CN115561173A - In-vitro medical diagnosis device and system based on micro-fluidic chip - Google Patents

Abstract

The invention discloses an in vitro medical diagnosis device and system based on a microfluidic chip, which comprises the microfluidic chip, a main control module, a magnetic field control and vibration module, a weak signal detection module and a laser excitation module, wherein the microfluidic chip is introduced to realize detection, rapid detection can be realized only by dropping a little blood to the microfluidic chip, and laser is output to right face an illumination station to perform laser excitation on a detected sample in the microfluidic chip so as to gasify the surface air of the detected sample, so that the detection speed can be accelerated; the unique magnetic field control and vibration module can conveniently control the vibration and the directional movement of the magnetic nano particles/magnetic micro particles so as to achieve the aim of quick detection; the air pump is utilized to pump air into the reagent installation groove during detection, so that the blood is driven to move, and excessive bubbles are avoided; and a constant temperature and illumination catalysis module is arranged to accelerate the reaction speed of the reagent.

Description

In-vitro medical diagnosis device and system based on micro-fluidic chip

Technical Field

The invention relates to the field of medical instruments, in particular to an in-vitro medical diagnosis device and system based on a microfluidic chip.

Background

Fever, cough and the like are common symptoms which are easy to occur in ordinary life and are caused by cold, mycoplasma pneumoniae infection and the like, but doctors are very difficult to accurately judge and discriminate the symptoms, and the phenomenon of mutual cross infection among different individuals occurs. The symptoms can cause dizziness, brain swelling, nasal obstruction, hypodynamia, aversion to cold and other uncomfortable states, and can cause severe uncomfortable symptoms such as high fever, severe cold, mycoplasma pneumonia and the like which need hospitalization, and even need ICU rescue. The causes of the above symptoms are many, such as: caused by bacteria, viruses, mycoplasma pneumoniae, chlamydia infection, tumors, tubercle bacillus, etc. The method is characterized in that the symptoms such as fever, cough and the like are mainly caused by upper respiratory tract infection (cold) and lower respiratory tract infection (pneumonia), and most of the cold and pneumonia have the characteristics of infectivity, stubborn property, easy recurrence, difficult recovery, variable and complex conditions, difficult accurate and quick detection and the like. In addition, in the conventional method for testing blood by drawing blood, about 5ml of whole blood is usually needed, the detection time is long, the rapid detection and diagnosis are difficult to realize, the methods such as chest X-ray, intensified CT lung tumor marker detection and the like are influenced by electromagnetic radiation, a certain damage is caused to health by multiple detections, the detection time of the methods is difficult to realize rapid, timely and accurate detection, the detection cost is relatively high, and an instrument capable of carrying out minimally invasive collection and low-cost rapid and accurate detection on the causes (cold, pneumonia, mycoplasma pneumoniae infection) of fever, cough and the like caused by symptoms is unavailable.

Disclosure of Invention

The technical problem to be solved by the present invention is to provide an in vitro medical diagnostic device and system that can detect various pathologies (causes caused by symptoms such as fever, cough (mycoplasma pneumoniae infection), rickets with bone density, bladder cancer) quickly, inexpensively and accurately, in view of the above-mentioned drawbacks of the prior art.

The technical scheme adopted by the invention for solving the technical problems is as follows: the in-vitro medical diagnosis device based on the micro-fluidic chip is constructed and comprises the micro-fluidic chip, a main control module, a weak signal detection module and a laser excitation module, wherein the micro-fluidic chip comprises six stations of injection, mixing, illumination, reaction, filtration and detection, the injection station is used for injecting blood to be detected, and the main control module is connected with the weak signal detection module and is used for detecting the detection station of the micro-fluidic chip through the weak signal detection module to obtain a detection result; the laser excitation module is used for exciting the surface of the sample to be measured in the micro-fluidic chip to gasify the air on the surface of the sample to be measured.

Preferably, the microfluidic chip is disposed on a stage, and the laser excitation module includes: two laser generators for generating two paths of laser, a first optical filter/variable density sheet, a second optical filter/variable density sheet, a first objective lens, a first motor, a second motor, a third motor, a fourth motor and a fifth motor;

the optical filter/variable density lens focusing device comprises a first motor, a second motor, a third motor, a fourth motor, a fifth motor, a third motor, a fourth motor and a fifth motor, wherein the first motor is used for driving a first optical filter/variable density lens to rotate, the second motor is used for driving a second optical filter/variable density lens to rotate, the third motor is used for driving a first objective lens to move in the vertical direction so as to focus the first objective lens, and the fourth motor and the fifth motor are used for driving an objective table to move in the vertical direction and the horizontal direction;

the two paths of laser respectively reach a first objective lens through a first optical filter/variable density sheet and a second optical filter/variable density sheet, and the first objective lens focuses the two paths of laser to the illumination station of the microfluidic chip;

the first optical filter/variable density sheet and the second optical filter/variable density sheet are divided into different area blocks along the rotation direction, wherein one area block is a lighttight pure laser shielding plate/laser absorbing plate, and the other area blocks are optical filters or variable density sheets which transmit different wavelengths.

Preferably, the device further comprises a third optical filter/variable density sheet, a sixth motor, a second objective lens and a baffle plate with a small hole;

the structure of the third optical filter/variable density sheet is the same as that of the first optical filter/variable density sheet and that of the second optical filter/variable density sheet, the sixth motor is used for driving the third optical filter/variable density sheet to rotate, the third optical filter/variable density sheet is arranged on one side, away from the objective table, of the first objective lens, two paths of laser entering the first objective lens reach the first objective lens through the third optical filter/variable density sheet, light of a detection station of the microfluidic chip reaches the second objective lens through the third optical filter/variable density sheet to be converged, and then is subjected to small-hole imaging through the small hole of the baffle plate to be detected by the weak signal detection module.

