CN114130318A - Large-scale production equipment for microspheres - Google Patents
Large-scale production equipment for microspheres Download PDFInfo
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- CN114130318A CN114130318A CN202111467335.0A CN202111467335A CN114130318A CN 114130318 A CN114130318 A CN 114130318A CN 202111467335 A CN202111467335 A CN 202111467335A CN 114130318 A CN114130318 A CN 114130318A
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- 239000004005 microsphere Substances 0.000 title claims abstract description 165
- 238000011031 large-scale manufacturing process Methods 0.000 title claims abstract description 21
- 238000004132 cross linking Methods 0.000 claims abstract description 350
- 238000004140 cleaning Methods 0.000 claims abstract description 232
- 230000007246 mechanism Effects 0.000 claims abstract description 83
- 238000005507 spraying Methods 0.000 claims abstract description 29
- 238000005516 engineering process Methods 0.000 claims abstract description 12
- 239000007788 liquid Substances 0.000 claims description 227
- 239000002699 waste material Substances 0.000 claims description 54
- 238000003860 storage Methods 0.000 claims description 37
- 238000002347 injection Methods 0.000 claims description 30
- 239000007924 injection Substances 0.000 claims description 30
- 238000001723 curing Methods 0.000 claims description 24
- 239000002994 raw material Substances 0.000 claims description 21
- 238000002156 mixing Methods 0.000 claims description 18
- 239000007921 spray Substances 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 14
- 238000011084 recovery Methods 0.000 claims description 12
- 238000007599 discharging Methods 0.000 claims description 7
- 238000010146 3D printing Methods 0.000 claims description 3
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 3
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 3
- 239000011521 glass Substances 0.000 claims description 3
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims description 3
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims description 3
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 27
- 238000004519 manufacturing process Methods 0.000 abstract description 23
- 238000002360 preparation method Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
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- 230000008569 process Effects 0.000 description 18
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- 229910021641 deionized water Inorganic materials 0.000 description 1
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- 230000010102 embolization Effects 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B3/00—Cleaning by methods involving the use or presence of liquid or steam
- B08B3/02—Cleaning by the force of jets or sprays
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- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
The invention discloses large-scale production equipment for microspheres, and belongs to the technical field of microsphere preparation by a microfluidic method. The device comprises a microfluidic device, a cross-linking device and a cleaning device, wherein the cross-linking device is arranged on the front side of a station of the microfluidic device; the spraying mechanism comprises a spraying pipe and a receiving groove, and a nozzle is arranged on the spraying pipe; the cross-linking device comprises at least one cross-linking unit, and the cross-linking unit is connected with the rotating mechanism through a connecting rod I; the cleaning device comprises at least one cleaning unit, and the cleaning unit is connected with the rotating mechanism through a connecting rod II. The invention solves the problem that the prior equipment can not realize large-scale production in the prior art, realizes automation, large-scale production and the like of the microsphere production process, pushes the microfluidic microsphere production technology to industrialization, and provides effective precondition guarantee for the subsequent application and production of microspheres.
Description
Technical Field
The invention relates to a production device of microspheres, in particular to a device for producing the microspheres in a large scale based on a microfluidic technology, and belongs to the technical field of microsphere preparation by a microfluidic method.
Background
Microspheres (microspheres) generally refer to spherical particles, mostly solid particles or spheres, with a particle size between 50nm and 2 mm. The carrier materials for preparing the microspheres are many, and are mainly divided into natural polymer microspheres (such as starch microspheres, albumin microspheres, gelatin microspheres, chitosan microspheres and the like) and synthetic polymer microspheres (such as polylactic acid microspheres) and the like.
The microfluidic droplet technology is a new technology for researching generation, control and application of micro-droplets in a scale range from several micrometers to hundreds of micrometers, which is developed on a microfluidic chip in recent years. In the process of generating droplets by a microfluidic method, two (or more than three) liquids which are not mutually soluble are respectively used as a continuous phase and a dispersed phase, and respectively enter different microchannels in a microfluidic chip under the drive of an injection pump with a fixed volume flow rate, when two (or more than three) flows meet at a cross point, the dispersed phase fluid continuously extends to form a plug-shaped or jet-shaped liquid column, then the plug-shaped or jet-shaped liquid column is broken due to the instability of a free interface under the shearing and extrusion action of the continuous phase fluid, the plug-shaped or jet-shaped liquid column is pinched off and dispersed in the continuous phase in the form of a micro volume unit to form droplets, and then the droplets are crosslinked and cleaned to obtain the microspheres. The micro-fluidic chip is used as a micro-reactor, can realize biochemical reaction, rapid reagent mixing, micro-particle synthesis and the like, and greatly strengthens the advantages of low consumption, automation, high flux and the like of the micro-fluidic chip.
At present, due to the limitation of the particularity of the microsphere production process, the existing equipment conditions and the like, the microsphere production process is difficult to realize continuity, batch and industrialization, and the microsphere preparation process has more manual operation procedures, so that the product performance is easily inconsistent, and the product pollution risk is increased. Such as: in the process of preparing the embolism microsphere, the internal phase liquid and the external phase liquid are respectively injected into a microfluidic chip through an injection pump, and are sheared into liquid drops in the microfluidic chip, and then subsequent crosslinking and cleaning are carried out, wherein most of the related devices such as the microfluidic shearing, crosslinking and cleaning are small devices in a laboratory stage, and manual connection of all processing steps is needed, so that the standardization of each procedure is difficult to control, and the devices are difficult to put into a factory for large-scale and industrial continuous production and become a bottleneck limiting the industrial production of the microfluidic microsphere production technology; moreover, the artificial operation has the risks of nonuniform crosslinking and cleaning results, easy introduction of foreign impurities and the like, and increases the uncertainty and instability of the quality of the microsphere product.
The prior art CN105709696A discloses a 'chitosan microsphere micro-fluidic one-step synthesis method for heavy metal wastewater treatment', which comprises the following steps: preparing a chitosan aqueous solution as a dispersion phase; preparing an oil phase added with a cross-linking agent as a continuous phase; introducing the obtained continuous phase and the dispersed phase into a micro-fluidic chip for shearing to form chitosan droplets, and performing cross-linking and curing; cleaning the obtained cross-linked and cured chitosan particles, and drying to obtain chitosan microspheres, wherein corresponding production equipment is not involved or disclosed;
in addition, CN208732742U discloses an "automatic microorganism immobilization forming apparatus", in which a carrier is dropped into a reaction barrel, and reacts with a curing agent to form immobilized microorganism microspheres, which are discharged from a discharge port; and the automatic microorganism immobilization forming equipment also comprises a cleaning device, the cleaning device is arranged below the discharge port of the reaction barrel, and the formed immobilized microorganism microspheres are discharged into the cleaning device from the discharge port and then cleaned by deionized water. CN102211008A discloses a detachable T-shaped microchannel device and a method for preparing monodisperse polymer microspheres by using the same, which only relates to that under the action of a shaking table, an organic solvent is diffused from liquid drops, and the liquid drops are solidified to form polymer microspheres with uniform particle size; CN104829851A discloses a method for preparing monodisperse gelatin embolization microspheres with accurately controlled particle size, wherein a disperse phase I, a disperse phase II and a continuous phase are respectively loaded into an injector and are respectively connected with a microchannel reactor through a micro-injection pump, the structure of the microchannel reactor consists of a theta tube, a collecting tube and an outer tube, the formation process of gelatin droplets is completed in the microchannel reactor, and the flowing directions of the disperse phase and the continuous phase are the same or opposite; taking gelatin aqueous solution and cross-linking agent aqueous solution as two paths of dispersed phases, and simultaneously enabling the two paths of dispersed phases to parallelly enter a microchannel reactor; collecting the generated gelatin liquid drops, placing the gelatin liquid drops in a drying oven for heat preservation, carrying out crosslinking curing reaction on gelatin to obtain cured gelatin microspheres, and then carrying out microsphere separation and drying to obtain the gelatin microspheres.
