Detection module and biochemical sensing system
By integrating the data reading submodule and the sensor submodule in the detection module, the timing adjustment of the sensor components and control components in the array arrangement is solved, and the problem of high-throughput biochemical detection in the prior art is achieved, and fast and accurate biological sample detection is achieved.
Patent Information
- Application Number
- CN202510204207.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-24
- Publication Date
- 2025-05-30
AI Technical Summary
It is difficult for the prior art to achieve high-throughput biochemical detection and traditional nucleic acid detection and synthesis schemes cannot detect tens of millions of samples at the same time, while ensuring the accuracy of the detection.
By integrating the data reading submodule and the sensor submodule in the detection module, the sensor submodule includes sensor components arranged in an array. The data reading submodule adjusts the operating timing of each sensor component to support high-throughput detection of biological samples and ensures the accuracy of detection.
It realizes high-throughput detection of biological samples, reduces the experimental cycle, improves the efficiency and accuracy of the detection, and has great medical applicability.
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Figure CN120060447A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of biological sample detection, and more particularly, to a detection module and a biochemical sensing system. Background Art
[0002] In many fields such as medical health, scientific research, and environmental monitoring, biochemical detection plays a crucial role. With the development of genomics and molecular biology, taking nucleic acid probes, which are molecular tools used to detect and quantify specific nucleic acid sequences, as an example, traditional biochemical detection techniques rely on large and expensive laboratory equipment and complex sample processing procedures. This not only takes a long time and limits the real-time nature of detection, but also requires a large amount of labor costs to improve detection accuracy.
[0003] Generally, traditional nucleic acid probe synthesis schemes cannot meet high-throughput detection, that is, they cannot detect tens of millions of samples at the same time, or cannot ensure the accuracy of detection when detecting tens of millions of samples at the same time.
[0004] Based on this, there is an urgent need for a biological sample detection scheme that can support high-throughput detection and ensure the accuracy of detection. Summary of the Invention
[0005] In view of this, the purpose of the present invention is to provide a detection module and a biochemical sensing system, which relate to the technical field of biological sample detection. By integrating a data reading sub-module and a sensor sub-module in the detection module, where the sensor sub-module includes sensor components arranged in an array, and then adjusting the working timings of the respective sensor components through the data reading sub-module, it is possible to support high-throughput detection of biological samples and ensure the accuracy of detection.
[0006] To achieve the above purpose, the technical solutions adopted in the embodiments of the present invention are as follows:
[0007] In a first aspect, the present invention provides a detection module. The detection module is applied to a biochemical sensing system, and the biochemical sensing system at least includes a detection probe and a detection chamber. The detection module is used to obtain parameters of a biochemical sample to be detected when using the detection probe to detect the biochemical sample to be detected in the detection chamber. The detection module includes a sensor sub-module and a data reading sub-module; the data reading sub-module includes a control component and a conversion component; the sensor sub-module includes a plurality of sensor components, and the respective sensor components are arranged in an array and are respectively connected to the control component and the conversion component;
[0008] The sensor component is used to obtain the analog change amount generated when an electrochemical reaction occurs between the detection probe and the biochemical substance to be detected in the detection chamber;
[0009] A control component for turning on or off each sensor component so that, in a preset time series, a data reading sub-module can obtain the analog variation transmitted by the sensor component;
[0010] A conversion component is also used to convert the analog variation into a digital signal to generate the parameters of the biochemical sample to be measured.
[0011] In a second aspect, the present invention provides a biochemical sensing system, which includes a detection probe, a detection chamber, and a detection module applied to any one of the above first aspects.
[0012] The detection module and the biochemical sensing system provided by the embodiments of the present invention have the following beneficial effects:
[0013] The present invention provides a detection module, which is applied to a biochemical sensing system. The biochemical sensing system at least includes a detection probe and a detection chamber. The detection module is used to obtain the parameters of the biochemical sample to be measured when using the detection probe to detect the biochemical sample to be measured in the detection chamber. The detection module includes a sensor sub-module and a data reading sub-module; the data reading sub-module includes a control component and a conversion component; the sensor sub-module includes a plurality of sensor components, and the sensor components are arranged in an array and are respectively connected to the control component and the conversion component. The sensor component is used to obtain the analog variation generated during the electrochemical reaction between the detection probe and the biochemical substance to be measured in the detection chamber; the control component is used to turn on or off each sensor component so that, in a preset time series, the data reading sub-module can obtain the analog variation transmitted by the sensor component; the conversion component can convert the analog variation into a digital signal to generate the parameters of the biochemical sample to be measured. Based on this, the present invention can, through the data reading sub-module and the sensor sub-module integrated in the detection module, where the sensor sub-module includes sensor components arranged in an array, and then adjust the working time sequence of each sensor component through the data reading sub-module, support the high-throughput detection of biological samples, and ensure the accuracy of detection.
[0014] To make the above objects, features, and advantages of the present invention more obvious and understandable, the following specific preferred embodiments are given, and in conjunction with the accompanying drawings, the detailed description is as follows. Description of the Drawings
[0015] To more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required in the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.