Preferably, the laser excitation module further includes: the first reflector, the second reflector, the third reflector and the fourth reflector; the apparatus further comprises a fifth mirror;

one path of laser sequentially passes through the first optical filter/variable density sheet and the first reflector to reach the third reflector upwards, the other path of laser sequentially passes through the second optical filter/variable density sheet and the second reflector to reach the third reflector upwards, the third reflector reflects the two paths of laser to the fourth reflector along the horizontal direction, and the fourth reflector reflects the two paths of laser downwards to the third optical filter/variable density sheet; and after the light of the detection station of the microfluidic chip upwards reaches the fifth reflector through the third optical filter/density variable sheet, the light is reflected to the second reflector by the fifth reflector along the horizontal direction.

Preferably, the two paths of laser have the same or different wavelengths, and the first motor and the second motor drive the first optical filter/variable density sheet and the second optical filter/variable density sheet to rotate to appropriate area blocks so as to filter the laser with specific wavelength, or change the energy density excited by the two paths of laser, or realize the complete shielding of the two paths of laser in a weak fluorescence detection link so as to reduce the influence of the laser on a detection result; and the third motor drives the third optical filter/variable density sheet to rotate to a proper area block so as to realize the acquisition of reference data by completely shielding light in the weak fluorescence detection link.

Preferably, the microfluidic chip has magnetic nanoparticles/magnetic microparticles with targeted characteristic particles, the device further comprises a magnetic field control and vibration module, the magnetic field control and vibration module comprises a first guide rail, a static magnet, a trolley with a plurality of eccentric wheels arranged at the bottom and capable of moving along the first guide rail, and a plurality of seventh motors driving the eccentric wheels, the seventh motors are connected with the main control module, the state of the eccentric wheels can be changed under the control of the main control module to change the state of the static magnet, and the direction and the magnitude of a magnetic field can be adjusted by changing the state of the static magnet, so that the magnetic nanoparticles/magnetic microparticles are controlled to vibrate and directionally move.

Preferably, the device further comprises a gas injection module, wherein the gas injection module comprises a gas pump, a reagent mounting groove containing a substrate reagent, and an injection channel for connecting the reagent mounting groove and the microfluidic chip so as to introduce the substrate reagent into the microfluidic chip; the air pump is connected with the main control module and used for pumping air into the reagent mounting groove to push the substrate reagent to enter the micro-fluidic chip after passing through the injection channel during detection, and enabling blood injected into the micro-fluidic chip to move to enter each station of the micro-fluidic chip.

Preferably, the injection channel comprises a narrow slit hard tube for preventing liquid from naturally flowing backwards, a bag ball, a hose, a soft rubber sealing suction nozzle, a second guide rail, a fixed gear, a rotating gear and an eighth motor, wherein the first end of the narrow slit hard tube is connected with the bottom of the reagent mounting groove, the bag ball is connected with the second end of the narrow slit hard tube and the first end of the hose, the second end of the hose is connected with the soft rubber sealing suction nozzle, the hose is fixed along the second guide rail, the soft rubber sealing suction nozzle is fixed at the end part of the second guide rail, the second guide rail is connected with the fixed gear, the fixed gear is meshed with the rotating gear, the eighth motor is connected with the main control module and the rotating gear, and the eighth motor is used for driving the rotating gear to rotate to drive the second guide rail to move under the control of the main control module, so as to drive the soft rubber sealing suction nozzle to be in butt joint with the main gas inlet of the micro-fluidic chip.

Preferably, the device further comprises a constant-temperature and illumination catalysis module which is connected with the main control module and is right opposite to the illumination station of the microfluidic chip, and the constant-temperature and illumination catalysis module is used for providing illumination with a specific wavelength for the illumination station of the microfluidic chip in an infrared mode for catalysis, heating and stabilizing the temperature at a preset temperature;

the constant-temperature and illumination catalysis module comprises two paths of infrared excitation circuits which emit the same frequency and the same power, the first path of infrared excitation circuit is over against an illumination window of an illumination station of the microfluidic chip, the second path of infrared excitation circuit is over against the temperature detection film, and the distance between the first path of infrared excitation circuit and the illumination window and the distance between the second path of infrared excitation circuit and the temperature detection film are consistent;

the two infrared excitation circuits are connected with the main control module, the main control module is further connected with a temperature detection circuit for monitoring the temperature of the temperature detection film, and the main control module is used for sensing the temperature in the microfluidic biochip by detecting the temperature of the temperature detection film and controlling the light output power of the two infrared excitation circuits according to the sensed temperature.

In another aspect, the invention also provides an in-vitro medical diagnosis system based on the microfluidic chip, which comprises the in-vitro medical diagnosis device and a server, wherein the in-vitro medical diagnosis device is also used for sending measurement data to the server, the measurement data comprises result data of measuring the measured disease and measurement environment data, the measurement environment data comprises temperature, humidity, GPS position and weather,

the server is used for storing the measurement data uploaded by the in-vitro medical diagnosis device, constructing a disease prediction module according to the historical stored measurement data, and predicting the disease recurrence condition of the user based on the environmental data of a period of time in the future.

The in-vitro medical diagnosis device and system based on the microfluidic chip have the following beneficial effects: the micro-fluidic chip is introduced to realize detection, rapid detection can be realized only by dropping a little blood into the micro-fluidic chip, and the laser output by the laser excitation module is right opposite to the illumination station and used for carrying out laser excitation on the sample to be detected in the micro-fluidic chip so as to gasify the air on the surface of the sample to be detected, thereby accelerating the detection speed;

furthermore, the invention also designs a unique magnetic field control and vibration module which comprises a guide rail, a static magnet, a trolley with eccentric wheels arranged at the bottom and a motor for driving the eccentric wheels, wherein the state of the eccentric wheels is changed by controlling the motor to change the state of the static magnet, and the direction and the size of a magnetic field are adjusted by changing the state of the static magnet;

furthermore, the invention also provides a method for placing the substrate reagent outside the microfluidic chip, and inflating the reagent installation groove by using an air pump during detection so as to push the substrate reagent into the microfluidic chip, so that blood injected into the microfluidic chip moves to enter each station of the microfluidic chip along with the pushing of the substrate reagent, thereby driving the blood to move, and simultaneously, the gas is not directly pumped to avoid excessive bubbles;

furthermore, the invention also provides a constant temperature and illumination catalysis module, which is used for providing illumination with specific wavelength for an illumination station of the microfluidic chip in an infrared mode for catalysis, heating and stabilizing the temperature at a preset temperature, controlling the reaction temperature of the mixture in the microfluidic biochip to be in an optimal temperature state, and illuminating and catalyzing the mixture through the specific wavelength, so that the reaction speed of the reagent is accelerated, and the detection time is finally shortened.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts:

