Microfluidics-based particle detectors

Abstract

A microfluidics-based particle detector is disclosed, which consists of a sample preparation module, a sample injection module, a sample pretreatment module, a particle focusing module, a system monitoring and control module, a sensor module, a signal output and processing module, and a display and printing module. The sample preparation module completes the preparation of the particle sample liquid to be detected. The sample injection module realizes the automatic, quantitative, and continuous filling of the particle sample liquid. The sample pretreatment module removes the impurity particles in the sample liquid and regulates the lateral position of the particles. The particle focusing module focuses the target particles to the detection area. The system monitoring and control module monitors the changes of various parameters in real time and controls various action components. The sensor module realizes accurate detection of the target particles. The signal output and processing module reduces noise, amplifies, and outputs the detected signal. The display and printing module displays the final information such as the number, concentration, and size of the particles on the screen, and outputs it to the printer for printing a written report.

Description

Technical Field

[0001] The invention belongs to the technical field of particle detection, in particular to a particle detector based on microfluidics. Background Art

[0002] Particle detection has a wide range of applications in the fields of atmospheric monitoring, environmental (water) governance, industrial pharmaceuticals, clinical diagnosis, biotechnology, food testing, and mechanical testing. For example, by detecting the concentration and size distribution of atmospheric aerosol particles, the characteristics and sources of particles can be understood and the air quality can be evaluated; by detecting the size and number of bacteria and viruses in industrial wastewater, the quality of wastewater can be judged; by classifying and counting bacterial particles in urine samples, the clinical symptoms of urinary tract infections can be analyzed, which is more efficient and accurate than traditional sediment analysis methods; the precise quantitative estimation of transgenic drugs with transgenic adenovirus as a vector helps to ensure the successful expression of therapeutic genes while avoiding excessive intake of adenovirus; the counting of bacterial particles in foods such as dairy products is used to evaluate the quality of products; the health status monitoring of parts in engines, rotating machines or gearboxes can be achieved by detecting the particle size and concentration of metal abrasive particles in lubricating oil. It can be seen that microparticle detection is a key indicator for relevant environmental safety assessment and product quality assessment. Therefore, particle detection is crucial to the guarantee of environmental safety and product quality in the above fields.

[0003] A typical particle detector is a flow cytometer used in the biomedical field, which uses the scattering characteristics of cell particles or the fluorescence intensity of the attached probe for detection. It is expensive, bulky and complex to operate. With the development of microfluidic technology and the needs of more and more application scenarios, microfluidic particle detectors have been widely studied due to their advantages of low sample consumption and portability. There are two main particle detection principles based on microfluidic technology: optical signal detection and electrical signal detection. The resistance detection method is actually the integration of a Coulter counter in a microchannel, but since an electrolyte environment is required to generate a resistance response, a resistive particle detector using DC resistance as a detection signal is difficult to detect metal particles in an insulating fluid (such as lubricating oil). Although a capacitive particle detector using AC capacitance as a detection signal can detect particles in a low conductivity fluid, it requires a frequency modulation controller for strictly regulating the frequency of the AC voltage. Like a resistive particle detector, it is difficult to avoid impedance distortion caused by the charge shielding effect at the contact interface between the electrode and the fluid to be tested. The detection component has a complex structure and the required auxiliary detection equipment is expensive. The optical signal detection method has no specific requirements for the particles to be detected, but the optical signal-based detectors currently available on the market, such as light scattering counters, require precise and expensive optical components due to their complex optical paths. The light blocking detectors that use the light blocking principle detect and count particles by detecting the lightless areas blocked by particles, but the light blocking detectors currently on the market are usually used to detect large-sized objects and cannot accurately detect micro-nano-scale objects. This is because the light-receiving surface is large, and the lightless areas blocked by particles account for a small proportion of it, resulting in a relatively low signal-to-noise ratio and detection accuracy. In addition, the size of optical fibers used for optical detection on the market is usually fixed and cannot be flexibly adjusted, making it extremely difficult to control the signal-to-noise ratio by adjusting the size of the optical fiber.

[0004] In addition, precise hydrodynamic focusing of particles upstream of the detection area is a necessary prerequisite for accurate particle detection. Existing devices usually use sheath flow extrusion to achieve particle focusing, which makes it difficult to strictly control the particles to pass through the detection area in a single file, easily causing false detection and low detection rate.

[0005] In summary, there is an urgent need to develop a micro / nanoparticle detector with high accuracy, low cost, strong applicability, small size and portability.

[0006] The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art. Summary of the invention

[0007] In response to the problems existing in the prior art, the present invention proposes a microfluidics-based particle detector with functions such as automatic sample preparation, sample injection, sample pretreatment, particle focusing, system detection and control, particle detection, signal output and processing, result display and printing, etc. It has great application potential in the fields of biomedicine, food safety testing and environmental monitoring.

[0008] The purpose of the present invention is achieved through the following technical solutions:

[0009] A microfluidics-based particle detector includes,

[0010] A particle focusing module, which is located on the microfluidic chip and is a plurality of focusing channels with different channel diameters, wherein the focusing channels are microchannels whose cross sections are first reduced and then increased so as to pass through target particles one by one;

[0011] a sensor module located downstream of the plurality of focusing channels, the sensor module comprising:

[0012] A plurality of laser pointers, each of which vertically illuminates the downstream of the focusing channel,

[0013] The incident light hole layer is a light-proof layer attached to one side of the microfluidic chip, and the incident light hole layer has a first through hole aligned with the laser pen in the vertical direction.