[0016] Figure 1 Shows one of the schematic structural diagrams of the biochemical sensing system provided by the embodiments of the present invention;
[0017] Figure 2 Shows the second structural schematic diagram of the biochemical sensing system provided by the embodiment of the present invention;
[0018] Figure 3 Shows the first structural schematic diagram of the detection module provided by the embodiment of the present invention;
[0019] Figure 4 Shows the second structural schematic diagram of the detection module provided by the embodiment of the present invention;
[0020] Figure 5 Shows the third structural schematic diagram of the detection module provided by the embodiment of the present invention;
[0021] Figure 6 Shows the first structural schematic diagram of the amplifier component provided by the embodiment of the present invention;
[0022] Figure 7 Shows the second structural schematic diagram of the amplifier component provided by the embodiment of the present invention;
[0023] Figure 8 Shows the structural schematic diagram of the control component provided by the embodiment of the present invention;
[0024] Figure 9 Shows the first structural schematic diagram of the sensor component provided by the embodiment of the present invention;
[0025] Figure 10 Shows the second structural schematic diagram of the sensor component provided by the embodiment of the present invention;
[0026] Figure 11 Shows the first circuit schematic diagram of the sensing control unit provided by the embodiment of the present invention;
[0027] Figure 12 Shows the second circuit schematic diagram of the sensing control unit provided by the embodiment of the present invention;
[0028] Figure 13 Shows the circuit schematic diagram of the detection probe synthesis unit provided by the embodiment of the present invention;
[0029] Figure 14 Shows the first chip structural schematic diagram of the sensor component provided by this embodiment;
[0030] Figure 15 Shows the second chip structural schematic diagram of the sensor component provided by this embodiment;
[0031] Figure 16 Shows the third chip structural schematic diagram of the sensor component provided by this embodiment;
[0032] Figure 17It is a test example diagram for applying this embodiment to the corresponding biochemical sensing system in the field of nucleic acid detection;
[0033] Figure 18 It is a test example diagram for applying this embodiment to the corresponding biochemical sensing system in the field of antibody detection;
[0034] Figure 19 It is a test example diagram of the detection module in this embodiment.
[0035] Icons: 10 - Biochemical sensing system; 11 - Detection module; 12 - Detection probe; 13 - Detection chamber; 14 - Stage; 21 - Sensor sub-module; 22 - Data reading sub-module; 23 - Reference electrode; 24 - Amplifier assembly; 31 - Control assembly; 32 - Conversion assembly; 33 - Sensor assembly; 41 - Amplifier; 42 - Control unit; 43 - Row selection unit; 44 - Column reading unit; 45 - Sensing control unit; 46 - Detection probe synthesis unit; 47 - Column writing unit; 103A - Transistor region structure; 103B - Capacitance region structure; 10401 - Substrate; 10402 - Gate layer; 10403 - Gate dielectric layer; 10404 - Active channel layer; 10405 - Etch stop layer; 10406 - First passivation layer; 10407 - Source / drain layer; 10408 - Second passivation layer; 10409 - Top electrode; 10410 - Top capping layer; 1030 - Working electrode layer; 10302 - Anode; 10303 - Cathode; 10301 - Detection electrode; TFT1 - First thin film transistor; TFT2 - Second thin film transistor; C1 - First filter capacitor; TFT3 - Third thin film transistor; TFT4 - Fourth thin film transistor; TFT5 - Fifth thin film transistor; C2 - First storage capacitor; TFT6 - Sixth thin film transistor; C3 - Second filter capacitor; V1 - First voltage. Detailed implementation manners
[0036] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Usually, the components of the embodiments of the present invention described and illustrated here can be arranged and designed in various different configurations.
[0037] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed present invention, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts fall within the protection scope of the present invention.
[0038] It should be noted that relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprising", "including" or any other variant thereof are intended to cover non-exclusive inclusion, such that a process, method, article or device comprising a series of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article or device. Without further limitation, an element defined by the statement "comprising an..." does not exclude the presence of additional identical elements in the process, method, article or device comprising the element.
[0039] As described in the background art, there is a lack of a technical solution in the prior art that can support high-throughput biochemical detection.
[0040] Based on this, the present embodiment provides a technical solution that can support high-throughput biochemical detection and at the same time ensure the accuracy of detection.
[0041] Please refer to Figure 1 , Figure 1 , which shows a schematic structural diagram of the biochemical sensing system provided in the present embodiment; in the present embodiment, the biochemical sensing system 10 includes a detection probe 12, a detection chamber 13 and a detection module 11. When the detection module 11 uses the detection probe 12 to detect a biochemical sample to be tested in the detection chamber 13, the parameters of the biochemical sample to be tested can be obtained. Among them, a plurality of sensor components are integrated on the detection module 11 in an array, and at the same time, the working timings of the sensor components are adjusted to simultaneously realize the detection of a large number of detection probes.
[0042] In the present embodiment, the detection probe may include a nucleic acid probe or an antibody probe. Taking the antibody probe as an example, the detection principle of the biochemical sensing system at this time is as follows: the antibody probe hybridizes and captures the biochemical sample to be detected, such as the target protein, in the detection chamber in an electrolyte environment. This biochemical reaction will cause a potential change on the surface of the detection module, which is then acquired by the detection module to obtain an analog change amount. Thus, the detection module generates the parameters of the biochemical sample to be tested based on the analog change amount, so that the biological sample detection platform or the upper computer can perform biochemical evaluation based on the parameters of the biochemical sample to be tested.
[0043] In a possible implementation manner, since the above-mentioned analog change amount changes its own change trend with the concentration of the biochemical sample to be detected, the biochemical sensing system provided in the present embodiment can be used by the biological sample detection platform or the upper computer to determine effective detection information such as the type, positive / negative, concentration of the biochemical sample to be detected, and the detection limit, specificity, kinetic change and error of the detection module itself based on the above change trend.
[0044] Based on this, this embodiment not only greatly improves the speed of biochemical detection, ensures the accuracy of detection, but also increases more sample parameters available for evaluation, greatly shortens the experimental period of biological samples, improves the efficiency of research and detection, has great medical applicability, and promotes the level of disease detection.
[0045] Please, on the basis of Figure 1 , refer to Figure 2 , Figure 2 which shows another structural schematic diagram of the biochemical sensing system provided by this embodiment; the biochemical sensing system is sequentially provided with a detection module 11, a detection chamber 13, and a stage 14 from top to bottom; among them, the detection chamber 13 is arranged on the stage 14, and a groove with the same shape as the detection chamber 13 is correspondingly arranged on the stage 14 to fix the detection chamber 13 on the stage 14 through the groove and provide a stable working environment for the detection chamber 13.
[0046] With a similar idea to the previous embodiment, please refer to Figure 3 , Figure 3 which shows the structural schematic diagram of the detection module provided by the embodiment of the present invention; this detection module can be used to obtain the parameters of the biochemical sample to be detected when using a detection probe to detect the biochemical sample to be detected in the detection chamber.