FIG. 1 is a schematic structural diagram of a specific embodiment of a medical rapid detection device based on a microfluidic chip;

FIG. 2 is a schematic structural diagram of a microfluidic chip;

FIG. 3 is a schematic structural diagram of a laser excitation module;

FIG. 4 is a schematic diagram of a magnetic field control and vibration module;

FIG. 5 is a schematic diagram of a gas injection module;

FIG. 6 is a schematic diagram of a constant temperature and photocatalytic module.

Detailed Description

In order to timely, accurately and low-cost quickly and quantitatively detect and analyze reasons (whether mycoplasma pneumoniae infection and infection degree) caused by symptoms such as fever and cough, quickly screen related pathological characteristics, and screen and diagnose diseases such as rickets and bladder cancer in early stage, so as to realize intelligent early-stage accurate detection of the diseases/symptoms, the invention provides that detection is realized based on a micro-fluidic chip, the micro-fluidic chip internally comprises a plurality of test channels, and each test channel can test one disease, so that not only can a plurality of diseases be simultaneously measured by one person, but also a plurality of persons can be simultaneously measured, each test channel comprises six stations of injection, mixing, illumination, reaction, filtration and detection, and blood to be detected is injected from an injection station, sequentially passes through mixing, illumination, reaction and filtration, and finally reaches a detection station and is detected by a weak signal detection module. In order to improve the detection sensitivity and universality, the laser is adopted to carry out laser excitation on the detected sample, so that the air on the surface of the detected sample is gasified, and then the spectrum condition of the detected sample is obtained through a weak signal detection module, so that the elements contained in the detected sample are further obtained. After different diseases and diseases are mixed with various chemical reagents in the microfluidic biochip, the mixture is reacted, filtered and the like, characteristic molecules can be obtained according to different diseases, and the characteristic molecules gasify the surfaces of the characteristic molecules under the action of double-path/single-path laser excitation to obtain different element spectrums in the molecules. The weak signal detection module is used for detecting the generated spectrum, and the device is used for analyzing and reducing the detected elements, so that the type of the characteristic molecules can be judged, the cause of diseases can be reversely deduced, and the early cancer characteristic molecules are captured, so that the early cancer diagnosis and detection can be realized.

To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying drawings. Exemplary embodiments of the invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete. It should be understood that the embodiments and specific features in the embodiments of the present invention are described in detail in the present application, but not limited to the present application, and the features in the embodiments and specific features in the embodiments of the present invention may be combined with each other without conflict.

Referring to fig. 1, the medical rapid detection device based on the microfluidic chip according to the embodiment of the present invention includes: the device comprises a micro-fluidic chip, a main control module, a magnetic field control and vibration module, a weak signal detection module, a gas injection module, a constant temperature and illumination catalysis module, a battery, a power management module, a high-voltage output control module, a touch display control screen, a voice module, a key module, a storage module, a wireless communication module and a laser excitation module.

Referring to fig. 2, the microfluidic chip generally includes a gas injection hole, a blood filling and sealing hole, a gas discharge hole, and a detection window. Referring to fig. 4 and 6, the microfluidic chip comprises six stations of injection, mixing, illumination, reaction, filtration and detection. The micro-fluidic chip is internally provided with magnetic nano particles/magnetic micro particles with magnetic nano particles and targeting characteristic particles, and the magnetic nano particles/magnetic micro particles can vibrate up and down, left and right under the action of a magnetic field and can also directionally move along the arrangement direction of the stations under the action of the magnetic field.

Injecting blood to be detected into the microfluidic chip from an injection station, sequentially carrying out mixing, illumination, reaction and filtration, then reaching a detection station, and detecting the detection station of the microfluidic chip by using a weak signal detection module to obtain a detection result.

The function and implementation of each module are described in turn below.

The laser excitation module:

and the laser output by the laser excitation module is opposite to the illumination station and used for carrying out laser excitation on the measured sample in the microfluidic chip so as to gasify the air on the surface of the measured sample.

The invention adopts the optical detection platform to realize the focusing excitation of the single-path/double-path laser, realizes the selection of the single-path or double-path laser, the energy density and the purity of each path of laser, no laser and the like through the optical detection platform, and realizes the selective reflection and reception of weak fluorescence through the optical detection platform. Specifically, referring to fig. 3, the microfluidic chip is placed on the stage 5. The laser excitation module includes: the laser system comprises two laser generators for generating two paths of laser, a first optical filter/variable density sheet 101, a second optical filter/variable density sheet 102, a first objective lens 401, a first motor 201, a second motor 202, a third motor 203, a fourth motor 204, a fifth motor 205, a first reflector 301, a second reflector 302, a third reflector 303 and a fourth reflector 304. Preferably, the apparatus further comprises a fifth mirror 305, a third filter/density variation plate 103, a sixth motor 206, a second objective 402 and a baffle 6 with apertures. Wherein, the wavelengths of the two laser beams are the same or different.

Wherein, all the reflectors are obliquely arranged, and the first optical filter/variable density sheet 101 and the first reflector 301 are arranged left and right separately. The second optical filter/variable density sheet 102 and the second reflecting mirror 302 are arranged in a left-right separated manner. The third mirror 303 is above the first mirror 301 and the second mirror 302. The third mirror 303 and the fourth mirror 304 are arranged to be left and right apart. Both the fourth mirror 304, the fifth mirror 305 are above the first objective 401. The first objective lens 401 is above the stage 5. The third optical filter/variable density plate 103 is disposed on a side of the first objective lens 401 away from the stage 5, and below both the fourth reflector 304 and the fifth reflector 305, so that two paths of laser light and light of the detection station of the microfluidic chip need to pass through the third optical filter/variable density plate 103. The baffle 6 with the small holes, the second objective lens 402 and the fifth reflecting mirror 305 are arranged in order from left to right.