From the above, in the process of producing microspheres, the related production equipment is either small equipment in a laboratory stage, or is separately arranged in the microsphere production process, namely, firstly, the liquid drops are sheared, then, the liquid drops are crosslinked and solidified to obtain microspheres, and finally, the obtained microspheres are collected to be correspondingly cleaned. Therefore, an equipment for solving the problems of incapability of automatic, continuous, industrialized and large-scale production in the microsphere production process is urgently needed.
Disclosure of Invention
The invention aims to solve the problem that the existing equipment cannot realize large-scale production in the prior art, and provides a large-scale production device for microspheres. In the technical scheme, the automation, the continuity, the industrialization and the scale of the microsphere production process are realized by arranging the micro-fluidic device, the spraying mechanism, the cross-linking device, the cleaning device and the like, the micro-fluidic microsphere production technology is promoted to the industrialization, and an effective precondition guarantee is provided for the subsequent application and production of the microspheres.
In order to achieve the technical purpose, the following technical scheme is proposed:
the large-scale production equipment for the microspheres comprises a microfluidic device, a cross-linking device and a cleaning device, wherein the cross-linking device is arranged on the front side of a station of the microfluidic device, and a spraying mechanism is arranged between the microfluidic device and the cross-linking device;
the spraying mechanism comprises a spraying pipe for conveying the cross-linking liquid and a receiving groove for receiving the cross-linking liquid and liquid drops (the liquid drops are obtained by shearing through the micro-fluidic device), and a nozzle is arranged on the spraying pipe; the receiving groove is arranged on the front side of the station of the microfluidic device, the microfluidic device is connected with a droplet discharge pipe, the other end of the droplet discharge pipe extends to the lower part and/or the bottom of the receiving groove, the bottom of the receiving groove is provided with a microsphere outlet, the microsphere outlet is arranged on the rear side of the station of the crosslinking device, and a passage for generating droplets and discharging the droplets after the droplets are pre-crosslinked and cured into microspheres is formed among the microfluidic device, the droplet discharge pipe, the receiving groove and the microsphere outlet;
the cross-linking device is arranged on the rotating mechanism and comprises at least one cross-linking unit, the cross-linking unit is connected with the rotating mechanism through a connecting rod I, and the rotation of the rotating mechanism can drive the cross-linking unit to rotate, so that on one hand, the cross-linking time of the pre-cross-linked and cured microspheres can be well controlled, on the other hand, the pre-cross-linked and cured microspheres can contact cross-linking liquid with proper concentration in different cross-linking units by adjusting the cross-linking time of the pre-cross-linked and cured microspheres, namely, the cross-linking efficiency and quality can be ensured, and in addition, the next batch of pre-cross-linked and cured microspheres can be well linked for cross-linking; the cross-linking unit comprises a cross-linking groove and a cross-linking funnel, the cross-linking funnel is detachably fixed in the cross-linking groove, the cross-linking funnel is arranged on the front side of the microsphere outlet station, and a passage for droplet generation, pre-cross-linking solidification and cross-linking is formed among the micro-fluidic device, the droplet discharge pipe, the receiving groove, the microsphere outlet and the cross-linking groove. After the microspheres to be pre-crosslinked and cured are crosslinked in the crosslinking solution, the microspheres can be collected only by taking out the crosslinking funnel from the crosslinking groove, so that the subsequent operation can be carried out, a crosslinking space and the like can be provided for the next batch of microspheres to be crosslinked and cured, and the crosslinking groove and the like can be cleaned and replaced conveniently;
the cleaning device is arranged on the front side of the station of the cross-linking device and comprises at least one cleaning unit, the cleaning unit is connected with the rotating mechanism through a connecting rod II, and the rotating mechanism rotates to drive the cleaning unit to rotate, so that the cleaning time of the microspheres can be better controlled, the microspheres can be adjusted to contact with clean cleaning liquid in different cleaning units, the cleaning efficiency and the cleaning quality are ensured, and in addition, the next batch of microspheres can be better connected for cleaning; the cleaning unit comprises a cleaning tank and a cleaning funnel, the cleaning funnel is detachably fixed in the cleaning tank, and a liquid drop generating, pre-crosslinking curing, crosslinking and cleaning passage is formed among the micro-fluidic device, the liquid drop discharge pipe, the receiving tank, the microsphere outlet, the crosslinking tank and the cleaning tank. After the microspheres are cleaned in the cleaning solution, the cleaned microspheres can be collected only by taking out the cleaning funnel from the cleaning tank, so that the subsequent operation can be performed, meanwhile, a cleaning space and the like are provided for the next batch of microspheres to be cleaned, and meanwhile, the cleaning tank and the like can be cleaned and replaced conveniently.
Preferably, the microfluidic device is a microfluidic chip, a PDMS microfluidic chip or a glass capillary microfluidic chip prepared based on a 3D printing technology. The micro-fluidic chip can be prepared in a refined and productive manner, and the micro-sphere can be produced in a large scale by the production equipment. At least two injection pumps are arranged on the rear side of the station of the microfluidic chip, the injection pumps are respectively communicated with inlets in the microfluidic chip, and an outlet in the microfluidic chip is connected with a liquid drop discharge pipe; and a raw material storage tank is arranged on the rear side of the station of the injection pump, the raw material storage tank is correspondingly connected with the injection pump, the raw materials in the raw material storage tank are introduced into the microfluidic chip through the injection pump, liquid drops are generated through the acting force between the raw materials in the microfluidic chip, and then the subsequent pre-crosslinking curing, crosslinking, cleaning and the like are carried out.
Preferably, a fixing mechanism for fixing the liquid drop discharge pipe is arranged in the receiving groove, the fixing mechanism comprises at least two fixing units, each fixing unit comprises a positioning plate and a fixing rod with a bayonet at the lower end, a through hole for installing the fixing rod is formed in the positioning plate, and a screw hole for locking the fixing rod is formed in the side surface of the positioning plate; the bayonet is matched with the liquid drop discharge pipe. The liquid drop discharge pipes are arranged in the receiving groove in order, so that the liquid drop discharge pipes are not intertwined, the orderliness of corresponding stations is improved, and the liquid drops can be discharged from the lower part and/or the bottom of the receiving groove and directly enter the crosslinking liquid to be prevented from rolling off on the wall of the receiving groove.
