Consumable biochemical substance analysis apparatus and biochemical substance analysis method, disposable base recognition device, and sequencing method

Abstract

A consumable biochemical analysis device includes a housing, a biochip, and a liquid dispensing device. The housing encloses a sealed reaction chamber. The biochip includes a biosensor layer and a sensor layer, with the biosensor layer fixing the sample to be tested. The liquid dispensing device is located above the biochip and contains a reagent stored in its inkjet chip. The inkjet chip is used to load the reagent onto the biochip. A heating cap heats the reaction chamber, causing the sample to react with the reagent and generate a light signal. The sensor layer collects the light signal, converts it into a digital signal, and outputs it to a client. This application also provides a biochemical analysis method, a disposable base recognition device, and a sequencing method. By making the biochip and liquid dispensing device consumables and combining them with client-side APP process control and data processing, this application enables the entire biochemical analysis process to be consumable, lowering the sequencing threshold and reducing fixed investment.

Description

Consumable biochemical substance analysis equipment and biochemical substance analysis method, disposable base recognition device and sequencing method Technical Field

[0001] The present application relates to the technical field of biochemical substance analysis, and in particular to consumable biochemical substance analysis equipment and biochemical substance analysis methods, disposable base recognition devices and sequencing methods. Background Art

[0002] Existing sequencing methods typically rely on a combination of sequencing instruments and consumables (e.g., reagents, bioslides, etc.). This results in high fixed investment costs for sequencing instruments, often in the millions of RMB, significantly increasing the user burden. Furthermore, in current mainstream sequencing technologies, sequencing instruments primarily utilize fluorescence microscopy systems to capture base signals, and sequencing slides utilize encapsulated flow cells, where reagents are exchanged and reactions proceed. This approach, in addition to the high cost of sequencing instruments, also suffers from the complex and inconvenient process of loading liquid into the flow cell.

[0003] Summary of the Invention

[0004] In order to solve at least one of the above-mentioned drawbacks, it is necessary to provide a consumable biochemical substance analysis device and a biochemical substance analysis method.

[0005] In addition, the present application also proposes a disposable base recognition device and sequencing method.

[0006] In a first aspect, an embodiment of the present application provides a consumable biochemical substance analysis device, comprising: a housing, a biochip, a liquid adding device, and a controller, the housing comprising a carrier and a heating cover, the carrier and the heating cover forming a sealed reaction chamber; the biochip is located on the carrier, the biochip comprising a biosensing layer and a sensor layer located below the biosensing layer, the biosensing layer comprising array sites for fixing samples to be detected, and the biochip is an open carrier; the liquid adding device is located on top of the heating cover and above the biochip, the liquid adding device comprises an inkjet chip, and the inkjet chip encapsulates reagents required for biochemical reactions; the controller is respectively connected to the biochip, the inkjet chip, and the heating cover, the inkjet chip is configured to load the reagents into the biochip under the control of the controller, the heating cover is configured to heat the reaction chamber under the control of the controller, so that the sample to be detected on the biosensing layer reacts with the reagents and generates an optical signal, the sensor layer is configured to collect the optical signal under the control of the controller, and the controller includes a communication signal processing unit to communicate and output the digital signal to a client.

[0007] In some possible embodiments, the liquid adding device further includes a driving mechanism provided on the shell, and a rotating disk provided on the driving mechanism, a plurality of the inkjet chips are provided on the rotating disk, and the controller pre-stores reagent loading sequence instructions for controlling the plurality of the inkjet chips.

[0008] In some possible embodiments, the inkjet chip includes: a liquid storage structure and a print head arranged below the liquid storage structure, the liquid storage structure includes a liquid storage cavity, the liquid storage cavity encapsulates the reagent, the print head is connected to the liquid storage cavity, and a nozzle is provided on the print head, and the print head is used to load the reagent onto the biochip through the nozzle.

[0009] In some possible embodiments, the print head includes a liquid adding chamber and a driving structure, the liquid adding chamber is connected to the liquid storage chamber, a driving port is formed on the side of the liquid adding chamber close to the liquid storage structure, the driving structure covers the driving port, the nozzle is provided on the side of the print head away from the liquid storage structure and is connected to the liquid adding chamber, the driving structure is connected to the controller to drive the reagent in the liquid adding chamber to be ejected through the nozzle according to the reagent loading sequence instruction so as to be loaded onto the biochip.

[0010] In some possible embodiments, the driving structure includes a deformable layer covering the driving port, and a driving circuit located on the deformable layer, wherein the deformable layer is configured to deform under the control of the driving circuit to squeeze the reagent located in the liquid adding chamber so that the reagent is ejected through the spray hole;

[0011] Alternatively, the driving structure includes a heating layer covering the driving port and a driving circuit located on the heating layer, wherein the heating layer is used to heat the reagent located in the liquid adding chamber under the control of the driving circuit to generate bubbles, and the bubbles are used to squeeze the reagent so that the reagent is ejected through the nozzle.

[0012] In some possible embodiments, there is one liquid adding chamber, which has one driving port and multiple nozzles arranged in an array, and the driving circuit adopts a switch type control method to control all the nozzles to start printing or stop printing at the same time.

[0013] In some possible embodiments, the consumable biochemical substance analysis equipment further includes a liquid removal device, which is used to remove residual reagents in the biochip after the biochemical reaction is completed by blowing or siphoning.

[0014] In some possible embodiments, the liquid removal device includes a positive pressure source and an airflow guiding structure, wherein the airflow guiding structure is located on one side of the biochip and has a gap formed on a side of the airflow guiding structure close to the biochip. The positive pressure source is used to generate gas under the action of an external force, and the gas is guided to the surface of the biochip through the gap to remove the residual reagent.

[0015] Alternatively, the liquid removal device includes absorbent paper, and the absorbent paper is used to absorb the residual reagent.

[0016] In some possible embodiments, the sensor layer includes: a semiconductor layer, a light sensing component, at least one dielectric layer, and a metal wiring layer, wherein the semiconductor layer has a light sensing region and a non-sensing region; the light sensing component is located in the light sensing region; at least one dielectric layer is stacked on a surface of the semiconductor layer; a metal wiring layer is located within the dielectric layer, and along the stacking direction, a vertical projection of the metal wiring layer is located in the non-sensing region, and the metal wiring layer is electrically connected to the light sensing component;

[0017] The biosensing layer includes a passivation layer, which is located on a surface of the dielectric layer facing away from the semiconductor layer, or on a surface of the semiconductor layer facing away from the dielectric layer. The passivation layer has an opening corresponding to the light sensing area, and the array site is located in the opening.

[0018] In some possible embodiments, along the stacking direction, the thickness of the passivation layer is greater than the thickness of the array site, so that a reaction groove is formed between the sidewall of the opening corresponding to the passivation layer and the surface of the array site.

