CN107976402B

CN107976402B - Modular biological analysis system based on liquid drop array chip and application thereof

Info

Publication number: CN107976402B
Application number: CN201710978928.0A
Authority: CN
Inventors: 刘大渔; 舒博文
Original assignee: Guangzhou First Peoples Hospital
Current assignee: Guangzhou First Peoples Hospital
Priority date: 2017-10-19
Filing date: 2017-10-19
Publication date: 2021-06-04
Anticipated expiration: 2037-10-19
Also published as: CN107976402A

Abstract

The invention discloses a modular biological analysis system based on a liquid drop array chip and application thereof. The system comprises at least one group of functional modules and more than one battery and electronic circuit module; the functional module comprises an optical detection module, a chip motion control module, a magnetic field control module and a temperature control module; the optical detection module, the chip motion control module, the magnetic field control module and the temperature control module are respectively connected with the battery and the electronic circuit module, the optical detection module is connected with the chip motion control module, and the magnetic field control module and the temperature control module are located below the chip motion control module. The application of the modular bioanalysis system based on the liquid drop array chip is applied to biological detection. The system has the advantages of convenient operation, flexible application, high information flux, high automation degree and the like, and is very suitable for basic level clinics, bedside diagnosis, on-site detection and development of biological detection in areas with limited medical resources.

Description

Modular biological analysis system based on liquid drop array chip and application thereof

Technical Field

The invention belongs to the technical field of biological analysis and medical inspection, and particularly relates to a modular biological analysis system based on a liquid drop array chip and application thereof.

Background

Biological analysis and medical testing typically involve multiple types of testing, such as biochemical testing, nucleic acid testing, immunological testing, microbiological testing, and the like. At present, most of the detection contents adopt mutually independent analysis systems, and the analysis process involves multi-step operation. Therefore, the traditional biological analysis and medical examination not only has higher requirements on sites and quality of operators, but also has the problems of complex operation, long analysis time and high test cost.

The recently developed microfluidic droplet technology (droplet microfluidics) has the advantages of high analysis flux and low sample consumption, and is a powerful tool for realizing rapid biomedical analysis. Despite the significant advances made in microfluidic droplet analysis technology, there are several aspects to be perfected, such as: (1) balance between functional integration and test throughput: at present, most of fully integrated microfluidic devices can only analyze one sample at a time, and a high-throughput analysis device cannot integrate the whole process of nucleic acid analysis, so that the development of an integrated micro-analysis device with higher throughput can better meet the clinical application requirement; (2) there is a need for a simple and flexible liquid transfer scheme: quantitative and positional transfer of reagents and samples is an important challenge facing microfluidic chips; although a series of chip micropump micro-valve technologies are reported before, the technology is difficult to popularize due to the problems of high processing cost, complex control system and the like; (3) the problem of chip-test tube butt joint is solved: how to introduce the reagent and the sample stored in the test tube into the closed chip is another problem which needs to be solved when the microfluidic chip is moved to actual medical application; batch sample operation is often performed in analysis, and the realization of chip-test tube butt joint is necessary for automatic liquid transfer operation; (4) the chip processing cost is reduced: most of the microfluidic chips need a professional micromachining technology, so that the manufacturing cost is high, and the popularization of the technology is seriously influenced. The solution of the problems is helpful to promote the micro-fluidic drop analysis technology to be practically applied.

Disclosure of Invention

The invention provides a modular bioanalysis system based on a liquid drop array chip, which aims to overcome the defects of the prior art.

It is another object of the present invention to provide applications of the modular bio-analysis system based on a droplet array chip.

The purpose of the invention is realized by the following technical scheme: a modularized biological analysis system based on a liquid drop array chip comprises at least one group of functional modules and at least one battery and electronic circuit module; the functional module comprises an optical detection module, a chip motion control module, a magnetic field control module and a temperature control module; the optical detection module, the chip motion control module, the magnetic field control module and the temperature control module are respectively connected with the battery and the electronic circuit module, the optical detection module is connected with the chip motion control module, and the magnetic field control module and the temperature control module are positioned below the chip motion control module;

the chip motion control module comprises a motor and a chip bracket connected with the motor;

the optical detection module comprises a photoelectric detector, an optical dark cabin and a light/electric excitation control and signal acquisition processing circuit; the optical dark cabin is of a box body structure, the bottom of the optical dark cabin is provided with a chip bracket inlet, and the photoelectric detector is connected with the optical/electric excitation control and signal acquisition processing circuit; the photoelectric detector is positioned above the entrance of the chip bracket;

the magnetic field control module comprises a magnet and a circuit connected with the magnet, and the magnet is vertically arranged above or below the chip bracket;

the temperature control module comprises a plurality of channels of temperature controllers and a plurality of mutually independent heating modules connected with the temperature controllers, and the heating modules are arranged below the chip bracket.

Specifically, the chip motion control module is used for driving the chip to enter/exit the optical dark chamber, making relative motion of the chip relative to the magnetic field control module and the temperature control module, making relative motion of the chip relative to the optical detector, and making relative motion of the liquid drop and the chip. Specifically, the method comprises the following steps: the driving chip performs the actions of entering/exiting an optical dark chamber so as to facilitate the placement/replacement of the chip and the loading of the sample/reagent: the driving chip makes relative motion relative to the magnetic field control module to realize the operations of moving, fusing, splitting and the like of liquid drops: the driving chip makes relative motion with respect to the temperature control module to realize heating, temperature switching or thermal circulation of the chip/liquid drop, thermal triggering fusion of the liquid drop and the like; driving the relative movement of the chip and the optical detector to realize the alignment of the chip detection area and the optical detector or the scanning operation of the optical detector on the chip detection area; the driving chip moves relative to the liquid drops to realize the oscillation and uniform mixing operation of the liquid drops.

The structure of the chip carrier is preferably as follows: the two sides of the chip bracket are respectively provided with a bracket arm, the bracket arm on one side is provided with a semi-open chute for clamping the optical axis of the ferrule, the bracket arm on the other side is provided with a limiting arm, a slide block bolt, a slide block and a through hole parallel to the direction of the optical axis, the limiting arm is just positioned above the screw rod when the chip bracket is installed in place, and the slide block is fixed on the chip bracket through the slide block bolt; one side of the slide block, which is far away from the chip bracket, is provided with a slide block convex tooth which is in contact with the screw rod, and the trend of the slide block convex tooth is parallel to the screw rod thread groove precession direction, so that the screw rod rotates under the action of the motor to drive the slide block and further drive the chip bracket to operate.