[0047] In this embodiment, the detection module 11 includes a sensor sub-module 21 and a data reading sub-module 22. The data reading sub-module 22 includes a control component 31 and a conversion component 32; the sensor sub-module 21 includes a plurality of sensor components 33, and the sensor components 33 are arranged in an array and are respectively connected to the control component 31 and the conversion component 32.
[0048] Among them, the sensor component 33 is used to obtain the analog change amount generated when the detection probe and the biochemical substance to be detected undergo an electrochemical reaction in the detection chamber. The control component 31 is used to turn on or off each sensor component so that the data reading sub-module can obtain the analog change amount transmitted by the sensor component in a preset time sequence. The conversion component 32 is also used to convert the analog change amount into a digital signal to generate the parameters of the biochemical sample to be detected.
[0049] In this embodiment, a working electrode layer is integrated on the sensor component, so that when the detection probe and the biochemical substance to be detected undergo an electrochemical reaction in the detection chamber, a potential change is generated on the working electrode layer, and then it is captured by the sensor component to form the analog change amount described in this embodiment.
[0050] The control component 31 is used to adjust the working timings of the respective sensor components, so as to turn on or off each sensor component in a preset time sequence, enabling the detection module to quickly obtain a large amount of sample data in one sampling period. In a possible implementation manner, the control component may turn on the sensor components arranged in an array row by row and column by column, and complete the traversal of the sensor components within a preset time frame. Based on this, the data reading sub-module can perform a fast and sequential scan within the preset time frame to generate the biochemical sample parameters to be measured.
[0051] It should be noted that this embodiment does not limit the specific manner in which the control component implements the scan, as long as it can turn on or off each sensor component in a preset time sequence, complete the traversal, and obtain the biochemical sample parameters to be measured. For example, in this embodiment, the control component only needs to perform unified logical control and time sequence control on each sensor component to accurately achieve the synchronous or asynchronous relationship between the output signals of the corresponding sensor components. The above description is only a possible implementation manner.
[0052] In this embodiment, the conversion component 32 is used to convert the analog change amount sequentially scanned by the data reading sub-module within a preset time frame into a digital quantity, so as to facilitate the acquisition and evaluation of the digital quantity by the host computer or the like.
[0053] Based on this, this embodiment can achieve high-throughput detection of biological samples through the data reading sub-module and the sensor sub-module integrated in the detection module, ensuring the accuracy of the detection.
[0054] Please, on the basis of Figure 3 , refer to Figure 4 , Figure 4 which shows another structural schematic diagram of the detection module 11 provided by the embodiment of the present invention. In a possible implementation manner, to enable the sensor component 33 to generate an analog change amount, the detection module 11 in this embodiment further includes a reference electrode 23; the reference electrode 23 is connected to a power supply and is used to receive a preset voltage to provide a reference voltage for the sensor component.
[0055] The sensor component 33 is further used to obtain the analog quantity generated during the electrochemical reaction between the detection probe and the biochemical substance to be measured in the detection cavity.
[0056] The sensor component 33 is further used to determine the analog change amount based on the reference voltage and the analog quantity.
[0057] To ensure the accuracy of signal transmission and detection, please, on the basis of Figure 4 , refer to Figure 5 , Figure 5Another structural schematic diagram of the detection module 11 provided by an embodiment of the present invention is shown. In this embodiment, the detection module 11 further includes an amplifier assembly 24; the sensor assembly 33 is connected to the conversion assembly 32 through the amplifier assembly 24; when the analog change amount acquired by the sensor assembly 33 is a voltage change value, the amplifier assembly 24 is configured to amplify the voltage change value or synchronize it into a current signal. The conversion assembly 32 is further configured to convert the current signal into a digital signal.
[0058] Based on this, in this embodiment, the amplifier 41 can amplify the voltage change value or synchronize it into a current signal, and amplify the converted current signal, so as to facilitate acquisition by the subsequent biological sample detection platform or the host computer.
[0059] In a possible implementation manner, please Figure 5 on the basis of Figure 6 , Figure 6 A structural schematic diagram of the amplifier assembly provided by an embodiment of the present invention is shown. In this embodiment, the amplifier assembly 24 includes a plurality of amplifiers 41; each amplifier 41 corresponds to each link formed by the sensor assemblies arranged in columns, and the input end of each amplifier 41 is connected to the output end of the corresponding link. In this embodiment, the number of amplifiers is the same as the number of columns corresponding to the sensor component matrix in the sensor sub-module.
[0060] In this embodiment, for any one amplifier 41, the amplifier 41 is configured to amplify the voltage change value on the corresponding link, and convert the amplified or synchronized voltage change value into a current signal.
[0061] In another possible implementation manner, please Figure 5 on the basis of Figure 7 , Figure 7 Another structural schematic diagram of the amplifier assembly provided by an embodiment of the present invention is shown. In this embodiment, the amplifier assembly 24 includes a plurality of amplifiers 41; each amplifier 41 is correspondingly connected to each sensor assembly 33. Among them, Figure 7 taking any one sensor assembly 33 as an example, each sensor assembly 33 is connected to the corresponding amplifier 41. In this embodiment, the number of amplifiers is the same as the number of sensor assemblies.
[0062] In this embodiment, for any one amplifier 41, the amplifier 41 is configured to amplify the voltage change value on the corresponding sensor assembly 33, and convert the amplified or synchronized voltage change value into a current signal.
[0063] In this embodiment, the amplifier can be a silicon-based CMOS signal amplifier or a TFT signal amplifier. When the sensor component includes a thin-film transistor (TFT) chip, the silicon-based CMOS signal amplifier can be integrated outside the thin-film transistor chip (backplane) to convert the voltage signal into a current signal, detect the biochemical voltage signal, and simultaneously amplify the proximal biosensing signal. Furthermore, the circuit characteristics of the silicon-based CMOS signal amplifier can be utilized to improve the sensitivity of the detection module.