[0019] In some possible embodiments, the controller is integrated on a control circuit board, the control circuit board is located on the carrier, and the biochip is arranged on the control circuit board; the consumable biochemical material analysis equipment also includes a power module, and the power module is electrically connected to the control circuit board.

[0020] In some possible embodiments, a circuit is provided on the housing, and the circuit electrically connects the control circuit board and the liquid adding device.

[0021] In some possible embodiments, a heating circuit is provided in the heating cover, and the heating circuit is electrically connected to the control circuit board.

[0022] In some possible embodiments, a water storage cavity is provided on the heating cover, and an ultrasonic element is provided at a portion of the water storage cavity close to the reaction chamber. The ultrasonic element is electrically connected to the control circuit board, and is used to atomize the water in the water storage cavity and conduct the atomized water vapor to the reaction chamber.

[0023] In a second aspect, the present invention further provides a method for analyzing biochemical substances, the method comprising:

[0024] Loading the biochip: The biochip is loaded into the reaction chamber of the housing and positioned below the liquid adding device. The biochip includes a biosensing layer and a sensor layer positioned below the biosensing layer. Samples to be tested are fixed to array sites of the biosensing layer. The biochip is an open slide. The liquid adding device includes an inkjet chip, which stores reagents required for biochemical reactions.

[0025] Reagent loading: loading the reagent onto the biochip through the inkjet chip;

[0026] Biochemical reaction: controlling the heating cover of the housing to heat the reaction chamber so that the sample to be detected on the biosensor layer reacts with the reagent and generates a light signal; and

[0027] Signal acquisition and processing: The optical signal is collected through the sensor layer, converted into a digital signal, and output to the client for analysis.

[0028] In some possible embodiments, the liquid adding device includes a plurality of inkjet chips, each of which stores one of the reagents.

[0029] The step of loading the reagent comprises:

[0030] rotating one of the inkjet chips onto the biochip according to a reagent loading sequence instruction, and loading a reagent onto the biochip;

[0031] After the biochemical reaction step, the reagent loading step further includes:

[0032] Removing residual reagents from the biochip after the reaction by a liquid removal device; and

[0033] According to the reagent loading sequence instruction, another inkjet chip is rotated to above the biochip, and another reagent is loaded onto the biochip, and another reagent is loaded onto the inkjet chip through another inkjet chip.

[0034] In a third aspect, the embodiments of the present application further provide a disposable base recognition device, comprising: a housing, a sequencing chip, a liquid adding device, and a controller, wherein the housing comprises a carrier and a heating cover, wherein the carrier and the heating cover form a sealed reaction chamber; the sequencing chip is located on the carrier, wherein the sequencing chip comprises a biosensing layer and a sensor layer located below the biosensing layer, wherein the biosensing layer comprises an array site for fixing a sample to be detected, wherein the biochip is an open slide, and wherein the sample to be detected comprises a nucleic acid sequencing library; the liquid adding device is located on top of the heating cover and above the sequencing chip, wherein the liquid adding device comprises an inkjet chip, wherein the liquid adding device comprises a liquid adding device; .... The inkjet chip is encapsulated with reagents required for biochemical reactions; the controller is respectively connected to the sequencing chip, the inkjet chip and the heating cover; the inkjet chip is configured to load the reagents into the biochip under the control of the controller; the heating cover is configured to heat the reaction chamber under the control of the controller so that the sample to be detected on the biosensing layer reacts with the reagents and generates a light signal; the sensor layer is configured to collect the light signal under the control of the controller and convert the light signal into a digital signal; the controller includes a communication signal processing unit to communicate and output the digital signal to the client.

[0035] In some possible embodiments, the disposable base recognition device further includes a power module, and the power module is electrically connected to the sensor layer, the liquid adding device, and the heating cover respectively.

[0036] In a fourth aspect, an embodiment of the present application further provides a sequencing method using a disposable base recognition device, comprising:

[0037] Loading a sequencing chip: The sequencing chip is loaded into the reaction chamber of the housing of the disposable base recognition device and is located below the liquid adding device. The sequencing chip includes a biosensing layer and a sensor layer located below the biosensing layer. Samples to be detected are fixed on array sites of the biosensing layer. The samples to be detected include a nucleic acid sequencing library. The sequencing chip is an open slide. The liquid adding device includes an inkjet chip. The inkjet chip stores reagents required for biochemical reactions.

[0038] Reagent loading: loading the reagents onto the sequencing chip through the inkjet chip;

[0039] Biochemical reaction: controlling the heating cover of the housing to heat the reaction chamber so that the sample to be detected on the biosensor layer reacts with the reagent and generates a light signal; and

[0040] Signal acquisition and processing: The optical signal is collected through the sensor layer, converted into a digital signal, and communicated and output to the client for analysis.

[0041] In some possible embodiments, the liquid adding device includes a plurality of inkjet chips, each of which stores one of the reagents.

[0042] The step of loading the reagent comprises:

[0043] Rotating one of the inkjet chips onto the sequencing chip according to a reagent loading sequence instruction, and loading a reagent onto the sequencing chip;

[0044] After the biochemical reaction step, the reagent loading step further includes:

[0045] Removing residual reagents from the biochip after the reaction by a liquid removal device; and

[0046] According to the reagent loading sequence instruction, another inkjet chip is rotated to above the sequencing chip, and another reagent is loaded onto the sequencing chip.

[0047] The consumable biochemical substance analysis equipment provided by this application has the following beneficial effects:

[0048] (1) By making biochips and liquid adding devices consumables and combining them with process control and data processing of the client APP, the biochemical substance analysis process does not require traditional biochemical substance analysis instruments, which is conducive to reducing costs, lowering the sequencing threshold, and reducing fixed investment, which is conducive to promoting the widespread application of consumable biochemical substance analysis equipment.

[0049] (2) Using inkjet to load reagents onto the biochip helps reduce reagent usage and costs. In addition, one reagent is encapsulated in one inkjet chip, and a single drive mechanism is used to rotate the rotary disk to complete the movement and switching of the inkjet chip during printing. The switch-type control method is used to simplify the inkjet control method, further reducing costs and operational difficulty. It is also conducive to realizing the consumables of the liquid adding device, eliminating the need for a traditional fluid control system.

[0050] (3) Integrating the sensor layer on the biochip, such as CMOS direct photosensor technology and MEMS sensing sequencing technology (sensing of ion intermediates in sequencing reactions and sensing of electrical signals generated by sequencing reactions), is conducive to making the core biochip consumable and using clients such as mobile phones / personal computers to complete operation control and result analysis without the need for traditional optical imaging systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments of the present application. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0052] FIG1 is a schematic structural diagram of a consumable biochemical substance analysis device in one embodiment of the present application.

[0053] FIG2 is a partial enlarged view of the consumable biochemical substance analysis device in FIG1 .