[0014] The exit light hole layer is a light-proof layer attached to one side of the microfluidic chip, and the exit light hole layer has a second through hole vertically aligned with the first through hole or at a certain angle to the first through hole, wherein the incident light hole layer and the exit light hole layer can be on the same side or on different sides,

[0015] A photoelectric conversion element collects the optical signal from the laser pen via the second through hole to generate detection information of the target particles.

[0016] In the microfluidics-based particle detector, the elastic microstructure screens target particles smaller than a predetermined size in the particle sample liquid to enter the focusing channel. The elastic microstructure is a solid or hollow rod with a height greater than the diameter of the target particle. The elastic microstructure is connected to an air pump via a hose to adjust the spacing between the elastic microstructures.

[0017] In the microfluidics-based particle detector, the apertures of the first through hole and the second through hole are adjustable.

[0018] In the microfluidics-based particle detector, the photoelectric conversion element has an optical fiber head for receiving optical signals, and the angle of the optical fiber head is adjustable to receive light scattering signals at different angles.

[0019] In the microfluidics-based particle detector, the signal output and processing module is connected to the photoelectric conversion element to generate the particle size, number or concentration of the particles to be measured based on the detection information, and the display and printing module is connected to the signal output and processing module for display and printing.

[0020] In the microfluidics-based particle detector, the fluid in the focusing channel is a viscoelastic fluid solution.

[0021] In the microfluidics-based particle detector, the viscoelastic fluid solution is polyvinyl pyrrolidone or polyethylene oxide solution.

[0022] In the microfluidics-based particle detector, the microfluidics-based particle detector further includes a system monitoring and control module connected to a sample preparation module, a sample injection module, a sample preprocessing module, a particle focusing module, a sensor module, a signal output and processing module, and a display and printing module.

[0023] The system monitoring and control module controls the flow metering switch, the first electric control switch, the second electric control switch, the magnetic stirrer and the ultrasonic oscillator to prepare the particle sample liquid to be detected.

[0024] In response to the pressure data and flow data, the system monitoring and control module controls the pump to pump the particle sample liquid to be detected.

[0025] The system monitoring and control module controls the air pump to adjust the spacing between the elastic microstructures based on the predetermined size, controls the optical parameters of the laser pen, the apertures of the first through hole and the second through hole, and controls the signal output and processing module to generate the detection results and display and print them via the display and printing module.

[0026] When the focusing channel is blocked, the system monitoring and control module adjusts the suction action of the pump to change the upstream and downstream pressures to make the fluid flow in the reverse or reciprocating direction to clear the focusing channel.

[0027] A pressure sensor or a thin film sensor based on the principle of optical interference is provided on the inner side wall of the tapered section of the focusing channel. When blockage occurs in the tapered section channel, the signal output of the pressure sensor or the new thin film sensor based on the principle of optical interference provides a basis for the system monitoring and control module to determine whether the channel is blocked.

[0028] Preferably, in another set of technical solutions, a microfluidics-based particle detector includes:

[0029] The sample preprocessing module includes a particle liquid filtering submodule and a particle sorting submodule, wherein the particle liquid filtering submodule includes:

[0030] A pipeline, which introduces the particle sample liquid to be detected,

[0031] A fence structure is vertically arranged in the pipeline to pass target particles smaller than a predetermined size in the particle sample liquid, wherein the fence structure is composed of an elastic microstructure.

[0032] The particle sorting submodule is located downstream of the particle liquid filtering submodule and includes:

[0033] The microfluidic chip includes an inlet connected to the pipeline for introducing the target particles and an upstream channel of a focusing channel with a tapered structure connected to the inlet.

[0034] Functional microstructures or ultrasonic fingers, which generate lateral driving forces to regulate the lateral positions of target particles of different sizes so that they enter the corresponding focusing channels of the downstream particle focusing module;

[0035] A particle focusing module, which is located downstream of the particle sorting submodule on the microfluidic chip, is a plurality of focusing channels with different channel diameters. The focusing channels are microchannels whose cross sections are first reduced and then increased to allow target particles to pass through one by one;

[0036] a sensor module located downstream of the plurality of focusing channels, the sensor module comprising:

[0037] A plurality of laser pointers, each of which vertically illuminates the downstream of the focusing channel,

[0038] The incident light hole layer is a light-proof layer attached to one side of the microfluidic chip, and the incident light hole layer has a first through hole aligned with the laser pen in the vertical direction.

[0039] The exit light hole layer is a light-proof layer attached to one side of the microfluidic chip, and the exit light hole layer has a second through hole vertically aligned with the first through hole or at a certain angle to the first through hole, wherein the incident light hole layer and the exit light hole layer can be on the same side or on different sides,

[0040] A photoelectric conversion element collects the optical signal from the laser pen via the second through hole to generate detection information of the target particles.

[0041] In the microfluidics-based particle detector, the elastic microstructure is a solid or hollow rod whose height is greater than the diameter of the target particle, and the elastic microstructure is connected to the air pump outside the pipeline via a hose to adjust the spacing between the elastic microstructures.

[0042] In the microfluidics-based particle detector, the apertures of the first through hole and the second through hole are adjustable.