[0064] If a TFT signal amplifier is used, it can be integrated within the thin-film transistor chip (backplane) to amplify the proximal biosensing signal, thereby improving the integration of the biochemical sensing system and reducing the signal quality loss in the detection loop.
[0065] In a possible implementation manner, when each amplifier in the sensor component corresponds to each sensor component, a TFT signal amplifier can be used and integrated on the sensor component for an integrated design to reduce the device size.
[0066] In another possible implementation manner, when each amplifier 41 in the sensor component 33 corresponds to each link formed by the sensor components 33 arranged in columns, a silicon-based CMOS signal amplifier 41 can be used, such that each column of sensor links shares one silicon-based CMOS signal amplifier 41 to further improve the detection accuracy of the sensor component 33.
[0067] The control component in this embodiment will be introduced in detail below. Please refer to Figure 8 , Figure 8 which shows a schematic structural diagram of the control component 31 provided by the embodiment of the present invention; the control component 31 includes a control unit 42, a row selection unit 43, and a column reading unit 44; the control unit 42 is respectively connected to the row selection unit 43 and the column reading unit 44.
[0068] When the links formed by the sensor components 33 arranged in rows are row pixel circuits; and the links formed by the sensor components 33 arranged in columns are column pixel circuits, the row selection unit 43 is further connected to the control ports of the sensor components 33 on the row pixel circuits; the column reading unit 44 is further connected to the reading ports of the sensor components 33 on the column pixel circuits.
[0069] Among them, the control unit 42 is configured to send control signals to the row selection unit 43 and the column reading unit 44 respectively to adjust the working timings of the row selection unit 43 and the column reading unit 44.
[0070] The row selection unit 43 is configured to turn on or off the sensor components 33 under the row pixel circuits according to the control signals.
[0071] A column reading unit 44 is configured to turn on or off the sensor components 33 under each column pixel circuit according to a control signal; and read the analog variation obtained by each sensor component 33.
[0072] In this embodiment, the column reading unit 44 controls the TFT through the DATA control signal sent by the row selection unit 43, and then reads the analog variation (such as the output current Iout) obtained by each sensor component 33. The row selection unit 43 is connected to the row pixel circuit through the SCAN signal line to perform gating and scanning of the row pixel circuit.
[0073] Please continue to refer to Figure 8 , in this embodiment, the sensor components 33 arranged in an array include at least M columns of column pixel circuits and N rows of row pixel circuits. Among them, the sequences corresponding to each column pixel circuit can be respectively expressed as I-1, …, I-M; similarly, the sequences corresponding to each row pixel circuit can be respectively expressed as S-1, …, S-N; the control unit 42 sends signals to the row selection unit 43 and the column reading unit 44 to instruct the row selection unit 43 and the column reading unit 44 to respectively adjust the corresponding pixel circuits to ensure that the row selection unit 43 and the column reading unit 44 execute the same control logic, and ensure that signal interaction is performed in a preset time sequence to ensure the accuracy of the synchronous and asynchronous relationships between signals.
[0074] In this embodiment, the sensor component includes a working electrode layer, which is usually disposed on the surface of the sensor component. Among them, the surface of the working electrode layer is the working surface for the detection probe 12 to hybridize and capture the target nucleic acid fragment in the electrolyte environment in this embodiment (or the working surface for electro-induced modification / electrodeposition of the detection probe 12).
[0075] Please refer to Figure 9 , Figure 9 shows a schematic structural diagram of the working electrode layer provided by an embodiment of the present invention; in this embodiment, the working electrode layer 1030 includes an anode 10302, a cathode 10303, and a detection electrode 10301. Among them, the anode 10302 and the cathode 10303 are components actually participating in the synthesis of nucleic acid probes, and the detection electrode 10301 is used to achieve biochemical sensing, that is, the sensor component 33 in this embodiment is actually used to obtain the above-mentioned fluctuations of the working electrode layer during the biochemical reaction process.
[0076] Please refer to Figure 10 , Figure 10 shows a schematic structural diagram of the sensor component provided by an embodiment of the present invention; in this embodiment, the control component further includes a column writing unit 47, and the sensor component 33 further includes a sensing control unit 45 and a detection probe synthesis unit 46. The detection probe synthesis unit 46 is connected to the column writing unit 47 and the row selection unit 43; the sensing control unit 45 is respectively connected to the row selection unit 43 and the column reading unit 44.
[0077] Among them, the column writing unit 47 is further configured to write a working voltage to the detection probe synthesis unit 46 and send a first control instruction to adjust the working state of the detection probe synthesis unit 46.
[0078] In this embodiment, after the column writing unit 47 writes the working voltage and sends the first control instruction, the detection probe synthesis unit 46 can, after being in a conducting state, fix the detection probe 12 on the surface of the working electrode layer 1030 by means of electroinduced modification / electrodeposition based on the working voltage. In this embodiment, the first control instruction is equivalent to a trigger signal for the electroinduced modification / electrodeposition process.
[0079] The row selection unit 43 is further configured to send a second control instruction to the detection probe synthesis unit 46 to turn on the detection probe synthesis unit 46, and then sequentially turn on the sensor components 33 under each column pixel circuit in a certain time sequence.
[0080] The detection probe synthesis unit 46 is further configured to, when in a conducting state, electroinducedly modify / electrodeposit the detection probe 12 on a preset surface based on the working voltage.
[0081] The row selection unit 43 is further configured to send a third control instruction to the sensing control unit 45 to adjust the conducting state of the sensing control unit 45, and then sequentially turn on the sensor components 33 under each row pixel circuit in a certain time sequence relationship to realize the traversal of the sensor components.
[0082] The sensing control unit 45 is configured to, when in a conducting state, obtain the analog change amount generated when the detection probe 12 detects the biochemical sample to be measured, and at the same time send the above analog change amount to the column reading unit 44.