The chip motion control module also comprises a motion base for supporting the chip bracket; a screw rod is arranged on one side of the motion base, and the screw rod is coaxial with the motor; optical axes parallel to the screw rod are respectively arranged on two sides of the moving base;

the motion base further comprises a magnetic field control module interface and a temperature control module interface, and the magnetic field control module interface and the temperature control module interface are arranged below the motion space of the chip bracket.

The motor is preferably a stepper motor or a servo motor.

Specifically, the optical detection module is used for detecting optical signals in chip liquid drops. When the modular bioanalysis system based on the droplet array chip is started or adopts fluorescence detection, the modular bioanalysis system based on the droplet array chip also comprises a photoelectric exciter, and the photoelectric exciter is connected with the optical/electric excitation control and signal acquisition processing circuit and is positioned above the inlet of the chip bracket; the photoelectric exciter is a fluorescence excitation module which comprises a fluorescence light source, an excitation optical filter and an emission optical filter, the fluorescence light source, the excitation optical filter, the emission optical filter and the photoelectric detector are sequentially arranged along the advancing direction of light rays, the light path is designed to be a 45-degree oblique light path or a coaxial light path, and the fluorescence light source is an LED bulb or an LED bulb array; the emission filter can be selected from a condensing lens, a dichroic filter and the like. When the modular bioanalytical system based on a droplet array chip is activated or chemiluminescent detection is employed, the photoexcitation device is not activated or is in default.

The photoelectric detector can be selected from a CCD image sensor, a CMOS image sensor, a photomultiplier tube, a photodiode array or other photoelectric conversion devices.

In particular, the magnetic field control module is used for driving the movement of the magnetic particles. The magnet is a permanent magnet or an electromagnet. When the magnet is a permanent magnet, the circuit is a driving circuit; the permanent magnet is movably and vertically arranged above or below the chip bracket, preferably below the chip bracket, so that the permanent magnet can be close to or far away from the chip in the direction vertical to the plane of the chip to control the existence and intensity of a magnetic field applied to the corresponding area of the chip, and further control the transfer, aggregation or dispersion of magnetic particles in the liquid drops of the chip. When the magnet is an electromagnet, the circuit is a control circuit; the electromagnet is fixedly and vertically arranged above or below the chip bracket, preferably below the chip bracket, so that the transfer, aggregation or dispersion of the magnetic particles in the chip liquid drop is controlled by controlling the current direction, magnitude or existence of the electromagnet or the electromagnetic array.

The number of the permanent magnets is more than one; when the number of the permanent magnets is 2 or more, a permanent magnet array is formed.

The number of the electromagnets is more than one; when the number of the electromagnet arrays is more than 2, the electromagnet arrays are formed.

When the magnet is a permanent magnet, the magnetic field control module further comprises a permanent magnet bracket, an optical axis, a base, a lead screw, a motor, a slide bar, a slide block and a convex tooth; the permanent magnet is arranged on the permanent magnet bracket; the screw rod is coaxial with a motor in the circuit, and the motor is fixed on the base through a motor bracket; one end of the sliding rod is fixed on the base, the sliding block penetrates through the sliding rod and is relatively fixed on the sliding rod, and the sliding block is in contact connection with the screw rod; through holes for the optical axis to pass through are formed in the two sides of the permanent magnet bracket, the lower end of the optical axis is fixed on the base, and the permanent magnet bracket is oppositely fixed on the base through the optical axis; the convex teeth are arranged on one side surface of the permanent magnet bracket and connected with the sliding block; under the action of the motor, the screw rod rotates to drive the sliding block to move, and then the permanent magnet bracket is driven to move.

The motor is preferably a stepper motor.

Specifically, the temperature control module is used for controlling the temperature in the chip reaction tank. The heating module comprises a heat conduction block, a temperature sensor, a heater and a heat insulation device, wherein the heating plane of the heat conduction block is attached to the bottom plane of the chip in parallel, the temperature sensor is arranged in the central area of the heating plane of the heat conduction block, and the heater is embedded in the heat conduction block or sandwiched between the heat conduction block and the heat insulation device; when the heater is embedded in the heat conducting block, the bottom surface of the heat conducting block parallel to the heating plane is attached to the heat insulation device; the heat insulation device is a heat insulation base; or comprises a heat dissipation base and a heat dissipation fan, wherein the heat dissipation fan is arranged near the heat dissipation base. When the modularized bioanalysis system based on the liquid drop array chip adopts a constant temperature heating mode, the temperature control module starts or adopts a group of temperature controller channels and a heating module, the bottom surface of a heat conduction block in the heating module is connected with a heat insulation base, and the temperature controller controls the current provided for a heater or the on-off time and frequency of the voltage of the heater according to a signal fed back by the temperature sensor so as to reach or maintain a set temperature; when the system adopts a temperature-changing heating mode (such as polymerase chain reaction), the temperature control module starts or adopts a group of temperature controller channels and a heating module, the bottom surface of a heat-conducting block in the heating module is connected with a heat-radiating base, and the temperature controller controls the direction and the magnitude of current supplied to the heater according to a signal fed back by the temperature sensor so as to reach or maintain a preset temperature; when the system adopts a constant-temperature thermal cycle heating mode (fluid moves across a plurality of constant-temperature areas), the temperature control module starts or adopts a plurality of groups of temperature controller channels and heating modules, the bottom surfaces of the heat conducting blocks in the heating modules are connected with the heat insulation base, and the temperature controller controls the current magnitude or the on-off time and frequency of the voltage of the heater provided for the corresponding heater according to the signals fed back by the temperature sensors in the heating modules so as to reach or maintain the preset temperature.

When the heat insulation device is a heat dissipation base and a heat dissipation fan, the heater is preferably a semiconductor refrigeration sheet.

The modularized biological analysis system based on the liquid drop array chip also comprises intelligent terminal equipment, and the intelligent terminal equipment is connected with the optical detection module.

The connection mode comprises a wired connection mode and a wireless connection mode.

The intelligent terminal equipment comprises a computer and a mobile phone.

The application of the modular bioanalysis system based on the droplet array chip in biological detection comprises the following steps:

(1) after adding a reaction reagent and a sample into the liquid drop array chip, placing the liquid drop array chip on a chip bracket, and enabling the chip bracket to enter an optical dark cabin;

(2) the chip motion control module drives the liquid drop array chip to move to the position above the temperature control module or the magnetic field control module, and the reaction temperature of the temperature control module and the sequential operation mode of the temperature control module and the magnetic field control module are set according to actual requirements;

(3) starting an optical detection module for detection;

(4) and after the reaction is finished, taking the chip out of the bin, and taking down the liquid drop array chip.

