Nucleic acid synthesis device and system

Abstract

The invention provides a nucleic acid synthesis device and system, and relates to the technical field of nucleic acid synthesis control. The nucleic acid synthesis device comprises an acquisition module, a temperature control module and an electrochemical reaction module, the temperature control module comprises a temperature control unit and a plurality of heating units, the electrochemical reaction module comprises a reaction control unit and a plurality of pixel circuits, and each pixel circuit corresponds to one heating unit; the arrangement rule of the plurality of heating units is consistent with the arrangement rule of the plurality of pixel circuits. Wherein the acquisition module is used for acquiring reaction parameters of a reaction chamber where a pixel circuit is located; the temperature control unit receives the temperature data and adjusts the input current of the heating unit according to the temperature data so as to change the temperature of the reaction cavity where the electrochemical reaction module is located; the reaction control unit is used for receiving the reaction current and adjusting the reaction process of each pixel circuit according to the reaction current. On the basis, a control model capable of accurately and efficiently realizing biological nucleic acid synthesis is constructed.

Description

Technical Field

[0001] This invention relates to the field of nucleic acid synthesis technology, and more specifically, to a nucleic acid synthesis apparatus and system. Background Technology

[0002] The existing nucleic acid chain synthesis process typically includes the following steps: first, deprotection of the solid support, followed by sequential chemical reactions such as nucleotide coupling, blocking of unreacted sites, and oxidative stabilization. Only one nucleotide can be added per cycle, resulting in a significant time consumption when synthesizing longer nucleic acid chains. Furthermore, the incompleteness of the chemical reactions leads to the accumulation of erroneous sequences, especially when the synthesized length exceeds 200 base pairs, where the error rate increases significantly.

[0003] With the rapid development of fields such as synthetic biology and gene therapy, the demand for high-quality, long-fragment nucleic acids is increasing. Existing technologies are struggling to meet the ever-growing requirements for speed, length, and accuracy in nucleic acid synthesis for research and industrial applications. The limitations of traditional methods are particularly evident when synthesizing complex gene circuits or entire genomes.

[0004] Therefore, there is an urgent need for a precise and efficient biological nucleic acid synthesis scheme. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a nucleic acid synthesis device and system, which constructs a processing model including a data acquisition module, a temperature control module, and an electrochemical reaction module. The data acquisition module acquires the reaction parameters in the reaction chamber, so that the temperature control module and the electrochemical reaction module can adjust the operating parameters of the heating unit and the pixel circuit accordingly, thereby improving the nucleic acid synthesis reaction.

[0006] To achieve the above objectives, the technical solutions adopted in the embodiments of the present invention are as follows: In a first aspect, the present invention provides a nucleic acid synthesis apparatus, the nucleic acid synthesis apparatus comprising: The system comprises a data acquisition module, a temperature control module, and an electrochemical reaction module. The temperature control module includes a temperature control unit and multiple heating units. The electrochemical reaction module includes a reaction control unit and multiple pixel circuits, with each pixel circuit corresponding to one heating unit. The arrangement of the multiple heating units follows the same rule as the arrangement of the multiple pixel circuits. The data acquisition module is connected to the reaction control unit and the temperature control unit. The reaction control unit is connected to the control terminal of each pixel circuit. The temperature control unit is connected to the control terminal of each heating unit. The projection of the pixel circuit onto the backplane of the biochip coincides with the projection of the heating unit onto the backplane of the biochip. The acquisition module is used to acquire the reaction parameters of the reaction chamber where the pixel circuit is located. The reaction parameters include at least temperature data and reaction current. The temperature control unit is used to receive and adjust the input current of the heating unit according to the temperature data, so as to change the temperature of the reaction chamber in which the electrochemical reaction module is located. The reaction control unit is also used to receive and adjust the reaction process of each pixel circuit according to the reaction current.

[0007] Optionally, the acquisition module includes a current monitoring unit, which is connected to the input terminal of the reaction control unit and the sampling terminal of each pixel circuit; The current monitoring unit is used to acquire and preprocess the reaction current of each pixel circuit; For any pixel circuit, the reaction control unit is used to acquire and determine whether the current pixel circuit meets the preset reaction rules based on the preprocessed reaction current. If it does not meet the rules, the operating parameters of the current pixel circuit are adjusted. The operating parameters include at least the driving voltage and the reaction time.

[0008] Optionally, the current monitoring unit includes a current acquisition component, a current amplifier, and an analog-to-digital converter; the input terminal of the current acquisition component is connected to the sampling terminal of each pixel circuit; the output terminal of the current acquisition component is connected to the input terminal of the current amplifier, the output terminal of the current amplifier is connected to the input terminal of the analog-to-digital converter, and the output terminal of the analog-to-digital converter is connected to the input terminal of the reaction control unit. The current acquisition component is used to acquire the reaction current of each pixel circuit. For any pixel circuit's reaction current, a current amplifier is used to amplify the current reaction current of the current pixel circuit according to a preset amplification rule; An analog-to-digital converter is used to convert the amplified reactive current into a digital signal to obtain a preprocessed reactive current.