Preferably, the plurality of nozzles are uniformly distributed on the spray pipe, and the arrangement enables the cross-linking liquid to enter the receiving groove in a uniform, dispersed and large-range manner, so that the contact rate of the cross-linking liquid and the liquid drops is increased, namely, the contact and mutual dissolution between the liquid drops are effectively blocked, and the cross-linking curing rate of the liquid drops is improved. The nozzle is one or the combination of more than two of a rotary nozzle, a fan-shaped nozzle, a column flow nozzle and a direct flow nozzle, the spraying area of the cross-linking liquid is increased, and the contact probability between the cross-linking liquid and the liquid drops is improved; the spray pipe is fixedly arranged on the inner wall of the receiving tank, the nozzle is arranged on the rear side of a station at the outlet of the liquid drop discharge pipe, crosslinking liquid uniformly sprayed from the nozzle continuously washes microspheres crosslinked and solidified by the crosslinking liquid, the microspheres are ensured to smoothly enter a subsequent station along with the flowing of the crosslinking liquid, and the conditions of accumulation, blockage and the like of the microspheres in the receiving tank are also avoided.
Preferably, the receiving groove is provided with a plate-shaped fence member, and the shower pipe is fixedly arranged on the fence member. The arrangement can prevent the cross-linking liquid and the liquid drops from being influenced by the outside to a certain extent, ensure the stability of the liquid drop collection and pre-cross-linking curing process, prevent the microspheres formed by the process from being polluted by the outside and the like; the longitudinal section of the receiving groove is trapezoidal, U-shaped or V-shaped, so that liquid drops are driven to sink to the bottom of the groove body due to the self gravity, the contact probability between the liquid drops and the crosslinking liquid is ensured, the pre-crosslinking curing efficiency and quality are improved, and the uniformity of formed microspheres is indirectly improved; the inclination of the inclined plane of the receiving groove is 15-80 degrees. The receiving tank can be arranged on the lifting type supporting frame, the position of the receiving tank can be adjusted conveniently according to actual requirements, and the receiving tank is better matched with the liquid drop discharge pipe and the cross-linking device, so that the practicability of the receiving tank is improved.
Preferably, rotary mechanism includes the roating seat, and the roating seat is connected with the rotary pump, and the cross-linking unit passes through connecting rod I to be connected with the roating seat, and the cleaning unit passes through connecting rod II to be connected with the roating seat, and the rotary pump provides power for the rotation of roating seat, and then transmits respectively for cross-linking unit and cleaning unit. Wherein, connecting rod I and connecting rod II are hydraulic pressure connecting rod.
Preferably, the number of the cross-linking units is at least two, the number of the cleaning units is at least two, and the cross-linking units and the cleaning units are respectively arranged on the circumference with the rotating seat as the center of a circle, so that cross-linking and cleaning of each batch of microspheres subjected to pre-cross-linking and curing are facilitated, and the orderliness of cross-linking and cleaning operations is ensured.
Preferably, the crosslinking tank is provided with a crosslinking liquid inlet and a crosslinking waste liquid outlet, the crosslinking liquid inlet is connected with a crosslinking liquid storage tank through a crosslinking liquid pipe, the crosslinking waste liquid outlet is connected with a crosslinking waste liquid recovery tank through a crosslinking waste liquid recovery pipe, the crosslinking waste liquid recovery tank is connected with the spray pipe, a mixing tank is arranged between the spray pipe and the crosslinking waste liquid recovery tank, and the mixing tank is connected with a high-concentration crosslinking liquid storage tank; the crosslinking liquid orderly and effectively enters the crosslinking tank, and the crosslinking waste liquid is recycled, wherein the high-concentration crosslinking liquid storage tank and the mixing tank are arranged for preparing the crosslinking liquid with the concentration meeting the requirement for the spraying mechanism, so that the reutilization of the crosslinking waste liquid is improved, the economy of the crosslinking process related to the device is ensured, and the cost is effectively saved; the cross-linking groove one side is provided with elevating system I, and the cross-linking funnel cover is established on elevating system I, and after the microballon of a cross-linking unit department accomplished the cross-linking, the accessible will be equipped with the cross-linking funnel of microballon and propose from the cross-linking inslot, and then be convenient for control cross-linking time, simultaneously, also make things convenient for cleanness such as cross-linking groove and change etc. realize automation, serialization etc. of this equipment.
Preferably, the cleaning tank is provided with a cleaning liquid inlet and a cleaning waste liquid outlet, the cleaning liquid inlet is connected with a cleaning liquid storage tank through a cleaning liquid pipe, the cleaning waste liquid outlet is connected with a cleaning waste liquid storage tank through a cleaning waste liquid discharge pipe, so that the cleaning liquid can orderly and effectively enter the cleaning tank, and meanwhile, the cleaning waste liquid is collected, so that the stability, controllability and environmental friendliness of the cleaning process related to the device are ensured; cleaning tank one side is provided with elevating system II, and the washing funnel cover is established on elevating system II, and after the microballon of a cleaning unit department was accomplished and is washd, the accessible will be equipped with the washing funnel self-cleaning tank of microballon and propose, and then be convenient for control cleaning time, simultaneously, also make things convenient for cleaning such as washing tank and change etc. realize automation, serialization etc. of this equipment.
Preferably, the lifting mechanism I and the lifting mechanism II are both sliding type lifting mechanisms and comprise mounting columns and lead screws arranged on the mounting columns, and the cross-linking funnel and/or the cleaning funnel are/is sleeved on the lead screws; be provided with the guide rail on the erection column, be provided with on cross-linking funnel and/or the washing funnel with guide rail matched with slider, this setting can realize the semi-automatization of this device, and then guarantee the continuity of cross-linking, washing process.
Preferably, the cross-linking tank, the cleaning tank and the mixing tank are all provided with stirring mechanisms. In the crosslinking tank, on one hand, the stirring mechanism can uniformly mix the newly added crosslinking liquid and avoid the conditions of layering, segregation and the like of the crosslinking liquid in the crosslinking tank; on the other hand, the crosslinking liquid is stirred to drive the microspheres in the crosslinking tank to move ceaselessly, so that the crosslinking of the microspheres is more uniform and complete. In the cleaning tank, on one hand, the stirring mechanism uniformly disperses the cleaned waste substances in the cleaning solution by stirring so as to avoid the accumulation of the waste substances in the cleaning tank; on the other hand, the cleaning solution is stirred to drive the microspheres in the cleaning tank to move ceaselessly, so that the cleaning effect is improved.
In this technical scheme, according to actual demand, set up liquid pump, diaphragm pump, solenoid valve, conductivity detector etc. and set up corresponding motor and control system (including control panel, central processing unit and detector) etc. on corresponding pipeline, for example: controlling the raw material liquid in the raw material storage tank to be sent into the microfluidic chip through an injection pump for shearing; controlling the conveying and spraying of the crosslinking liquid to the receiving tank to ensure the pre-crosslinking solidification of the liquid drops; controlling the cross-linking liquid to enter a cross-linking tank, and discharging and recycling the cross-linking waste liquid; controlling the cleaning solution to enter a cleaning tank and discharging cleaning waste liquid; the rotating speed of the rotating mechanism is controlled to control the crosslinking of liquid drops, the cleaning batch and time and the like. The related liquid pump, diaphragm pump, electromagnetic valve, conductivity detector, motor and control system (including control panel, central processor and detector) are all the existing mature technologies. In addition, a liquid level sensor and the like may be provided in the mixing tank, the receiving tank, the crosslinking tank, the cleaning tank, and each tank body.
