CN117695908A

CN117695908A - Mixing device and mixing system

Info

Publication number: CN117695908A
Application number: CN202211086047.5A
Authority: CN
Inventors: 宋相容; 莫邦辉; 辜勇军; 魏霞蔚; 魏于全
Original assignee: Chengdu Westin Biomedical Technology Co ltd
Current assignee: Chengdu Westin Biomedical Technology Co ltd
Priority date: 2022-09-06
Filing date: 2022-09-06
Publication date: 2024-03-15

Abstract

The present disclosure provides a mixing device, comprising: a mixing tube having a liquid inlet and a liquid outlet; a first mixing portion provided in the mixing pipe, at least a portion of the first mixing portion being formed in a spiral shape; the spiral first mixing part is provided with an accommodating space; and a second mixing part provided in the accommodation space; wherein a gap is formed between the second mixing part and the first mixing part, so that the liquid to be mixed can enter the mixing pipe from the liquid inlet, and at least flow and mix from the gap and then be discharged from the liquid outlet. The present disclosure also provides a mixing system.

Description

Mixing device and mixing system

Technical Field

The present disclosure relates to mixing devices, and more particularly, to a passive nano-formulation mixing device.

Background

Microfluidic fishbone mixer (Bellveau et al 2012). The fish bone mixer is a mixing structure with herring bone grooves, shaped like a fish bone, with two inlets, one for the ethanol solution of lipids and the other for the RNA buffer solution. In preparing the sample, the lipid ethanol solution and RNA buffer are pumped into the two inlets of the fishbone mixer by syringe pump, when the two fluids meet at the mixing structure of the herringbone groove, they fold and wind each other, the diffusion length between the two fluids is exponentially reduced, which allows the two fluids to be rapidly mixed on the millisecond time scale, the lipid-containing ethanol solution is rapidly diluted during mixing, resulting in precipitation of lipid material from the ethanol phase, and self-assembly with RNA to form lipid nanoparticle particles or liposomes. The encapsulation rate of RNA in the RNA-lipid nanoparticle particles or liposome complexes prepared by the method can exceed 90 percent. The particle size is adjusted by varying the PEG lipid content of the formulation and the mixing flow rate.

The limitations of microfluidic fishbone mixers are: the micro-fluidic chip is only suitable for small-scale production and preparation of laboratory level, and is formed by processing cycloolefin copolymer, so that the use of solvents is limited, and the micro-channel with the shape of fishbone is complex in structure, high in pressure drop, easy to block and unable to bear high flow rate, so that the micro-fluidic chip is not suitable for large-scale production.

T-tube mixers (Jeffs et al 2005). In this method, the nucleic acid is dissolved in an acidic buffer, while the cationic lipid, DSPC, cholesterol and PEG lipids are dissolved in an ethanol solution. When the two solutions are pumped into a T-shaped pipe mixer for mixing by adopting a peristaltic pump, the ethanol solution containing the lipid is rapidly diluted, so that the lipid material is separated out of the ethanol phase, wherein positively charged cationic lipid and nucleic acid are adsorbed together through static electricity, and the positively charged cationic lipid and other lipids are self-assembled to form the lipid nanoparticle. The residual ethanol in the final mixture was removed by dialysis. The method can prepare particles with the diameter of 70 to 80 nanometers, and the RNA encapsulation efficiency can exceed 90 percent.

The limitations of T-tube mixers are: it is difficult to apply the process to laboratory preparation scale due to the high flow rates required to achieve rapid mixing.

Disclosure of Invention

In order to solve one of the above technical problems, the present disclosure provides a mixing device.