[0009] Optionally, the heating unit includes heating resistors and switching transistors. When multiple pixel circuits are arranged in a matrix, the heating resistors corresponding to the multiple heating units are arranged in a matrix. Each heating resistor is connected to the power supply through at least two switching transistors. The control terminal of each switching transistor is connected to the temperature control unit. For any heating unit, the temperature control unit is also used to receive and adjust the on / off state of the switching transistor according to the temperature data of the reaction chamber where the pixel circuit corresponding to the current heating resistor is located, so as to change the temperature of the reaction chamber where the electrochemical reaction module is located.

[0010] Optionally, the temperature control unit includes a row control component and a column control component; when the link composed of each heating resistor and each switching transistor arranged in rows in the matrix is ​​a row heating link; when the link composed of each heating resistor and each switching transistor arranged in columns in the matrix is ​​a column heating link, the row control component is connected to the control terminal of each switching transistor under the row heating link; the column control component is connected to the control terminal of each switching transistor under the column heating link.

[0011] Optionally, the nucleic acid synthesis device also includes a housing, on which an inlet / liquid channel, an outlet / liquid channel, and a groove are provided; The groove is used to accommodate the electrochemical reaction module and to form reaction chambers with each pixel circuit under the electrochemical reaction module. The reaction chamber includes an inlet / liquid port and an outlet / liquid port. The inlet / liquid port is connected to the inlet / liquid channel, and the outlet / liquid port is connected to the outlet / liquid channel. The reaction chamber is a closed cavity used to characterize the nucleic acid synthesis of each pixel circuit.

[0012] Optionally, the nucleic acid synthesis device also includes a gas / liquid control module; the acquisition module is also connected to the gas / liquid control module; The acquisition module is also used to acquire the air / liquid channel and / or the liquid / gas parameters under the air / liquid channel; The gas / liquid control module is also used to acquire and adjust the gas / liquid pressure and gas / liquid flow rate of the gas / liquid inlet channel and / or gas / liquid outlet channel based on the liquid / gas parameters; The gas / liquid control module is also used to acquire and adjust the dosage and / or type of reactants based on the reaction current.

[0013] Optionally, the gas / liquid control module includes a liquid drive component and a gas drive component; A liquid-driven component is used to adjust the flow rate of reactants when an abnormal flow rate is detected based on liquid / gas parameters. A gas-driven assembly is used to pretreat the reaction chamber before nucleic acid synthesis to adjust the pressure state of the reaction chamber.

[0014] Optionally, the nucleic acid synthesis device also includes a control panel; the control panel is connected to the acquisition module, the temperature control module, and the electrochemical reaction module, respectively; Control panel for real-time display of temperature data and reaction current; The control panel is also used to adjust the initial control parameters of the electrochemical reaction module; the initial control parameters include at least the initial operating parameters.

[0015] In a second aspect, the present invention also provides a nucleic acid synthesis system, including the nucleic acid synthesis apparatus described in any of the first aspects above.

[0016] The nucleic acid synthesis apparatus and system provided in this invention have the following beneficial effects: The nucleic acid synthesis apparatus in this application includes a data acquisition module, a temperature control module, and an electrochemical reaction module. The temperature control module includes a temperature control unit and multiple heating units. The electrochemical reaction module includes a reaction control unit and multiple pixel circuits, each pixel circuit corresponding to a heating unit. The arrangement of the multiple heating units is consistent with the arrangement of the multiple pixel circuits. The data acquisition module is connected to the reaction control unit and the temperature control unit. The reaction control unit is connected to the control terminal of each pixel circuit. The temperature control unit is connected to the control terminal of each heating unit. The projection of the pixel circuit on the PCB board coincides with the projection of the heating unit on the PCB board. The data acquisition module is used to acquire the reaction parameters of the reaction chamber where the pixel circuit is located. The temperature control unit receives and adjusts the input current of the heating unit according to the temperature data to change the temperature of the reaction chamber where the electrochemical reaction module is located. Correspondingly, the reaction control unit receives and adjusts the reaction process of each pixel circuit according to the reaction current. Based on this, this application constructs a model including a data acquisition module, a temperature control module, and an electrochemical reaction module. The data acquisition module acquires the reaction parameters in the reaction chamber, which are then used by the temperature control module and the electrochemical reaction module to adjust the operating parameters of the heating units and pixel circuits accordingly, thereby improving the nucleic acid synthesis reaction.