The first motor 201 is used for driving the first optical filter/variable density sheet 101 to rotate; the second motor 202 is used for driving the second optical filter/variable density sheet 102 to rotate; the third motor 203 is used for driving the first objective lens 401 to move in the vertical direction so as to focus the first objective lens 401; the fourth motor 204 and the fifth motor 205 are used for driving the object stage 5 to move in the vertical and horizontal directions, so as to control the micro-fluidic biochip fixed on the object stage 5 to vibrate back and forth, so as to achieve sufficient mixing, and also move the object stage, so as to achieve batch excitation and detection of different samples (a plurality of measurement channels are arranged in the same micro-fluidic chip); the sixth motor 206 is used for driving the third filter/density variable sheet 103 to rotate.

The first filter/density variation sheet 101, the second filter/density variation sheet 102, and the third filter/density variation sheet 103 are divided into different area blocks along the rotation direction, wherein one area block is a light-tight pure laser shielding plate/laser absorption plate, and the other area blocks are filter sheets or density variation sheets that transmit different wavelengths. Therefore, the first motor 201 and the second motor 202 can be used for driving the first optical filter/variable density sheet 101 and the second optical filter/variable density sheet 102 to rotate to a proper area block so as to filter the laser with a specific wavelength, or change the energy density excited by the two paths of laser, or realize the complete shielding of the two paths of laser in a weak fluorescence detection link so as to reduce the influence of the laser on a detection result; the third motor 203 can be used to drive the third optical filter/variable density filter 103 to rotate to a suitable area block, so that the reference data can be acquired by completely blocking light in the weak fluorescence detection link, and then the third optical filter/variable density filter 103 is driven to rotate to a suitable area block for light transmission.

On the one hand, one of them way laser via first light filter/variable density piece 101 level arrival first speculum 301, first speculum 301 up reflection laser reachs third speculum 303, another way laser via second light filter/variable density piece 102 level arrival second speculum 302, second speculum 302 up reflection laser reachs third speculum 303, and third speculum 303 reflects two way laser to fourth speculum 304 along the horizontal direction, and fourth speculum 304 down reflects two way laser to reach first objective 401 after third light filter/variable density piece 103 filters, and first objective 401 focuses on two way laser to the illumination station of micro-fluidic chip.

On the other hand, after the light of the detection station of the microfluidic chip passes through the third optical filter/variable density sheet 103 upwards to reach the fifth reflector 305, the light is reflected to the second reflector 402 by the fifth reflector 305 along the horizontal direction to be converged, and then is subjected to small-hole imaging by the small holes of the baffle plate to be detected by the weak signal detection module.

Magnetic field control and vibration module:

magnetic nano particles/magnetic micro particles with magnetic nano particles containing targeted characteristic particles are arranged in a test channel of the microfluidic chip, and the particles are used for mixing blood, reagents and directionally moving through vibration. And a magnetic field control and vibration module is arranged for driving the particles to vibrate, and the magnetic field control and vibration module can change the states of the eccentric wheels under the control of the main control module to change the state of the static magnet, and adjust the direction and the magnitude of a magnetic field by changing the state of the static magnet, thereby controlling the vibration and the directional movement of the magnetic nano particles/magnetic micro particles.

Referring to fig. 4, the magnetic field control and vibration module of the present embodiment includes a first guide rail, a static magnet, a trolley having a bottom portion provided with a plurality of eccentrics movable along the first guide rail, and a plurality of seventh motors driving the plurality of eccentrics. The seventh motors are connected with the main control module, the states of the eccentric wheels can be changed under the control of the main control module to change the state of the static magnet, and the direction and the size of a magnetic field can be adjusted by changing the state of the static magnet, so that the vibration and the directional movement of the magnetic nano particles/magnetic micro particles are controlled.

The plurality of eccentric wheels comprise a pair of eccentric driving wheels and a pair of eccentric driven wheels which are positioned at four corners of the trolley, and the seventh motor is a stepping motor. The main control module can control the stepping motor to realize fine adjustment through the PWM signal.

The extending direction of the first guide rail determines the moving direction of the trolley, and also determines the directional moving direction of the magnetic nano particles/magnetic micro particles, so that the extending direction of the first guide rail is set to be consistent with the station arrangement direction of the microfluidic chip, and the direction is defined as the X-axis direction. The magnetic nano particles/magnetic micro particles can be driven to move directionally as long as the trolley is controlled to move along the first guide rail. Meanwhile, the trolley moves through the eccentric wheel, so that the trolley can vibrate synchronously. Therefore, under the control of the MCU chip of the main control module, the state of the eccentric wheel can be controlled, so that the magnetic nano particles/magnetic particles move in a specified direction, the separation from other specific particles is realized, the back-and-forth vibration of the magnetic nano particles/magnetic particles is realized, the sufficient mixing of nano particles is realized, the reaction time is shortened, the chemical reaction speed is accelerated, and the aim of rapid detection is fulfilled.

A gas injection module:

the gas injection module is used for pushing the blood in the microfluidic chip to flow. Referring to fig. 5, the gas injection module includes a gas pump, a reagent mounting groove containing a substrate reagent, and an injection channel for connecting the reagent mounting groove and the microfluidic chip to introduce the substrate reagent into the microfluidic chip; the air pump is connected with the main control module and used for pumping air into the reagent mounting groove to push the substrate reagent to enter the micro-fluidic chip after passing through the injection channel during detection, and enabling blood injected into the micro-fluidic chip to move to enter each station of the micro-fluidic chip.

Specifically, a triode can be arranged in a control path of the air pump, and the on-off time and the pulse width of the triode are controlled by outputting a PWM wave through an IO port of an MCU chip of the main control module, so that the on-off time and the ventilation volume of the air pump are controlled.