[0043] In the microfluidics-based particle detector, the photoelectric conversion element has an optical fiber head for receiving optical signals, and the angle of the optical fiber head is adjustable to receive light scattering signals at different angles.

[0044] In the microfluidics-based particle detector, the signal output and processing module is connected to the photoelectric conversion element to generate the particle size, number or concentration of the particles to be measured based on the detection information, and the display and printing module is connected to the signal output and processing module for display and printing.

[0045] In the microfluidics-based particle detector, the fluid in the focusing channel is a viscoelastic fluid solution.

[0046] In the microfluidics-based particle detector, the viscoelastic fluid solution is a polyvinyl pyrrolidone solution or a polyethylene oxide solution.

[0047] The microfluidics-based particle detector further includes a sample preparation module for preparing a particle sample solution to be detected, which includes:

[0048] A liquid storage tank contains solvents. The bottom of the liquid storage tank is connected to an outlet pipe, and the outlet pipe is provided with a flow metering switch.

[0049] A sample feeding chamber, which contains particle samples, is suspended via an electronic spring mass meter and has a first electric control switch at the bottom for controlling quantitative sample feeding.

[0050] A solid powder storage bin containing solutes, the solid powder storage bin is suspended via an electronic spring mass meter and a second electric control switch for controlling quantitative injection is provided at the bottom.

[0051] The sample preparation bin is located below the liquid storage bin, the solid powder storage bin and the sample introduction bin to prepare the particle sample liquid to be tested separately or simultaneously. The outer wall of the sample preparation bin is provided with an ultrasonic oscillator.

[0052] A rectangular flat plate supports the bottom of the sample preparation chamber and is fixed on a retractable bracket. A magnetic stirrer is arranged below the rectangular flat plate. When the retractable bracket is in a retracted state, the sample preparation chamber is located on the magnetic stirrer to magnetically stir the fluid working medium therein. When the retractable bracket is in an extended state, the sample preparation chamber and the rectangular flat plate are separated from the magnetic stirrer thereunder, and at this time, an ultrasonic oscillator starts to work to evenly mix the sample particles with the fluid working medium.

[0053] The microfluidics-based particle detector further includes a sampling module connected to the pipeline, which includes:

[0054] The first end of the pipeline can be retracted to enter and exit the sample preparation chamber, and the tail end is connected to the pipeline.

[0055] A pump connected to the pipeline to pump the particle sample liquid to be detected,

[0056] a pressure sensor connected to the pipeline to measure pressure data of the pipeline,

[0057] A flow meter is connected to the pipeline to measure flow data of the pipeline.

[0058] The microfluidics-based particle detector also includes a system monitoring and control module connected to a sample preparation module, a sample injection module, a sample pretreatment module, a particle focusing module, a sensor module, a signal output and processing module, and a display and printing module.

[0059] The system monitoring and control module controls the flow metering switch, the first electric control switch, the second electric control switch, the magnetic stirrer and the ultrasonic oscillator to prepare the particle sample liquid to be detected.

[0060] In response to the pressure data and flow data, the system monitoring and control module controls the pump to pump the particle sample liquid to be detected.

[0061] The system monitoring and control module controls the air pump to adjust the spacing between the elastic microstructures based on the predetermined size, controls the optical parameters of the laser pen, the apertures of the first through hole and the second through hole, and controls the signal output and processing module to generate the detection results and display and print them via the display and printing module.

[0062] In the microfluidics-based particle detector, when the pipeline is blocked, the system monitoring and control module adjusts the suction action of the pump to change the upstream and downstream pressures to make the fluid flow in the opposite direction or reciprocate to clear the pipeline.

[0063] In the microfluidics-based particle detector, a pressure sensor or a thin film sensor based on the principle of optical interference is provided on the inner side wall of the tapered section of the focusing channel. When blockage occurs in the tapered section channel, the signal output of the pressure sensor or the new thin film sensor based on the principle of optical interference provides a basis for the system monitoring and control module to determine whether the channel is blocked.

[0064] Compared with the prior art, the present invention has the following advantages: the detection accuracy and precision of the present invention are high. The present invention pre-treats the particles to be detected by microfluidic technology, eliminates the interference of impurity particles, regulates the lateral position of the particles to be detected, and allows the particles to pass through the detection area in turn, avoiding mutual interference between different particles, thereby greatly improving the accuracy of particle detection. At the same time, by designing the incident light hole layer and the exit light hole layer, and regulating the size of the through holes thereon, the incident light area and the optical fiber receiving area are changed, thereby effectively regulating the signal-to-noise ratio of the particle detection signal, thereby greatly improving the accuracy and precision of particle detection. It can significantly avoid the low signal-to-noise ratio and detection accuracy caused by the use of standardized optical fibers for detection on the market. The present invention is low in cost. The preparation technology of microfluidic chips is mature, the required consumables are small, and the current commercial preparation cost is low. Secondly, in terms of optical detection, the present invention can complete the detection using ordinary laser pens and optical fiber detectors, which are easy to align, do not need to embed optical fibers into microchannels, and have no expensive and complex auxiliary equipment; the present invention has a high degree of automation, intelligence, and is simple and easy to operate. The whole process of sample preparation, sample injection and detection can be realized automatically and has the function of early warning and elimination of channel blockage faults, and the operation is simple and easy. The present invention is small in size and portable. The present invention is based on microfluidic chips and optical fiber detection technology, and has the advantages of small size, easy integration and portability. The present invention has a wide range of applications. The present invention has no special requirements on the properties of the particles to be tested, and has broad application prospects in the fields of biomedicine, environmental monitoring, mechanical detection, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0065] By reading the detailed description of the preferred specific embodiments below, various other advantages and benefits of the present invention will become clear to those of ordinary skill in the art. The drawings in the specification are only for the purpose of illustrating the preferred embodiments and are not considered to be limitations of the present invention. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative work. Moreover, the same reference numerals are used to represent the same components throughout the drawings.