[0054] FIG3 is a schematic structural diagram of a biochip in one embodiment of the present application.

[0055] FIG4 is a schematic structural diagram of a biochip in another embodiment of the present application.

[0056] FIG5 is a schematic structural diagram of a biochip in another embodiment of the present application.

[0057] FIG6 is a schematic structural diagram of the liquid adding device in FIG2 .

[0058] FIG7 is a cross-sectional view of the inkjet chip in FIG6.

[0059] FIG8 is a top view of the inkjet chip in FIG6 .

[0060] FIG9 is a schematic diagram of an inkjet chip in an embodiment of the present application when the liquid adding chamber is filled with reagent and no liquid is added.

[0061] FIG10 is a schematic diagram of an inkjet chip ejecting reagents in one embodiment of the present application.

[0062] FIG11 is a schematic diagram of the structure of an inkjet chip ejecting reagents in another embodiment of the present application.

[0063] FIG12 is a flow chart of a biochemical substance analysis method according to an embodiment of the present application.

[0064] FIG13 is a system framework diagram of a disposable base recognition device in one embodiment of the present application.

[0065] FIG. 14 is a flow chart of a sequencing method using the disposable base recognition device of FIG. 13 .

[0066] Description of main component symbols

[0067] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0068] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0069] It should be noted that when a component is referred to as being "fixed to" or "mounted on" another component, it may be directly on the other component or there may be a central component. When a component is referred to as being "disposed on" another component, it may be directly on the other component or there may be a central component. As used herein, the term "and / or" includes all and any combinations of one or more of the relevant listed items.

[0070] Please refer to Figures 1 to 3. An embodiment of the present application provides a consumable biochemical substance analysis device 100. The consumable biochemical substance analysis device 100 is a disposable device, comprising: a housing 1, a biochip 2, a liquid adding device 3, and a controller 9. The housing 1 comprises a carrier 11 and a heating cover 12, and the carrier 11 and the heating cover 12 form a sealed reaction chamber 13. The biochip 2 is located on the carrier 11. The biochip 2 comprises a biosensing layer 22 and a sensor layer 21 located below the biosensing layer 22. The biosensing layer 22 comprises an array site for fixing a sample to be detected. The biochip 2 is an open carrier. The liquid adding device 3 is located on the top of the heating cover 12 and above the biochip 2. The liquid adding device 3 comprises an inkjet chip 4. The inkjet chip 4 encapsulates reagents required for biochemical reactions. It is understandable that the sample to be detected and the cleaning reagent for cleaning can also be encapsulated in the inkjet chip 4. Among them, the inkjet chip 4 is configured to load the reagent onto the biochip 2 under the control of the controller 9, and specifically, a reagent layer of a preset thickness can be printed on the biochip 2 by inkjet printing. The heating cover 12 is configured to heat the reaction chamber 13 under the control of the controller 9, so that the sample to be detected on the biosensor layer 22 reacts with the reagent and generates a light signal. Specifically, the temperature in the reaction chamber 13 can be adjusted according to the biochemical reaction between the sample to be detected and the reagent layer, thereby heating the biochip 2 so that the sample to be detected in the biochip 2 reacts with the reagent layer. The sensor layer 21 is configured to collect the light signal under the control of the controller 9, and process the collected light signal to convert the light signal into a digital signal. The controller 9 includes a communication signal processing unit that can output the digital signal to the client, which can be, for example, a mobile phone or a personal computer. It can be understood that an APP software is provided with the consumables, and the APP software can be installed on the client to calculate and analyze the output digital signal.

[0071] The housing 1 is a disposable consumable material made of plastic. It can be formed into an integrated structure through injection molding, or the carrier 11 and heating cover 12 can be made separately and then covered together during use. It is understood that in order to clearly show the internal structure of the housing 1, only one side wall of the housing 1 is shown in Figure 1. In fact, the housing 1 also includes three other side walls, which can form a closed reaction chamber 13 inside.

[0072] Please refer to Figures 2 and 3. The consumable biochemical substance analysis equipment 100 also includes a control circuit board 5. The controller 9 is integrated on the control circuit board 5. The control circuit board 5 is arranged on the carrier 11 and is connected to the biochip 2 and the liquid adding device 3 by signal. In addition, the control circuit board 5 can also be connected to the client signal in a wired or wireless manner, and the operation control of the biochemical reaction and the biological information analysis are performed through the client APP. Specifically, the signal connection with the client APP is realized through the controller 9. By integrating the fluid control function of the liquid adding process and the signal acquisition function of the life reaction process into a control circuit board 5, and performing operation control and result analysis through the client APP, the circuit design of the equipment can be simplified, the cost can be reduced, and it is easy to operate, which is conducive to the realization of full consumables of biochemical substance analysis equipment.

[0073] In some embodiments, the biochip 2 is directly mounted on the control circuit board 5, and the sensor layer 21 is signal-connected to the control circuit board 5. For example, the biochip 2 can be directly mounted on the control circuit board 5 and electrically connected to the control circuit board 5 by soldering or other methods. It is understood that electrical connection contacts can also be provided on the control circuit board 5 and the biochip 2. Before use, the biochip 2 is mounted on the control circuit board 5, which facilitates loading of a sample to be tested onto the biochip 2 from outside the housing 1.

[0074] In some embodiments, the control circuit board 5 and the liquid adding device 3 are connected by signals. For example, a circuit can be formed on the housing 1 by printing or electroplating, thereby achieving an electrical connection between the control circuit board 5 and the liquid adding device 3. Specifically, the circuit can be provided on the surface of the housing 1 or embedded in the housing 1. The electrical connection between the control circuit board 5 and the liquid adding device 3 can also be achieved by providing an exposed wire. In some embodiments, a heating circuit is provided in the heating cover 12, and the heating circuit is electrically connected to the control circuit board 5, thereby enabling the heating cover 12 to heat the reaction chamber 13.

[0075] In some embodiments, the control circuit board 5 further includes a power module 51, which is electrically connected to a battery (not shown) disposed on the housing 1 to power the control circuit board 5 and, in turn, the entire device. Specifically, the housing 1 further includes a battery compartment (not shown), within which the battery is removably disposed.

[0076] Referring again to Figures 1 and 2 , the consumable biochemical substance analysis device 100 further includes a water storage chamber 14 disposed on the heating cover 12 . An ultrasonic element 15 is disposed in the portion of the water storage chamber 14 adjacent to the reaction chamber 13 . The ultrasonic element 15 is electrically connected to the control circuit board 5 . The ultrasonic element 15 is configured to atomize water within the water storage chamber 14 and conduct the atomized water vapor to the reaction chamber 13 , thereby suppressing evaporation of the reagent within the reaction chamber 13 and reducing reagent loss.