In the technical solution, the positional relationships such as "front side of the station", "between", "up", "other end", "lower part and/or bottom", "rear side of the station", "inside", "lower end", "side", "uniform distribution", "inner wall", "center of circle", "on circumference", "one side" and the like are defined according to the actual usage state, and are conventional terms in the technical field and conventional terms in the actual usage process of the person skilled in the art.
In the description of the present technical solution, it should be noted that, unless explicitly stated or limited otherwise, the terms "disposed" and "connected" should be understood broadly, for example, they may be fixedly connected, conveniently connected, or integrally connected; can be mechanically or electrically connected; either directly or indirectly through intervening media, or may be interconnected between two elements unless otherwise specifically limited or defined herein. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
By adopting the technical scheme, the beneficial technical effects brought are as follows:
1) the invention has simple structure, reasonable design and simple operation, can be better matched with the microsphere production process, and ensures the controllability, continuity and stability of the microsphere production process. The micro-fluidic device, the spraying mechanism, the cross-linking device, the cleaning device and the like are arranged, so that automation, continuity, industrialization and scale of the microsphere production process are realized, the micro-fluidic microsphere production technology is pushed to industrialization, and effective precondition guarantee is provided for the subsequent application and production of microspheres. Meanwhile, the problem that the existing equipment device in the prior art cannot realize large-scale production is solved;
2) in the invention, by arranging the spraying mechanism, a cross-linking liquid environment is provided for liquid drops cut by the microfluidic chip, so that the liquid drops are pre-cross-linked and solidified into microspheres at the spraying mechanism, and the liquid drops are prevented from being mutually dissolved to form uneven microspheres after being contacted. The receiving groove is arranged to receive the liquid drops cut by the microfluidic chip and ensure that the liquid drops enter a subsequent crosslinking device in an orderly and controllable manner; on the other hand, a pre-crosslinking environment is provided, the droplets are pre-crosslinked and cured to form microspheres, the microspheres are prevented from being mutually dissolved to form large droplets in the crosslinking liquid environment, and the uniformity of the particle size of the droplets before crosslinking is effectively ensured, namely, the problems that the droplets are easily mutually dissolved to form large droplets, the subsequent microspheres are uneven in particle size, the index is difficult to control and the like in the prior art are solved; in addition, the microspheres subjected to pre-crosslinking continuously enter a subsequent flow under the flowing and scouring action of a crosslinking liquid discharged by a spray pipe, so that the problems of accumulation, blockage and the like of the microspheres in a receiving groove are avoided;
3) in the invention, the crosslinking device comprises at least one crosslinking unit, the crosslinking unit comprises a crosslinking groove and a crosslinking funnel, one side of the crosslinking groove is provided with a lifting mechanism I, the crosslinking funnel is sleeved on the lifting mechanism I, the crosslinking funnel is arranged at the front side of a station of the microfluidic chip, after microspheres are crosslinked and cured in crosslinking liquid, the microspheres can be collected only by taking the crosslinking funnel out of the crosslinking groove (the crosslinking funnel is lifted), so that the subsequent cleaning is facilitated, meanwhile, a crosslinking space and the like are provided for the next batch of microspheres to be crosslinked, and the cleaning, the replacement and the like of the crosslinking groove and the like are facilitated; in addition, the matched arrangement of the crosslinking groove and the crosslinking funnel realizes the re-crosslinking of the microspheres and the convenient collection of the crosslinked microspheres;
4) according to the invention, the cleaning device comprises at least one cleaning unit, the cleaning unit comprises a cleaning tank and a cleaning funnel, a lifting mechanism II is arranged on one side of the cleaning tank, the cleaning funnel is sleeved on the lifting mechanism II, after microspheres are cleaned in cleaning liquid, the cleaned microspheres can be collected only by taking out the cleaning funnel from the cleaning tank (the cleaning funnel is lifted), so that the subsequent treatment and the like are facilitated, meanwhile, a cleaning space and the like are provided for the next batch of microspheres to be cleaned, and the cleaning tank and the like are also convenient to clean and replace; in addition, the cleaning tank and the cleaning funnel are matched, so that the microspheres are cleaned, and the microspheres are convenient to collect after being cleaned;
5) in the invention, the rotation of the rotating mechanism can drive the cross-linking unit and the cleaning unit to rotate, so that on one hand, the cross-linking time and the cleaning time of the microspheres subjected to pre-cross-linking and curing can be better controlled, on the other hand, the microspheres subjected to pre-cross-linking and curing can be contacted with cross-linking liquid with proper concentration in different cross-linking units by adjusting, so that the cross-linking efficiency and the quality are ensured, and the microspheres subjected to cross-linking and curing can be contacted with clean cleaning liquid in different cleaning units by adjusting, so that the cleaning efficiency and the quality are ensured; in addition, the microspheres to be crosslinked in the next batch can be well linked for crosslinking and/or the microspheres to be cleaned in the next batch can be cleaned;
6) in the present invention, the cross-linking tank, the cleaning tank and the mixing tank are provided with stirring mechanisms. In the crosslinking tank, on one hand, the stirring mechanism can uniformly mix the newly added crosslinking liquid and avoid the conditions of layering, segregation and the like of the crosslinking liquid in the crosslinking tank; on the other hand, the crosslinking liquid is stirred to drive the microspheres in the crosslinking tank to move ceaselessly, so that the crosslinking of the microspheres is more uniform and complete. In the cleaning tank, on one hand, the stirring mechanism uniformly disperses the cleaned waste substances in the cleaning solution by stirring so as to avoid the accumulation of the waste substances in the cleaning tank; on the other hand, the cleaning solution is stirred to drive the microspheres in the cleaning tank to move ceaselessly, so that the cleaning effect is improved;
7) in the invention, the cross-linking device is arranged at the front side of the station of the micro-fluidic device, the spraying mechanism is arranged between the micro-fluidic device and the cross-linking device, and the cleaning device is arranged at the front side of the station of the cross-linking device, namely, the specific composition, specific position association and connection relation of each part ensure the orderliness, controllability, continuity, economy, environmental protection and the like of the procedures of liquid drop generation, pre-cross-linking solidification, cross-linking, cleaning, corresponding conveying and discharging and the like, and simultaneously realize the automation of the equipment, facilitate the arrangement of the equipment and save the limited space occupied by production.
