, as shown in Figure 16, the detection device includes a dielectric layer 1, a source electrode 2, a drain electrode 3, a gate electrode 4, and an emitter electrode 7. The dielectric layer 1 is a vacuum layer, and the dielectric layer 1, the source electrode 2, the drain electrode 3, and the emitter electrode 7 are encapsulated inside a glass cover g. The gate electrode 4 is located outside the glass cover g, and the sample detection area is disposed on the gate electrode 4. A surface modification layer K covers the portion of the gate electrode 4 located in the sample detection area. The surface modification layer is configured to form a covalent bond with the detector. The detector is configured to cause a change in the electrical signal of the gate electrode 4 after reacting with the sample S to be detected.

[0211] For example, the distance between the gate electrode and the glass cover ranges from 50 μm to 500 μm.

[0212] The emitting electrode 7 uses a low work function material to achieve electron excitation, such as metals (platinum), metal oxides (nickel, etc.), and alloys (such as beryllium copper, silver magnesium, copper aluminum magnesium).

[0213] The glass cover needs to provide a stable external frame to protect the internal components, especially during liquid sample processing, to prevent external interference and maintain the system's vacuum environment. Commonly used glass materials include silicate glass (such as Pyrex), which has excellent transparency, thermal stability, and chemical stability, making it suitable for biological sample analysis.

[0214] In practical applications, laser welding technology can be used to encapsulate the glass into a sealed cavity to ensure that no air enters through the seams. Additionally, before forming the sealed cavity, the source and drain electrodes are connected to an external data acquisition system via wires.

[0215] During the detection process, thiols are used to modify the gate electrode. Specifically, the pretreated gate electrode (e.g., gold, Au) is immersed in a solution containing thiols. The thiol molecules form covalent bonds with the gold atoms on the gate electrode surface through the thiol groups (-SH), thereby achieving the self-assembly of thiols on the gold electrode surface.

[0216] If a thiol molecule contains a mercapto group (-SH) at one end and a carboxylic acid group (-COOH) at the other end, a thiol solution can be coated onto the surface of the gate electrode. Then, it can be activated by using a mixture of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxythiosuccinimide (S-NHS) to form a surface modification layer K with carboxyl groups (-COOH) on the gate electrode surface. Further processing allows the surface modification layer K to be connected to the detector, thus successfully connecting the detector to the gate electrode.

[0217] The following example, using a metal oxide as the emitting electrode 7, illustrates its preparation method:

[0218] 1. First, it is necessary to prepare the coating of the emitting electrode 7. This usually involves making a mixture of raw material compounds such as barium oxide, strontium oxide and calcium oxide, such as alkaline earth metal carbonates, into powder and suspending them in a solvent to form a slurry.

[0219] 2. Before coating the emitter electrode 7, the drain electrode on the substrate of the emitter electrode 7 is cleaned and annealed to eliminate internal stress and improve adhesion.

[0220] 3. Coat the prepared slurry onto the pretreated drain electrode;

[0221] 4. The coated emitting electrode 7 is sintered in a hydrogen atmosphere at a temperature range of 1200℃ to 1300℃ for about 20-30 minutes to transform the coating material into the desired oxide structure.

[0222] 5. The sintered emission electrode 7 coating also needs to undergo activation treatment to improve its electron emission performance. This typically involves treating the cathode at a certain temperature (e.g., 200°C to 400°C) to form an electronic semiconductor and increase oxygen vacancies.

[0223] Additionally, it should be noted that when the aforementioned vacuum tube is used as a detection device, the specific process of detecting the concentration of the target marker in the sample S to be tested is as follows:

[0224] First, before modifying the gate electrode, a fixed voltage is input to the gate electrode, the voltage range of which can be 10 to 200mV. Electron excitation between the source electrode and the drain electrode is achieved by heating the vacuum tube, and the current I0 between the source electrode and the drain electrode is detected.