The liquid drop array chip comprises a plurality of parallel series-connected micro-pool structures; the micro pools connected in series are communicated through a slit; the micro-pool is wholly or partially provided with an open structure, namely, an opening on the top surface is communicated with the outside.

The liquid drop biological analysis chip also comprises a hydrophobic coating, and the hydrophobic coating is arranged on the surfaces of the micro-pool and the slit.

The hydrophobic coating is preferably a Teflon AF1600 hydrophobic coating.

The material of the liquid drop array chip is preferably glass, plastic, polytetrafluoroethylene, polypropylene or silica gel.

The area of the liquid drop array chip is preferably 10-100 square centimeters.

The technical principle of the invention is as follows: in a micro-cell with a hydrophobic surface, an oil phase and an aqueous phase solution are sequentially loaded, forming water-in-oil droplets due to the surface tension effect. The micro-cells are communicated by slits, and under the action of surface tension, the oil phase can fill the slits, but the water phase cannot. When the liquid drops carried by the micro-pool contain magnetic particles, the external magnetic field can be used for driving the magnetic particles to move; when the magnetic force borne by the magnetic particles is greater than the tension of the oil-water interface, the magnetic particles can break through the oil-water interface and are split from the original liquid drop; the separated magnetic particle liquid drop can enter another liquid drop or enter a liquid drop contained in another micro-pool through a slit under the driving of a magnetic field. Thus, in combination with droplet and magnetic manipulation, detection object capture, magnetic particle washing (and sample elution) and reactions involved in bioanalysis can be accomplished; and finally, detecting a reaction signal in the liquid drop so as to determine the detection object and the content. Thus, the open type liquid drop chip can be used as a basic operation platform, and different analysis functions can be realized in different modules by similar operation flows. By using a wired or wireless communication mode, a plurality of modules can be controlled by one terminal, and different detection requirements can be flexibly met.

Compared with the prior art, the invention has the following advantages and effects:

(1) the modularized biological analysis system provided by the invention can finish different types of detection contents in the same system, and meets the requirements of single-sample multi-index analysis and parallel analysis of batch samples. The system has the advantages of flexible application and high information flux.

(2) The modular bioanalysis system provided by the invention uses an open droplet array chip, which has extremely low processing cost.

(3) The whole process of the reagent/sample on the open type liquid drop array chip exists in a water-in-oil mode, evaporation loss is small, reaction conditions are stable, and the sample analysis volume is flexible and variable and reagent consumption is small.

(4) The chip analysis in the modularized biological analysis system adopts a full integration mode, and has simple and convenient operation and quick analysis.

(5) The modularized biological analysis system has the advantages of small size, portability, low energy consumption and high automation degree, and is very suitable for basic level clinics, bedside diagnosis, field detection and development of biological detection in areas with limited medical resources.

Drawings

FIG. 1 is a schematic diagram of a modular bio-analysis system based on a droplet array chip.

Fig. 2 is a schematic structural diagram of an optical detection module.

3A-3D show the chip motion control module; fig. 3A is a top view of the chip motion module, fig. 3B is a schematic structural diagram of the motion base, fig. 3C is a schematic structural diagram of the chip carrier, and fig. 3D is a schematic structural diagram of the slider.

FIGS. 4A-4B illustrate a magnetic field control module; fig. 4A is a front view of the magnetic field control module, and fig. 4B is a disassembled view of the magnetic field control module.

Fig. 5A is a disassembled view of the temperature control module without the heat dissipation base and the heat dissipation fan, and fig. 5B is a disassembled view of another view angle of the temperature control module.

FIG. 6 is a schematic diagram of the operation of a modular bioanalytical system based on a droplet array chip.

FIG. 7 is a schematic diagram of a droplet array chip suitable for the modular bioanalytical system; wherein, the A-E areas shown by the dotted line frames are respectively a sample micro-pool, a washing micro-pool 1, a washing micro-pool 2, an elution micro-pool and a reaction micro-pool in sequence.

FIG. 8 is a schematic diagram of a modular bio-analysis system.

Fig. 9 is a schematic diagram of the structure of a networked distributed modular bio-analysis system.

1 is an optical detection module, 2 is a chip motion control module, 3 is a magnetic field control module, 4 is a temperature control module, 5 is a battery and electronic circuit module, 6 is a liquid drop array chip, 7 is a smart phone, and 8 is a notebook computer; 1-1 is a photoelectric detection device, 1-2 is a photoelectric detection device installation interface, 1-3 is an emission filter, 1-4 is an excitation light source installation card box, 1-5 is an excitation light source, 1-6 is an excitation filter, and 1-7 is an optical dark cabin; 2-1 is a chip bracket, 2-2 is a motion base, 2-3 is a screw rod, 2-4 is a motor, 2-5 is an optical axis, 2-6 is a magnetic field control module interface, 2-7 is a temperature control module interface, 2-8 is a magnet mounting bin, 2-9 is a motor mounting position, 2-10 is a half-opening chute, 2-11 is a through hole, 2-12 is a limiting arm, 2-13 is a slider bolt, 2-14 is a slider, 2-15 is a slider clamping groove, and 2-16 is a slider convex tooth; 3-1 is a permanent magnet array, 3-2 is a permanent magnet array bracket, 3-3 is an optical axis, 3-4 is a base, 3-5 is a screw rod, 3-6 is a slide rod, 3-7 is a stepping motor, 3-8 is a stepping motor bracket, 3-9 is a slide block, and 3-10 is a convex tooth; 4-1 is a heat conducting block, 4-2 is a temperature sensor, 4-3 is a heater, 4-4 is a heat insulating base, 4-5 is a heat radiating base, and 4-6 is a heat radiating fan.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.

Example 1

As shown in fig. 1, a liquid drop array chip-based modular bioanalysis system comprises an optical detection module 1, a chip motion control module 2, a magnetic field control module 3, a temperature control module 4 and a battery and electronic circuit module 5. The optical detection module 1, the chip motion control module 2, the magnetic field control module 3 and the temperature control module 4 are subsystems capable of independently operating and controlling, and are supported and cooperatively controlled by power provided by the battery and electronic circuit module 5. The optical detection module 1, the magnetic field control module 3 and the temperature control module 4 are respectively connected with the chip motion control module 2.