[0066] In the attached picture:

[0067] Figure 1 It is a schematic diagram of the structure of a particle detector based on microfluidic technology of the present invention;

[0068] Figure 2 It is a structural schematic diagram of a particle detector sample preparation module based on microfluidic technology of the present invention;

[0069] Figure 3 It is a schematic diagram of the structure of the particle detector sampling module and the particle liquid filtering submodule based on the microfluidic technology of the present invention;

[0070] Figure 4It is a schematic diagram of the structure of the particle sorting submodule and the particle focusing module of the particle detector based on microfluidic technology of the present invention;

[0071] Figure 5 It is a structural schematic diagram of a sensor module and a signal output and processing module of a particle detector based on microfluidic technology of the present invention;

[0072] Figure 6 It is a work flow diagram between the modules of the present invention and a control logic diagram of the system monitoring and control module;

[0073] The numbers in the figure are: 1. Sample preparation module; 2. Sample injection module; 3. Sample pretreatment module; 4. Particle focusing module; 5. System monitoring and control module; 6. Sensor module, 7. Signal processing and output module; 8. Display and printing module; 11. Liquid storage bin; 12. Solid powder storage bin; 13. Sample injection bin; 14. Control panel; 15. Electronic spring mass meter; 16. First electric control switch; 17. Second electric control switch; 18. Flow metering switch; 19. Sample preparation bin; 110. Ultrasonic transducer; 111. Rectangular plate; 112. Retractable bracket; 113. Magnetic stirrer; 114. Magnetic capsule; 21. Retractable pipe; 22. Pump; 23. Flow meter ; 24. Air pump; 25. Hose; 26. Fence structure; 27. Pressure sensor; 31. Particle sorting channel; 32, 33, 34. Particle focusing channel; 35. Laser pen; 36. Wedge-shaped closed cavity; 37. Particle detection area; 38. Sample outlet; 39. Sample inlet; 310. Ultrasonic fork finger; 311. Thin film photosensitive element; 41. Laser pen; 42. Incident light hole layer; 43. Microfluidic chip; 44. Exit light hole layer; 45. Signal output and processing module; 46. Photoelectric conversion element; 47. First through hole; 48. Second through hole; 49. Particles to be detected; 410. Optical fiber; 81. Printing component; 82. Display screen; 83. Waste liquid tank.

[0074] The present invention is further explained below in conjunction with the accompanying drawings and embodiments. DETAILED DESCRIPTION

[0075] The following will refer to the attached Figures 1 to 6 Specific embodiments of the present invention are described in more detail. Although specific embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0076] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" is an open term, so it should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present invention, but the description is based on the general principles of the specification and is not intended to limit the scope of the present invention. The scope of protection of the present invention shall be determined by the attached claims.

[0077] To facilitate understanding of the embodiments of the present invention, further explanation will be given below by taking specific embodiments as examples in conjunction with the accompanying drawings, and each of the accompanying drawings does not constitute a limitation on the embodiments of the present invention.

[0078] For better understanding, in one embodiment, Figures 1 to 6 As shown, a microfluidics-based particle detector includes a sample preparation module 1 for configuring a required fluid working medium, a sample injection module 2 for automatic, quantitative, and continuous filling of a particle sample solution, a sample pretreatment module 3 for removing impurity particles in the sample solution, a particle focusing module 4 for accurately focusing target particles on a detection area, a system monitoring and control module 5 for real-time monitoring of changes in various system parameters and controlling various action components, a sensor module 6 for accurately detecting target particles, a signal output and processing module 7 for outputting and statistically analyzing detection signals, and a display and printing module 8 for generating a final written report.