According to one aspect of the present disclosure, there is provided a mixing device comprising:

a mixing tube having a liquid inlet and a liquid outlet;

a first mixing portion provided in the mixing pipe, at least a portion of the first mixing portion being formed in a spiral shape; the spiral first mixing part is provided with an accommodating space; and at least part of the helical portion of the first mixing section is in contact with the inner wall of the mixing tube; and

a second mixing part provided in the accommodation space;

wherein a gap is formed between the second mixing part and the first mixing part, so that the liquid to be mixed can enter the mixing pipe from the liquid inlet, and at least flow and mix from the gap and then be discharged from the liquid outlet.

In accordance with at least one embodiment of the present disclosure, the first mixing part includes a coil spring having an outer diameter equal to or smaller than an inner diameter of the mixing tube.

According to the mixing device of at least one embodiment of the present disclosure, the second mixing part includes a plurality of balls provided in a flow direction of the liquid, the balls having a diameter smaller than an inner diameter of the coil spring, thereby having a gap between the balls and the coil spring.

In accordance with a mixing device of at least one embodiment of the present disclosure, the liquid to be mixed flows at least along the outer surface of the sphere.

According to a mixing device of at least one embodiment of the present disclosure, the gap has a size of 0.005-10mm.

Preferably 0.01-1mm.

Preferably 0.02-0.5mm.

According to the mixing device of at least one embodiment of the present disclosure, at least one end of the mixing tube is provided with a clamping double-pass joint for restricting the first mixing part and the second mixing part.

In accordance with at least one embodiment of the present disclosure, the two-way joint has a flow channel therein, and the flow channel of the two-way joint has a cross-sectional area substantially the same as an effective cross-sectional area of the mixing device.

A mixing device according to at least one embodiment of the present disclosure, further comprising:

the liquid discharge pipe is connected to the clamping double-pass joint and provided with a circulating channel, and the cross section area of the circulating channel of the liquid discharge pipe is approximately the same as the effective cross section area of the mixing device.

According to another aspect of the present disclosure, there is provided a mixing system comprising the mixing device described above.

A mixing system according to at least one embodiment of the present disclosure, further comprising:

a first liquid inlet pipe for providing a first liquid to the mixing pipe; and

and a second liquid inlet pipe for supplying a second liquid to the mixing pipe so that the first liquid and the second liquid can be mixed in the mixing pipe.

According to the mixing system of at least one embodiment of the present disclosure, the first liquid inlet pipe and/or the second liquid inlet pipe are/is provided with a buffer device.

In accordance with a hybrid system of at least one embodiment of the present disclosure, the damping device includes a fluid pulse damper and/or a fluid pulse buffer.

In accordance with a mixing system of at least one embodiment of the present disclosure, the first liquid inlet tube is connected to a distributor for dividing liquid entering the first liquid inlet tube into at least two paths.

an inlet fitting comprising a plurality of liquid inlets and at least one liquid outlet, wherein a first liquid of the at least two paths enters the inlet fitting from a different liquid inlet, a second liquid enters the inlet fitting from a separate liquid inlet, and the mixing tube is connected to the liquid outlet of the inlet fitting.

According to the mixing system of at least one embodiment of the present disclosure, a bit inhibitor is further disposed between the mixing tube and the drain tube.

Drawings

The accompanying drawings, which are included to provide a further understanding of the disclosure and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the disclosure and together with the description serve to explain the principles of the disclosure.

Fig. 1 is a schematic structural view of a mixing device according to one embodiment of the present disclosure.

Fig. 2 is a schematic structural view of a hybrid system according to one embodiment of the present disclosure.

Fig. 3 is a schematic structural view of a fluid pulse damper according to one embodiment of the present disclosure.

Fig. 4 is a use effect diagram of a fluid pulse damper according to one embodiment of the present disclosure.

Fig. 5 is an effect diagram of an unused fluid pulse damper in the prior art.

Fig. 6 is a schematic structural view of a fluid pulse damper according to another embodiment of the present disclosure.

Fig. 7 is a schematic structural view of a fluid pulse buffer according to another embodiment of the present disclosure.