More specifically, the passageway of infusing includes narrow slit hard tube, bag ball, hose, the sealed suction nozzle of flexible glue, second guide rail, guide rail mounting fixture, fixed gear, rotary gear and the eighth motor that prevents the natural refluence of liquid, the first end of narrow slit hard tube with the bottom of reagent mounting groove is connected, the bag ball is connected the second end of narrow slit hard tube with the first end of hose, the second end of hose is connected the sealed suction nozzle of flexible glue, the hose is followed the second guide rail is fixed, for example can be from the inside passing of second guide rail, and the second guide rail can pass through guide rail mounting fixture centre gripping, and guide rail mounting fixture mainly restricts the second guide rail and removes along specific direction, for example removes along X axle direction. The flexible glue sealing suction nozzle is fixed at the end part of the second guide rail, the second guide rail is connected with a fixed gear, the fixed gear is meshed with a rotating gear, the eighth motor is connected with the main control module and the rotating gear, and the eighth motor is used for driving the rotating gear to rotate under the control of the main control module to drive the second guide rail to move so as to drive the flexible glue sealing suction nozzle to be in butt joint with a main gas inlet of the microfluidic chip.

Constant temperature and illumination catalysis module:

referring to fig. 6, the constant temperature and light catalysis module is connected to the main control module and faces the light station of the microfluidic chip. The constant-temperature and illumination catalysis module is used for providing illumination with specific wavelength for an illumination station of the microfluidic chip in an infrared mode for catalysis, heating and stabilizing the temperature at a preset temperature.

Specifically, the constant-temperature and illumination catalysis module comprises two paths of infrared excitation circuits which emit the same frequency and the same power, the first path of infrared excitation circuit faces an illumination window of an illumination station of the microfluidic chip, the second path of infrared excitation circuit faces the temperature detection film, the distance between the first path of infrared excitation circuit and the illumination window and the distance between the second path of infrared excitation circuit and the temperature detection film are the same, so that the temperature of the temperature detection film is ensured to be the same as the temperature in the chip as far as possible, and the temperature in the chip can be determined by detecting the temperature of the temperature detection film.

The two infrared excitation circuits are connected with the main control module, the main control module is further connected with a temperature detection circuit for monitoring the temperature of the temperature detection film, and the main control module is used for sensing the temperature in the microfluidic biochip by detecting the temperature of the temperature detection film and controlling the light output power of the two infrared excitation circuits according to the sensed temperature.

A weak signal detection module:

referring to fig. 1, the weak signal detection module includes a photoelectric detection module and a conversion processing operational amplification module connected to the photoelectric detection module and the main control module. The photoelectric detection module is aligned with a detection window of a detection station of the microfluidic chip and is used for detecting photon signals emitted by the self-luminous substance in the process of returning from an excited state to a ground state under a specific condition and generating electric signals to the conversion processing operation amplification module, for example, the detection is generally carried out by adopting a photomultiplier tube. The conversion processing operational amplification module is used for performing voltage conversion and operational amplification on the received signals and then outputting the signals to the main control module.

In a specific embodiment, the photoelectric detection module preferably adopts a multi-pin multi-stage amplification PMT photomultiplier 978 or 931A of Hamamatsu corporation of japan to detect weak fluorescent signals of different wavelengths, and the PMT photomultiplier receives the weak fluorescent current signal (anode photocurrent signal) and transmits the signal to the conversion processing operational amplification module for voltage conversion, and then performs operational amplification to output a 0-3.3V voltage. In this embodiment, the LM358 integrated operational amplifier is preferably used as the conversion processing operational amplifier module.

Voltage dependent modules: battery, power management module and high-voltage output control module:

the power management module is used for accessing an external power supply, controlling the charging of the battery and converting the voltage of the external power supply/the battery to obtain various low-voltage power supplies. For example, the voltage of the battery is 3.3-4.2V, the battery is also charged for 3.3V by accessing an external power supply (5-12V) through a universal Type-C interface, the output voltage of the power management module comprises 3.3V and 5-12V, the working voltage of most modules is 3.3V, and the working voltage of most modules is 5-12V, and the working voltage is supplied to the high-voltage output control module.

The high-voltage output control module is used for boosting the 5-12V low-voltage power supply output by the power supply management module to obtain high voltage suitable for the photoelectric detection module. Specifically, a main control MCU chip of the main control module outputs a voltage signal of 0-3.3V to control the high-voltage output control module to output high-voltage direct current voltage (400-1500V) so as to be used for high voltage required by a weak signal detection module (photomultiplier), wherein the 5-12V direct current voltage is obtained by mainly performing DC-DC conversion on battery voltage through a power management module, or can be obtained by performing DC-DC conversion on an external power supply when the external power supply is connected.

An input-output module: the device comprises a touch display control screen, a voice module and a key module.

The touch display control screen, the voice module and the key module are respectively connected with the main control module and used for providing an information input and output function.

The voice module is used for decoding text voice, then power amplification is carried out on the decoded audio, and voice playing is carried out through a loudspeaker, so that the voice module aims to carry out voice prompt on pathological abnormal conditions (such as rickets, bladder cancer and the like), system working states, equipment fault conditions and the like in the medical rapid detection process, for example, a CN-TTS module can be adopted, the CN-TTS module is a voice synthesis module with high integration, chinese, english and digital voice synthesis can be realized, the customization requirements of user command words or prompt tones are supported, the control is simple, the use is flexible, the GBK code is sent only through a serial port, and the TTL module is compatible with a mainstream 5V or 3.3V TTL voltage MCU.

The key module is mainly used for realizing the connection and disconnection of the input voltage of the power management module and realizing the on-off function of the whole device.

The touch display control screen is used for inputting information such as name, age, telephone, sex and the like of a detected user by a worker/detected user in a touch mode during rapid detection, and the information of weak fluorescence with different wavelengths of the detected user is displayed through the module. Different pieces of pathological information are reflected by different pieces of fluorescence information, so that the disease/pathological reason of the tested user is displayed, and then a report is generated to inform medical staff or the tested user.