[0225] Secondly, the gate electrode is modified and a detector is connected to it. The sample to be tested is dropped onto the gate electrode, and the detector captures the target protein marker in the sample. The vacuum tube is excited under the same conditions and tested. The current I1 between the source electrode and the drain electrode is detected. The current I1 is the current after the gate electrode voltage interferes with the field effect of electron transport in the vacuum tube after capturing the target marker (it can be understood that the process of capturing the target marker will cause a change in the charge on the gate electrode, thereby causing a change in the gate electrode voltage, and the change in the gate electrode voltage will cause a change in the current between the source electrode and the drain electrode).

[0226] Finally, by comparing and analyzing the difference between current I0 and current I1, the concentration of the target marker in the sample S to be tested can be calculated.

[0227] In practical applications, a set of data tables is obtained before detection. These data tables record the relationship between the changes in channel current (e.g., the difference between current I0 and current I1) and the concentration of the target biomarker under the same conditions. Based on the difference between current I0 and current I1 obtained from each test and the data table, the concentration of the target biomarker can be calculated.

[0228] In the detection device provided in the embodiments of this application, by setting a vacuum tube, the influence of transmission distance on electrons is greatly reduced, and the field effect of the gate electrode effectively improves the non-uniformity of the small electrical signal of low-concentration protein markers, thereby improving the detection accuracy and sensitivity of the detection device.

[0229] Embodiments of this application provide a sensor comprising an array of multiple detection devices as described in any of the preceding descriptions.

[0230] Based on the above technical solution, applying the detection device proposed in this application to a biosensor can effectively improve the selectivity of the biosensor for target biomarkers, minimize the combination of the biosensor with non-specific substances (i.e., non-target biomarkers), and further improve the transistor integration, response speed and sensitivity of the biosensor.

[0231] Embodiments of this application provide a detection chip, which includes a sensor as described above, and a controller electrically connected to the sensor. The controller is configured to perform concentration analysis of a target biomarker in the sample to be detected based on an electrical signal in the detection device.

[0232] Based on the above technical solution, applying the sensor proposed in this application to a biological detection chip can effectively improve the selectivity of the detection chip for target markers, minimize the combination of the detection chip with non-specific substances (i.e., non-target markers), and further improve the transistor integration, response speed and sensitivity of the detection chip.

[0233] An embodiment of this application provides a detection method applied to the detection device described above, the detection method comprising:

[0234] S1. Apply a first voltage signal to one of the source electrode or the drain electrode using the first probe;

[0235] For example, a first voltage signal can be applied to the source electrode using a first probe in the probe station. Then, the channel current between the source electrode and the drain electrode can be detected subsequently using the drain electrode.

[0236] S2. Apply a second voltage signal to the gate electrode using the second probe;

[0237] S3. Use the third probe to detect the reference channel current value I0 through another source or drain electrode;

[0238] For example, a first voltage signal can be applied to the source electrode using a first probe in the probe station. Then, the channel current between the source electrode and the drain electrode can be detected using a third probe through the drain electrode.

[0239] At this point, the detected channel current is the reference channel current value, also known as the current value of the reference group, which is used to compare with the changed channel current value when testing samples in the future.

[0240] S4. Perform surface modification on the sample test area of ​​the dielectric layer to obtain a surface modification layer;

[0241] Surface modification is performed only after the reference channel current value is obtained during each test to avoid interference from the surface modification layer on the reference channel current value and reduce test accuracy.

[0242] S5. Connect the detection body using a surface modification layer;

[0243] For example, the detection subject can be an antibody.

[0244] S6. Add the sample to be tested;

[0245] The changes in channel current differ depending on whether the sample to be tested contains the target biomarker or not.

[0246] After adding the sample to be tested, a preset time needs to be waited for the target biomarker in the sample to come into repeated contact and react with the test subject.

[0247] The preset time mentioned above is related to the type of target biomarker and antibody, and no specific limitation is made here.