The reference numerals in the drawings specifically are:

10. mixing system

100. Mixing device

110. Mixing tube

120. A first mixing part

130. A second mixing part

140. Clamping double-way joint

150. Liquid discharge pipe

200. Fluid pulse damper

210. Fluid distribution part

220. Fluid junction

230. Connecting pipeline

231. Flow limiting device

260. Buffer device

261. Fluid flow tube

262. Buffer part

270. Tee joint connector

280. Air damper

300. Inlet fitting

400. First liquid inlet pipe

500. Second liquid inlet pipe

600. Dispenser

700. Position blocking device

800. A back pressure pipe.

Detailed Description

The present disclosure is described in further detail below with reference to the drawings and the embodiments. It is to be understood that the specific embodiments described herein are merely illustrative of the relevant content and not limiting of the present disclosure. It should be further noted that, for convenience of description, only a portion relevant to the present disclosure is shown in the drawings.

In addition, embodiments of the present disclosure and features of the embodiments may be combined with each other without conflict. The technical aspects of the present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.

Unless otherwise indicated, the exemplary implementations/embodiments shown are to be understood as providing exemplary features of various details of some ways in which the technical concepts of the present disclosure may be practiced. Thus, unless otherwise indicated, features of the various implementations/embodiments may be additionally combined, separated, interchanged, and/or rearranged without departing from the technical concepts of the present disclosure.

The use of cross-hatching and/or shading in the drawings is typically used to clarify the boundaries between adjacent components. As such, the presence or absence of cross-hatching or shading does not convey or represent any preference or requirement for a particular material, material property, dimension, proportion, commonality between illustrated components, and/or any other characteristic, attribute, property, etc. of a component, unless indicated. In addition, in the drawings, the size and relative sizes of elements may be exaggerated for clarity and/or descriptive purposes. While the exemplary embodiments may be variously implemented, the specific process sequences may be performed in a different order than that described. For example, two consecutively described processes may be performed substantially simultaneously or in reverse order from that described. Moreover, like reference numerals designate like parts.

When an element is referred to as being "on" or "over", "connected to" or "coupled to" another element, it can be directly on, connected or coupled to the other element or intervening elements may be present. However, when an element is referred to as being "directly on," "directly connected to," or "directly coupled to" another element, there are no intervening elements present. For this reason, the term "connected" may refer to physical connections, electrical connections, and the like, with or without intermediate components.

For descriptive purposes, the present disclosure may use spatially relative terms such as "under … …," under … …, "" under … …, "" lower, "" above … …, "" upper, "" above … …, "" higher "and" side (e.g., as in "sidewall"), etc., to describe one component's relationship to another (other) component as illustrated in the figures. In addition to the orientations depicted in the drawings, the spatially relative terms are intended to encompass different orientations of the device in use, operation, and/or manufacture. For example, if the device in the figures is turned over, elements described as "under" or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus, the exemplary term "below" … … can encompass both an orientation of "above" and "below". Furthermore, the device may be otherwise positioned (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, when the terms "comprises" and/or "comprising," and variations thereof, are used in the present specification, the presence of stated features, integers, steps, operations, elements, components, and/or groups thereof is described, but the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof is not precluded. It is also noted that, as used herein, the terms "substantially," "about," and other similar terms are used as approximation terms and not as degree terms, and as such, are used to explain the inherent deviations of measured, calculated, and/or provided values that would be recognized by one of ordinary skill in the art.

Fig. 1 is a schematic structural view of a mixing device 100 according to one embodiment of the present disclosure.

As shown in fig. 1, a mixing device 100 of the present disclosure may include: mixing tube 110, first mixing section 120, and second mixing section 130.

In one embodiment, the mixing tube 110 has a fluid channel within which fluid can flow and be mixed within the mixing tube 110. In the present disclosure, the mixing tube 110 may be made of plastic or metal, such as PEEK or stainless steel.