As shown in fig. 2, the optical detection module 1 includes a photoelectric detection device 1-1, a photoelectric detection device installation interface 1-2, an emission filter 1-3, an excitation light source installation card box 1-4, an excitation light source 1-5, an excitation filter 1-6, an optical dark chamber 1-7, and a light/electric excitation control and signal acquisition processing circuit. The photoelectric detection device 1-1 and the photoelectric converter installation interface 1-2 are positioned at the top of the optical dark bin 1-7 and are used for connecting and fixing the photoelectric detection device 1-1 and the excitation light source 1-5 to be respectively connected with the optical/electric excitation control and signal acquisition processing circuit. The excitation light source installation card box 1-4 is installed on the inner side face of the optical dark bin 1-7, the excitation light source 1-5 is installed in the excitation light source card box 1-4, the excitation light filter 1-6 is located in front of the excitation light source 1-5, the installation faces of the excitation light source 1-5 and the excitation light filter 1-6 and the plane of the emission light filter 1-3 form an included angle of 45 degrees and irradiate downwards, and when detection is carried out, light energy irradiates on the liquid drop array chip 6 placed at the bottom of the optical dark bin 1-7. The photodetector is preferably a CMOS image sensor or a CCD image sensor. The excitation light source is preferably a blue light LED array or a blue light LED surface light source.

As shown in fig. 3A-3D, the chip motion control module 2 mainly includes a motor and a chip carrier driven by the motor and capable of performing one-dimensional motion; the magnetic field control device specifically comprises a chip bracket 2-1, a moving base 2-2, a screw rod 2-3, a motor 2-4, an optical axis 2-5, a magnetic field control module interface 2-6, a temperature control module interface 2-7, a magnet installation bin 2-8, a motor installation position 2-9, a half-open chute 2-10, a through hole 2-11, a limiting arm 2-12, a slider bolt 2-13, a slider 2-14, a slider clamping groove 2-15 and a slider convex tooth 2-16. The screw rod 2-3 is arranged on one side of the moving base 2-2, the motor 2-4 is fixed on the moving base 2-2 through a motor mounting position 2-9, the motor 2-4 is coaxial with the screw rod 2-3, and the optical axis 2-5 is arranged on two sides of the moving base 2-2 and is parallel to the screw rod 2-3 respectively. The chip bracket 2-1 is arranged on the moving base 2-2, the chip bracket 2-1 does one-dimensional movement along the direction parallel to the optical axis 2-5, the center of the chip bracket 2-1 is provided with a clamping groove for placing a liquid drop array chip 6, two sides of the chip bracket 2-1 are respectively provided with a bracket arm, the bracket arm at one side is provided with a semi-open chute 2-10 for clamping the optical axis 2-5 of a card sleeve, the bracket arm at the other side is provided with a through hole 2-11 parallel to the optical axis 2-5 direction, a limiting arm 2-12, a sliding block bolt 2-13 and a sliding block 2-14, the limiting arm 2-12 is just above the screw rod 2-3 in the in-place state, the sliding block 2-14 is fixed on the chip bracket 2-1 through the sliding block bolt 2-13, one side of the sliding block 2-14, which is positioned on the screw, the direction of the convex teeth 2-16 of the sliding block is parallel to the screwing direction of the thread groove 2-3 of the screw rod, one side of the sliding block 2-14, which is far away from the screw rod 2-3, is provided with a round slot, the round plug pin is matched with the round slot 2-13, and the distance between the round plug pin and the round slot 2-13 is controlled by a spring. A magnetic field control module interface 2-6 and a temperature control module interface 2-7 are arranged on the motion base 2-2 and are positioned right below the chip motion space. The motor is a stepping motor or a servo motor. The magnet installation bin 2-8 is arranged at the bottom of the moving base 2-2 and used for accurate installation and operation protection of the magnetic array.

As shown in fig. 4A and 4B, the magnetic field control module 3 is installed below the chip motion control module 2, and includes a permanent magnet array 3-1, a permanent magnet array bracket 3-2, an optical axis 3-3, a base 3-4, a lead screw 3-5, a slide bar 3-6, a stepping motor 3-7, a stepping motor bracket 3-8, a slider 3-9, and a convex tooth 3-10. The permanent magnet arrays 3-1 are arranged in the row holes of the permanent magnet array bracket 3-2 at equal intervals, and through holes are respectively arranged at two sides of the row holes of the permanent magnet array bracket 3-2. The optical axis 3-3 passes through the through hole, and the lower end of the optical axis is fixed in the mounting hole of the base 3-4. A stepping motor support 3-8 and a guide rail for supporting a stepping motor 3-7 are fixed on a base 3-4, the stepping motor 3-7 is coaxial with a screw rod 3-5, a convex tooth 3-10 on a permanent magnet array bracket 3-2 is clamped in a clamping groove of a sliding block 3-9, one end of the sliding rod 3-6 is fixed on the base 3-4, the sliding block 3-9 is provided with a through hole for penetrating through the sliding rod 3-6, and the sliding block 3-9 relatively fixed on the sliding rod 3-6 can move along the screw rod 3-5. The permanent magnet array 3-1 moves up and down to approach or be far away from the liquid drop array chip, the existence and the size of a magnetic field applied to the liquid drop array chip are controlled, and the magnetic driving and the magnetic operation of the liquid drops are realized by matching with the one-dimensional movement of the chip movement module.

The temperature control module 4 comprises a plurality of temperature control channels or temperature controllers and corresponding heating modules connected with the temperature control channels or temperature controllers. As shown in fig. 5A and 5B, the heating module includes a heat conducting block 4-1, a temperature sensor 4-2, a heater 4-3, and a heat insulating device; the heat insulation device is a heat insulation base 4-4 or comprises a heat dissipation base 4-5 and a heat dissipation fan 4-6 arranged near the heat dissipation base 4-5. The heating plane of the heat conducting block 4-1 is attached to the bottom plane of the chip in parallel, the temperature sensor 4-2 is arranged in the central area of the heating plane of the heat conducting block 4-1, and the heater 4-3 is embedded in the heat conducting block 4-1 or sandwiched between the heat conducting block 4-1 and the heat insulation device; when the heater 4-3 is embedded in the heat conducting block 4-1, the bottom surface of the heat conducting block 4-1 parallel to the heating plane is attached to the heat insulation device. As shown in FIG. 5A, the constant temperature type heating module is composed of a heat conducting block 4-1, a temperature sensor 4-2, a heater 4-3 and a heat insulating base 4-4 which are connected in sequence, wherein the preferred temperature sensor 4-2 is an NTC film resistor or a thermocouple, and the preferred heater 4-3 is a polyamide film heater or an alumina ceramic heating plate. As shown in fig. 5B, the temperature-variable heating module comprises a heat-conducting block 4-1, a temperature sensor 4-2, a heater 4-3, a heat-dissipating base 4-5 and a heat-dissipating fan 4-6, wherein the heat-conducting block 4-1, the temperature sensor 4-2, the heater 4-3 and the heat-dissipating base 4-5 are sequentially connected, and the heat-dissipating fan 4-6 is disposed beside the heat-dissipating base 4-5; the heat conducting block 4-1 and the heat dissipation base 4-5 are preferably made of aluminum, the temperature sensor 4-2 is preferably a thermocouple, and the heater 4-3 is preferably a TE semiconductor refrigeration piece.