[0077] In some embodiments, the side wall of the heating cover 12 may be provided with ventilation holes (not shown), and the reaction chamber 13 is connected to the outside through the ventilation holes. The ventilation holes can be provided to guide the atomized water vapor out of the reaction chamber 13 through air flow.

[0078] Referring to FIG. 3 , in conjunction with FIG. 2 , the biochip 2 can be a biosensor or an integrated biosensor formed by integrating multiple biosensors through a semiconductor packaging process. For example, it can be a semiconductor wafer containing one or more front-side illuminated (FSI) image sensors. As shown in FIG. 3 , for example, the biochip 2 includes a biosensor, wherein the sensor layer 21 primarily comprises: a semiconductor layer 211 having a light-sensing region A and a non-sensing region B; a light-sensing component 212 located in the light-sensing region A; at least one dielectric layer 213 stacked on a surface of the semiconductor layer 211; and a metal wiring layer 214 located within the dielectric layer 213. The biosensor layer 22 includes a passivation layer 221 and array sites 222 located on a surface of the dielectric layer 213 facing away from the semiconductor layer 211. The passivation layer 221 has an opening 223 formed corresponding to the light-sensing region A, exposing the surface of the dielectric layer 213 through the opening 223; and the array sites 222 are located within the opening 223. Among them, along the stacking direction b, the vertical projection of the metal wiring layer 214 is located in the non-sensing area B, and the metal wiring layer 214 is electrically connected to the light sensing component 212. The metal wiring layer 214 can also be used for interconnection of integrated circuit materials and external electrical connections. Along the stacking direction b, the vertical projection of the array site 222 is located in the light sensing area A, and chemical or biological samples can be placed on the array site 222 for analysis. Generally, for DNA sequencing, the biological sample contains a DNA sequencing library, wherein the DNA sequencing library is mainly DNA nanoballs, referred to as DNBs, which are adsorbed on the array site 222 for biochemical reactions before gene sequencing. The biochip 2 based on the semiconductor image sensor can be integrated in the packaging stage, supporting single biosensor packaging and multiple biosensor array packaging to form a biochip 2 together, thereby preparing a larger area biochip to achieve ultra-high throughput sequencing. The biochip 2 can be used in non-excitation light imaging sequencing systems, such as direct photosensitivity technology of semiconductor image sensors, as well as other sensing sequencing technologies such as capacitance, voltage, current, and ions, to achieve sensing of intermediate products of biochemical reactions and sensing of electrical signals generated by biochemical reactions.

[0079] In some embodiments, the semiconductor layer 211 may be made of any suitable material, and the material of the semiconductor layer 211 may be silicon.

[0080] In some embodiments, the sensor layer 21 can use a CMOS image sensor or a MEMS sensor to read the sequencing signal. For example, the light sensing component 212 can be a photodiode, or it can be other photosensitive components that can be used. The photodiode can convert the measured light signal into an electric current. The photodiode can include a source and a drain of a MOS transistor (not shown), and the converted current can be transmitted to other components through the MOS transistor. The other components may include a reset transistor, a current source follower, or a row selector for converting the current into a digital signal. Afterwards, the digital signal will be transmitted to the client through the output circuit on the control circuit board 5. For example, it can be transmitted to a client such as a mobile phone or a personal computer via a wired or wireless method (such as a USB interface, Bluetooth or Wifi connection). Finally, the digital signal will be processed by the APP installed on the client for calculation and analysis to obtain the result. For example, when a sequencing reaction is performed, the digital signal can be calculated and analyzed by the corresponding APP to identify the base and obtain the sequencing result.

[0081] In some embodiments, the dielectric layer 213 may be made of a transparent electrically insulating material, such as silicon dioxide.

[0082] In some embodiments, the material of the array sites 222 may be at least one of Ta2O5, TiO2, HfO2, etc. The array sites 222 may be used to suppress dark current in the light sensing components 212 such as photodiodes.

[0083] In some embodiments, the passivation layer 221 can be deposited on the surface of the dielectric layer 213 by conventional semiconductor processing technology (for example, low temperature plasma chemical vapor deposition, PECVD, sputtering, ALD, spin coating, dip coating, etc.), and then the passivation layer 221 can be patterned by an etching process to form an opening 223 corresponding to the light sensing area A. The passivation layer 221 can include any suitable protective material. For example, the passivation layer 221 can include dielectric materials such as silicon nitride and silicon oxide. The passivation layer 221 can be used to construct different reaction areas, has a reflective effect on light, and can improve the light collection efficiency. In some embodiments, as shown in the cross-sectional view of Figure 3, the cross-sectional shape of the opening 223 etched on the passivation layer 221 is roughly rectangular. It can be understood that the cross-sectional shape of the opening 223 can also be roughly V-shaped, circular, elliptical, etc. By controlling the shape and size of the opening 223, the efficiency of light collection can be improved.

[0084] In some embodiments, along the stacking direction b, the thickness of the passivation layer 221 is greater than the thickness of the array site 222, so that a reaction groove can be formed through the sidewall of the corresponding opening 223 of the passivation layer 221 and the array site 222, thereby constructing different reaction areas and confining the biological sample or chemical sample within the opening 223 constructed by the passivation layer 221.

[0085] In other embodiments, as shown in FIG4 , biochip 2a may also be a semiconductor wafer containing one or more backside-illuminated (BSI) image sensors. This differs from the aforementioned biochip 2 in that the passivation layer 221 and array sites 222 in biochip 2a are both located on the surface of the semiconductor layer 211 facing away from the dielectric layer 213. Passivation layer 221 has openings 223 formed corresponding to the light-sensing regions A, exposing the surface of the semiconductor layer 211 through openings 223. The array sites 222 are located within openings 223. Compared to frontside-illuminated (FSI) image sensors, the light-sensing elements 212 of a backside-illuminated (BSI) image sensor are closer to the array sites 222. This shortens the distance that fluorescence from a biological sample reacts to reach the light-sensing elements 212, resulting in less light attenuation and loss.

[0086] In other embodiments, as shown in FIG5 , the biochip 2b may also be a semiconductor wafer comprising one or more backside-illuminated (BSI) image sensors. The difference from the aforementioned biochip 2a is that the dielectric layer 213 in the biochip 2b is multi-layered, each dielectric layer 213 is embedded with a metal wiring layer 214, and the multi-layer dielectric layer 213 is formed on a base layer 215, which can realize a larger array and more functional biochemical reactions.

[0087] Referring to FIG. 6 , and in conjunction with FIG. 2 , the liquid adding device 3 further comprises a drive mechanism 31 disposed on the housing 1 and a rotary disk 32 disposed on the drive mechanism 31. The rotary disk 32 is provided with a plurality of inkjet chips 4, each of which stores a reagent. The reagents are encapsulated within the inkjet chips 4. This method eliminates the rotary valve, syringe pump, piping, and reagent kit components of conventional instruments, eliminating the cost of fluid components, facilitating the reduction of consumables in the liquid adding device 3, and reducing operational difficulty and cost.