Drawings
FIG. 1 is a schematic structural view of the present invention;
FIG. 2 is a schematic diagram of the operation of the present invention;
FIG. 3 is a schematic structural view of a spraying mechanism according to the present invention;
FIG. 4 is a schematic view showing the structure of a receiving groove in the present invention;
FIG. 5 is a schematic structural view of a fixing unit according to the present invention;
FIG. 6 is a schematic structural view of a microfluidic device and a spraying mechanism in practical application;
FIG. 7 is a schematic structural view of a crosslinking unit in the present invention;
FIG. 8 is a schematic view of the structure of a crosslinking bath in the present invention;
FIG. 9 is a schematic view of the structure of a cleaning unit according to the present invention;
FIG. 10 is a schematic view of the cleaning tank of the present invention;
FIG. 11 is a schematic structural view (one) of the cross-linking funnel or the washing funnel in the lifting state of the present invention;
FIG. 12 is a schematic diagram of the lifting state of the cross-linking funnel or the washing funnel according to the present invention;
wherein: 1. a micro-fluidic chip, 101, a liquid drop discharge pipe, 2, a rotating mechanism, 201, a rotating base, 3, a cross-linking device, 31, a connecting rod I, 32, a cross-linking groove, 33, a cross-linking funnel, 34, a lifting mechanism I, 4, a cleaning device, 41, a connecting rod II, 42, a cleaning groove, 43, a cleaning funnel, 44, a lifting mechanism II, 5, a spraying mechanism, 51, a spraying pipe, 52, a receiving groove, 53, a nozzle, 54, a microsphere outlet, 55, a microsphere discharge pipe, 6, an injection pump, 7, a raw material storage tank, 8, a fixing mechanism, 81, a positioning plate, 82, a fixing rod, 83, a bayonet, 84, a through hole, 85, a screw hole, 9, a cross-linking piece, 10, a cross-linking liquid inlet, 11, a cross-linking waste liquid outlet, 12, a cross-linking fence liquid pipe, 13, a cross-linking liquid storage tank, 14, a cross-linking waste liquid recycling pipe, 15, a cross-linking waste recycling tank, 16, a cleaning liquid inlet, 17 and a cleaning waste outlet, 18. a cleaning liquid pipe 19, a cleaning liquid storage tank 20, a cleaning waste liquid discharge pipe 21, a cleaning waste liquid storage tank 22, a mounting column 23, a screw rod 24, a guide rail 25, a slide block 26, a stirring mechanism 27, a mixing tank 28 and a high-concentration cross-linking liquid storage tank.
Detailed Description
In the following, the technical solutions in the embodiments of the present invention are clearly and completely described, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
As shown in fig. 1-2: the large-scale production equipment for the microspheres comprises a microfluidic device, a cross-linking device 3 and a cleaning device 4, wherein the cross-linking device 3 is arranged on the front side of a station of the microfluidic device, and a spraying mechanism 5 is arranged between the microfluidic device and the cross-linking device 3;
as shown in fig. 3: the spraying mechanism 5 comprises a spraying pipe 51 for conveying the cross-linking liquid and a receiving groove 52 for receiving the cross-linking liquid and liquid drops (the liquid drops are obtained by shearing through the microfluidic device), and a nozzle 53 is arranged on the spraying pipe 51; the receiving groove 52 is arranged at the front side of the station of the microfluidic device, the microfluidic device is connected with a droplet discharge pipe 101, the other end of the droplet discharge pipe 101 extends to the lower part and/or the bottom of the receiving groove 52, the bottom of the receiving groove 52 is provided with a microsphere outlet 54, the microsphere outlet 54 is arranged at the rear side of the station of the crosslinking device 3, and a passage for generating droplets, pre-crosslinking and solidifying the droplets into microspheres and discharging the microspheres is formed among the microfluidic device, the droplet discharge pipe 101, the receiving groove 52 and the microsphere outlet 54 (as shown in fig. 6);
wherein, the microsphere outlet 54 is connected with a microsphere discharge pipe 55 (hose), and the other end of the microsphere discharge pipe 55 extends into the crosslinking device 3; the receiving groove 52 is arranged on the lifting type supporting frame, so that the position of the receiving groove 52 can be conveniently adjusted according to actual requirements, namely the receiving groove is better matched with the pre-crosslinking curing process, and the practicability of the receiving groove 52 is further improved;
the cross-linking device 3 is arranged on the rotating mechanism 2, the cross-linking device 3 comprises at least one cross-linking unit, the cross-linking unit is connected with the rotating mechanism 2 through a connecting rod I31, and the rotation of the rotating mechanism 2 can drive the cross-linking unit to rotate, so that on one hand, the cross-linking time of the pre-cross-linked and cured microspheres can be better controlled, on the other hand, the pre-cross-linked and cured microspheres can contact cross-linking liquid with proper concentration in different cross-linking units by adjusting the pre-cross-linked and cured microspheres, namely, the cross-linking efficiency and quality are ensured, and in addition, the next batch of pre-cross-linked and cured microspheres can be better linked for cross-linking; as shown in fig. 7, the crosslinking unit includes a crosslinking groove 32 and a crosslinking funnel 33, the crosslinking funnel 33 is detachably fixed in the crosslinking groove 32, the crosslinking funnel 33 is disposed at the front side of the microsphere outlet 54, and a droplet generation, pre-crosslinking curing and crosslinking path is formed among the microfluidic device, the droplet discharge pipe 101, the receiving groove 52, the microsphere outlet 54 and the crosslinking groove 32. After the microspheres to be pre-crosslinked and cured are crosslinked in the crosslinking solution, the microspheres can be collected only by taking out the crosslinking funnel 33 from the crosslinking groove 32, so that the subsequent operation can be performed, a crosslinking space and the like can be provided for the next batch of microspheres to be crosslinked and cured, and the crosslinking groove 32 and the like can be cleaned and replaced conveniently;
the cleaning device 4 is arranged on the front side of the station of the cross-linking device 3, the cleaning device 4 comprises at least one cleaning unit, the cleaning unit is connected with the rotating mechanism 2 through a connecting rod II 41, and the rotating mechanism 2 rotates to drive the cleaning unit to rotate, so that the cleaning time of the microspheres can be controlled better, the microspheres can be contacted with clean cleaning liquid in different cleaning units by adjusting the microspheres, the cleaning efficiency and the cleaning quality are ensured, and in addition, the next batch of microspheres can be better connected for cleaning; as shown in fig. 9, the cleaning unit includes a cleaning tank 42 and a cleaning funnel 43, the cleaning funnel 43 is detachably fixed in the cleaning tank 42, and a path for droplet generation, pre-crosslinking curing, crosslinking, and cleaning is formed among the microfluidic device, the droplet discharge pipe 101, the receiving tank 52, the microsphere outlet 54, the crosslinking tank 32, and the cleaning tank 42. After the microspheres are cleaned in the cleaning solution, the cleaned microspheres can be collected by taking out the cleaning funnel 43 from the cleaning tank 42, so that the subsequent operation can be performed, a cleaning space is provided for the next batch of microspheres to be cleaned, and the cleaning tank 42 and the like can be cleaned and replaced conveniently.
Wherein, the cross-linking funnel 33 and/or the cleaning funnel 43 are provided with a plurality of filtering holes of 100 meshes which are uniformly distributed. After the cross-linking funnel 33 and/or the cleaning funnel 43 are taken out from the cross-linking tank 32 and/or the cleaning tank 42, the cross-linking liquid or the cleaning liquid is filtered and discharged through the filter holes, and the collection of the microspheres is further realized.
In this embodiment, the cross-linking unit and the washing unit may be configured to be identical, such as: the method specifically comprises the steps that the structure, the shape, the component composition, the position, the connection relation and the like are consistent, and when a crosslinking liquid medium is put into the unit, the unit is a crosslinking unit, so that the re-crosslinking of pre-crosslinking curing is realized; when a cleaning liquid medium is put into the unit, the cleaning unit is used for cleaning the microspheres. And further, the assembly, the replacement and the cleaning are convenient, the processing, the assembly, the arrangement and the like are also convenient, and one mechanism can be a cross-linking unit and a cleaning unit.