[0248] S7. Apply a first voltage signal to one of the source electrode or the drain electrode using the first probe;

[0249] Using the same method as before the surface modification step, for example, a first voltage signal can be applied to the source electrode using a first probe in the probe station.

[0250] S8. Apply a second voltage signal to the gate electrode using the second probe;

[0251] S9. Use the third probe to detect the target channel current value I1 through another source electrode or drain electrode;

[0252] For example, the target channel current value between the source electrode and the drain electrode can be detected by using the third probe through the drain electrode 3;

[0253] The target channel current value is the channel current value obtained after adding the sample to be tested.

[0254] S10. Determine the concentration of the target biomarker in the sample to be tested based on the difference between the reference channel current value and the target channel current value.

[0255] The probe station includes a first probe, a second probe, and a third probe.

[0256] In practical applications, a set of data tables is obtained before detection. These data tables record the relationship between the changes in channel current under the same conditions (e.g., the difference between the reference channel current value I0 and the target channel current value I1) and the concentration of the target biomarker. Based on the difference between the reference channel current value I0 and the target channel current value I1 obtained from each test and the data table, the concentration of the target biomarker can be calculated.

[0257] The detection device provided in the embodiments of this application has a simple structure. It can simultaneously apply an input signal (e.g., a first voltage signal) and detect an output signal (e.g., detect channel current) through the source electrode and the drain electrode. Its detection method is simple, the detection efficiency is high, and the operation is convenient.

[0258] The following describes the detection method of the detection device when a first detection electrode and a second detection electrode are set in the detection device.

[0259] This application provides a detection method, which includes the detection device as described in some of the embodiments above. The detection method includes:

[0260] S21. Apply a first voltage signal between the source electrode and the drain electrode using the first probe and the third probe;

[0261] It can be understood that a voltage difference is applied between the source electrode and the drain electrode using the first probe and the third probe, and this voltage difference is called the first voltage signal;

[0262] S22. Apply a second voltage signal to the gate electrode using the second probe;

[0263] S23. Use the fourth and fifth probes to detect the reference channel current value between the first and second detection electrodes;

[0264] Compared to using source or drain electrodes to detect the reference channel current value, the embodiments of this application use a first detection electrode and a second detection electrode disposed in the sample detection area to detect the reference channel current value. This avoids interference from the input signal (e.g., the first voltage signal) of the source or drain electrode to the output signal (e.g., the channel current value), thereby improving the detection accuracy of the detection device.

[0265] It should be noted that the channel current detected at this time is the reference channel current value, also known as the current value of the reference group, which is used to compare with the changed channel current value when testing samples in the future.

[0266] S24. Perform surface modification on the sample test area of ​​the dielectric layer to obtain a surface modification layer;

[0267] Surface modification is performed only after the reference channel current value is obtained during each test to avoid interference from the surface modification layer on the reference channel current value and reduce test accuracy.

[0268] S25. Connect the detection body using a surface modification layer;

[0269] For example, the detection subject can be an antibody.

[0270] S26. Add the sample to be tested;

[0271] The changes in channel current differ depending on whether the sample to be tested contains the target biomarker or not.

[0272] After adding the sample to be tested, a preset time needs to be waited for the target biomarker in the sample to come into repeated contact and react with the test subject.

[0273] The preset time mentioned above is related to the type of target biomarker and antibody, and no specific limitation is made here.

[0274] S27. Apply a first voltage signal between the source electrode and the drain electrode using the first probe and the third probe;

[0275] The signal is reapplied to the detection device in the same manner as before the surface modification step.

[0276] S28. Apply a second voltage signal to the gate electrode using the second probe;

[0277] S29. Use the fourth and fifth probes to detect the target channel current value between the first and second detection electrodes;

[0278] The target channel current value is the channel current value obtained after adding the sample to be tested.