[0088] Specifically, the drive mechanism 31 is electrically connected to the controller 9 in the control circuit board 5. The controller 9 is pre-set with a reagent loading sequence instruction. The controller 9 can control the start and stop of the drive mechanism 31 according to the reagent loading sequence instruction, and then rotate the rotary disk 32 to rotate the required inkjet chip 4 to the top of the biochip 2 and start printing. At the same time, the rotation of the rotary disk 32 realizes line scanning liquid addition of the inkjet chip 4. When it is necessary to replace another reagent, the controller 9 can start the drive mechanism 31 according to the reagent loading sequence instruction, drive the rotary disk 32 to rotate, rotate the inkjet chip 4 encapsulated with another reagent to the top of the biochip 2, and add liquid.

[0089] Please refer to Figures 7 and 8, and refer to Figures 2 and 6 together. The inkjet chip 4 mainly includes: a liquid storage structure 6 and a print head 7 arranged below the liquid storage structure 6. The liquid storage structure 6 includes a liquid storage cavity 61, and the liquid storage cavity 61 encapsulates a reagent. The print head 7 is connected to the liquid storage cavity 61, and the print head 7 is provided with a nozzle 71. The print head 7 is used to load the reagent onto the biochip 2 through the nozzle 71.

[0090] The print head 7 may include a liquid adding chamber 72 and a drive structure 73. The liquid adding chamber 72 is in communication with the liquid storage chamber 61. The reagent encapsulated in the liquid storage chamber 61 can enter the liquid adding chamber 72 by gravity. A drive port 74 is formed on the side of the liquid adding chamber 72 near the liquid storage structure 6. The drive structure 73 covers the drive port 74. The nozzle 71 is provided on the side of the print head 7 facing away from the liquid storage structure 6 and is in communication with the liquid adding chamber 72. The drive structure 73 is used to drive the reagent in the liquid adding chamber 72 to be ejected through the nozzle 71 for loading onto the biochip 2.

[0091] In some embodiments, as shown in Figures 9 and 10, the drive structure 73 can use piezoelectric inkjet printing technology to print the reagent in the liquid addition chamber 72 onto the biochip 2. Piezoelectric inkjet printing technology uses piezoelectric ceramics to deform due to the application of voltage, squeezing the liquid to generate high pressure and eject the liquid. Specifically, the drive structure 73 includes a deformation layer 731 covering the drive port 74 and a drive circuit 732 located on the deformation layer 731. The deformation layer 731 is used to deform under the control of the drive circuit 732 to squeeze the reagent in the liquid addition chamber 72, so that the reagent is ejected through the nozzle 71. The inkjet chip 4's liquid addition principle involves applying a voltage to the deformable layer 731 via a drive circuit 732 (e.g., an electrode sheet attached to the deformable layer 731). Because the deformable layer 731 can be made of piezoelectric ceramic, it is affected by the voltage and undergoes instantaneous deformation. This momentary deformation can then be controlled to bulge into the liquid addition chamber 72. This instantaneous deformation squeezes the reagent within the liquid addition chamber 72, and the reagent is ejected from the nozzle 71 at high pressure to form droplets, which are then printed onto corresponding locations on the biochip 2. By using micro-piezoelectric technology to achieve the printing of reagent samples, the volume of the printed reagent droplets can be precisely controlled, thereby reducing reagent loss.

[0092] It is understood that in other embodiments, as shown in FIG11 , the drive structure 73 may also employ thermal bubble inkjet printing technology to achieve liquid spraying. The drive structure 73 may include a heating layer 733 covering the drive port 74 and a drive circuit 734 located on the heating layer 733. The heating layer 733 is configured to heat the reagent within the liquid adding chamber 72 under the control of the drive circuit 734 to generate bubbles. The bubbles are configured to squeeze the reagent so that the reagent is ejected through the nozzle 71 to achieve the purpose of inkjet printing. For example, the drive structure 73 may be a heater.

[0093] Referring again to Figure 7 , the print head 7 can be a multi-layer structure, specifically comprising a substrate 75, a resin layer 76 stacked on the substrate 75, and a nozzle plate 77 stacked on the surface of the substrate 75 facing away from the resin layer 76. The drive port 74 is provided on the resin layer 76, and the drive structure 73 is located on the surface of the resin layer 76. It will be appreciated that the resin layer 76 can be a single layer or multiple layers. The portion of the liquid adding chamber 72 corresponding to the resin layer 76 forms a first through hole 721, the portion of the liquid adding chamber 72 corresponding to the substrate 75 forms a second through hole 722, and the portion of the liquid adding chamber 72 corresponding to the nozzle plate 77 forms the nozzle orifice 71.

[0094] In some embodiments, along the extension direction a of the print head 7, the inner diameters of the first through hole 721, the second through hole 722, and the nozzle hole 71 decrease in sequence, i.e., the nozzle hole 71 has the smallest diameter, which can better limit the outflow rate of the droplets and better control the volume of the droplets printed each time. In addition, the smaller diameter of the nozzle hole 71 can better maintain the reagent within the liquid addition chamber 72 under the influence of external atmospheric pressure when liquid addition is not being performed. In addition, the relatively large inner diameter of the first through hole 721 can accommodate a larger amount of reagent.

[0095] In some embodiments, the material of the substrate 75 can be silicon, and the material of the resin layer 76 can be polyimide. A second through hole 722 with a smaller inner diameter can be formed on the substrate 75, and a first through hole 721 with a larger inner diameter can be formed on the resin layer 76 by chemical etching. Since the resin layer 76 can be formed into holes through an etching process, it is easier to form holes than the silicon substrate 75. Therefore, the inner diameter of the first through hole 721 can be precisely controlled according to actual needs, thereby improving the accuracy of the volume control of the liquid adding chamber 72 and ensuring the accuracy of the reagent amount. In some embodiments, the volume of the liquid adding chamber 72 can be 9pL to 50pL. For example, the volume of the liquid adding chamber 72 can be 9pL, 10pL, 15pL, 20pL, 25pL, 30pL, 35pL, 40pL, 45pL or 50pL, etc.

[0096] 7 and 8 , the print head 7 further includes at least one liquid inlet 78 , which connects the liquid storage chamber 61 with the liquid adding chamber 72 . In some embodiments, the opening of the liquid inlet 78 may be formed on the resin layer 76 of the print head 7 .

[0097] In some embodiments, each inkjet chip 4 is encapsulated with a reagent, which is encapsulated in a liquid storage chamber 61. Accordingly, the print head 7 is provided with a liquid addition chamber 72. During the printing process, the reagent in the liquid storage chamber 61 enters the heating chamber 72 through the liquid inlet 78 by its own gravity. In addition, the liquid addition chamber 72 can have a drive port 74, and a drive structure 73 is provided on the drive port 74 to simplify the circuit design of the printing operation, reduce the difficulty and cost of operation, and further realize the consumable material of the liquid addition device 3.