[0017] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, preferred embodiments are described below in detail with reference to the accompanying drawings. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 One of the structural diagrams of the nucleic acid synthesis apparatus provided in the embodiments of the present invention is shown; Figure 2 The second structural diagram of the nucleic acid synthesis apparatus provided in the embodiment of the present invention is shown; Figure 3 A structural diagram of the acquisition module provided in an embodiment of the present invention is shown; Figure 4 A structural diagram of the current monitoring unit provided in an embodiment of the present invention is shown; Figure 5 A structural diagram of the reaction control unit provided in an embodiment of the present invention is shown; Figure 6 One of the structural diagrams of the heating unit provided in an embodiment of the present invention is shown; Figure 7A second structural diagram of the heating unit provided in an embodiment of the present invention is shown; Figure 8 The third structural diagram of the heating unit provided in the embodiment of the present invention is shown; Figure 9 A structural diagram of the temperature control unit provided in an embodiment of the present invention is shown; Figure 10 The third structural diagram of the nucleic acid synthesis apparatus provided in this embodiment of the invention is shown; Figure 11 The fourth structural diagram of the nucleic acid synthesis apparatus provided in this embodiment of the invention is shown; Figure 12 The fifth structural diagram of the nucleic acid synthesis apparatus provided in the embodiments of the present invention is shown; Figure 13 This is the sixth structural diagram of the nucleic acid synthesis apparatus provided in an embodiment of the present invention.

[0020] Icons: 10-Nucleic acid synthesis device; 101-Acquisition module; 102-Temperature control module; 103-Electrochemical reaction module; 104-Outer shell; 105-Gas / liquid control module; 106-Control panel; 201-Reaction control unit; 202-Pixel circuit; 203-Temperature control unit; 204-Heating unit; 205-Current monitoring unit; 301-Current acquisition component; 302-Current amplifier; 303-Analog-to-digital converter; 401-Control subunit; 402-Row selection subunit; 403-Column multiplexing subunit; 404-Row control component; 405-Column control component; 501-Liquid drive component; 502-Gas drive component; 1-Gas / liquid inlet channel; 2-Gas / liquid outlet channel; 3-Groove. Detailed Implementation

[0021] definition As used herein, the following terms are intended to have the meanings set forth below. It should be understood that these definitions are provided to aid in understanding the invention and are not intended to be limiting. Unless the context clearly specifies otherwise, the singular forms “a,” “an,” and “the” include plural referents.

[0022] When a term is not specifically defined, it shall be given its common and customary meaning as understood by one of ordinary skill in the art at the time of this invention. In the event of any conflict between any definition generally accepted in the art and the definition provided herein, the definition provided herein shall prevail.

[0023] Various aspects of this invention are presented in scope form. It should be understood that the scope format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of this invention. Therefore, the scope description should be considered as having specifically disclosed all possible sub-scopes and common individual values ​​within those scopes.

[0024] Unless otherwise stated, the present invention can be practiced using conventional techniques of organic chemistry, polymer technology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology, which are within the scope of this art. Such conventional techniques include polymer array synthesis, hybridization, ligation, and detection of hybridization using labels. Specific descriptions of suitable techniques can be obtained by referring to the examples below. However, other equivalent conventional procedures can certainly be used. Such conventional techniques can be found in standard laboratory manuals.

[0025] The term "nucleic acid" can include any polymer or oligomer of pyrimidine and purine bases, preferably cytosine, thymine, and uracil, and adenine and guanine, respectively. In fact, the invention contemplates any deoxyribonucleotide, ribonucleotide, or peptide nucleic acid component, and any chemical variants thereof, such as methylated, hydroxymethylated, or glycosylated forms of these bases. The polymer or oligomer can be heterogeneous or homogeneous in composition and can be isolated from naturally occurring sources or can be artificially or synthetically produced. Furthermore, nucleic acids can be DNA or RNA, or mixtures thereof, and can exist permanently or intermittently in single-stranded or double-stranded form, including homoduplex, heteroduplex, and hybrid states.

[0026] The term "biochip" can include any solid, semi-solid, or composite substrate used for biomolecular analysis, reaction, or detection. In fact, this invention considers any form of substrate, whether its material is organic (e.g., various polymers, hydrogels) or inorganic (e.g., glass, quartz, silicon, ceramics, or metals), and its morphology can be rigid, flexible, porous, or three-dimensional. Furthermore, the substrate surface can be planar or contain microscopic or nanoscopic topologies formed by any means such as etching, molding, printing, or deposition, such as micropores, micropillars, nanopores, or microfluidic channels. The chip can integrate any functional elements, including but not limited to electrodes, heaters, waveguides, or semiconductor-based (e.g., CMOS or TFT) sensor arrays, to achieve the conversion and readout of signals such as electrochemical, optical, thermal, or mass changes. Finally, the biomolecules immobilized or interacting with the chip surface can be of any kind, including but not limited to nucleic acids, proteins, peptides, antibodies, aptamers, and even cells, tissues, or organelles, whether naturally derived or synthetically produced. In the context of this invention, the term "biochip" should be understood broadly and used interchangeably with a variety of other terms, including but not limited to: "microarray", "microarray chip", "gene chip", "protein chip", "cell chip", "microfluidic chip", "lab-on-a-chip", "biosensor", "biosensor array", and "organ-on-a-chip".