[0079] The sample preparation module 1 uses a liquid storage bin 11 and a solid powder storage bin 12 to pre-store solvents and solutes for the required fluid working medium. The sample injection bin 13 is used to add sample particles or sample liquid to be detected into the fluid working medium. The liquid storage bin 11, the solid powder storage bin 12, and the sample injection bin 13 are arranged side by side on the same side of the upper layer of the particle detector. The bottom of the cylindrical liquid storage bin 11 is connected to an outlet pipe, and a flow metering switch 18 is provided. The solid powder storage bin 12 and the sample injection bin 13 have the same shape, with the upper side for sample injection and the lower side for sample discharge. Two electronic spring mass meters 15 are hung on the top of the particle detector, and the bottom ends are both electrically controlled shutter switches. The bottom end of the sample injection chamber 13 is a first electrically controlled switch 16, and the bottom end of the solid powder storage chamber 12 is a second electrically controlled switch 17, which are used to control quantitative injection. The cylindrical sample preparation chamber 19 is located below the positions of the liquid storage chamber 11, the solid powder storage chamber 12, and the sample injection chamber 13. The three can be injected separately or simultaneously. The sample liquid to be tested is prepared in the sample preparation chamber 19. The bottom of the sample preparation chamber 19 is connected to a rectangular flat plate 11. 1, the four corners of the rectangular plate 111 are respectively fixed on the retractable bracket 112 at the bottom of the particle detector, and a magnetic stirrer 113 is arranged directly below the rectangular plate. When the retractable bracket 112 is in a retracted state, the sample preparation chamber 19 is located on the magnetic stirrer 113 below it. At this time, the magnetic stirrer 113 cooperates with the magnetic capsule 114 in the sample preparation chamber 19 to stir the fluid working medium therein evenly. A plurality of groups of ultrasonic transducers 110 are arranged circumferentially on the outer side of the chamber wall of the sample preparation chamber 19 to form an ultrasonic oscillator. When the retractable bracket 112 is in a retracted state, the sample preparation chamber 19 is located on the magnetic stirrer 113 below it. At this time, the magnetic stirrer 113 cooperates with the magnetic capsule 114 in the sample preparation chamber 19 to stir the fluid working medium therein evenly. When the retractable bracket 112 is in an extended state, the sample preparation bin 19 and the rectangular flat plate 111 are separated from the magnetic stirrer 113 thereunder, and the ultrasonic oscillator 110 starts working at this time, so as to mix the sample and the fluid working medium evenly; in addition, the injection amount of the liquid storage bin 11, i.e., the control of the flow metering switch 18, the injection amount of the solid powder storage bin 12, i.e., the control of the second electric control switch 17, the injection amount of the sample injection bin 13, i.e., the control of the first electric control switch 16, the duration of magnetic stirring, and the duration of ultrasonic oscillation can all be adjusted on the control panel 14.

[0080] The sample preparation module 1 can also be directly used to store the particle sample solution to be tested that has been prepared outside the instrument.

[0081] The sample injection module 2 includes a pump 22, a flow meter 23 and a retractable pipe 21 at the head end. The pump 22 is used to automatically, quantitatively, stably and continuously inject the sample liquid to be tested in the sample preparation chamber from the pipeline into the downstream sample pretreatment module. The flow meter 23 is used to monitor the pipeline flow. The retractable pipe at the head end is in a retracted state during the sample preparation stage, and automatically extends into the sample preparation chamber 19 to extract the sample liquid to be tested after the sample preparation is completed.

[0082] The sample pretreatment module 3 includes a particle liquid filtering submodule and a particle sorting submodule. The particle liquid filtering submodule is located in the downstream circular pipeline of the sample injection module. It is a fence structure 26 composed of solid or hollow rod-shaped elastic microstructures with a certain spacing, arranged perpendicular to the channel direction, and a height much greater than the diameter of the target particles. It is used to remove large-sized impurities outside the target particles. Different elastic microstructures are connected to an air pump 24 outside the pipeline through a hose 25. By controlling the air pump, the spacing between adjacent elastic microstructures can be effectively regulated, thereby achieving the purpose of removing impurities of different sizes. The particle sorting submodule 31 adopts the channel structure effect or the effect of an external force field, such as the acoustic radiation force generated by the ultrasonic fork finger 310 to laterally regulate the position of target particles of different particle sizes, so that the target particles enter the corresponding focusing channel after entering from the inlet 39 and are grouped according to particle size, and then detected separately.

[0083] The particle focusing module 4 is a microchannel part located on the microfluidic chip downstream of the particle sorting submodule, and includes a plurality of particle focusing microchannels (three are used as an example in the figure) 32, 33, and 34. The particle focusing channels 32, 33, and 34 are microchannels whose cross sections are first reduced and then increased. The number of channels corresponds to the number of particle size groups of the sample liquid to be tested in the particle sorting module. Under the combined action of the above-mentioned channel structure and the viscoelastic fluid working medium (such as polyvinyl pyrrolidone), the target particles of nanometer, submicron and micron levels can be efficiently focused at the center of their respective channels and pass through the downstream detection area in a single row and in sequence, and finally discharged from the outlet 38 to the waste liquid bin 83.

[0084] The sensor module 6 is composed of a laser pen 41, an incident light hole layer 42, an exit light hole layer 44, and a photoelectric conversion element 46 connected to an optical fiber 410. The laser pen 41 is vertically arranged downstream of the focusing channel in the particle focusing module 4. The incident light hole layer 42 and the exit light hole layer 44 are respectively provided with a first through hole 47 and a second through hole 48, and both are thin layers that are opaque except for the through holes, and are respectively located at the top and bottom of the microfluidic chip 43, and are bonded to the microfluidic chip 43 as a whole. The through hole is used to effectively modulate the parallelism of the laser and the laser irradiation area through the light hole. The first through hole position is vertically aligned with the detection area where the target particles are passed through in a single row and in sequence at the downstream of each focusing channel in the particle focusing module 4, and the through hole is a structure whose diameter can be adjusted according to the target particle size to be measured. If the signal output and the photoelectric conversion element 46 signal change on the processing module 45 are not enough to trigger the count when the target particle passes through the detection area, it means that the particle size of the target particle is much smaller than the diameter of the thin layer through hole, that is, the light blocking area of ​​the particle accounts for an insufficient proportion of the effective incident light area of ​​the optical fiber. At this time, the diameter of the through hole on the corresponding thin layer at the corresponding focusing channel can be adjusted to appropriately reduce it. The diameter of the effective light incident surface of the optical fiber on the photoelectric conversion element is not less than the diameter of the second through hole 48 on the exit light hole layer 44 to ensure that all effective light enters the photoelectric conversion element through the optical fiber and is then converted into detection information of the target particle. The second through hole 48 can be at any angle with the first through hole 47 in space to detect multi-angle scattered light of the target particle.