[0083] In this embodiment, the working mode of the column writing unit 47 is as follows: write the working voltage to the detection probe synthesis unit 46 through the VDD common signal line, send the first control instruction (or DATA control signal) through the DATA signal line, and then when the detection probe synthesis unit 46 is in a conducting state, after receiving the working voltage, fix the detection probe 12 on the surface of the working electrode layer 1030 by means of electroinduced modification / electrodeposition based on the first control instruction, so as to facilitate the sensing control unit 45 to obtain the analog change amount generated when the detection probe 12 detects the biochemical sample to be measured for the sensing control unit 45 to obtain, and then obtain more accurate parameters of the biochemical sample to be measured.
[0084] Among them, the surface of the working electrode layer 1030 in this embodiment can be the surface of the detection electrode 10301 or the surface of the anode 10302. Taking the surface of the anode 10302 as an example, the column reading unit 44 provides a working voltage for the detection probe synthesis unit 46 through the VDD common signal line and the DATA signal line, and then electroinduces and modifies / electrodeposits the detection probe 12 (for example, a biological nucleic acid probe) on the surface of the anode 10302, so that the detection probe 12 hybridizes and captures the target nucleic acid fragment on the surface of the anode 10302 in the electrolyte environment, and then the sensing control unit 45 obtains the potential change generated during the process of hybridizing and capturing the target nucleic acid fragment, that is, the analog change amount described in this embodiment.
[0085] The process of electroinducing and modifying / electrodepositing the detection probe described in this embodiment is a way to fix the detection probe on the surface of the anode 10302.
[0086] It should be noted that the sensing control unit 45 and the detection probe synthesis unit 46 in the sensor assembly 33 in this embodiment are relatively independent sub-units.
[0087] In a possible implementation manner, the sensor assembly 33 can be composed of a thin-film transistor (TFT), a micro-nano storage capacitor (Cst), and a micro-nano metal trace. Among them, the working electrode layer 1030 is disposed on the upper surface of the sensor assembly 33.
[0088] In a possible implementation manner, please Figure 10 on the basis of Figure 11 , Figure 11 show the circuit schematic diagram of the sensing control unit 45 provided by the embodiment of the present invention; the sensing control unit 45 includes a first thin-film transistor TFT1, a second thin-film transistor TFT2, and a first filter capacitor C1.
[0089] The control end of the first thin-film transistor TFT1 is connected to the first end of the first filter capacitor C1 and is connected to the detection electrode 10301 in the working electrode layer 1030 on the sensor assembly 33; the second end of the first filter capacitor C1 is connected to the second end of the first thin-film transistor TFT1, and at the same time, the power supply unit also provides a first voltage V1 for the second end of the first filter capacitor C1; the third end of the first thin-film transistor TFT1 is connected to the first end of the second thin-film transistor TFT2; the second end of the second thin-film transistor TFT2 is used as the detection output end Iout of the sensing control unit 45 and is connected to the column reading unit 44; the control end of the second thin-film transistor TFT2 is connected to the row selection unit 43.
[0090] In another possible implementation manner, please Figure 10 on the basis of Figure 12 ,Figure 12 Another circuit schematic diagram of the sensing control unit 45 provided by an embodiment of the present invention is shown; the sensing control unit 45 includes a sixth thin-film transistor TFT6 and a second filter capacitor C3; the control terminal of the sixth thin-film transistor TFT6 is connected to the first terminal of the second filter capacitor C3 and the detection electrode 10301; the second terminal of the second filter capacitor C3 is connected to the first terminal of the sixth thin-film transistor TFT6, and at the same time, the power supply unit also provides a first voltage V1 to the second terminal of the second filter capacitor C3; the second terminal of the sixth thin-film transistor TFT6 serves as the detection output terminal Iout of the sensing control unit 45 and is connected to the column reading unit 44.
[0091] Please, on the basis of Figure 10 , refer to Figure 13 , Figure 13 A circuit schematic diagram of the detection probe synthesis unit provided by an embodiment of the present invention is shown; the detection probe synthesis unit 46 includes a third thin-film transistor TFT3, a fourth thin-film transistor TFT4, a fifth thin-film transistor TFT5, and a first storage capacitor C2.
[0092] The control terminal of the third thin-film transistor TFT3 is connected to the row selection unit 43, the first terminal is connected to the DATA terminal on the column reading unit 44, and the second terminal is respectively connected to the control terminal of the fourth thin-film transistor TFT4 and the first terminal of the first storage capacitor C2; the first terminal of the fourth thin-film transistor TFT4 is connected to the common VDD signal terminal on the column reading unit 44; the second terminal of the first storage capacitor C2 is connected to the anode 10302 in the working electrode layer 1030 of the sensor assembly 33; the second terminal of the fourth thin-film transistor TFT4 is connected to the first terminal of the fifth thin-film transistor TFT5; the control terminal of the fifth thin-film transistor TFT5 is connected to the row selection unit 43; the second terminal of the fifth thin-film transistor TFT5 is connected to the common ground terminal VSS.
[0093] It should be noted that in this embodiment Figures 10 to 13 the shown SCAN terminal is the second control instruction input terminal or the third control instruction input terminal of the row selection unit 43, and the control instructions of each SCAN terminal can be the same or different. The VDD terminal is the working voltage output terminal of the column writing unit 47, and the DATA terminal is the first control instruction input terminal of the column writing unit 47.
[0094] In this embodiment, any thin-film transistor in the sensing control unit and / or the detection probe synthesis unit is a control transistor, which can perform active addressing during the synthesis (nucleic acid probe modification) stage and perform electro-induced modification / electrodeposition of biological nucleic acid probes on the working electrode; second, it can perform charge reset of the floating working electrode during the test stage.
[0095] Based on this, the detection module provided in this embodiment can support high-throughput detection of biological samples and ensure the accuracy of detection.
[0096] In a possible implementation manner, the sensor component in this embodiment may be composed of a thin-film transistor and a micro-nano storage capacitor. In a possible implementation manner, the processing methods of the thin-film transistor and the micro-nano storage capacitor can be obtained by amorphous silicon (α-Si), indium gallium zinc oxide (IGZO), low-temperature polycrystalline silicon (LTPS), and organic thin-film transistor process technologies.