And other modules: the device comprises a storage module and a wireless communication module.

The storage module and the wireless communication module are respectively connected with the main control module. The storage module is used for storing detection data, the wireless communication module is used for realizing the connection of the device and the remote server, and a user can access the data of the remote server in a mode of logging in a WeChat applet or a mobile phone APP or a WEB webpage and the like.

In this embodiment, the storage module adopts a Flash storage chip or an SD card. When the MCU chip of the main control module detects that the wireless communication module is abnormal in communication, information such as patient information, sex, age, weak fluorescent voltage signals and system working state is stored in the storage module, and the information is uploaded to the server through the wireless communication module until the MCU detects that the wireless communication module is normal in communication.

The main control module:

the module comprises a main control MCU chip, wherein a DSP, an FPGA or an ARMport-M series chip can be adopted as the main control MCU chip, which is the core brain of the whole device and is responsible for the control of other modules and the coordination of all the modules. For example, the output control is performed on the source management module; the voltage output control module is used for carrying out feedback regulation control on the voltage output of the high-voltage output control module and accurately controlling and outputting high-voltage for the photomultiplier to use; used for controlling the voice module to carry out corresponding voice operation; the analog-to-digital converter is used for carrying out analog-to-digital converter (ADC) acquisition on the voltage signal output by the conversion processing operational amplification module; for operating the gas injection module to control the gas injection time and the gas injection amount; the touch display control screen is used for receiving the input of the touch display control screen and displaying the corresponding output result (the number of photoelectrons), the working state of the whole device and other information through the touch display control screen; the system comprises a server, a server and a data processing module, wherein the server is used for encrypting and compressing data of received weak fluorescent signals, system working states, user information and the like, then sending the data to the server with a remote appointed IP address through a wireless communication module, decompressing and decrypting received data blocks through the server, and then storing the data blocks in the server; the magnetic nano/magnetic particles are controlled to move in the appointed direction by controlling the state and rotation of an eccentric wheel of the trolley, so that specific particle separation is realized, the magnetic nano/magnetic particles and a reagent in the microfluidic biochip are controlled to vibrate back and forth, the nano-scale particles are fully mixed, the chemical reaction speed is accelerated, and the aim of rapid detection is fulfilled.

In addition, the main control MCU chip can automatically turn on or turn off the power supply of the peripheral circuit according to the current state information of the whole device, most of the time, the whole device is in a low-power consumption standby mode, at the moment, the MCU can control the power management module to turn off the wireless communication module, the voice module, the weak signal detection module, the storage module, the magnetic field control and vibration module, the high-voltage output control module and the power supply of the gas injection module, the touch display control screen enters a low-power consumption touch wake-up mode (a screen-rest state), the touch display control screen can be wakened up to normally display the touch display control screen only when a user touches the touch display control screen again, and only when the user normally loads the micro-fluidic chip and starts detection through the touch display control screen, the main control MCU chip can automatically provide a control command for starting the external power supply for the power management module, and then the power supply output is started.

The use and the working process of the device are as follows: in the process of detecting trace blood, a user performs related detection operations successively according to voice prompt. Firstly, two-dimensional codes on the device are scanned through WeChat or user identity information is input through touch, collected fresh blood of about 50uL is injected into a microfluidic chip, then the microfluidic chip is placed into a consumable box (different microfluidic chips are used for detecting different diseases/diseases), the microfluidic chip is fixed, a soft rubber sealing suction nozzle is aligned to a gas injection hole of the microfluidic chip, then a proper substrate reagent is selected, an MCU controls an air pump to pump air, the substrate reagent is pushed into the microfluidic chip, meanwhile, the fresh blood moves for a certain distance in the microfluidic chip, further, the fresh blood enters a biochemical reaction link of the microfluidic chip, the MCU controls laser output by a laser excitation module to be opposite to an illumination station, the measured sample in the microfluidic chip is subjected to laser excitation to gasify the surface air of the measured sample, the state of an eccentric wheel of the MCU controls the state of the trolley to vibrate magnetic nano particles/magnetic particles, the reaction is fully generated, and then the MCU controls the magnetic nano particles/magnetic particles to move in a designated direction, so that the separation from other particles is realized. The MCU controls the power management module to convert the battery voltage into 5V or 12V direct current voltage, and the converted voltage is boosted to 400-1500V direct current output again through the high-voltage output control module. The weak signal detection is mainly realized through a photomultiplier, optical signals with different wavelengths such as weak fluorescence of a detection station of a microfluidic chip are converted into current signals, then current-voltage conversion and operational amplification are carried out, the current signals are sent to an ADC (analog-to-digital converter) in the MCU for analog-to-digital acquisition, the MCU receives the weak fluorescence voltage signals with different wavelengths, then data compression and encryption are realized by combining user information, system working state and other information, then the data are sent to a designated server through a wireless communication module for data storage, when the wireless communication module cannot be networked, the MCU stores the compressed signals in a storage module for temporary storage, and once the networking is recovered, the data in the storage module are uploaded to a server database for background further analysis and processing. Meanwhile, the MCU can also dynamically display the received weak fluorescent signals with different wavelengths through the touch control display screen module, and once the detected index exceeds a certain threshold value, the MCU can inform a user through screen flashing, voice warning and background abnormity early warning modes.

The invention also constructs an in-vitro medical diagnosis system based on the microfluidic chip, which comprises the in-vitro medical diagnosis device and the server, wherein the in-vitro medical diagnosis device is also used for sending measurement data to the server, the measurement data comprises result data of measured diseases and measurement environment data, and the measurement environment data comprises temperature, humidity, GPS position and weather. The server is used for storing the measurement data uploaded by the in-vitro medical diagnosis device, constructing a disease prediction module according to the historical stored measurement data, and predicting the disease recurrence condition of the user based on the environmental data of a period of time in the future.