[0279] S30. Determine the concentration of the target biomarker in the sample to be tested based on the difference between the reference channel current value and the target channel current value.

[0280] The probe station includes a first probe, a second probe, a third probe, a fourth probe, and a fifth probe.

[0281] In practical applications, a set of data tables is obtained before detection. These data tables record the relationship between the changes in channel current under the same conditions (e.g., the difference between the reference channel current value I0 and the target channel current value I1) and the concentration of the target biomarker. Based on the difference between the reference channel current value I0 and the target channel current value I1 obtained from each test and the data table, the concentration of the target biomarker can be calculated.

[0282] The detection device provided in the embodiments of this application, by having a first detection electrode and a second detection electrode, detects the reference channel current value through the first detection electrode and the second detection electrode, thereby avoiding interference of the input signal (e.g., the first voltage signal) of the source electrode or drain electrode on the output signal (e.g., the channel current value), thus improving the detection accuracy of the detection device.

[0283] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A detection device applied to the detection of a target biomarker, wherein, include: A medium layer includes a sample testing area configured to hold a sample to be tested and cause a change in the electrical signal of the medium layer, wherein the sample to be tested may or may not contain the target biomarker. The source electrode and the drain electrode are located on opposite sides of the dielectric layer along the normal direction of the dielectric layer, and the orthographic projections of the source electrode and the drain electrode on the dielectric layer overlap. A gate electrode, wherein at least a portion of the source electrode and the drain electrode are disposed on the same side of the dielectric layer, and the orthographic projections of the gate electrode and the source electrode and the drain electrode onto the dielectric layer do not overlap; Wherein, the electrical signal strength of the dielectric layer along the normal direction is less than or equal to one-thousandth of the electrical signal strength of the dielectric layer in the plane.

2. The detection device according to claim 1, wherein, The detection device further includes a surface modification layer and a detector. The surface modification layer covers at least the portion of the dielectric layer located in the sample testing area. The surface modification layer is configured to form a covalent bond with the detector. The detector is configured to cause a change in the electrical signal of the dielectric layer after reacting with the sample to be tested.

3. The detection device of claim 2, wherein, The orthogonal projection of the gate electrode onto the dielectric layer partially overlaps with the sample test area.

4. The detection device of claim 3, wherein, A portion of the gate electrode and the source electrode are disposed on the same side of the dielectric layer, and a portion of the gate electrode is disposed on the side of the dielectric layer parallel to the normal direction of the dielectric layer.

5. The detection device of claim 4, wherein, The detection device further includes a first detection electrode and a second detection electrode disposed in the sample testing area, wherein the first detection electrode and the second detection electrode are respectively located on both sides of the dielectric layer.

6. The detection device of claim 5, wherein, The orthographic projections of the first detection electrode and the second detection electrode on the dielectric layer overlap.

7. The detection device according to claim 5 or 6, wherein, The material of the dielectric layer is graphene.

8. The detection device according to claim 5 or 6, wherein, The material of the dielectric layer is molybdenum disulfide.

9. The detection device according to any one of claims 4 to 6, wherein, The detection device further includes an adjustment unit configured to improve the in-plane charge transport speed and charge distribution uniformity in the dielectric layer.

10. The detection device of claim 9, wherein, The material of the dielectric layer is a two-dimensional ferromagnetic material.

11. The detection device of claim 10, wherein, The adjustment unit includes a magnet and a support. The magnet is fixed on the support and is configured to rotate around the support and provide a magnetic field. The dielectric layer is configured to be disposed in the area covered by the magnetic field.

12. The detection device of claim 11, wherein, The magnetic field has a magnetic induction intensity range of 0.1T to 1T, and the magnet has a rotation frequency range of 10Hz to 100Hz.