The working principle of the modular bioanalysis system based on the droplet array chip is shown in fig. 6, wherein the chip motion control module 2 controls the droplet array chip 6 to enter an optical dark chamber 1-7 of the optical detection module 1; when the liquid drops loaded by the micro-pool of the chip contain magnetic particles, the external magnetic field control module 3 can be used for driving the magnetic particles to move; when the magnetic force borne by the magnetic particles is greater than the tension of the oil-water interface, the magnetic particles can break through the oil-water interface and are split from the original liquid drop; the separated magnetic particle liquid drop can enter another liquid drop or enter a liquid drop contained in another micro-pool through a slit under the driving of a magnetic field. Thus, in combination with droplet and magnetic manipulation, detection object capture, magnetic particle washing (and sample elution) and reactions involved in bioanalysis can be accomplished; finally, the optical detection module 1 is used for detecting the reaction signal in the liquid drop so as to determine the detection object and the content.

A droplet array chip suitable for the modular bioanalytical system is shown in fig. 7 and comprises a plurality of sets of micro-wells connected in series; each group of micro-pools connected in series are communicated through a slit; the micro-cells have an open structure in whole or in part. The preferred structure is as follows: the device comprises 15 groups of series-connected micro-pools, wherein each group of series-connected micro-pools comprises 5 micro-pools A-E which respectively correspond to a sample micro-pool, a washing micro-pool 1, a washing micro-pool 2, an elution micro-pool and a reaction micro-pool.

Example 2

A building block type modularized biological analysis system, as shown in figure 8, comprises a plurality of sets of functional modules and battery and electronic circuit modules 5 which operate independently, wherein the functional modules are respectively connected with the battery and electronic circuit modules 5; each functional module comprises an optical detection module 1, a chip motion control module 2, a magnetic field control module 3 and a temperature control module 4 shown in figure 1; the optical detection module 1, the chip motion control module 2, the magnetic field control module 3 and the temperature control module 4 are respectively as described in embodiment 1. The detection signal collected by the optical detection module 1 is transmitted to an intelligent terminal device such as an intelligent mobile phone 7 and a notebook computer 8 in a wireless mode, and the result is displayed and output.

Example 3

A network distributed modular bioanalysis system, as shown in fig. 9, comprises a plurality of sets of modular bioanalysis subsystems as described in embodiment 1, or modular bioanalysis subsystems as described in embodiment 2, or any combination of the two, each subsystem is connected to a host computer through a wired network (such as LAN or ethernet) to perform monitoring of system device status, task allocation and management of detection items, and summary analysis and distribution of detection results.

Example 4

The neisseria gonorrhoeae RNA detection and analysis process based on real-time fluorescent nucleic acid isothermal amplification (SAT) on a droplet array chip was performed using the droplet array chip-based modular bioanalytical system described in example 1 (the temperature control module was a temperature-variable heating module).

(1) Chip preparation: a quantity of mineral oil and reagent were added to each micro-well of a droplet array chip (shown in fig. 7) to form individual water-in-oil droplets, respectively. Wherein, 25 mul of mineral oil and 20 mul of RNA capture magnetic particle suspension are added into a sample pool, 20 mul of mineral oil and 100 mul of washing liquid are added into a washing pool 1, 20 mul of mineral oil and 100 mul of washing liquid are added into a

washing pool

2, 10 mul of mineral oil and 16 mul of SAT amplification reaction liquid are added into an elution pool, and 10 mul of mineral oil and 4 mul of enzyme liquid are added into a reaction pool;

(2) loading: respectively adding 100 mu L of swab eluent or negative control samples or positive control samples into each sample microcell of the droplet array chip;

(3) and (3) loading: taking the chip bracket out of the warehouse (optical dark warehouse), pressing the liquid drop array chip into the clamping groove of the chip bracket 2-1, and taking the chip bracket into the warehouse;

(4) driving the liquid drop array chip to move above the temperature control module, enabling the sample micro-pool on the liquid drop array chip to be close to the heat conducting strip, setting the temperature of the heat conducting strip to be 65 ℃, driving the chip to do small-amplitude high-frequency reciprocating motion, oscillating and uniformly mixing the sample and the RNA to capture magnetic particle suspension, and maintaining the process for 3-5 minutes;

(5) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip, the liquid drop array chip 6 is driven to enable the chip sample micro-pool to slowly pass through the upper part of the permanent magnet array until the center of the washing micro-pool 1 is positioned right above the permanent magnet array, and then the permanent magnet array is descended back to the initial position;

(6) driving the droplet array chip to reciprocate in small amplitude and high frequency, oscillating and uniformly mixing the magnetic particle suspension and the washing solution, and maintaining the process for 1-3 minutes;

(7) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip, the chip is driven to enable the washing micro-pool 1 of the chip to slowly pass through the upper part of the permanent magnet array until the center of the washing micro-pool 2 is positioned right above the permanent magnet array, and then the permanent magnet array descends to the initial position;

(8) repeating the step (6);

(9) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip 6, the chip is driven to enable the washing micro-pool 2 of the chip to slowly pass through the upper part of the permanent magnet array until the center of the elution micro-pool is positioned right above the permanent magnet array, and then the permanent magnet array is descended back to the initial position;

(10) repeating the step (6);

(11) driving the liquid drop array chip to move above the temperature control module 4, enabling the elution micro-pool to be tightly attached to the heat conducting sheet, maintaining the temperature of the heat conducting sheet at 65 ℃, and simultaneously driving the chip to do reciprocating motion with small amplitude and high frequency for 1-3 minutes;

(12) starting the magnetic field control module, lifting the permanent magnet array to be close to the bottom surface of the droplet array chip, driving the chip to enable the elution micro-pool and the reaction micro-pool of the chip to slowly pass through the upper part of the permanent magnet array in sequence until the center of the reaction micro-pool is far away from the permanent magnet array, and then descending the permanent magnet array to the initial position;

(13) the driving chip moves above the temperature control module, so that the reaction micro-pool is tightly attached to the heat conducting fin, the temperature of the heating fin is maintained at 42 ℃, and meanwhile, the driving chip is driven to do reciprocating motion with small amplitude and high frequency at certain time intervals, and the process is maintained for 20-40 minutes;

(14) starting an optical detection module during the execution period of the step (14), exciting fluorescence at a certain frequency, collecting a fluorescence signal of the chip reaction micro-pool, and extracting fluorescence intensity information to draw an amplification curve;

(15) and after the reaction is finished, taking the chip out of the bin, and taking down the liquid drop array chip.