The embodiment of the invention has the beneficial effects that:

1) The invention introduces the micro-fluidic chip to realize the detection, and the corresponding micro-fluidic chip is selected, and the corresponding substrate reagent is contained in the reagent mounting groove, so that the rapid, accurate and low-cost diagnosis can be carried out on the early screening of various diseases such as mycoplasma pneumoniae infection, rickets with bone density, bladder cancer and the like, which are one of the pathological reasons generated by symptoms such as fever, cough and the like; the order is not required to be opened one by a doctor, the disease is not required to be checked one by one, the frequent detection for a plurality of times is reduced, the cost is low, the cross infection is not easy to cause, and the optimal treatment time is not easy to delay; minimally invasive sample collection, a small amount of blood below 50uL is taken through a finger puncture needle for detection, a detection report can be obtained within 10-15 minutes, and rapid detection and diagnosis are realized; the method is not influenced by electromagnetic radiation, does not damage health after multiple detections, and has relatively low detection cost and low-cost quick detection compared with the existing detection method; according to the different injected reaction reagents in the microfluidic biochip, the diseases/diseases which can be detected are different, and a plurality of test channels with the same reaction reagents are arranged in the same microfluidic biochip: if the same reaction reagent is injected, but the blood comes from different patients, the same disease/illness of a plurality of patients can be detected quickly and accurately in batches; if a plurality of different reagents are injected, but the blood comes from the same person, the diagnosis device can simultaneously and accurately detect different diseases of the same patient.

2) The laser output by the laser excitation module is right opposite to the illumination station and used for carrying out laser excitation on the measured sample in the microfluidic chip so as to gasify the air on the surface of the measured sample, and therefore the detection speed can be accelerated. In order to more accurately obtain the reasons of disease/illness and improve the detection sensitivity and the detection accuracy, the invention is combined with double excitation sources and adopts two paths of laser to excite the tested sample.

3) A unique magnetic field control and vibration module is designed, so that magnetic nano particles/magnetic micro particles can be accurately controlled, and the magnetic nano particles/magnetic micro particles can accurately move in a specified direction, so that specific particles can be separated, and the micro-nano particle movement can be accurately controlled, so that the detection accuracy can be greatly improved; the magnetic nano particles/magnetic particles can also vibrate back and forth up and down, so that the nanoscale full mixing is realized, the reaction time is shortened, the chemical reaction speed is accelerated, and the aim of rapid detection is fulfilled.

4) A substrate reagent is placed outside the micro-fluidic chip, the reagent mounting groove is inflated by an air pump during detection, so that the substrate reagent is pushed into the micro-fluidic chip, and blood injected into the micro-fluidic chip moves into each station of the micro-fluidic chip along with the pushing of the substrate reagent, so that the blood is driven to move, and meanwhile, the gas is not directly pumped, so that excessive bubbles are avoided;

5) The constant temperature and illumination catalysis module is arranged, illumination with specific wavelength is provided for an illumination station of the microfluidic chip in an infrared mode for catalysis, heating is carried out, the temperature is stabilized at a preset temperature, the reaction temperature of the mixture in the microfluidic biochip is controlled to be in an optimal temperature state, and the mixture is catalyzed by illumination with specific wavelength, so that the reaction speed of the reagent is accelerated, and the detection time is finally shortened.

6) The system combines temperature, humidity, GPS position and weather to realize accurate detection of multi-data fusion, improves detection sensitivity and accuracy, simultaneously combines over the years local data, current local temperature and humidity and the disease condition that can be detected in a district, predicts whether a future period is high morbidity time of one or more diseases in advance through artificial intelligence big data technology, and can timely remind a user to pay attention to prevention and avoid infection risks. Therefore, medical expenses and various discomfort caused by diseases are reduced for users from the source, and real health early warning service is achieved.

It will be understood that when an element is referred to herein as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "upper", "lower", "left", "right" and the like are used herein for illustrative purposes only.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

The terms including ordinal numbers such as "first", "second", and the like used in the present specification may be used to describe various components, but the components are not limited by the terms. These terms are used only for the purpose of distinguishing one constituent element from other constituent elements. For example, a first component may be termed a second component, and, similarly, a second component may be termed a first component, without departing from the scope of the present invention.

While the present invention has been described with reference to the embodiments shown in the drawings, the present invention is not limited to the embodiments, which are illustrative and not restrictive, and it will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (10)

1. An in-vitro medical diagnosis device based on a microfluidic chip is characterized by comprising the microfluidic chip, a main control module, a weak signal detection module and a laser excitation module, wherein the microfluidic chip comprises six stations for injection, mixing, illumination, reaction, filtration and detection, the injection station is used for injecting blood to be detected, and the main control module is connected with the weak signal detection module and is used for detecting the detection station of the microfluidic chip through the weak signal detection module to obtain a detection result; the laser output by the laser excitation module is opposite to the illumination station and used for carrying out laser excitation on the sample to be measured in the microfluidic chip so as to gasify the air on the surface of the sample to be measured.

2. The microfluidic chip-based in vitro medical diagnostic apparatus according to claim 1, wherein the microfluidic chip is placed on a stage, and the laser excitation module comprises: the laser system comprises two laser generators for generating two paths of laser, a first optical filter/variable density sheet, a second optical filter/variable density sheet, a first objective lens, a first motor, a second motor, a third motor, a fourth motor and a fifth motor;

the first motor is used for driving the first optical filter/variable density sheet to rotate, the second motor is used for driving the second optical filter/variable density sheet to rotate, the third motor is used for driving the first objective lens to move in the vertical direction so as to focus the first objective lens, and the fourth motor and the fifth motor are used for driving the objective table to move in the vertical direction and the horizontal direction;

the two paths of laser respectively pass through a first optical filter/variable density sheet and a second optical filter/variable density sheet and then reach a first objective lens, and the first objective lens focuses the two paths of laser to the illumination station of the microfluidic chip;

the first optical filter/variable density sheet and the second optical filter/variable density sheet are divided into different area blocks along the rotation direction, wherein one area block is a lighttight pure laser shielding plate/laser absorbing plate, and the other area blocks are optical filters or variable density sheets which transmit different wavelengths.