13. The detection device of claim 9, wherein, The dielectric layer is made of piezoelectric semiconductor material.

14. The detection device of claim 13, wherein, The adjustment unit includes a radio frequency signal generation structure, which is configured to generate a radio frequency signal, and electrons in the piezoelectric semiconductor material are configured to migrate and generate periodic electrical signals under the action of the radio frequency signal.

15. The detection device of claim 14, wherein, The radio frequency signal generation structure includes an interdigitated electrode pair, wherein one of the source electrode and the drain electrode is disposed on the same side of the dielectric layer as the interdigitated electrode pair, and the interdigitated electrode pair does not overlap with the orthographic projections of the source electrode, the drain electrode and the gate electrode on the dielectric layer.

16. The detection device of claim 15, wherein, The interdigitated electrode pair includes a plurality of first interdigitated electrodes and a plurality of second interdigitated electrodes, wherein the first interdigitated electrodes and the second interdigitated electrodes are alternately arranged; The frequency range of the signals applied to the first interdigital electrode and the second interdigital electrode is 5MHz to 10MHz, and the intensity range of the signals applied to the first interdigital electrode and the second interdigital electrode is 24dBm to 33dBm.

17. The detection device of claim 15, wherein, The first interdigital electrode and the second interdigital electrode are configured to apply the same signal.

18. The detection device of claim 2, wherein, The detection device further includes a hydrophobic layer that covers the portion of the dielectric layer located in the sample testing area; the surface modification layer is located on the side of the hydrophobic layer away from the dielectric layer.

19. The detection device of claim 2, wherein, The detection device further includes a groove disposed on the portion of the dielectric layer located in the sample testing area, and the surface modification layer covers the bottom and sidewalls of the groove.

20. The detection device of claim 2, wherein, The surface modification layer includes thiol groups and / or carboxyl groups, and the detector is attached to the sample test area through the thiol groups and / or carboxyl groups.

21. A sensor, wherein, It includes multiple detection devices arranged in an array as described in any one of claims 1 to 20.

22. A detection chip, wherein, The device includes the sensor as described in claim 21, and further includes a controller electrically connected to the sensor, the controller being configured to perform concentration analysis of the target biomarker in the sample to be tested based on an electrical signal in the detection device.

23. A method of detection, wherein, The detection method, applied to the detection device as described in any one of claims 2 to 20, comprises: A first voltage signal is applied to one of the source electrode or the drain electrode using a first probe; A second voltage signal is applied to the gate electrode using a second probe; The third probe is used to detect the reference channel current value through another of the source or drain electrodes; The sample test area of ​​the dielectric layer is surface-modified to obtain a surface-modified layer; The detection body is connected using the surface modification layer; Add the sample to be tested; The first voltage signal is applied to one of the source electrode or the drain electrode using the first probe; The second voltage signal is applied to the gate electrode using the second probe; The target channel current value is detected by using a third probe through another of the source or drain electrodes; The concentration of the target biomarker in the sample to be tested is determined based on the difference between the reference channel current value and the target channel current value. The probe station includes the first probe, the second probe, and the third probe.

24. A method of detection, wherein, The detection method, applied to the detection device as described in any one of claims 4 to 17, comprises: A first voltage signal is applied between the source electrode and the drain electrode using a first probe and a third probe; A second voltage signal is applied to the gate electrode using a second probe; The reference channel current value is detected between the first detection electrode and the second detection electrode using the fourth and fifth probes; The sample test area of ​​the dielectric layer is surface-modified to obtain a surface-modified layer; The detection body is connected using the surface modification layer; Add the sample to be tested; The first voltage signal is applied between the source electrode and the drain electrode using the first probe and the third probe; applying, by the second probe, the second voltage signal to the gate electrode; detecting, by the fourth probe and the fifth probe, a target channel current value between the first detection electrode and the second detection electrode; determining a concentration of the target biomarker in the sample to be detected according to a difference between the reference channel current value and the target channel current value; wherein the probe table comprises the first probe, the second probe, the third probe, the fourth probe, and the fifth probe.

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