[0098] As shown in Figures 6 and 8, the print head 7 can be provided with a plurality of nozzles 71, so that the reagents can be evenly spread on the surface of the biochip 2 during the printing process. Specifically, the plurality of nozzles 71 can be arranged in an array, for example, along a straight line. In some embodiments, the drive circuit of the print head 7 can adopt a switch-type control method to control all nozzles 71 to start printing or stop printing at the same time. That is, the complex addressing-single-hole drive mode of the traditional print head is abandoned, and a start-stop switch-type control method is adopted to enable all nozzles 71 on the print head 7 to start printing or stop printing at the same time, which can significantly reduce costs and realize the consumables of fluid control.

[0099] Please refer to FIG. 1 and FIG. 2 again. The consumable biochemical substance analysis device 100 further includes a liquid removal device 8 . The liquid removal device 8 is used to remove residual reagents after the biochemical reaction in the biochip 2 by blowing or siphoning.

[0100] In some embodiments, the liquid removal device 8 includes a positive pressure source 81 and an airflow guiding structure 82. The airflow guiding structure 82 is located on one side of the biochip 2. A slit 83 is provided on the side of the airflow guiding structure 82 close to the biochip 2. Specifically, the slit 83 can be a blowing slit. The positive pressure source 81 is located on one side of the airflow guiding structure 82 and is used to generate gas under the action of an external force. The gas is guided to the surface of the biochip 2 through the slit 83 to remove residual reagents on the chip surface. In some embodiments, the positive pressure source 81 can be a syringe, wherein the syringe can be placed on a bracket located on one side of the airflow guiding structure 82 when in use to form a stable positive pressure airflow.

[0101] It is understandable that in other embodiments, the liquid removal device 8 may be absorbent paper, and the absorbent paper siphon method may be used to remove the residual reagent on the surface of the biochip 2 .

[0102] Referring to FIG. 12 , and in conjunction with FIG. 1 to FIG. 3 , and FIG. 6 and FIG. 7 , a method for performing biochemical substance analysis using the consumable biochemical substance analysis device 100 includes the following steps:

[0103] Step S1, loading the biochip 2: The biochip 2 is loaded into the reaction chamber 13 of the housing 1 and positioned below the liquid adding device 3. The biochip 2 includes a biosensing layer 22 and a sensor layer 21 positioned below the biosensing layer 22. Samples to be tested are fixed to the array sites of the biosensing layer 22. The biochip 2 is an open slide. The liquid adding device 3 includes an inkjet chip 4, which stores reagents required for biochemical reactions.

[0104] Step S2 , reagent loading: loading reagents onto the biochip 2 via the inkjet chip 4 .

[0105] Step S3, biochemical reaction: controlling the heating cover 12 of the housing 1 to heat the reaction chamber 13 so that the sample to be detected on the biosensor layer 22 reacts with the reagent and generates a light signal.

[0106] Step S4, signal acquisition and processing: the optical signal is acquired by the sensor layer 21, and the optical signal is converted into a digital signal, and output to the client for analysis.

[0107] Steps S2 and S3 can be repeated multiple times according to the reagent loading sequence instruction to achieve the loading of different reagents and different biochemical reaction processes on the biochip 2 until the biochemical reaction is completed. After each reagent reaction is completed, the analysis method also includes a step of removing residual reagents.

[0108] Specifically, in step S21 , an inkjet chip 4 is rotated to above the biochip 2 according to a reagent loading sequence instruction, and a reagent is loaded onto the biochip 2 .

[0109] Step S3, performing a biochemical reaction.

[0110] In step S22 , the residual reagents on the biochip 2 after the reaction are removed by the liquid removal device 8 .

[0111] In step S23 , another inkjet chip 4 is rotated to the top of the biochip 2 according to the reagent loading sequence instruction, and another reagent is loaded onto the biochip 2 .

[0112] Specifically, the specific process of using the above consumable biochemical substance analysis device 100 to perform gene sequencing includes the following steps:

[0113] The first step is to install batteries in the consumable biochemical substance analysis device 100, install the APP included with the consumables on a client such as a mobile phone / personal computer, and connect the client to the consumable biochemical substance analysis device 100, for example, wirelessly.

[0114] In the second step, the inkjet chip 4 encapsulated with the reagent is mounted on the rotating disk 32 .

[0115] The third step is to load the sample to be tested into the biochip 2, such as DNB containing a DNA sequencing library, and the DNB is adsorbed on the reaction area of ​​the biochip 2. This step can be performed outside the reaction chamber 13, by manually loading the sample to be tested onto the biochip 2, and then mounting the biochip 2 on the control circuit board 5 of the carrier 11. It is understandable that this step can also be completed in the reaction chamber 13, and the biochip 2 is directly set on the control circuit board 5 of the carrier 11, and the sample to be tested can be manually loaded onto the biochip 2. It is also understandable that the sample to be tested can also be encapsulated in advance in an inkjet chip 4 of the liquid adding device 3, and the sample to be tested can be loaded onto the biochip 2 by inkjet printing. In this embodiment, the sample to be tested is loaded onto the biochip 2 located in the reaction chamber 13 by manual dripping.

[0116] The fourth step is to start the heating cover 12 to heat to the target temperature.

[0117] In the fifth step, the atomization on the heating cover 12 is started and air is introduced into the reaction chamber 13. At the same time, the driving mechanism 31 of the liquid adding device 3 is controlled to start, the rotating disk 32 is rotated, and an inkjet chip 4 is rotated to the top of the biochip 2. The inkjet chip 4 is then started by controlling the client to load a reagent onto the biochip 2.

[0118] In the sixth step, the control circuit board 5 starts heating to heat the biochip 2 to the target temperature, so that the sample to be detected in the biochip 2 reacts with the reagent in the first step.

[0119] In the seventh step, the residual reagents on the biochip 2 after the reaction are removed by the liquid removal device 8. For example, the residual reagents can be blown away by manually controlling the syringe to blow air onto the biochip 2.

[0120] Step 8. Repeat steps 5 to 7 until the biochemical reaction is completed.

[0121] In the ninth step, the sensor layer 21 in the biochip 2 collects the optical signal generated by the reaction between the sample to be detected and the reagent, converts the optical signal into a digital signal, and transmits it to the client APP for calculation and analysis to complete the sequencing.

[0122] It is understandable that the biochemical substance analysis process can be performed at night while resting, which can make full use of the computing resources of the client such as mobile phone / personal computer. Users can perform relevant biochemical substance analysis at home, which is convenient and fast.