3. The microfluidic chip-based in vitro medical diagnostic apparatus according to claim 2, further comprising a third filter/densitometric plate, a sixth motor, a second objective lens, and a baffle with small holes;

the structure of the third optical filter/variable density sheet is the same as that of the first optical filter/variable density sheet and that of the second optical filter/variable density sheet, the sixth motor is used for driving the third optical filter/variable density sheet to rotate, the third optical filter/variable density sheet is arranged on one side, away from the objective table, of the first objective lens, two paths of laser entering the first objective lens reach the first objective lens through the third optical filter/variable density sheet, light of a detection station of the microfluidic chip reaches the second objective lens through the third optical filter/variable density sheet to be converged, and then is subjected to small-hole imaging through the small hole of the baffle plate to be detected by the weak signal detection module.

4. The microfluidic chip-based in vitro medical diagnostic apparatus according to claim 3, wherein the laser excitation module further comprises: the first reflector, the second reflector, the third reflector and the fourth reflector; the apparatus further comprises a fifth mirror;

one path of laser sequentially passes through the first optical filter/variable density sheet and the first reflector to reach the third reflector upwards, the other path of laser sequentially passes through the second optical filter/variable density sheet and the second reflector to reach the third reflector upwards, the third reflector reflects the two paths of laser to the fourth reflector along the horizontal direction, and the fourth reflector reflects the two paths of laser downwards to the third optical filter/variable density sheet; and after the light of the detection station of the microfluidic chip upwards reaches the fifth reflector through the third optical filter/density variable sheet, the light is reflected to the second reflector by the fifth reflector along the horizontal direction.

5. The in vitro medical diagnosis device based on the microfluidic chip according to claim 3, wherein the two lasers have the same or different wavelengths, and the first motor and the second motor drive the first optical filter/variable density sheet and the second optical filter/variable density sheet to rotate to appropriate area blocks so as to filter the lasers with specific wavelengths, or change the energy density excited by the two lasers, or realize the complete shielding of the two lasers in the weak fluorescence detection link so as to reduce the influence of the lasers on the detection result; and the third motor drives the third optical filter/variable density sheet to rotate to a proper area block so as to realize the acquisition of reference data by completely shielding light in a weak fluorescence detection link.

6. The in vitro medical diagnostic apparatus based on microfluidic chip of claim 1, wherein the microfluidic chip has magnetic nanoparticles/microparticles with targeting features, the apparatus further comprises a magnetic field control and vibration module, the magnetic field control and vibration module comprises a first guide rail, a static magnet, a cart having a plurality of eccentrics at the bottom thereof, the cart being movable along the first guide rail, and a plurality of seventh motors driving the eccentrics, the seventh motors being connected to the main control module, the states of the eccentrics being changed under the control of the main control module to change the state of the static magnet, and the direction and magnitude of the magnetic field being adjusted by changing the state of the static magnet, thereby controlling the vibration and directional movement of the magnetic nanoparticles/microparticles.

7. The microfluidic chip-based in vitro medical diagnostic apparatus according to claim 1, further comprising a gas injection module, the gas injection module comprising a gas pump, a reagent mounting groove containing a substrate reagent, an injection channel for connecting the reagent mounting groove and the microfluidic chip to introduce the substrate reagent into the microfluidic chip; the air pump is connected with the main control module and used for pumping air into the reagent mounting groove to push the substrate reagent to enter the micro-fluidic chip after passing through the injection channel during detection, and enabling blood injected into the micro-fluidic chip to move to enter each station of the micro-fluidic chip.

8. The in vitro medical diagnosis device based on the microfluidic chip of claim 7, wherein the injection channel comprises a narrow slit hard tube, a balloon, a hose, a soft rubber sealing nozzle, a second guide rail, a fixed gear, a rotating gear and an eighth motor for preventing liquid from flowing backwards naturally, the first end of the narrow slit hard tube is connected with the bottom of the reagent installation groove, the balloon is connected with the second end of the narrow slit hard tube and the first end of the hose, the second end of the hose is connected with the soft rubber sealing nozzle, the hose is fixed along the second guide rail, the soft rubber sealing nozzle is fixed at the end of the second guide rail, the second guide rail is connected with the fixed gear, the fixed gear is meshed with the rotating gear, the eighth motor is connected with the main control module and the rotating gear, and the eighth motor is used for driving the rotating gear to rotate under the control of the main control module to drive the second guide rail to move, so as to drive the soft rubber sealing nozzle to be in butt joint with the main gas inlet of the microfluidic chip.

9. The in vitro medical diagnosis device based on the microfluidic chip according to claim 1, further comprising a constant temperature and illumination catalysis module connected with the main control module and facing the illumination station of the microfluidic chip, for providing illumination with specific wavelength for the illumination station of the microfluidic chip in an infrared manner for catalysis, heating and stabilizing the temperature at a preset temperature;

the constant-temperature and illumination catalysis module comprises two paths of infrared excitation circuits which emit the same frequency and the same power, the first path of infrared excitation circuit is over against an illumination window of an illumination station of the microfluidic chip, the second path of infrared excitation circuit is over against the temperature detection film, and the distance between the first path of infrared excitation circuit and the illumination window and the distance between the second path of infrared excitation circuit and the temperature detection film are consistent;

the two infrared excitation circuits are connected with the main control module, the main control module is further connected with a temperature detection circuit for monitoring the temperature of the temperature detection film, and the main control module is used for sensing the temperature in the microfluidic biochip by detecting the temperature of the temperature detection film and controlling the light output power of the two infrared excitation circuits according to the sensed temperature.

10. An in-vitro medical diagnosis system based on a micro-fluidic chip, comprising the in-vitro medical diagnosis device according to any one of claims 1 to 9 and a server, wherein the in-vitro medical diagnosis device is further used for sending measurement data to the server, the measurement data comprises result data of the measured disease and measurement environment data, the measurement environment data comprises temperature, humidity, GPS position and weather,

the server is used for storing the measurement data uploaded by the in-vitro medical diagnosis device, constructing a disease prediction module according to the historical stored measurement data, and predicting the disease recurrence condition of the user based on the environmental data of a period of time in the future.

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