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0028] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0029] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0030] Please refer to Figure 1 , Figure 1 The diagram shows the structure of a nucleic acid synthesis device provided in an embodiment of the present invention. The nucleic acid synthesis device 10 includes a collection module 101, a temperature control module 102, and an electrochemical reaction module 103.

[0031] The temperature control module 102 includes a temperature control unit 203 and multiple heating units 204. The electrochemical reaction module 103 includes a reaction control unit 201 and multiple pixel circuits 202, with each pixel circuit 202 corresponding to one heating unit 204. The arrangement rule of the multiple heating units 204 is consistent with the arrangement rule of the multiple pixel circuits 202.

[0032] In this embodiment, the acquisition module 101 is connected to the reaction control unit 201 and the temperature control unit 203. The reaction control unit 201 is connected to the control terminal of each pixel circuit 202. The temperature control unit 203 is connected to the control terminal of each heating unit 204.

[0033] The acquisition module 101 is used to acquire the reaction parameters of the reaction chamber where the pixel circuit 202 is located. The reaction parameters include at least temperature data and reaction current.

[0034] Temperature control unit 203 is used to receive and adjust the input current of heating unit 204 according to temperature data, so as to change the temperature of the reaction chamber where electrochemical reaction module 103 is located.

[0035] The reaction control unit 201 is also used to receive and adjust the reaction process of each pixel circuit 202 according to the reaction current.

[0036] Please refer to Figure 2 , Figure 2 This diagram shows another structural diagram of the nucleic acid synthesis apparatus provided in an embodiment of the present invention, in which the projection of the pixel circuit 202 on the PCB board coincides with the projection of the heating unit 204 on the PCB board.

[0037] It should be noted that, Figure 2 This is just a schematic diagram. This application does not limit the relative position between the pixel circuit 202 and the heating unit 204. The heating unit 204 can be disposed above or below the pixel circuit 202.

[0038] In this embodiment, when the pixel circuit is in a conductive state within the reaction chamber, it can perform electro-induced modification / electrodeposition of the probe to be detected on its own working electrode based on the driving voltage (i.e., the working voltage for writing the pixel circuit), thus performing nucleic acid synthesis. Correspondingly, the reaction current can be the current generated when each pixel circuit and the biochemical substance to be tested undergo an electrochemical reaction within the reaction chamber.

[0039] The acquisition module is used to acquire the reaction current and current temperature data of each pixel circuit during nucleic acid synthesis in its corresponding reaction chamber. Subsequently, the temperature control unit and reaction control unit adjust the heating unit and pixel circuits according to the aforementioned reaction current and current temperature data in the reaction chamber. Based on this, this application embodiment constructs a nucleic acid synthesis control model including an acquisition module, a temperature control module, and an electrochemical reaction module. By monitoring the reaction parameters and temperature data in the reaction chamber in real time, the working state of the corresponding components can be controlled and adjusted in a timely manner to improve the nucleic acid synthesis reaction.

[0040] Please refer to Figure 3 , Figure 3 The diagram shows the structure of the acquisition module provided in the embodiment of the present invention. The acquisition module 101 includes a current monitoring unit 205, which is connected to the input terminal of the reaction control unit 201 and the sampling terminal of each pixel circuit 202.

[0041] The current monitoring unit 205 is used to acquire and preprocess the reaction current of each pixel circuit 202.

[0042] For any pixel circuit, the reaction control unit 201 is used to acquire and determine whether the reaction process of the current pixel circuit meets the preset reaction rules based on the preprocessed reaction current. If it does not meet the rules, the operating parameters of the current pixel circuit are adjusted. The operating parameters include at least the driving voltage and the reaction time.

[0043] In one possible implementation, the reaction control unit can determine whether the pre-processed reaction current is proportional to the reaction process. For example, an evaluation coefficient between the reaction process and the reaction current can be established, and then the evaluation coefficient can be used to feed back whether the reaction process of the current pixel circuit in the corresponding reaction cavity is under preset conditions, that is, the reaction current is proportional to the reaction process. If not, the driving time and reaction time of the current pixel circuit are adjusted so that the adjusted reaction current is proportional to the reaction process.