In addition, in this embodiment, according to actual requirements, a liquid pump, a diaphragm pump, an electromagnetic valve, a conductivity detector, etc. are disposed on corresponding pipelines, and a corresponding motor and control system (including a control panel, a central processing unit, and a detector) are disposed, for example: the raw material liquid in the raw material storage tank 7 is controlled to be sent into the microfluidic chip 1 through the injection pump 6 for shearing; controlling the transportation and ejection of the crosslinking liquid into the receiving tank 52 to ensure the pre-crosslinking solidification of the liquid droplets; controlling the cross-linking liquid to enter a cross-linking tank 32 and discharging and recycling the cross-linking waste liquid; controlling the cleaning liquid to enter the cleaning tank 42 and the discharge of the cleaning waste liquid; by controlling the rotation speed of the rotating mechanism 2, the droplet crosslinking, the cleaning lot and time, and the like are controlled. The related liquid pump, diaphragm pump, electromagnetic valve, conductivity detector, motor and control system (including control panel, central processor and detector) are all the existing mature technologies. Further, liquid level sensors and the like may be provided in the mixing tank 27, the receiving tank 52, the crosslinking tank 32, the cleaning tank 42, and the respective tanks.
Example 2
Based on example 1, this example relates to a specific setup of a microfluidic device, and further,
the micro-fluidic device is a micro-fluidic chip 1, a PDMS micro-fluidic chip or a glass capillary micro-fluidic chip which is prepared based on a 3D printing technology. The micro-fluidic chip 1 can be prepared in a refined and productive manner, and the production equipment can be used for producing the microspheres in a large scale.
In addition, the rear side of the working position of the microfluidic chip 1 is provided with at least two injection pumps 6, the injection pumps 6 are respectively communicated with inlets in the microfluidic chip 1, and an outlet in the microfluidic chip 1 is connected with a liquid drop discharge pipe 101; a raw material storage tank 7 is arranged on the rear side of a station of the injection pump 6, the raw material storage tank 7 is correspondingly connected with the injection pump 6, raw materials in the raw material storage tank 7 are introduced into the microfluidic chip 1 through the injection pump 6, liquid drops are generated through the acting force between the raw materials in the microfluidic chip 1, and then the subsequent pre-crosslinking curing, crosslinking, cleaning and the like are carried out.
The number and specific positions of the microfluidic chip 1, the syringe pump 6 and the raw material storage tank 7 can be further defined according to the shape and size of the receiving groove 52, the existing production space, and the like.
Such as: eight micro-fluidic chips 1 are arranged on one side of the receiving groove 52, eight injection pumps 6 (four inner phase liquid injection pumps 6 and four outer phase liquid injection pumps 6) and two raw material storage tanks 7 are correspondingly arranged on the eight micro-fluidic chips 1, one is an outer phase liquid storage tank, and the other is an inner phase liquid storage tank. When liquid drops are cut through the microfluidic chip 1A, the external phase liquid storage tank is connected with the injection pump 6A through the external phase liquid conveying pipe, and the injection pump 6A is connected with an external phase liquid inlet in the microfluidic chip 1A; the inner phase liquid storage tank is connected with an injection pump 6B through an inner phase liquid conveying pipe, and the injection pump 6B is connected with an outer phase liquid inlet in the microfluidic chip 1A;
when liquid drops are cut through the microfluidic chip 1B, the external phase liquid storage tank is connected with the injection pump 6A through the external phase liquid conveying pipe, and the injection pump 6A is connected with an external phase liquid inlet in the microfluidic chip 1B; the inner phase liquid storage tank is connected with an injection pump 6B through an inner phase liquid conveying pipe, and the injection pump 6B is connected with an outer phase liquid inlet in the microfluidic chip 1B.
The raw materials are provided for the shearing process of the microfluidic core, and the raw materials can enter the microfluidic core orderly and controllably, namely, the effectiveness and stability of the process are ensured.
Example 3
Based on embodiments 1-2, the present embodiment relates to the specific arrangement of the receiving groove 52, and further,
a fixing mechanism 8 for fixing the droplet discharge pipe 101 is arranged in the receiving groove 52, the fixing mechanism 8 comprises at least two fixing units, as shown in fig. 5, each fixing unit comprises a positioning plate 81 and a fixing rod 82 with a bayonet 83 at the lower end, a through hole 84 for installing the fixing rod 82 is arranged on the positioning plate 81, and a screw hole 85 for locking the fixing rod 82 is arranged on the side surface of the positioning plate 81; the bayonet 83 is provided in cooperation with the droplet discharge tube 101. The liquid drop discharge pipes 101 are arranged in the receiving groove 52 in order, so that the liquid drop discharge pipes 101 are not entangled with each other, the order of the corresponding stations is improved, and the liquid drops can be discharged from the lower part and/or the bottom of the receiving groove 52 and directly enter the crosslinking liquid, and the liquid drops are prevented from rolling off on the wall of the receiving groove 52.
Further, the receiving groove 52 is provided with a fence member 9 (shown in fig. 4) having a plate shape, and the shower pipe 51 is fixedly provided on the fence member 9 (having a plate shape). The arrangement can prevent the cross-linking liquid and the liquid drops from being influenced by the outside to a certain extent, ensure the stability of the liquid drop collection and pre-cross-linking curing process, prevent the microspheres formed by the process from being polluted by the outside and the like; the longitudinal section of the receiving groove 52 is trapezoidal, U-shaped or V-shaped, so that the liquid drops are driven to sink to the bottom of the groove body due to the self gravity, the contact probability between the liquid drops and the crosslinking liquid is ensured, the pre-crosslinking curing efficiency and quality are improved, and the uniformity of the formed microspheres is indirectly improved; the inclination of the inclined surface of the receiving groove 52 is 15 to 80. The receiving groove 52 can be arranged on the lifting support frame, so that the position of the receiving groove 52 can be conveniently adjusted according to actual requirements, the receiving groove is better matched with the liquid drop discharge pipe 101 and the cross-linking device 3, and the practicability of the receiving groove 52 is further improved.
Example 4
Based on embodiments 1-3, this embodiment relates to specific arrangements of the spray nozzles 53 and the shower pipes 51, and, further,
the plurality of nozzles 53 are uniformly distributed on the spray pipe 51, and the arrangement enables the cross-linking liquid to enter the receiving groove 52 uniformly, dispersedly and in a large range, the contact rate of the cross-linking liquid and liquid drops is increased, namely, the contact and mutual dissolution between the liquid drops are effectively blocked, and the cross-linking curing rate of the liquid drops is improved.
The nozzle 53 is one or a combination of more than two of a rotary nozzle 53, a fan-shaped nozzle 53, a column flow nozzle 53 and a straight flow nozzle 53, and the spraying area of the cross-linking liquid is increased, namely the contact probability between the cross-linking liquid and liquid drops is improved; the spray pipe 51 is fixedly arranged on the inner wall of the receiving groove 52, the nozzle 53 is arranged at the rear side of the station at the outlet of the liquid drop discharge pipe 101, and the crosslinking liquid uniformly sprayed from the nozzle 53 continuously washes the microspheres crosslinked and solidified by the crosslinking liquid, so that the microspheres are ensured to smoothly enter the subsequent station along with the flow of the crosslinking liquid, and the conditions of accumulation, blockage and the like of the microspheres in the receiving groove 52 are avoided.