Example 5

The procedure for the E.coli gene detection and analysis based on loop-mediated isothermal amplification (LAMP) on a droplet array chip using the apparatus described in example 1 (constant temperature heating module was used as the heating module in the temperature control module).

(1) Chip preparation: a quantity of mineral oil and reagent were added to each micro-well of a droplet array chip (shown in fig. 7) to form individual water-in-oil droplets, respectively. Wherein, 25 mul of mineral oil, 20 mul of lysis buffer, 50 mul of binding solution and 2 mul of magnetic particle suspension are added into a sample pool, 20 mul of mineral oil and 100 mul of washing solution are added into a washing pool 1, 20 mul of mineral oil and 100 mul of washing solution are added into a washing pool 2, 15 mul of mineral oil and 10 mul of eluent are added into an elution pool, 10 mul of mineral oil and 10 mul of 2 times LAMP reaction premix (containing conventional components, enzyme, primer and SYTO 81 fluorescent dye) are added into a reaction pool;

(2) loading: adding 20 mu L of sample or negative control or positive control to the lysis liquid drop in each sample micro-pool of the liquid drop array chip respectively;

(3) and (3) loading: taking the chip bracket out of the warehouse (optical dark warehouse), pressing the liquid drop array chip into the clamping groove of the chip bracket, and taking the chip bracket into the warehouse;

(4) driving the liquid drop array chip to move above the temperature control module, so that the sample micro-pool on the chip is close to the heat conducting strip, and the temperature of the heat conducting strip is set to be 56 ℃;

(5) the magnetic field control module is started, and the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip. The driving chip enables the magnetic particle suspension liquid drops, the binding liquid drops and the cracking liquid drops in the chip sample micro-pool to slowly pass through the upper part of the permanent magnet array in sequence and then slowly return to the initial position of the step. Repeating the action for 1-3 times, and finally, staying the central part of the sample micro-pool of the chip right above the permanent magnet array, and then descending the permanent magnet array to the initial position;

(6) driving the chip to do reciprocating motion with small amplitude and high frequency to uniformly mix in an oscillating way, and maintaining the process for 3-5 minutes;

(7) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip, the chip is driven to enable the sample micro-pool of the chip to slowly pass through the upper part of the permanent magnet array until the central part of the washing micro-pool 1 stays right above the permanent magnet array, and then the permanent magnet array descends to the initial position;

(8) driving the chip to do reciprocating motion with small amplitude and high frequency to uniformly mix in an oscillating way, and maintaining the process for 1-3 minutes;

(9) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip, the chip is driven to enable the washing micro-pool 1 of the chip to slowly pass through the upper part of the permanent magnet array until the central part of the washing micro-pool 2 stays right above the permanent magnet array, and then the permanent magnet array descends to the initial position;

(10) repeating the step (8);

(11) the driving chip moves above the temperature control module, so that the elution micro-pool is tightly attached to the heat conducting strip, the temperature of the heat conducting strip is maintained at 65 ℃, and meanwhile, the driving chip reciprocates in a small amplitude and high frequency mode for 1-3 minutes;

(13) the driving chip moves above the temperature control module, so that the reaction micro-pool is tightly attached to the heat conducting fin, the temperature of the heating fin is maintained at 65 ℃, and meanwhile, the driving chip is driven to do reciprocating motion with small amplitude and high frequency at certain time intervals, and the process is maintained for 10-40 minutes;

Example 6

Hepatitis B virus DNA detection and analysis flow based on time domain fluorescence quantitative PCR and melting curve analysis is realized on a droplet array chip by using the device described in example 1 (the heating module in the temperature control module is a temperature-variable heating module)

(1) Chip preparation: and adding a certain amount of mineral oil and reagents into each micro-pool of the droplet array chip to respectively form independent water-in-oil droplets. Wherein, 25 mul of mineral oil, 20 mul of lysis buffer, 50 mul of binding solution, 2 mul of magnetic particle suspension and the binding solution are added into a sample pool, 20 mul of mineral oil and 100 mul of washing solution are added into a washing pool 1, 20 mul of mineral oil and 100 mul of washing solution are added into a washing pool 2, 15 mul of mineral oil and 10 mul of eluent are added into an elution pool, 10 mul of mineral oil and 10 mul of 2 XPCR reaction premixed solution (containing conventional components, enzyme, primer and fluorescent dye or fluorescent probe) are added into a reaction pool;

(3) and (3) loading: delivering the chip bracket out of the warehouse, pressing the liquid drop array chip into a clamping groove of the chip bracket, and delivering the chip bracket into the warehouse;

(4) driving the chip to move above the temperature control module, so that the sample micro-pool on the chip is close to the heat conducting strip, and the temperature of the heat conducting strip is set to be 56 ℃;

(10) repeating the step (8);

(13) the driving chip moves above the temperature control module to enable the reaction micro-pool to be tightly attached to the heat conducting sheet, and simultaneously the driving chip reciprocates in a small amplitude and high frequency at a certain time interval, and the heater executes a conventional PCR thermal cycle program in the process;

(14) starting the optical detection module during the execution of the step (13), and exciting fluorescence and collecting a fluorescence signal of the chip reaction micro-pool when the temperature of the heat conducting strip reaches the extension temperature in each cycle to draw an amplification curve;

(15) after the last thermal cycle of PCR is finished, the temperature of the heater is firstly raised to the denaturation temperature and maintained for a plurality of seconds, then the temperature is rapidly reduced to the annealing temperature, and then the temperature is gradually raised to the annealing temperature according to a certain temperature raising rate. During the period, fluorescence is continuously excited and collected to draw a fluorescence melting curve;

(16) and after the reaction is finished, taking the chip out of the bin, and taking down the liquid drop array chip.