[0085] The signal output and processing module 7 is located below the particle focusing module 4 and is a subsequent signal noise reduction and amplification module, and finally transmits the particle size information of the target particles to the display and printing module 8 through a physical interface.

[0086] The display and printing module 8 includes a display screen 82 and a printing component 81, which are used to display and print information such as particle size grouping, particle quantity, concentration, etc. of the target particles.

[0087] The system monitoring and control module 5 adjusts the actions of each module in time by monitoring the operation status and parameter changes of each module to ensure the normal operation of the instrument. On the one hand, by collecting the pressure sensor 27 arranged in the flow path, the pressure change in the flow path is monitored in real time to determine whether the flow path is blocked by particles. When the flow path is blocked, the system monitoring and control module changes the pressure of the upstream and downstream of the flow path by adjusting the suction action of the pump, so that the fluid flows in the opposite direction or reciprocates to dredge the flow path; on the other hand, a pressure sensor or a new thin film sensor based on the principle of optical interference is set on the wall of the converging section channel that is most prone to blockage in the flow path, that is, a wedge-shaped closed cavity 36 is set on the outer side of the transparent flow path channel wall, and the closed cavity undergoes wedge interference under the action of the channel side laser pen 35. When the converging section channel is blocked, the fluid pressure changes dramatically, which will cause the thickness of the air wedge to change, and the shape and position of the generated interference fringes will change. The changes in the fringes are captured by the thin film photosensitive element 311 on the light side of the air wedge. The signal output of the pressure sensor or the new thin film sensor based on the principle of optical interference provides a basis for the system monitoring and control module 5 to determine whether the channel is blocked.

[0088] Example: Determine the particle size and concentration of yeast in a yeast solution. It is known that the diameter of the yeast is about 2 to 6 microns, and the solution contains 15 micron impurity particles.

[0089] See attached Figure 1 , an efficient and low-cost particle detector based on microfluidic chip technology, including a sample preparation module 1 for configuring the required fluid working medium, a sample injection module 2 for automatic, quantitative and continuous filling of particle sample liquid, a sample pretreatment module 3 for removing impurity particles in the sample liquid, a particle focusing module 4 for accurately focusing the target particles on the detection area, a system monitoring and control module 5 for real-time monitoring the changes of various system parameters and controlling various action components, a sensor module 6 for accurately detecting target particles, a signal output and processing module 7 for outputting and statistically analyzing detection signals, and a display and printing module 8 for generating a final written report.

[0090] See attached Figure 2The sample preparation module 1 uses a liquid storage bin 11 and a solid powder storage bin 12 to pre-store the solvent-water and solute-polyvinyl pyrrolidone equipped with the required fluid working medium. The sample injection bin 13 is used to quantitatively add the yeast solution to be detected into the fluid working medium. The liquid storage bin 11, the solid powder storage bin 12, and the sample injection bin 13 are arranged side by side on the same side of the upper layer of the particle detector. The bottom of the cylindrical liquid storage bin 11 is connected to the outlet pipe, and a flow metering switch 18 is provided. The solid powder storage bin 12 and the sample injection bin 13 have the same shape. The sample is injected from the upper side and discharged from the lower side. The top is suspended on the top of the particle detector by two electronic spring mass meters 15. The bottom is an electrically controlled shutter switch. The bottom of the injection chamber 13 is a first electrically controlled switch 16, and the bottom of the solid powder storage chamber 12 is a second electrically controlled switch 17, which are used to control quantitative injection. The cylindrical sample preparation chamber 19 is located below the liquid storage chamber 11, the solid powder storage chamber 12, and the injection chamber 13. The three can be injected separately or simultaneously. The sample liquid to be tested is prepared in the sample preparation chamber 19. The sample preparation chamber 19 can also be directly used to store the polyvinyl pyrrolidone-yeast sample liquid that has been prepared outside the instrument. The bottom of the sample preparation bin 19 is connected to a rectangular flat plate 111, and the four corners of the rectangular flat plate 111 are respectively fixed on a retractable bracket 112, and the retractable bracket 112 is fixed to the bottom of the particle detector. A magnetic stirrer 113 is arranged directly below the rectangular flat plate. When the retractable bracket 112 is in a retracted state, the sample preparation bin 19 is located on the magnetic stirrer 113 below it. At this time, the magnetic stirrer 113 cooperates with the magnetic capsule 114 in the sample preparation bin 19 to stir the fluid working medium therein evenly. A plurality of groups of ultrasonic transducers 110 are arranged circumferentially on the outer side of the bin wall of the sample preparation bin 19. , forming an ultrasonic oscillator. When the retractable bracket 112 is in an extended state, the sample preparation bin 19 and the rectangular flat plate 111 are separated from the magnetic stirrer 113 thereunder, and the ultrasonic oscillator 110 starts to work at this time, so that the sample particles and the fluid working medium can be mixed evenly. In addition, the injection amount of the liquid storage bin 11, i.e., the control of the flow metering switch 18, the injection amount of the solid powder storage bin 12, i.e., the control of the second electric control switch 17, the injection amount of the injection bin 13, i.e., the control of the first electric control switch 16, the magnetic stirring duration, and the ultrasonic oscillation duration can all be adjusted on the control panel 14.