For example, the mixing tube 110 has a liquid inlet from which the liquid to be mixed enters the mixing tube 110 and a liquid outlet from which the liquid is discharged after the mixing in the mixing tube 110 is completed.

In the present disclosure, the mixing tube 110 may be bent so as to be suitable for various applications. In one embodiment, the outer diameter of the mixing tube 110 is approximately 16mm and the inner diameter is approximately 1mm, and the length of the mixing tube 110 may be adaptively adjusted according to the nature of the liquid to be mixed.

The first mixing part 120 is provided in the mixing pipe 110, and at least part of the first mixing part 120 is formed in a spiral shape; the spiral first mixing part 120 is formed with a receiving space, and at least part of the spiral portion of the first mixing part 120 is in contact with the inner wall of the mixing tube 110.

In a specific embodiment, the first mixing part 120 may be a coil spring, and in this case, an inner space of the coil spring is the above-mentioned accommodating space. More specifically, the outer diameter of the coil spring is 1mm, thereby enabling the coil spring to contact the inner wall surface of the mixing tube 110.

The coil spring can have a wire diameter of 0.18mm and a free length of 20mm-50mm; in an exemplary embodiment, the free length of the coil spring is 35mm.

And thus the maximum diameter of the receiving space inside the coil spring is 0.64mm, it will be understood by those skilled in the art that the size of the coil spring is changed when the inner diameter of the mixing tube 110 is changed, thereby enabling the mixing device to operate in an optimal state.

The second mixing part 130 is disposed in the accommodating space; the second mixing part 130 and the first mixing part 120 have a gap therebetween so that the liquid to be mixed can enter the mixing pipe 110 from the liquid inlet and be discharged from the liquid outlet after flowing and mixing at least from the gap.

In one embodiment, the second mixing section 130 comprises a sphere, such as a steel ball or an object such as a steel ball. In one embodiment, the sphere is approximately 0.5mm in diameter, and thus the gap is 0.07mm (measured from the center of the sphere at the spring axis).

In the present disclosure, the diameter of the sphere may be 0.4mm to 0.6mm, and the diameter of the sphere can be selected according to the inner diameter of the coil spring.

The balls are provided in plurality along the flow direction of the liquid, and the diameter of the balls is smaller than the inner diameter of the coil spring, so that a gap is formed between the balls and the coil spring.

Therefore, when the mixing device disclosed by the invention is used, the spiral structure of the first mixing part can disturb the flow of liquid, namely, disturb the laminar boundary layer, so that the instantaneous mixing efficiency is improved, and the encapsulation efficiency of nucleic acid is improved.

In particular, when the portion of the spiral structure of the first mixing part is in contact with the inner wall surface of the mixing pipe 110, the liquid can be prevented from directly flowing along the inner wall surface, further improving the mixing effect.

In the present disclosure, the liquid to be mixed flows at least along the outer surface of the sphere, that is, the liquid is continuously dispersed by the sphere and is dispersed again by the sphere below after the spheres are converged below, so that the mixing device of the present disclosure can also have a better mixing effect.

In a specific embodiment, the gap is 0.005-10mm in size.

In a specific embodiment, the gap is 0.01-1mm in size.

In a specific embodiment, the gap is 0.02-0.5mm in size.

In the present disclosure, at least one end of the mixing tube 110 is provided with a click double-pass joint 140, and the click double-pass joint 140 is used to limit the first mixing part 120 and the second mixing part 130, thereby preventing the first mixing part 120 and the second mixing part 130 from being separated from the mixing tube 110.

Specifically, the click-through double-pass joint 140 has 10-32 threads and is formed as a standard 1/16 inch joint, and has a flow-through passage, the inside diameter of the flow-through passage of the click-through double-pass joint 140 being 0.25 mm to 0.5 mm; and preferably the cross-sectional area of the flow-through channel of the snap two-way joint 140 is substantially the same as the effective cross-sectional area of the mixing device 100 so that the flow of liquid remains uniform in the various parts of the mixing device.