[0044] In this embodiment, the preprocessing may include amplification and adjustment of the reaction current, as well as analog-to-digital conversion adjustment. Based on this, please refer to... Figure 4 , Figure 4 The diagram shows the structure of a current monitoring unit 205 provided in an embodiment of the present invention. The current monitoring unit 205 includes a current acquisition component 301, a current amplifier 302, and an analog-to-digital converter 303. The input terminal of the current acquisition component 301 is connected to the sampling terminal of each pixel circuit 202. The output terminal of the current acquisition component 301 is connected to the input terminal of the current amplifier 302, the output terminal of the current amplifier 302 is connected to the input terminal of the analog-to-digital converter 303, and the output terminal of the analog-to-digital converter 303 is connected to the input terminal of the reaction control unit 201.

[0045] In this embodiment, the current acquisition component 301 is used to acquire the reaction current of each pixel circuit 202.

[0046] For any pixel circuit 202, the current amplifier 302 is used to amplify the current of the current pixel circuit 202 according to a preset amplification rule.

[0047] The analog-to-digital converter 303 is used to convert the amplified reaction current into a digital signal to obtain the preprocessed reaction current.

[0048] It should be noted that in this embodiment... In addition, please refer to Figure 5 , Figure 5 The diagram illustrates the structure of the reaction control unit provided in this embodiment of the invention. When the pixel circuits 202 are arranged in a matrix, the links formed between the pixel circuits 202 arranged in rows in the array are called row pixel links; when the links formed between the pixel circuits 202 arranged in columns in the array are called column pixel links, the reaction control unit 201 includes a control subunit 401, a row selection subunit 402, and a column multiplexing subunit 403. The control subunit 401 is connected to the row selection subunit 402 and the column multiplexing subunit 403. The row selection subunit 402 is also connected to the control port of each pixel circuit 202 on the row pixel link; the column multiplexing subunit 403 is also connected to the input terminal of the current monitoring unit 205 and the reading port of each pixel circuit 202 on the column pixel link.

[0049] The control subunit 401 is used to send control signals to the row selection subunit 402 and the column multiplexing subunit 403 respectively, and adjust the working timing of the row selection subunit 402 and the column multiplexing subunit 403 so as to turn on and / or turn off the corresponding pixel circuit 202 according to the preset working timing.

[0050] Specifically, the row selection subunit 402 is used to turn on or off the pixel circuits under each row pixel link according to the control signal; the column multiplexing subunit 403 is used to turn on or off the pixel circuits under each column pixel link according to the control signal, and read the reaction current of each pixel circuit.

[0051] The column multiplexing subunit 403 is also used to write the working voltage to each pixel circuit 202, so that when the pixel circuit is in the conducting state, nucleic acid synthesis is performed based on the working voltage.

[0052] In one possible implementation, the reaction control unit in this embodiment can adjust the reaction process of each pixel circuit by adjusting the aforementioned operating voltage.

[0053] Please continue to refer to this. Figure 5 When the pixel circuits form an M*N matrix, that is, when the number of column pixel links is M and the number of row pixel links is N, the sequence corresponding to each column pixel link can be expressed as I. 1、…、I M; similarly, the sequences corresponding to the pixel links in each row can be represented as S respectively. 1、…、S When it is necessary to select the pixel circuit in the 1st row and 3rd column, the row selection subunit 402 selects the row pixel link with a row number of N=1, and the column multiplexing subunit 403 selects the column pixel link with a column number of S=3. Correspondingly, the column multiplexing subunit 403 is also used to write the operating voltage to the pixel circuit and read the reaction current of nucleic acid synthesis based on the operating voltage when the pixel circuit is turned on.

[0054] Based on this, when each heating unit includes a heating resistor, please refer to... Figure 6 , Figure 6 The diagram shows the structure of the heating unit provided in an embodiment of the present invention. Multiple heating resistors are arranged in a matrix, and the number of rows and columns is the same as the number of rows and columns of the pixel circuit.

[0055] Please refer to Figure 7 , Figure 7 This diagram illustrates another structural feature of the heating unit provided in this embodiment of the invention. When the power supply includes a common ground and a common power source, the power supply terminal of each heating resistor is connected to the common power source via a first switch, and the grounding terminal of the heating resistor is connected to the common ground via a second switch. The control terminals of each first switch and each second switch are connected to the temperature control unit 203. This embodiment includes multiple power rails with a voltage value of VCC and multiple ground wires with a voltage value of GND.

[0056] For any heating unit 204, the temperature control unit 203 is further configured to receive and adjust the on / off state of the switching transistor according to the temperature data of the reaction chamber where the pixel circuit corresponding to the current heating resistor is located, so as to adjust the temperature of the reaction chamber where the electro-chemical reaction module is located.