[0123] Please refer to FIG. 13 . Specifically, the consumable biochemical substance analysis device of the embodiment of the present application may be a disposable base recognition device 100 ′ for gene sequencing, wherein the biochip may be a sequencing chip 2 ′, and the sample to be detected includes a nucleic acid sequencing library.

[0124] Referring to FIG. 13 and FIG. 14 , and in conjunction with FIG. 1 to FIG. 3 , a method for performing gene sequencing using the disposable base recognition device 100 ′ includes:

[0125] Step S1a, loading the sequencing chip 2': The sequencing chip 2' is loaded into the reaction chamber 13 of the housing 1 of the disposable base call recognition device 100' and is located below the liquid adding device 3. The sequencing chip 2' includes a biosensing layer and a sensor layer located below the biosensing layer. Samples to be detected are fixed on the array sites of the biosensing layer. The samples to be detected include a nucleic acid sequencing library. The sequencing chip 2' is an open slide. The liquid adding device 3 includes an inkjet chip 4, which stores reagents required for biochemical reactions.

[0126] Step S2a, reagent loading: loading the reagent onto the sequencing chip 2 ′ via the inkjet chip 4 .

[0127] Step S3a, biochemical reaction: controlling the heating cover 12 of the housing 1 to heat the reaction chamber 13 so that the sample to be detected on the biosensor layer reacts with the reagent and generates a light signal.

[0128] Step S4a, signal acquisition and processing: the optical signal is acquired by the sensor layer, and the optical signal is converted into a digital signal, and then communicated and output to the client 200 for analysis.

[0129] Steps S2a and S3a can be repeated multiple times according to the reagent loading sequence instructions to load different reagents onto the sequencing chip and perform different sequencing processes until sequencing is complete. After each reagent reacts, the analysis method further includes a step of removing residual reagents.

[0130] Specifically, in step S21a, an inkjet chip 4 is rotated to above the sequencing chip 2' according to the reagent loading sequence instruction, and a reagent is loaded onto the sequencing chip 2'.

[0131] Step S3a, performing a biochemical reaction.

[0132] Step S22a: Removing residual reagents from the sequencing chip 2' after the reaction by using a liquid removal device.

[0133] In step S23a, another inkjet chip 4 is rotated to the top of the sequencing chip 2' according to the reagent loading sequence instruction, and another reagent is loaded onto the sequencing chip 2'.

[0134] The consumable biochemical substance analysis device 100 provided in the embodiment of the present application has the following beneficial effects:

[0135] (1) By making the biochip 2 and the liquid adding device 3 consumable and combining them with the process control and data processing of the client APP, the biochemical substance analysis process does not require traditional biochemical substance analysis instruments, so as to achieve full consumables, which is conducive to reducing costs, lowering the sequencing threshold, and reducing fixed investment, which is conducive to promoting the widespread application of consumable biochemical substance analysis equipment 100.

[0136] (2) Using inkjet to load reagents onto the biochip 2 helps reduce reagent usage and costs. Furthermore, each reagent is encapsulated in an inkjet chip 4, and a single drive mechanism 31 is used to rotate the rotary disk 32 to complete the movement and switching of the inkjet chip 4 during printing. The use of a switch-type control method simplifies the inkjet control method, further reducing costs and operational difficulty. This also helps to reduce the consumables of the liquid adding device 3, eliminating the need for a traditional fluid control system.

[0137] (3) Integrating the sensor layer 21 on the biochip 2, such as CMOS direct photosensor technology, MEMS sensing sequencing technology (sensing of ion intermediates of sequencing reactions, sensing of electrical signals generated by sequencing reactions), is conducive to making the core biochip 2 consumable, and using clients such as mobile phones / personal computers to complete operation control and result analysis without the need for traditional optical imaging systems.

[0138] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not intended to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A consumable biochemical substance analysis device, characterized in that include: The housing comprises a carrier and a heating cover, wherein the carrier and the heating cover form a sealed reaction chamber; A biochip, located on the carrier, the biochip comprising a biosensing layer and a sensor layer located below the biosensing layer, the biosensing layer comprising array sites for fixing samples to be detected, and the biochip is an open carrier; A liquid adding device, located on the top of the heating cover and above the biochip, the liquid adding device comprising an inkjet chip, wherein the inkjet chip is encapsulated with reagents required for biochemical reactions; as well as A controller, wherein the controller is respectively connected to the biochip, the inkjet chip and the heating cover, the inkjet chip is configured to load the reagent into the biochip under the control of the controller, the heating cover is configured to heat the reaction chamber under the control of the controller so that the sample to be detected on the biosensing layer reacts with the reagent and generates a light signal, the sensor layer is configured to collect the light signal under the control of the controller and convert the light signal into a digital signal, and the controller includes a communication signal processing unit to communicate and output the digital signal to the client.

2. The consumable biochemical substance analysis device according to claim 1, characterized in that, The liquid adding device also includes a driving mechanism arranged on the shell, and a rotating disk arranged on the driving mechanism, a plurality of the inkjet chips are arranged on the rotating disk, and the controller pre-stores reagent loading sequence instructions for controlling the plurality of the inkjet chips.

3. The consumable biochemical substance analysis device according to claim 2, wherein, The inkjet chip includes: a liquid storage structure and a print head arranged below the liquid storage structure, the liquid storage structure includes a liquid storage cavity, the liquid storage cavity encapsulates the reagent, the print head is connected to the liquid storage cavity, and the print head is provided with a nozzle, and the print head is used to load the reagent onto the biochip through the nozzle.

4. The consumable type biochemical substance analysis device according to claim 3, characterized in that, The print head includes a liquid adding chamber and a driving structure, the liquid adding chamber is connected to the liquid storage chamber, a driving port is formed on the side of the liquid adding chamber close to the liquid storage structure, the driving structure covers the driving port, the nozzle is arranged on the side of the print head away from the liquid storage structure and is connected to the liquid adding chamber, and the driving structure is connected to the controller to drive the reagent in the liquid adding chamber to be sprayed out through the nozzle according to the reagent loading sequence instruction so as to be loaded onto the biochip.

5. The consumable biochemical substance analysis device according to claim 4, wherein The driving structure includes a deformation layer covering the driving port and a driving circuit located on the deformation layer, wherein the deformation layer is used to deform under the control of the driving circuit to squeeze the reagent in the liquid adding cavity so that the reagent is sprayed out through the spray hole; Alternatively, the driving structure includes a heating layer covering the driving port and a driving electrode located on the heating layer. The heating layer is used to heat the reagent in the liquid adding chamber under the control of the driving circuit to generate bubbles, and the bubbles are used to squeeze the reagent so that the reagent is ejected through the spray hole.

6. The consumable type biochemical substance analysis device according to claim 5, wherein, There is one liquid addition chamber which has one driving port and multiple nozzle holes arranged in an array. The driving circuit adopts a switching control mode to control all the nozzle holes to be opened for printing simultaneously or stopped printing simultaneously.