[0097] Please refer to Figure 14 , Figure 14 , which shows the chip structure schematic diagram of the sensor component in this embodiment. Among them, the structure of the sensor component 33 can be divided into a transistor region structure 103A and a capacitor region structure 103B.
[0098] Among them, taking the transistor region as an example, the transistor region includes:
[0099] A substrate 10401;
[0100] A gate layer 10402 located on one side of the substrate 10401;
[0101] A gate dielectric layer 10403 located on one side of the substrate 10401; among them, the gate dielectric layer 10403 covers the gate layer 10402 and contacts one side surface of the substrate 10401;
[0102] An active channel layer 10404 is provided on a part of the side of the gate dielectric layer 10403 away from the substrate 10401;
[0103] A first passivation layer 10406, a source / drain layer 10407, and an etch stop layer 10405 are further provided on the side of the gate dielectric layer 10403 away from the substrate 10401 except for the part of the active channel layer 10404;
[0104] Among them, the etch stop layer 10405 covers the active channel layer 10404 and partially contacts the side of the gate dielectric layer 10403 away from the substrate 10401;
[0105] A source / drain layer 10407 and a second passivation layer 10408 are provided on the side of the etch stop layer 10405 away from the substrate 10401;
[0106] Among them, both the source / drain layer 10407 and the second passivation layer 10408 partially cover the side of the etch stop layer 10405 away from the substrate 10401, and the second passivation layer 10408 covers the side of the source / drain layer 10407 away from the substrate 10401;
[0107] On the side of the second passivation layer 10408 away from the substrate 10401, a top electrode 10409 and a top capping layer 10410 are provided.
[0108] Among them, the top electrode 10409 partially covers the side of the second passivation layer 10408 away from the substrate 10401, and at the same time partially contacts the source / drain layer 10407; the top capping layer 10410 respectively partially covers the side of the second passivation layer 10408 away from the substrate 10401 and the top electrode 10409.
[0109] On the side of the top electrode 10409 away from the substrate 10401, a working electrode layer 1030 is provided.
[0110] Among them, the working electrode layer 1030 covers the remaining part except for the part where the top capping layer 10410 partially covers the top electrode 10409, and also partially covers the top capping layer 10410.
[0111] Please continue to refer to Figure 14 , taking the capacitor region structure 103B as an example. The capacitor region structure 103B includes:
[0112] Substrate 10401;
[0113] A gate layer 10402 on one side of the substrate 10401;
[0114] A gate dielectric layer 10403 on one side of the substrate 10401; among them, the gate dielectric layer 10403 covers the gate layer 10402 and contacts the surface of one side of the substrate 10401.
[0115] On the side of the gate dielectric layer 10403 away from the substrate 10401, a first passivation layer 10406 and a source / drain layer 10407 are provided.
[0116] Among them, the source / drain layer 10407 partially covers the side of the gate dielectric layer 10403 away from the substrate 10401; the first passivation layer 10406 partially covers the remaining part except for the part where the source / drain layer 10407 partially covers the side of the gate dielectric layer 10403 away from the substrate 10401. At the same time, the first passivation layer 10406 also partially covers the source / drain layer 10407 and exposes a part of the surface of the source / drain layer 10407 on the side away from the substrate 10401.
[0117] On the side of the first passivation layer 10406 and the source / drain layer 10407 away from the substrate 10401, a second passivation layer 10408 is provided.
[0118] Among them, the second passivation layer 10408 covers the side of the first passivation layer 10406 and the source / drain layer 10407 away from the substrate 10401.
[0119] A working electrode layer 1030 is disposed on a side of the second passivation layer 10408 away from the substrate 10401;
[0120] Wherein, the working electrode layer 1030 partially covers the side of the second passivation layer 10408 away from the substrate 10401.
[0121] In this embodiment, the substrate 10401 may be glass with a thickness of 0.5 mm; the material of the gate layer 10402 may be AlNd / Mo or Mo / Ti / Cu, and the thickness may be 300 / 40 nm. Similarly, the gate dielectric layer 10403 may be SiNx:H with a thickness of 350 nm or G-SiNx:L with a thickness of 50 nm; the active channel layer 10404 may be IGZO with a thickness of 25 nm; the etch stop layer 10405 may be SiO with a thickness of 250 nm 2 ; the first passivation layer 10406 may be SiO with a thickness of 250 nm 2 ; the source / drain layer 10407 may be Mo with a thickness of 220 nm; the second passivation layer 10408 may be SiNx with a thickness of 250 nm; the top electrode layer may be ITO with a thickness of 50 nm; the top capping layer 10410 may be SiO with a thickness of 250 nm 2 or SiNx:H with a thickness of 350 nm; the working electrode layer 1030 may be Cr or Pt with a thickness of 15 nm or 85 nm.
[0122] It should be noted that, in this embodiment, to ensure the stability of the sensor assembly, a top capping layer 10410 must be provided on the top electrode 10409. The top capping layer 10410 is a thin film with good step coverage, good dielectric properties, and good water and oxygen barrier properties to provide coverage protection for the sensor assembly. At the same time, it also needs to have strong patterning characteristics to facilitate the patterning of the working electrode layer.
[0123] In a possible implementation manner, in this embodiment, the top capping layer needs to be a thickened single layer of dense SiO 2 、SiNx, Al 2 O 3 , HfO 2 etc. and thickened single layers of dense and water / oxygen barrier organic polymers (organic photoresist, polyimide, etc.), or alternating stacks of the above organic polymers, so as to isolate the intrusion of water and oxygen during use.
[0124] Please continue to refer to Figure 1 on the basis of Figure 9, in this embodiment, the working electrode layer 1030 may include an anode 10302, a cathode 10303, and a detection electrode 10301. The above electrodes are directly exposed to the synthetic reagent system or the reaction detection reagent system during the processes of electro-induced modification / electrodeposition of bio-nucleic acid probes and for biochemical sensing, and need to have strong chemical and electrochemical stability. In an achievable manner, noble metals such as Au, Pt, Ir, etc. or their laminates, or oxides with higher inertness can be selected. Among them, the setting process of the working electrode layer 1030 can adopt mild processes such as "direct photoresist development removal" and "photoresist-assisted stripping of metal and dielectric layers" to avoid the formation of pinholes, cracks, or concave-convex 3D structures on the surface or cross-section of the lower layer ("top capping layer 10410"), which may cause easier intrusion of subsequent water and oxygen.