[0057] Based on this, in this embodiment, the temperature data of the reaction chamber where the pixel circuit is located can be monitored in real time, and then when the temperature does not meet the preset conditions, the on / off state of the switching transistor can be controlled to improve the reaction temperature of its reaction chamber by conducting the heating resistor under the corresponding pixel circuit, thereby changing the activity of the reaction enzyme.

[0058] Please refer to Figure 8 , Figure 8 which shows another structural diagram of the heating unit provided by the embodiment of the present invention. In this embodiment, the heating unit 204 may include heating resistance wires. For any heating resistance wire, the heating resistance wire is arranged in a "son" shape to lay or fill the shaded surface of the corresponding pixel circuit at the PCB projection, and then by adjusting the input current of the heating resistance wire, the temperature of the reaction chamber of the corresponding pixel circuit can be uniformly improved.

[0059] With the same idea as the previous embodiment, for improving the control accuracy, please refer to Figure 9 , Figure 9 which shows the structural diagram of the temperature control unit provided by the embodiment of the present invention. The temperature control unit 203 includes a row control component 404 and a column control component 405; when the link composed of each heating resistor and each switching transistor arranged in rows in the matrix is the row heating link; and the link composed of each heating resistor and each switching transistor arranged in columns in the matrix is the column heating link, the row control component 404 is connected to the control ends of each switching transistor (i.e., the above-mentioned first switching transistor) under the row heating link; the column control component 405 is connected to the control ends of each switching transistor (i.e., the above-mentioned second switching transistor) under the column heating link.

[0060] Based on this, in this embodiment, the on-state of the heating resistors arranged in a matrix can be adjusted correspondingly by row and column control.

[0061] Please refer to Figure 10 , Figure 10 which shows another structural diagram of the nucleic acid synthesis device provided by the embodiment of the present invention. The nucleic acid synthesis device 10 further includes a housing 104, and an air / liquid outlet channel, an air / liquid inlet channel and a groove are provided on the housing 104. In this embodiment, the air / liquid inlet channel 1 is arranged at the upper part of the housing 104, and the air / liquid outlet channel 2 can be arranged at the lower part of the housing 104, so as to improve the effective contact area between the reactants and the electro-chemical reaction module, and then improve the nucleic acid synthesis efficiency.

[0062] In this embodiment, the groove 3 corresponds to an electrochemical reaction module 103 and forms an independent cavity. The cavity includes at least an air / liquid inlet and an air / liquid outlet. The air / liquid inlet is connected to the air / liquid inlet channel, and the air / liquid outlet is connected to the air / liquid outlet channel.

[0063] It should be noted that in this embodiment, the electrochemical reaction module 103 includes multiple pixel circuits 202, each of which forms an independent reaction chamber within the cavity. The reaction chamber is a closed cavity used to characterize the nucleic acid synthesis performed by each pixel circuit.

[0064] In one possible implementation, the upper and lower surfaces of the inner wall of the groove in this embodiment are respectively provided with partitions, which can then form independent closed cavities with the multiple pixel circuits 202 arranged according to preset rules in the electrochemical reaction module 103. Each independent closed cavity is provided with a liquid outlet hole communicating with the gas / liquid outlet channel and a liquid inlet hole communicating with the gas / liquid inlet channel, so as to adjust the reactant dosage of each independent reaction cavity and independently monitor the nucleic acid synthesis of each pixel circuit 202.

[0065] Please refer to Figure 11 , Figure 11 This diagram shows another structural diagram of the nucleic acid synthesis apparatus provided in an embodiment of the present invention. The nucleic acid synthesis apparatus 10 further includes a gas / liquid control module 105; the acquisition module 101 is also connected to the gas / liquid control module 105.

[0066] The acquisition module 101 is also used to acquire the air / liquid channel and / or the liquid / gas parameters under the air / liquid channel.

[0067] The gas / liquid control module 105 is also used to acquire and adjust the gas / liquid pressure and gas / liquid flow rate of the gas / liquid inlet channel and / or gas / liquid outlet channel according to the liquid / gas parameters.

[0068] The gas / liquid control module 105 is also used to acquire and adjust the dosage and / or type of reactant based on the reaction current.

[0069] Based on this, this embodiment can monitor the liquid circuit pressure and flow rate in real time through the acquisition module, and automatically calibrate by the gas / liquid control module in case of abnormality.

[0070] Please refer to Figure 12 , Figure 12 This diagram illustrates another structural diagram of the gas / liquid control module provided in an embodiment of the present invention. The gas / liquid control module 105 includes a liquid driving component 501 and a gas driving component 502; the liquid driving component 501 and the gas driving component 502 are connected to the acquisition module 101.

[0071] The liquid drive assembly 501 is used to adjust the flow rate of the reactants in the gas / liquid inlet channel when an abnormal flow rate is determined based on liquid / gas parameters. Gas-driven assembly 502 is used to pretreat the reaction chamber before nucleic acid synthesis to adjust the pressure state of the reaction chamber.