[0091] See attached Figure 3 The sample injection module 2 includes a pump 22, a flow meter 23 and a retractable pipe 21 at the head end. The pump 22 is used to automatically, quantitatively, stably and continuously inject the sample liquid to be tested in the sample preparation chamber from the pipeline into the downstream sample pretreatment module. The flow meter 23 is used to monitor the pipeline flow. The retractable pipe at the head end is in a retracted state during the sample preparation stage, and automatically extends into the sample preparation chamber 19 to extract the sample liquid to be tested after the sample preparation is completed.

[0092] See attached Figure 3The sample pretreatment module 3 includes a particle filtering submodule and a particle sorting submodule. The particle filtering submodule is located in the downstream circular pipeline of the sampling module. It is a fence structure 26 composed of hollow rod-shaped elastic microstructures with a certain spacing, arranged perpendicular to the channel direction, and a height much greater than the diameter of the target particles. It is used to remove large-sized impurities outside the target particles. Different elastic microstructures are connected to an air pump 24 outside the pipeline through a hose 25. By controlling the air pump, the spacing between adjacent elastic microstructures is regulated to achieve the purpose of removing 15-micron impurity particles; the particle sorting submodule includes a particle sorting microchannel 31, which uses the acoustic radiation force generated by the ultrasonic fork finger 310 to laterally regulate the position of yeasts of different particle sizes, so that the yeast is divided into three particle size ranges of 2-3 microns, 3-5 microns, and 5-6 microns after entering from the inlet 39 and enters the corresponding downstream focusing channel for subsequent detection.

[0093] See attached Figure 4 The particle focusing module 4 is a microchannel part located on the microfluidic chip downstream of the particle sorting submodule, and includes three particle focusing channels for respectively focusing on the yeast grouped by particle size in the upstream particle sorting submodule. The particle focusing channels 32, 33, and 34 are microchannels whose cross-sections are first reduced and then increased. Under the combined action of the above-mentioned channel structure and the viscoelastic fluid polyvinylpyrrolidone, yeasts in each particle size range can be efficiently focused at the center of their respective channels and pass through the downstream detection area in a single row and in sequence, and finally discharged from the outlet 38 to the waste liquid bin 83.

[0094] See attached Figure 5The sensor module 6 is composed of a laser pen 41, an incident light hole layer 42, an exit light hole layer 44, and a photoelectric conversion element 46 connected to an optical fiber. Three laser pens 41 are vertically arranged downstream of the three focusing channels in the particle focusing module 4. The incident light hole layer 42 and the exit light hole layer 44 are respectively provided with three first through holes 47 and three second through holes 48, and are thin layers that are opaque except for the through holes, and are respectively located at the top and bottom of the microfluidic chip 43, and are bonded to the microfluidic chip 43 as a whole. The three first through holes 47 and the three second through holes 48 are vertically arranged and correspond to each other in the particle detection area 37 at the downstream of the three focusing channels, so as to respectively detect the forward scattering information in the corresponding channels. The through hole is used to effectively modulate the parallelism of the laser and the laser irradiation area through the light hole. The first through hole position is vertically aligned with the detection area where yeasts pass through in a single row and in sequence at the downstream of each focusing channel in the particle focusing module 4, and the through hole is a structure whose diameter can be adjusted according to the particle size of the yeast to be tested. If the signal change of the photoelectric conversion element 46 on the signal output and processing module 45 is not enough to trigger the count when the yeast passes through the detection area, it means that the particle size of the yeast is much smaller than the diameter of the thin layer through hole, that is, the light blocking area accounts for an insufficient proportion of the effective incident light area of ​​the optical fiber. At this time, the diameter of the through hole on the corresponding thin layer at the corresponding focusing channel can be adjusted to appropriately reduce it. The diameter of the effective light incident surface of the optical fiber on the photoelectric conversion element is not less than the diameter of the second through hole 48 on the exit light hole layer 44, so as to ensure that all effective light enters the photoelectric conversion element through the optical fiber and is then converted into detection information of the yeast.

[0095] The signal output and processing module 7 is located below the particle focusing module 4, and is a noise reduction and amplification module for subsequent signals, and finally transmits the yeast particle size information to the display and printing module 8 through a physical interface. The display and printing module 8 includes a display screen 82 and a printing component 81, which are used to display and print information such as particle size grouping, particle quantity, concentration, etc. of the yeast solution.

[0096] The system monitoring and control module 5 adjusts the actions of each module in time by monitoring the operation status and parameter changes of each module to ensure the normal operation of the instrument. On the one hand, by collecting the pressure sensor 27 arranged in the flow path, the pressure change in the flow path is monitored in real time to determine whether the flow path is blocked by yeast. When the flow path is blocked, the system monitoring and control module changes the pressure of the upstream and downstream of the flow path by adjusting the suction action of the pump, so that the fluid flows in the opposite direction or reciprocates to dredge the flow path; on the other hand, a pressure sensor or a new thin film sensor based on the principle of optical interference is set on the wall of the converging section channel that is most prone to blockage in the flow path, that is, a wedge-shaped closed cavity 36 is set on the outer side of the transparent flow path channel wall, and the closed cavity undergoes wedge-tip interference under the action of the channel lateral laser pen 35. When the converging section channel is blocked, the fluid pressure changes dramatically, which will cause the thickness of the air wedge tip to change, and the shape and position of the generated interference fringes will change. The changes in the fringes are captured by the thin film photosensitive element 311 on the light side of the air wedge tip. The signal output of the pressure sensor or the new thin film sensor based on the principle of optical interference provides a basis for the system monitoring and control module 5 to determine whether the channel is blocked.