[0125] To save device size and structure, in a possible achievable manner, please refer to Figure 15 , Figure 15 shows another chip structure schematic diagram of the sensor assembly 33 provided in this embodiment; in this embodiment, each sensor assembly 33 under the detection module 11 can be a circular framework. Among them, the working electrode layer 1030 is arranged on one surface of the sensor assembly 33 and includes an anode 10302, a cathode 10303, and a detection electrode 10301. The above electrodes are all connected by independent signal lines passing through signal line vias without mutual crosstalk, so as to enable the sensor assembly to independently and parallelly realize signal control, and further ensure that the processes of electro-induced modification / electrodeposition of bio-nucleic acid probes and for biochemical sensing are carried out according to a predetermined time sequence and voltage (current) sequence.
[0126] In another possible achievable manner, please refer to Figure 16 , Figure 16 shows another chip structure schematic diagram of the sensor assembly 33 provided in this embodiment; in this embodiment, each sensor assembly 33 under the detection module 11 can be an oval framework to facilitate reducing the gap between each sensor assembly 33 and reducing the device size.
[0127] It should be noted that this implementation manner only simply shows the architecture of the sensor assembly 33. The structures of each device under the sensor assembly 33 are similar to those in the above embodiment and will not be elaborated here.
[0128] Please refer to Figure 17 , Figure 18 , Figure 17 is a test example diagram of the corresponding biochemical sensing system 10 after applying this embodiment to nucleic acid detection; Figure 18 is a test example diagram of the corresponding biochemical sensing system 10 after applying this embodiment to antibody detection, where the abscissa is the simulated voltage value; the ordinate is the output current value; with Figure 17Taking [Example], the curve corresponding to 601 represents the experimental results of nucleic acid detection using the traditional biochemical sensing system 10, and the curve corresponding to 602 represents the experimental results of nucleic acid detection by the biochemical sensing system 10 in this embodiment; the curve corresponding to 603 represents the experimental results when the concentration of the target nucleic acid is 1; the curve corresponding to 604 represents the experimental results when the concentration of the target nucleic acid is 2; the curve corresponding to 605 represents the experimental results when the concentration of the target nucleic acid is 3; the curve corresponding to 606 represents the experimental results when the concentration of the target nucleic acid is 4; the curve corresponding to 607 represents the experimental results when the concentration of the target nucleic acid is 5. Taking Figure 18 as an example, the curve corresponding to 701 represents the experimental results of antibody detection using the traditional biochemical sensing system 10, and the curve corresponding to 702 represents the experimental results of antibody detection by the biochemical sensing system 10 in this embodiment; the curve corresponding to 703 represents the experimental results when the concentration of the target protein is 1; the curve corresponding to 704 represents the experimental results when the concentration of the target protein is 2.
[0129] It can be seen from the illustrated curves that the change in potential varies with the concentration of the target nucleic acid / target protein in the sample to be detected, showing different "current-voltage" or "voltage (current)-time" change trends. Furthermore, effective detection information such as the type, positive / negative, concentration of the sample, and the sensitivity, detection limit, specificity, kinetic changes, and error of the sensor itself can be obtained by detecting the change in the signal.
[0130] Please refer to Figure 19 , Figure 19 which is a test example diagram of the detection module in this embodiment; when the detection module in this embodiment is composed of a sensor component matrix of 64*64, when the bio-nucleic acid probes distributed in the detection module hybridize and capture "target nucleic acid" fragments or "target protein" molecules in an electrolyte environment, the change in potential / voltage (current) obtained based on the data acquired by the column reading unit in the detection module can be analyzed with respect to the spatial distribution of the nucleic acid probes, thereby reflecting the spatial distribution of "target nucleic acid" fragments or "target protein" molecules in the sample to be detected.
[0131] In summary, the embodiments of the present invention provide a detection module and a biochemical sensing system. The detection module is applied to the biochemical sensing system, and the biochemical sensing system at least includes a detection probe and a detection chamber. The detection module is used to obtain parameters of a biochemical sample to be detected when using the detection probe to detect the biochemical sample to be detected in the detection chamber. The detection module includes a sensor sub-module and a data reading sub-module; the data reading sub-module includes a control component and a conversion component; the sensor sub-module includes a plurality of sensor components, and the sensor components are arranged in an array and are respectively connected to the control component and the conversion component. The sensor component is used to obtain the analog change amount generated when the detection probe and the biochemical substance to be detected undergo an electrochemical reaction in the detection chamber; the control component is used to turn on or off each sensor component so that the data reading sub-module obtains the analog change amount transmitted by the sensor component in a preset time sequence; the conversion component can convert the analog change amount into a digital signal to generate parameters of the biochemical sample to be detected. Based on this, the present invention can, through the data reading sub-module and the sensor sub-module integrated in the detection module, where the sensor sub-module includes sensor components arranged in an array, and then adjust the working timing of each sensor component through the data reading sub-module, support high-throughput detection of biological samples, and ensure the accuracy of detection.
[0132] In several embodiments provided in the present application, it should be understood that the disclosed devices and methods can also be implemented in other ways. The device embodiments described above are only illustrative. For example, the flowcharts and block diagrams in the accompanying drawings show the possible architectures, functions, and operations of devices, methods, and computer program products according to multiple embodiments of the present invention. In this regard, each block in the flowchart or block diagram may represent a module, a program segment, or a part of code, and the module, program segment, or part of code contains one or more executable instructions for implementing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the blocks may occur in a different order than marked in the accompanying drawings. For example, two consecutive blocks may actually be executed substantially in parallel, and they may sometimes be executed in the reverse order, depending on the functions involved. It should also be noted that each block in the block diagram and / or flowchart, as well as the combination of blocks in the block diagram and / or flowchart, can be implemented by a dedicated hardware-based system for performing the specified functions or actions, or can be implemented by a combination of dedicated hardware and computer instructions.