Example 7

The hepatitis B virus DNA detection and analysis process based on airspace fluorescence quantitative PCR is realized on a liquid drop array chip by using the device described in the embodiment 1 (the temperature control module is a multi-channel temperature control and multi-group constant-temperature type heating module, and the heat conduction blocks are respectively a heat conduction sheet A, a heat conduction sheet B and a heat conduction sheet C or more)

(4) driving the chip to move above the temperature control module, so that the sample micro-pool on the chip is close to the heat conducting strip A, and the temperature of the heat conducting strip A is set to be 56 ℃;

(10) repeating the step (8);

(13) the driver chip moves above the temperature control module, maintains the thermal conductive sheet A, B, C at an annealing temperature, an extension temperature, and a denaturation temperature, respectively, and activates the optical detection module. Driving the chip to enable the bottom of the chip reaction micro-pool to be sequentially attached to the heat conducting sheet C, the heat conducting sheet A and the heat conducting sheet B and stay on each heat conducting sheet for a certain time, finishing a PCR thermal cycle once repeating the action, and exciting fluorescence and collecting a fluorescence signal of the chip reaction micro-pool when the bottom of the chip reaction micro-pool stays on the heat conducting sheet B to draw an amplification curve;

(14) and after the reaction is finished, taking the chip out of the bin, and taking down the liquid drop array chip.

Example 8

The analysis procedure for quantitative detection of C-reactive protein (CRP) based on chemiluminescence was carried out on a droplet array chip using the apparatus described in example 1 (the heating module in the temperature control module was a constant temperature type heating module, and the optical/electrical exciter was either disabled or not enabled in the optical detection module).

(1) Chip preparation: and adding a certain amount of mineral oil and reagents into each micro-pool of the droplet array chip to respectively form independent water-in-oil droplets. Wherein, 25 mul of mineral oil, 50 mul of diluent, 2 mul of Bead Anti-CRP, 2 mul of biotin Anti-CRP and 2 mul of streptavidin Anti-HRP are added into a sample pool, 20 mul of mineral oil and 100 mul of washing liquid are added into a washing pool 1, 20 mul of mineral oil and 100 mul of washing liquid are added into a

washing pool

2, 10 mul of mineral oil and 15 mul of substrate reaction liquid are added into an elution pool, and 20 mul of mineral oil is added into a reaction pool;

(2) loading: respectively adding 2-5 mu L of sample or negative control or positive control into each sample micro-pool of the droplet array chip;

(4) driving the chip to move above the temperature control module, so that the sample micro-pool on the chip is close to the heat conducting strip, and the temperature of the heat conducting strip is set to be 37 ℃;

(5) the magnetic field control module is started, and the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip. And driving the chip to enable the Bead Anti-CRP liquid drop, the biotin Anti-CRP liquid drop, the streptavidin Anti-HRP liquid drop and the sample liquid drop in the chip sample micro-pool to slowly pass through the permanent magnet array in sequence, and then slowly returning to the initial position of the step. Repeating the action for 1-3 times, and finally, staying the central part of the sample micro-pool of the chip right above the permanent magnet array, and then descending the permanent magnet array to the initial position;

(6) driving the chip to do reciprocating motion with small amplitude and high frequency to uniformly mix in an oscillating way, and maintaining the process for 3-7 minutes;

(7) starting the magnetic field control module, lifting the permanent magnet array to be close to the bottom surface of the droplet array chip, driving the chip to enable the chip sample micro-pool to slowly pass through the upper part of the permanent magnet array until the center of the washing micro-pool 1 is positioned right above the permanent magnet array, and then descending the permanent magnet array to the initial position;

(8) driving the chip to do reciprocating motion with small amplitude and high frequency to uniformly mix in an oscillating way, and maintaining the process for 0.5 to 1 minute;

(9) the magnetic field control module is started, the permanent magnet array is lifted to be close to the bottom surface of the liquid drop array chip, the chip is driven to enable the washing micro-pool 1 of the chip to slowly pass through the upper part of the permanent magnet array until the center of the washing micro-pool 2 is positioned right above the permanent magnet array, and then the permanent magnet array descends to the initial position;

(10) driving the chip to do reciprocating motion with small amplitude and high frequency to uniformly mix in an oscillating way, and maintaining the process for 3-5 minutes;

(11) the driving chip moves above the temperature control module, so that the elution micro-pool is tightly attached to the heat conducting strip, the temperature of the heat conducting strip is maintained at 37 ℃, and meanwhile, the driving chip reciprocates in a small amplitude and high frequency mode for 1-3 minutes;

(12) starting an optical detection module during the execution of the step (11), collecting a chemiluminescence signal of the chip reaction micro-pool, and extracting an intensity value;

(13) and after the reaction is finished, taking the chip out of the bin, and taking down the liquid drop array chip.

Example 9

The flow of analysis for combined detection of nucleic acids, surface antigens and antibodies (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) in serum infected with hepatitis B virus using the modular droplet chip bioanalytical system described in example 2 (FIG. 8).

(1) Chip preparation: a quantity of mineral oil and reagents are added to each micro-well of the chip in block A, B to form independent water-in-oil droplets. Wherein, adding 25 mul of mineral oil, 20 mul of lysis buffer, 50 mul of binding liquid, 2 mul of magnetic particle suspension into a sample pool of the module A chip, adding 20 mul of mineral oil and 100 mul of washing liquid into a washing pool 1, adding 20 mul of mineral oil and 100 mul of washing liquid into a washing pool 2, adding 15 mul of mineral oil and 10 mul of eluent into an elution pool, adding 10 mul of mineral oil and 10 mul of 2 XPCR reaction premix (containing conventional components, enzyme, hepatitis B virus nucleic acid sequence specific primer and fluorescent dye or fluorescent probe) into a reaction pool; adding 25 mu L of mineral oil, 50 mu L of diluent, 2 mu L of antibody-labeled magnetic beads (labeled antibodies are Anti-HBsAg, Anti-HBsAb, Anti-HBeAg, Anti-HBeAb and Anti-HBcAb respectively), 2 mu L of biotinylated Anti-HBs ((or biotin-HBs or biotin-Anti-HBe or biotin-HBc), 2 mu L of streptavidin-HRP into 5 sample pools of a module B chip, adding 20 mu L of mineral oil and 100 mu L of washing solution into a washing pool 1, adding 20 mu L of mineral oil and 100 mu L of washing solution into a washing pool 2, adding 10 mu L of mineral oil and 15 mu L of substrate reaction solution into an elution pool, and adding 20 mu L of mineral oil into a reaction pool;

(2) loading: adding 20 mu L of sample or negative control or positive control to the lysis liquid drops in each sample micro-pool of the chip A respectively; 2-5 μ L of sample or negative control or positive control is added to each sample micro-pool of the B chip.