Example 5
Based on embodiments 1-4, this embodiment relates to the specific arrangement between the rotating mechanism 2, the cross-linking unit, the link i 31, the cleaning unit and the link ii 41, and further,
rotary mechanism 2 includes roating seat 201, and roating seat 201 is connected with the rotary pump, and the cross-linking unit is connected with roating seat 201 through connecting rod I31, and the cleaning unit is connected with roating seat 201 through connecting rod II 41, and the rotary pump provides power for the rotation of roating seat 201, and then transmits respectively to cross-linking unit and cleaning unit. Wherein, connecting rod I31 and connecting rod II 41 are hydraulic connecting rods.
The cross-linking units are at least two, the cleaning units are at least two, and the cross-linking units and the cleaning units are respectively arranged on the circumference with the rotating seat 201 as the circle center, so that cross-linking and cleaning of each batch of microspheres subjected to pre-cross-linking and curing are facilitated, and the orderliness of the cross-linking and cleaning operations is ensured.
When the number of the cross-linking units is at least three or/and the number of the cleaning units is at least three, the cross-linking units and the cleaning units can be alternately arranged, such as: the cross-linking unit, the cleaning unit, the cross-linking unit, the cleaning unit and the like are arranged in sequence; such as: the cross-linking unit, the cleaning unit, the cross-linking unit, the cleaning unit and the like are arranged in sequence; such as: the cross-linking unit, the cleaning unit and the like are arranged in sequence according to the law, and the like, and can be set according to actual requirements. The concentration of the crosslinking solution in each crosslinking unit can be kept consistent, and the concentration can also be set in a gradient manner, so that the crosslinking quality, the crosslinking efficiency and the like are mainly ensured in the crosslinking process.
Example 6
Based on examples 1-5, this example relates to a specific arrangement of the crosslinking grooves 32, and further,
as shown in fig. 2 and 8, a crosslinking liquid inlet 10 and a crosslinking waste liquid outlet 11 are provided in the crosslinking tank 32, the crosslinking liquid inlet 10 is connected to a crosslinking liquid storage tank 13 through a crosslinking liquid pipe 12, the crosslinking waste liquid outlet 11 is connected to a crosslinking waste liquid recovery tank 15 through a crosslinking waste liquid recovery pipe 14, the crosslinking waste liquid recovery tank 15 is connected to the spray pipe 51, a mixing tank 27 is provided between the spray pipe 51 and the crosslinking waste liquid recovery tank 15, and the mixing tank 27 is connected to a high-concentration crosslinking liquid storage tank 28. The crosslinking liquid orderly and effectively enters the crosslinking tank 32, and the crosslinking waste liquid is recycled, wherein the high-concentration crosslinking liquid storage tank and the mixing tank 27 are used for mixing the crosslinking liquid with the concentration meeting the requirement for the spraying mechanism 5, so that the availability of the crosslinking waste liquid is improved, the economy of the crosslinking process related to the device is ensured, and the cost is effectively saved; the specific positions (one above the other, or one left and one right) and the number of the crosslinking liquid inlet 10 and the crosslinking waste liquid outlet 11 on the crosslinking tank 32 can be adjusted according to actual requirements. Crosslinking groove 32 one side is provided with elevating system I34, and crosslinked funnel 33 cover is established on elevating system I34, and after the microballon of a crosslinking unit department accomplished the crosslinking, the accessible will be equipped with crosslinked funnel 33 of microballon and propose from crosslinking groove 32 in, and then be convenient for control the crosslinking time, simultaneously, also make things convenient for crosslinking groove 32 etc. clean and change etc. realize automation, serialization etc. of this equipment.
Among them, as shown in fig. 11-12: the lifting mechanism I34 is a sliding type lifting mechanism and comprises a mounting column 22 and a lead screw 23 arranged on the mounting column 22, and a cross-linking funnel 33 is sleeved on the lead screw 23; the installation column 22 is provided with a guide rail 24, and the cross-linking funnel 33 is provided with a slide block 25 matched with the guide rail 24, so that the automation of the equipment can be realized, and the continuity of a cross-linking process is further ensured.
And other lifting mechanisms known in the art may be used.
Example 7
Based on embodiments 1-6, this embodiment relates to a specific configuration of the cleaning tank 42, and further,
as shown in fig. 2 and 10, the cleaning tank 42 is provided with a cleaning solution inlet 16 and a cleaning waste solution outlet 17, the cleaning solution inlet 16 is connected to a cleaning solution storage tank 19 through a cleaning solution pipe 18, the cleaning waste solution outlet 17 is connected to a cleaning waste solution storage tank 21 through a cleaning waste solution discharge pipe 20, so that the cleaning solution can orderly and effectively enter the cleaning tank 42, and meanwhile, the cleaning waste solution is collected, so that the stability, controllability and environmental friendliness of the cleaning process related to the cleaning device are ensured, and the specific positions (one above the other, or one left and one right) and the number of the cleaning solution inlet 16 and the cleaning waste solution outlet 17 on the cleaning tank 42 are limited, and can be adjusted according to actual requirements; a lifting mechanism II 44 is arranged on one side of the cleaning tank 42, the cleaning funnel 43 is sleeved on the lifting mechanism II 44, and after the microspheres in one cleaning unit are cleaned, the cleaning funnel 43 filled with the microspheres can be lifted out of the cleaning tank 42, so that the cleaning time is convenient to control, meanwhile, the cleaning tank 42 and the like are convenient to clean and replace, and the automation, the continuity and the like of the equipment are realized.
Among them, as shown in fig. 11-12: the lifting mechanisms II 44 are sliding type lifting mechanisms and comprise mounting columns 22 and lead screws 23 arranged on the mounting columns 22, and the cleaning funnels 43 are sleeved on the lead screws 23; be provided with guide rail 24 on the erection column 22, be provided with on the washing funnel 43 with guide rail 24 matched with slider 25, this setting can realize the semi-automatization of this equipment, and then guarantee the continuity of washing process.
And other lifting mechanisms known in the art may be used.
Example 8
Based on examples 6-7, this example describes the cross-linking tank 32, the cleaning tank 42, and the mixing tank 27, and further,
the crosslinking tank 32, the cleaning tank 42 and the mixing tank 27 are provided with a stirring mechanism 26 (for example, SR-MS-20L magnetic stirrer). In the crosslinking tank 32, the stirring mechanism 26 can uniformly mix the newly added crosslinking liquid and avoid the conditions of crosslinking liquid layering, segregation and the like in the crosslinking tank 32; on the other hand, the crosslinking liquid is stirred to drive the microspheres in the crosslinking tank 32 to move ceaselessly, so that the crosslinking of the microspheres is more uniform and complete. In the cleaning tank 42, the stirring mechanism 26 uniformly disperses the cleaned waste substances in the cleaning solution by stirring to avoid the accumulation of the waste substances in the cleaning tank 42; on the other hand, the cleaning solution is stirred to drive the microspheres in the cleaning tank 42 to move ceaselessly, so that the cleaning effect is improved.