[0072] In one possible implementation, the liquid-driven component may include a liquid pump; the gas-driven component may include a gas pump. Based on this, in this embodiment, in addition to adjusting the flow rate of the reactants and the pressure of the reaction chamber, the liquid-driven component and the gas-driven component may also pump inert gas (such as nitrogen) into each reaction chamber to prevent oxidation side reactions.

[0073] Similarly, in this embodiment, reagents such as nucleotide monomers, activators, and cleaning solutions can be dispensed as needed using a liquid pump, and the cleaning solution in each reaction chamber can be discharged using an air pump after the reaction is completed, thereby discharging the reaction waste liquid and ensuring the cleanliness of the chambers for the next nucleic acid synthesis.

[0074] Please refer to Figure 13 , Figure 13 This diagram shows another structural diagram of the nucleic acid synthesis apparatus provided in an embodiment of the present invention. The nucleic acid synthesis apparatus 10 also includes a control panel 106. The control panel 106 is connected to the acquisition module 101, the temperature control module 102, and the electrochemical reaction module 103, respectively.

[0075] The control panel is used to display temperature data and reaction current in real time.

[0076] The control panel is also used to adjust the initial control parameters of the electrochemical reaction module; the initial control parameters include at least the initial operating parameters.

[0077] This embodiment enables human-computer interaction between the data acquisition module, temperature control module, and electrochemical reaction module via a control panel. For example, the control panel can be used to set the initial operating state of the electrochemical reaction module, providing the initial operating voltage, initial reaction voltage, and initial reaction time. Alternatively, the control panel can display real-time temperature and reaction data acquired by the data acquisition module. Furthermore, an alarm can be issued and a prompt window can be displayed when the reaction current is not proportional to the reaction progress, allowing the user to make timely adjustments.

[0078] When this embodiment also includes a gas / liquid control module, the control panel is also connected to the gas / liquid control module to set the reactant type, dosage, gas pressure, and driving time. Simultaneously, it displays the liquid / gas parameters acquired by the acquisition module, such as gas / liquid pressure and gas / liquid flow rate.

[0079] Based on this, this application constructs a model including a data acquisition module, a temperature control module, and an electrochemical reaction module. The data acquisition module is used to obtain the reaction parameters in the reaction chamber, so that the temperature control module and the electrochemical reaction module can adjust the working parameters of the heating unit and the pixel circuit accordingly, thereby improving the nucleic acid synthesis reaction.

[0080] Following the same approach as the previous embodiment, the present invention also provides a nucleic acid synthesis system, including the nucleic acid synthesis apparatus described in any of the above embodiments.

[0081] In the several embodiments provided in this application, it should be understood that the disclosed apparatus and methods can also be implemented in other ways. The apparatus embodiments described above are merely illustrative; for example, the flowcharts and block diagrams in the accompanying drawings illustrate the architecture, functionality, and operation of possible implementations of apparatus, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in a flowchart or block diagram may represent a module, segment, or portion of code containing one or more executable instructions for implementing a 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 those marked in the drawings. For example, two consecutive blocks may actually be executed substantially in parallel, and they may sometimes be executed in reverse order, depending on the functions involved. It should also be noted that each block in a block diagram and / or flowchart, and combinations of blocks in block diagrams and / or flowcharts, can be implemented using a dedicated hardware-based system that performs the specified function or action, or using a combination of dedicated hardware and computer instructions.

[0082] In addition, the functional modules in the various embodiments of the present invention can be integrated together to form an independent part, or each module can exist independently, or two or more modules can be integrated to form an independent part.

[0083] If the aforementioned functions are implemented as software functional modules and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this invention, or the part that contributes to the prior art, or a portion of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of this invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0084] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A nucleic acid synthesis apparatus, characterized in that, The nucleic acid synthesis apparatus includes: The system comprises a data acquisition module, a temperature control module, and an electrochemical reaction module. The temperature control module includes a temperature control unit and multiple heating units. The electrochemical reaction module includes a reaction control unit and multiple pixel circuits, each pixel circuit corresponding to one heating unit. The arrangement of the multiple heating units is consistent with the arrangement of the multiple pixel circuits. The data acquisition module is connected to the reaction control unit and the temperature control unit. The reaction control unit is connected to the control terminal of each pixel circuit. The temperature control unit is connected to the control terminal of each heating unit. The projection of the pixel circuit onto the backplane of the biochip coincides with the projection of the heating unit onto the backplane of the biochip. The acquisition module is used to acquire the reaction parameters of the reaction cavity where the pixel circuit is located. The reaction parameters include at least temperature data and reaction current. The temperature control unit is used to receive and adjust the input current of the heating unit according to the temperature data, so as to change the temperature of the reaction chamber in which the electrochemical reaction module is located. The reaction control unit is also used to receive and adjust the reaction process of each pixel circuit according to the reaction current.