(3) And (3) loading: and (3) delivering the chip bracket, pressing the chip A into the clamping groove of the chip bracket of the module A, pressing the chip B into the clamping groove of the chip bracket of the module B, and respectively delivering the chip brackets into the warehouse.

(4) Operation: the process as shown in steps (4) - (16) of example 7 was run on module a; the process as shown in steps (4) - (13) of example 8 was run on the B module.

(5) And (3) result transmission and display: the signal that will A, B the module was gathered is handled the conversion back through battery and electronic circuit module 5, transmits to intelligent terminal equipment through wireless mode (like WIFI, bluetooth etc.) and carries out the demonstration output and the interpretation of result.

Example 10

The analysis process of different item indexes 'follow-up' of different time series samples is carried out on the network distributed modular pathogen detection system described in example 3 (fig. 9).

(1) Chip preparation: adding a certain amount of mineral oil and reagents suitable for different detection indexes into each micro-pool of a batch of droplet array chips, and respectively forming independent water-in-oil droplets in the micro-pools; the prepared, preloaded reagent chips were stored in a sterile, closed environment at 4 ℃ prior to use.

(2) And (3) task allocation: and selecting corresponding pre-installed chips according to detection items/indexes required by samples to be inspected at different moments, and simultaneously allocating subsystems or sub-function modules with idle resources by a host task allocation management system according to the principles of 'first-come first-inspection' and 'emergency inspection first-priority', so as to ensure that the required detection items/indexes are executed on the computer in time.

(3) Analyzing and publishing results: matching the ID of the sample to be inspected, the ID of the inspection item/index, the ID of the task execution subsystem and the inspection result thereof to form an inspection report of 'sample-result'.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A modular bioanalysis system based on a droplet array chip, comprising: comprises at least one group of functional modules and more than one battery and electronic circuit module; the functional module comprises an optical detection module, a chip motion control module, a magnetic field control module and a temperature control module; the optical detection module, the chip motion control module, the magnetic field control module and the temperature control module are respectively connected with the battery and the electronic circuit module, the optical detection module is connected with the chip motion control module, and the magnetic field control module and the temperature control module are positioned below the chip motion control module;

the temperature control module comprises a temperature controller with a plurality of channels and a plurality of mutually independent heating modules connected with the temperature controller, and the heating modules are arranged below the chip bracket;

sequentially loading mineral oil and a reaction reagent in a micro-pool with a hydrophobic surface of a droplet array chip, and forming water-in-oil type droplets due to a surface tension effect; adding a sample into a micro-pool with a hydrophobic surface of the liquid drop array chip, and placing the liquid drop array chip on a chip bracket;

the two sides of the chip bracket are respectively provided with a bracket arm, the bracket arm on one side is provided with a semi-open chute for clamping the optical axis of the ferrule, the bracket arm on the other side is provided with a limiting arm, a slide block bolt, a slide block and a through hole parallel to the direction of the optical axis, the limiting arm is just positioned above the screw rod when the chip bracket is installed in place, and the slide block is fixed on the chip bracket through the slide block bolt; one side of the slide block, which is far away from the chip bracket, is provided with a slide block convex tooth which is in contact with the screw rod, and the trend of the slide block convex tooth is parallel to the screw rod thread groove precession direction, so that the screw rod rotates under the action of the motor to drive the slide block and further drive the chip bracket to operate.

2. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

the chip motion control module also comprises a motion base for supporting the chip bracket; a screw rod is arranged on one side of the motion base, and the screw rod is coaxial with the motor; and optical axes parallel to the screw rod are respectively arranged on two sides of the moving base.

3. The modular droplet array chip-based bioanalytical system as claimed in claim 2, wherein:

4. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

the modularized biological analysis system based on the liquid drop array chip also comprises a photoelectric exciter, and the photoelectric exciter is connected with the optical/electric excitation control and signal acquisition processing circuit and is positioned above the inlet of the chip bracket.

5. The modular droplet array chip-based bioanalytical system as claimed in claim 4, wherein:

the photoelectric exciter is a fluorescence excitation module which comprises a fluorescence light source, an excitation optical filter and an emission optical filter, the fluorescence light source, the excitation optical filter, the emission optical filter and the photoelectric detector are sequentially arranged along the advancing direction of light, the light path is designed to be a 45-degree oblique light path or a coaxial light path, and the fluorescence light source is an LED bulb or an LED bulb array.

6. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

the magnet is a permanent magnet or an electromagnet;

when the magnet is a permanent magnet, the circuit is a driving circuit; the permanent magnet is movably and vertically arranged above or below the chip bracket;

when the magnet is an electromagnet, the circuit is a control circuit; the electromagnet is fixedly and vertically arranged above or below the chip bracket.

7. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

when the magnet is a permanent magnet, the magnetic field control module further comprises a permanent magnet bracket, an optical axis, a base, a lead screw, a motor, a slide bar, a slide block and a convex tooth; the permanent magnet is arranged on the permanent magnet bracket; the screw rod is coaxial with a motor in the circuit, and the motor is fixed on the base through a motor bracket; one end of the sliding rod is fixed on the base, the sliding block penetrates through the sliding rod and is relatively fixed on the sliding rod, and the sliding block is in contact connection with the screw rod; through holes for the optical axis to pass through are formed in the two sides of the permanent magnet bracket, the lower end of the optical axis is fixed on the base, and the permanent magnet bracket is oppositely fixed on the base through the optical axis; the convex tooth is arranged on one side surface of the permanent magnet bracket and connected with the sliding block.

8. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

the heating module comprises a heat conduction block, a temperature sensor, a heater and a heat insulation device, wherein the heating plane of the heat conduction block is attached to the bottom plane of the chip in parallel, the temperature sensor is arranged in the central area of the heating plane of the heat conduction block, and the heater is embedded in the heat conduction block or sandwiched between the heat conduction block and the heat insulation device; when the heater is embedded in the heat conducting block, the bottom surface of the heat conducting block parallel to the heating plane is attached to the heat insulation device; the heat insulation device is a heat insulation base; or comprises a heat dissipation base and a heat dissipation fan, wherein the heat dissipation fan is arranged near the heat dissipation base.

9. The modular droplet array chip-based bioanalytical system as claimed in claim 1, wherein:

the intelligent terminal device is connected with the optical detection module.

10. Use of a droplet array chip based modular bio-analysis system according to any of claims 1 to 9, wherein: the method is applied to biological detection.