[0097] The present invention integrates an automated sample preparation, sample injection, sample pretreatment module, an accurate particle focusing module, a low-cost and accurate particle detection module, a system monitoring and control module for real-time feedback adjustment, a signal output and processing module, and a display and printing module. While being miniaturized and portable, it ensures the accuracy, reliability, and efficiency of particle detection, and has universal applicability to various cells and particles at the micron and submicron levels in various occasions. It has great application value and broad market prospects in related technical fields such as biomedicine, environmental quality monitoring, mechanical state detection, and food safety detection.

[0098] Although the embodiments of the present invention are described above in conjunction with the accompanying drawings, the present invention is not limited to the above specific embodiments and application fields, and the above specific embodiments are only illustrative and instructive, rather than restrictive. A person of ordinary skill in the art can also make many forms under the guidance of this specification and without departing from the scope of protection of the claims of the present invention, all of which belong to the protection of the present invention.

Claims

1. A microfluidics-based particle detector, characterized in that: These include, A particle focusing module, which is located on the microfluidic chip and is a plurality of focusing channels with different channel diameters, wherein the focusing channels are microchannels whose cross sections are first reduced and then increased so as to pass through target particles one by one; a sensor module located downstream of the plurality of focusing channels, the sensor module comprising: A plurality of laser pens, which respectively and vertically illuminate the downstream of the focusing channel; An incident light hole layer, which is a light-proof layer attached to one side of the microfluidic chip, and the incident light hole layer has a first through hole aligned with the laser pen in a vertical direction; An exit light hole layer, which is a light-proof layer attached to one side of the microfluidic chip, and has a second through hole vertically aligned with the first through hole or at a certain angle to the first through hole, wherein the incident light hole layer and the exit light hole layer can be on the same side or on different sides; a photoelectric conversion element, which collects the optical signal from the laser pen via the second through hole to generate detection information of the target particles, The microfluidic-based particle detector also includes a sample preparation module for configuring the required fluid working fluid, an injection module for automatic, quantitative, and continuous filling of particle sample liquid, a sample pretreatment module for removing impurity particles in the sample liquid, a particle focusing module for accurately focusing the target particles on the detection area, a system monitoring and control module for real-time monitoring of changes in various system parameters and controlling various action components, a sensor module for accurately detecting target particles, a signal output and processing module for outputting and statistically analyzing detection signals, and a display and printing module for generating a final written report. It also includes a sample preparation module, an injection module, a sample pretreatment module, and a particle A system monitoring and control module for the focusing module, the sensor module, the signal output and processing module, and the display and printing module. The system monitoring and control module controls the flow metering switch, the first electric control switch, the second electric control switch, the magnetic stirrer, and the ultrasonic oscillator to prepare the particle sample liquid to be detected. In response to the pressure data and the flow data, the system monitoring and control module controls the air pump to pump the particle sample liquid to be detected, controls the air pump to adjust the spacing between the elastic microstructures based on a predetermined size, controls the optical parameters of the laser pen, the apertures of the first through hole and the second through hole, and controls the signal output and processing module to generate the detection result and display and print it via the display and printing module.

2. The microfluidics-based particle detector according to claim 1, characterized in that: The elastic microstructure screens target particles smaller than a predetermined size in the particle sample liquid to enter the focusing channel. The elastic microstructure is a solid or hollow rod with a height greater than the diameter of the target particles. The elastic microstructure is connected to an air pump via a hose to adjust the spacing between the elastic microstructures.

3. The microfluidics-based particle detector according to claim 1, characterized in that: The apertures of the first through hole and the second through hole are adjustable.

4. The microfluidics-based particle detector according to claim 1, characterized in that: The photoelectric conversion element has an optical fiber head for receiving optical signals, and the angle of the optical fiber head is adjustable to receive light scattering signals at different angles.

5. The microfluidics-based particle detector according to claim 1, characterized in that: The signal output and processing module is connected to the photoelectric conversion element to generate the particle size, quantity or concentration of the particles to be detected based on the detection information, and the display and printing module is connected to the signal output and processing module for display and printing.

6. The microfluidics-based particle detector according to claim 1, characterized in that: The fluid in the focusing channel is a viscoelastic fluid solution.

7. The microfluidics-based particle detector according to claim 6, characterized in that: The viscoelastic fluid solution is polyvinyl pyrrolidone or polyethylene oxide solution.

8. The microfluidics-based particle detector according to claim 1, characterized in that: When the focusing channel is blocked, the system monitoring and control module adjusts the suction action of the pump to change the upstream and downstream pressures to make the fluid flow in the reverse or reciprocating direction to clear the focusing channel.

9. The microfluidics-based particle detector according to claim 1, characterized in that: A pressure sensor or a thin film sensor based on the principle of optical interference is provided on the inner side wall of the tapered section of the focusing channel. When blockage occurs in the tapered section channel, the signal output of the pressure sensor or the thin film sensor based on the principle of optical interference provides a basis for the system monitoring and control module to determine whether the channel is blocked.

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