2. The nucleic acid synthesis apparatus according to claim 1, characterized in that, The acquisition module includes a current monitoring unit, which is connected to the input terminal of the reaction control unit and the sampling terminal of each pixel circuit. The current monitoring unit is used to acquire and preprocess the reaction current of each pixel circuit; For any pixel circuit, the reaction control unit is used to acquire and determine whether the current pixel circuit meets the preset reaction rules based on the preprocessed reaction current. If it does not meet the rules, the operating parameters of the current pixel circuit are adjusted. The operating parameters include at least the driving voltage and the reaction time.

3. The nucleic acid synthesis apparatus according to claim 2, characterized in that, The current monitoring unit includes a current acquisition component, a current amplifier, and an analog-to-digital converter; the input terminal of the current acquisition component is connected to the sampling terminal of each pixel circuit; the output terminal of the current acquisition component is connected to the input terminal of the current amplifier, the output terminal of the current amplifier is connected to the input terminal of the analog-to-digital converter, and the output terminal of the analog-to-digital converter is connected to the input terminal of the reaction control unit. The current acquisition component is used to acquire the reaction current of each pixel circuit; For any pixel circuit's reaction current, the current amplifier is used to amplify the current reaction current of the current pixel circuit according to a preset amplification rule; The analog-to-digital converter is used to convert the amplified reaction current into a digital signal to obtain the preprocessed reaction current.

4. The nucleic acid synthesis apparatus according to claim 1, characterized in that, The heating unit includes heating resistors and switching transistors. When the multiple pixel circuits are arranged in a matrix, the heating resistors corresponding to the multiple heating units are arranged in a matrix. Each heating resistor is connected to the power supply through at least two switching transistors. The control terminal of each switching transistor is connected to the temperature control unit. For any heating unit, the temperature control unit is also used to receive and adjust the on / off state of the switching tube according to the temperature data of the reaction chamber where the pixel circuit corresponding to the current heating resistor is located, so as to change the temperature of the reaction chamber where the electrochemical reaction module is located.

5. The nucleic acid synthesis apparatus according to claim 4, characterized in that, The temperature control unit includes a row control component and a column control component; When the link composed of each heating resistor and each switching transistor arranged in a row in the matrix is ​​called a row heating link; and the link composed of each heating resistor and each switching transistor arranged in a column in the matrix is ​​called a column heating link, the row control component is connected to the control terminal of each switching transistor under the row heating link; and the column control component is connected to the control terminal of each switching transistor under the column heating link.

6. The nucleic acid synthesis apparatus according to claim 1, characterized in that, The nucleic acid synthesis device also includes a housing, on which a gas / liquid outlet channel, a gas / liquid inlet channel, and a groove are provided; The groove is used to accommodate the electrochemical reaction module and to form a reaction chamber with each pixel circuit under the electrochemical reaction module; the reaction chamber includes an inlet / liquid port and an outlet / liquid port; wherein the inlet / liquid port is connected to the inlet / liquid channel, and the outlet / liquid port is connected to the outlet / liquid channel; the reaction chamber is used to characterize the closed cavity for nucleic acid synthesis of each pixel circuit.

7. The nucleic acid synthesis apparatus according to claim 6, characterized in that, The nucleic acid synthesis device further includes a gas / liquid control module; the acquisition module is also connected to the gas / liquid control module. The acquisition module is also used to acquire the air / liquid channel and / or the liquid / gas parameters under the air / liquid channel; The gas / liquid control module is also used to acquire and adjust the gas / liquid pressure and gas / liquid flow rate of the gas / liquid inlet channel and / or the gas / liquid outlet channel according to the gas / liquid parameters. The gas / liquid control module is also used to acquire and adjust the dosage and / or type of reactant based on the reaction current.

8. The nucleic acid synthesis apparatus according to claim 7, characterized in that, The gas / liquid control module includes a liquid drive component and a gas drive component; The liquid-driven component is used to adjust the flow rate of the reactants when an abnormal flow rate is determined based on the liquid / gas parameters. The gas-driven assembly is used to pre-treat the reaction chamber before nucleic acid synthesis to adjust the pressure state of the reaction chamber.

9. The nucleic acid synthesis apparatus according to claim 1, characterized in that, The nucleic acid synthesis device also includes a control panel; the control panel is connected to the acquisition module, the temperature control module, and the electrochemical reaction module respectively; The control panel is used to display the temperature data and the reaction current in real time; The control panel is also used to adjust the initial control parameters of the electrochemical reaction module; the initial control parameters include at least the initial operating parameters.

10. A nucleic acid synthesis system, characterized in that, Includes the nucleic acid synthesis apparatus according to any one of claims 1-9 above.

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