[0133] In addition, in each embodiment of the present invention, the functional modules can be integrated together to form an independent part, or each module can exist alone, or two or more modules can be integrated to form an independent part.
[0134] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.
Claims
1. A detection module, the detection module is applied to a biochemical sensing system, the biochemical sensing system at least comprises a detection probe and a detection chamber, the detection module is used to obtain the parameters of the biochemical sample to be tested when the biochemical sample to be tested is detected by the detection probe in the detection chamber, characterized in that: The detection module includes a sensor submodule and a data reading submodule; the data reading submodule includes a control component and a conversion component; the sensor submodule includes a plurality of sensor components, each of which is arranged in an array and is connected to the control component and the conversion component respectively; The sensor assembly is used to obtain the simulated change amount generated when the detection probe and the biochemical substance to be detected undergo an electrochemical reaction in the detection chamber; The control component is used to turn on or off each of the sensor components, so that the data reading submodule obtains the analog variation transmitted by the sensor components under a preset time sequence; The conversion component is also used to convert the analog variation into a digital signal to generate the biochemical sample parameter to be tested.
2. The detection module according to claim 1, characterized in that: The control component includes a control unit, a row selection unit, and a column reading unit; the control unit is connected to the row selection unit and the column reading unit respectively; when the link formed by the sensor components arranged in rows in the array is the row pixel circuit; when the link formed by the sensor components arranged in columns in the array is the column pixel circuit, the row selection unit is also connected to the control port of each sensor component on the row pixel circuit; the column reading unit is also connected to the reading port of each sensor component on the column pixel circuit; Wherein, the control unit is used to send control signals to the row selection unit and the column reading unit respectively to adjust the working timing of the row selection unit and the column reading unit; The row selection unit is used to turn on or off the sensor components under each row of pixel circuits according to the control signal; The column reading unit is used to turn on or off the sensor components under each column pixel circuit according to the control signal; and read the analog change amount obtained by each sensor component.
3. The detection module according to claim 2, characterized in that: The control component further includes a column writing unit; the sensor component includes a sensing control unit, a detection probe synthesis unit and a working electrode layer; the detection probe synthesis unit is respectively connected to the row selection unit and the column writing unit; the sensing control unit is respectively connected to the row selection unit and the column reading unit; The column writing unit is used to write the working voltage to the detection probe synthesis unit; and send a first control instruction to adjust the working state of the detection probe synthesis unit; The row selection unit is further used to send a second control instruction to the detection probe synthesis unit to adjust the conduction state of the detection probe synthesis unit; The detection probe synthesis unit is used to electrically induce modification / electrodeposition of the detection probe on the working electrode layer based on the working voltage when in a conducting state; The row selection unit is further used to send a third control instruction to the sensor control unit to adjust the conduction state of the sensor control unit; The sensing control unit is used to obtain the analog variation generated when the detection probe detects the biochemical sample to be detected when it is in the on state, and send the analog variation to the column reading unit.
4. The detection module according to claim 3, characterized in that: The sensing control unit includes a first thin film transistor, a second thin film transistor and a first filter capacitor; The control end of the first thin film transistor is connected to the first end of the first filter capacitor and to the working electrode layer; the second end of the first filter capacitor is connected to the second end of the first thin film transistor; the third end of the first thin film transistor is connected to the first end of the second thin film transistor; the second end of the second thin film transistor serves as the detection output end of the sensing control unit and is connected to the column reading unit; the control end of the second thin film transistor is connected to the row selection unit.
5. The detection module according to claim 3, characterized in that: The detection probe synthesis unit includes a third thin film transistor, a fourth thin film transistor, a fifth thin film transistor and a first storage capacitor; The control end of the third thin film transistor is connected to the row selection unit, the first end is connected to the column reading unit, and the second end is respectively connected to the control end of the fourth thin film transistor and the first end of the first storage capacitor; the first end of the fourth thin film transistor is connected to the column reading unit; the second end of the first storage capacitor is connected to the working electrode layer on the sensor component; the second end of the fourth thin film transistor is connected to the first end of the fifth thin film transistor; the control end of the fifth thin film transistor is connected to the row selection unit; the second end of the fifth thin film transistor is connected to the common ground terminal.
6. The detection module according to claim 1, characterized in that: The detection module further includes a reference electrode; the reference electrode is connected to a power supply and is used to receive a preset voltage to provide a reference voltage for the sensor component; The sensor assembly is also used to obtain the analog quantity generated when the detection probe and the biochemical substance to be detected undergo an electrochemical reaction in the detection chamber; The sensor component is also used to determine the analog change amount based on the reference voltage and the analog amount.
7. The detection module according to any one of claims 1 to 6, characterized in that: The detection module also includes an amplifier component; the sensor component is connected to the conversion component through the amplifier component; when the analog change value obtained by the sensor component is a voltage change value, The amplifier component is used to amplify the voltage change value or synchronously convert it into a current signal; The conversion component is also used to convert the current signal into the digital signal.
8. The detection module according to claim 7, characterized in that: The amplifier assembly includes a plurality of amplifiers; each amplifier corresponds to each link formed by the sensor assemblies arranged in columns, and the input end of each amplifier is connected to the output end of the corresponding link; For any amplifier, the amplifier is used to amplify the voltage change value on the corresponding link and convert the amplified or synchronized voltage change value into a current signal.
9. The detection module according to claim 7, characterized in that: The amplifier assembly includes a plurality of amplifiers; each amplifier is correspondingly connected to each sensor assembly; For any amplifier, the amplifier is used to amplify the voltage change value on the corresponding sensor component and convert the amplified voltage change value into a current signal.
10. A biochemical sensing system, characterized in that: The biochemical sensing system comprises a detection probe, a detection chamber and a detection module as described in any one of claims 1 to 9.