7. The consumable type biochemical substance analysis device according to claim 1, characterized in that, It further includes a liquid removal device which is used to remove the residual reagent after the biochemical reaction in the biochip by means of blowing air or siphoning.

8. The consumable biochemical substance analysis device according to claim 7, characterized in that, The liquid removal device includes a positive pressure source and an air flow guiding structure. The air flow guiding structure is located on one side of the biochip. There is a slit on the side of the air flow guiding structure close to the biochip. The positive pressure source is used to generate gas under an external force. The gas is guided to the surface of the biochip through the slit to remove the residual reagent. Alternatively, the liquid removal device includes blotting paper which is used to absorb the residual reagent.

9. The consumable biochemical substance analysis device according to claim 1, characterized in that, The sensor layer includes: A semiconductor layer having a light sensing region and a non-sensing region; A light sensing component located in the light sensing region; At least one dielectric layer stacked on one surface of the semiconductor layer; and A metal wiring layer located in the dielectric layer. Along the stacking direction, the vertical projection of the metal wiring layer is located in the non-sensing region, and the metal wiring layer is electrically connected to the light sensing component. The bio-sensing layer includes a passivation layer which is located on the surface of the dielectric layer facing away from the semiconductor layer or on the surface of the semiconductor layer facing away from the dielectric layer. The passivation layer is formed with an opening corresponding to the light sensing region, and the array sites are located within the opening.

10. The consumable biochemical substance analysis device according to claim 9, wherein, Along the stacking direction, the thickness of the passivation layer is greater than the thickness of the array sites, so that the side wall of the passivation layer corresponding to the opening and the surface of the array sites form a reaction groove.

11. The consumable biochemical substance analysis device according to claim 1, wherein, The controller is integrated on a control circuit board which is located on the carrier stage, and the biochip is arranged on the control circuit board. The consumable type biochemical substance analysis device further includes a power supply module which is electrically connected to the control circuit board.

12. The consumable type biochemical substance analysis device according to claim 11, wherein, There is a circuit on the housing which is electrically connected to the control circuit board and the liquid addition device.

13. The consumable biochemical substance analysis device according to claim 11, characterized in that, There is a heating circuit in the heating cover which is electrically connected to the control circuit board.

14. The consumable biochemical substance analysis device according to claim 13, characterized in that, There is a water storage cavity on the heating cover. An ultrasonic element is provided at a part of the water storage cavity close to the reaction chamber. The ultrasonic element is electrically connected to the control circuit board and is used to atomize the water in the water storage cavity and conduct the atomized water vapor to the reaction chamber.

15. A method for analyzing biochemical substances, characterized in that, It includes: Loading the biochip: Loading the biochip into the reaction chamber of the housing and below the liquid addition device. The biochip includes a bio-sensing layer and a sensor layer located below the bio-sensing layer. The array sites of the bio-sensing layer are fixed with samples to be detected. The biochip is an open slide. The liquid addition device includes an inkjet chip which stores the reagents required for the biochemical reaction. Reagent loading: Loading the reagents onto the biochip through the inkjet chip. Biochemical reaction: controlling the heating cover of the housing to heat the reaction chamber so that the sample to be detected on the bio-sensing layer reacts with the reagent to generate an optical signal; and Signal acquisition and processing: collecting the optical signal through the sensor layer, converting the optical signal into a digital signal, and outputting it to the client for analysis.

16. The biochemical substance analysis method according to claim 15, characterized in that, The liquid adding device includes a plurality of the inkjet chips, and each inkjet chip stores one kind of the reagent. The step of reagent loading includes: Rotating one inkjet chip above the biochip according to the reagent loading sequence instruction and loading one kind of reagent onto the biochip; After the step of the biochemical reaction, the step of reagent loading further includes: Removing the residual reagent after the reaction on the biochip through a liquid removing device; and Rotating another inkjet chip above the biochip according to the reagent loading sequence instruction and loading another kind of reagent onto the biochip.

17. A disposable base recognition device, characterized in that, Comprising: A housing, including a stage and a heating cover, the stage and the heating cover form a sealed reaction chamber; A sequencing chip, located on the stage, the sequencing chip includes a bio-sensing layer and a sensor layer located below the bio-sensing layer, the bio-sensing layer includes array sites for fixing the sample to be detected, the biochip is an open slide, and the sample to be detected includes a nucleic acid sequencing library; A liquid adding device, located at the top of the heating cover and above the sequencing chip, the liquid adding device includes an inkjet chip, and the inkjet chip is encapsulated with reagents required for the biochemical reaction; And A controller, the controller is respectively connected to the sequencing chip, the inkjet chip and the heating cover, the inkjet chip is configured to load the reagent onto the biochip under the control of the controller, the heating cover is configured to heat the reaction chamber under the control of the controller so that the sample to be detected on the bio-sensing layer reacts with the reagent to generate an optical signal, the sensor layer is configured to collect the optical signal under the control of the controller and convert the optical signal into a digital signal, and the controller includes a communication signal processing unit to communicate and output the digital signal to the client.

18. The disposable base recognition device according to claim 17, wherein, It further includes a power module, and the power module is electrically connected to the sensor layer, the liquid adding device and the heating cover respectively.

19. A sequencing method using a disposable base recognition device, characterized in that, Comprising: Loading the sequencing chip: loading the sequencing chip into the reaction chamber of the housing of the disposable base recognition device and located below the liquid adding device, the sequencing chip includes a bio-sensing layer and a sensor layer located below the bio-sensing layer, the array sites of the bio-sensing layer are fixed with the sample to be detected, the sample to be detected includes a nucleic acid sequencing library, the sequencing chip is an open slide, the liquid adding device includes an inkjet chip, and the inkjet chip stores reagents required for the biochemical reaction; Reagent loading: loading the reagent onto the sequencing chip through the inkjet chip; Biochemical reaction: controlling the heating cover of the housing to heat the reaction chamber so that the sample to be detected on the bio-sensing layer reacts with the reagent to generate an optical signal; and Signal acquisition and processing: The optical signal is acquired through the sensor layer, converted into a digital signal, and communicated and output to the client for analysis.

20. The sequencing method according to claim 19, characterized in that, The liquid addition device includes a plurality of the inkjet chips, and each of the inkjet chips stores one of the reagents. The steps of reagent loading include: Rotating one of the inkjet chips above the sequencing chip according to the reagent loading sequence instruction, and loading one of the reagents onto the sequencing chip. After the steps of the biochemical reaction, the steps of reagent loading further include: Removing the residual reagent that has reacted on the biochip through the liquid removal device; and Rotating another one of the inkjet chips above the sequencing chip according to the reagent loading sequence instruction, and loading another one of the reagents onto the sequencing chip.

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