And, other agitators known in the art may be used.
Claims (10)
1. The large-scale production equipment of the microspheres is characterized by comprising a micro-fluidic device, a cross-linking device (3) and a cleaning device (4), wherein the cross-linking device (3) is arranged on the front side of a station of the micro-fluidic device, and a spraying mechanism (5) is arranged between the micro-fluidic device and the cross-linking device (3);
the spraying mechanism (5) comprises a spraying pipe (51) for conveying the cross-linking liquid and a receiving groove (52) for receiving the cross-linking liquid and the liquid drops, and a nozzle (53) is arranged on the spraying pipe (51); the receiving groove (52) is arranged on the front side of a station of the microfluidic device, the microfluidic device is connected with a droplet discharge pipe (101), the other end of the droplet discharge pipe (101) extends to the lower part and/or the bottom of the receiving groove (52), a microsphere outlet (54) is arranged at the bottom of the receiving groove (52), the microsphere outlet (54) is arranged on the rear side of the station of the crosslinking device (3), and a passage for generating, pre-crosslinking, curing and discharging droplets is formed among the microfluidic device, the droplet discharge pipe (101), the receiving groove (52) and the microsphere outlet (54);
the cross-linking device (3) is arranged on the rotating mechanism (2), the cross-linking device (3) comprises at least one cross-linking unit, and the cross-linking unit is connected with the rotating mechanism (2) through a connecting rod I (31); the cross-linking unit comprises a cross-linking groove (32) and a cross-linking funnel (33), the cross-linking funnel (33) is detachably fixed in the cross-linking groove (32), the cross-linking funnel (33) is arranged on the front side of a microsphere outlet (54) station, and a passage for generating droplets, pre-cross-linking and curing and cross-linking is formed among the microfluidic device, the droplet discharge pipe (101), the receiving groove (52), the microsphere outlet (54) and the cross-linking groove (32);
the cleaning device (4) is arranged on the front side of the station of the cross-linking device (3), the cleaning device (4) comprises at least one cleaning unit, and the cleaning unit is connected with the rotating mechanism (2) through a connecting rod II (41); the cleaning unit comprises a cleaning tank (42) and a cleaning funnel (43), the cleaning funnel (43) is detachably fixed in the cleaning tank (42), and a passage for generating liquid drops, pre-crosslinking and curing, crosslinking and cleaning is formed among the micro-fluidic device, the liquid drop discharge pipe (101), the receiving tank (52), the microsphere outlet (54), the crosslinking tank (32) and the cleaning tank (42).
2. The large-scale production equipment of the microspheres according to claim 1, wherein the microfluidic device is a microfluidic chip (1), a PDMS microfluidic chip or a glass capillary microfluidic chip prepared based on a 3D printing technology, at least two injection pumps (6) are arranged on the rear side of a station of the microfluidic chip (1), the injection pumps (6) are respectively communicated with corresponding inlets in the microfluidic chip (1), and an outlet in the microfluidic chip (1) is connected with a droplet discharge pipe (101); a raw material storage tank (7) is arranged on the rear side of the station of the injection pump (6), and the raw material storage tank (7) is correspondingly connected with the injection pump (6).
3. The large-scale production equipment of the microspheres as claimed in claim 1, wherein a fixing mechanism (8) for fixing the liquid droplet discharge pipe (101) is arranged in the receiving groove (52), the fixing mechanism (8) comprises at least two fixing units, each fixing unit comprises a positioning plate (81) and a fixing rod (82) with a bayonet (83) at the lower end, a through hole (84) for installing the fixing rod (82) is formed in the positioning plate (81), and a screw hole (85) for locking the fixing rod (82) is formed in the side surface of the positioning plate (81); the bayonet (83) is matched with the liquid drop discharge pipe (101).
4. Equipment for the large-scale production of microspheres according to claim 3, wherein the number of nozzles (53) is multiple and evenly distributed on the spray pipe (51); the spray pipe (51) is fixedly arranged on the inner wall of the receiving groove (52), and the spray nozzle (53) is arranged at the rear side of the station at the outlet of the liquid drop discharge pipe (101).
5. The large-scale production equipment of the microspheres according to claim 3 or 4, wherein the receiving groove (52) is provided with a plate-shaped fence member (9), and the spray pipe (51) is fixedly arranged on the fence member (9); the longitudinal section of the receiving groove (52) is trapezoidal, U-shaped or V-shaped, and the inclination of the inclined surface of the receiving groove (52) is 15-80 degrees.
6. The large-scale production equipment of the microspheres according to claim 1, wherein the rotating mechanism (2) comprises a rotating base (201), the rotating base (201) is connected with a rotary pump, the cross-linking unit is connected with the rotating base (201) through a connecting rod I (31), the cleaning unit is connected with the rotating base (201) through a connecting rod II (41), and the connecting rod I (31) and the connecting rod II (41) are hydraulic connecting rods.
7. The large-scale production equipment of microspheres according to claim 6, wherein the number of the cross-linking units is at least two, the number of the cleaning units is at least two, and the cross-linking units and the cleaning units are respectively arranged on a circumference with the rotating base (201) as a center.
8. The large-scale production equipment of the microspheres according to claim 1, wherein the crosslinking tank (32) is provided with a crosslinking liquid inlet (10) and a crosslinking waste liquid outlet (11), the crosslinking liquid inlet (10) is connected with a crosslinking liquid storage tank (13) through a crosslinking liquid pipe (12), the crosslinking waste liquid outlet (11) is connected with a crosslinking waste liquid recovery tank (15) through a crosslinking waste liquid recovery pipe (14), the crosslinking waste liquid recovery tank (15) is connected with the spray pipe (51), a mixing tank (27) is arranged between the spray pipe (51) and the crosslinking waste liquid recovery tank (15), and the mixing tank (27) is connected with a high-concentration crosslinking liquid storage tank (28); one side of the cross-linking groove (32) is provided with a lifting mechanism I (34), and a cross-linking funnel (33) is sleeved on the lifting mechanism I (34);
the cleaning tank (42) is provided with a cleaning liquid inlet (16) and a cleaning waste liquid outlet (17), the cleaning liquid inlet (16) is connected with a cleaning liquid storage tank (19) through a cleaning liquid pipe (18), and the cleaning waste liquid outlet (17) is connected with a cleaning waste liquid storage tank (21) through a cleaning waste liquid discharge pipe (20); one side of the cleaning tank (42) is provided with a lifting mechanism II (44), and the cleaning funnel (43) is sleeved on the lifting mechanism II (44).
9. The large-scale production equipment of the microspheres according to claim 8, wherein the lifting mechanism I (34) and the lifting mechanism II (44) are both sliding type lifting mechanisms, and comprise mounting columns (22) and lead screws (23) arranged on the mounting columns (22), and the cross-linking funnel (33) and/or the cleaning funnel (43) are/is sleeved on the lead screws (23); the mounting column (22) is provided with a guide rail (24), and the cross-linking funnel (33) and/or the cleaning funnel (43) is/are provided with a slide block (25) matched with the guide rail (24).
10. The large-scale production equipment of the microspheres according to claim 8, wherein the cross-linking tank (32), the cleaning tank (42) and the mixing tank (27) are all provided with stirring mechanisms (26).
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