In the present disclosure, the mixing device 100 may further include: a drain pipe 150, wherein the drain pipe 150 is connected to the click double-pass joint 140, and the drain pipe 150 has a flow channel, and the flow channel of the drain pipe 150 has a cross-sectional area substantially equal to an effective cross-sectional area of the mixing device 100.

In a specific embodiment, the drain pipe 150 may be selected to have a pipe length substantially the same as the mixing pipe 110, for example, the drain pipe 150 may have an outer diameter of 1.6cm, an inner diameter of about 0.25-0.75mm, and a length of 100mm to 150mm.

According to another aspect of the present disclosure, as shown in fig. 2, the present disclosure provides a mixing system comprising the mixing device described above.

In this disclosure, the mixing system 10 may further include: a first inlet pipe 400, a second inlet pipe 500, and the like.

Wherein the first liquid inlet pipe 400 is used for providing the first liquid to the mixing pipe 110; and the second liquid inlet pipe 500 is used for supplying the second liquid to the mixing pipe 110 so that the first liquid and the second liquid can be mixed in the mixing pipe 110.

In this disclosure, the mixing system 10 may further include: an inlet joint 300, the mixing device 100 being connected to the inlet joint 300, and the inlet joint 300 being further connected to a first inlet pipe 400 and a second inlet pipe 500; in the present disclosure, the inlet connector 300 includes: y-joint, T-joint, V-joint, etc., in which case the first and second inlet pipes 400 and 500 can be directly connected to the inlet joint 300, and correspondingly the mixing pipe 110 can also be directly connected to the inlet joint.

In another embodiment, the inlet connector 300 may be a cross-type connector, however, the total amount of the liquid inlet and the liquid outlet of the inlet connector 300 may be more than 4, which is not listed here.

When the inlet fitting 300 is a cross fitting, it has one liquid outlet and three liquid inlets; on the one hand, three liquid inlets enable mixing of three different liquids, and on the other hand, when two different liquids are to be mixed, one of them can be fed from two liquid inlets into the inlet fitting 300.

In the present disclosure, the first liquid inlet pipe 400 is connected to the distributor 600, and the distributor 600 is configured to divide the liquid entering the first liquid inlet pipe 400 into at least two paths.

At this time, the first liquid flowing in at least two paths enters the inlet joint 300 through different liquid inlets of the inlet joint 300; in one embodiment, the liquid inlet into which the first liquid is made is located on the same straight line, and the liquid inlet into which the second liquid is made and the liquid outlet are located on the same straight line, whereby the first liquid can enter from both sides of the second liquid, so that the first liquid and the second liquid have a better mixing effect.

The inlet fitting 300 has an interior tube, which may also be circular in cross-section, with a diameter of between 0.18mm and 1mm, and preferably 0.25mm-0.5mm.

In the present disclosure, the cross-sectional area of the inner conduit is substantially the same as the effective cross-sectional area of the mixing device 100, thereby maintaining a substantially uniform liquid flow rate among the various components of the mixing system.

In the present disclosure, the effective cross-sectional area of the mixing device refers to the area of the void of the cross-section of the liquid flow channel of the mixing device.

As a specific implementation, the inlet connector 300 is formed in a cylindrical shape, the diameter of the cylindrical shape may be about 30mm, the height of the cylindrical shape may be about 10mm, and the circumferential surface of the cylindrical shape is formed with a hole, which is a standard 10-32 thread and corresponds to a standard 1/16 inch connector.

In a specific embodiment, the inlet fitting 300 is a cross fitting having an inner diameter of 0.25 mm; the inner diameter of the mixing tube 110 is 1mm, the specification of the embedded spiral spring of the mixing tube 110 is 0.18mm (wire diameter) x1mm (outer diameter) x35mm (length), and the diameter of the embedded steel ball of the spiral spring is 0.6 mm; the inner diameter of the liquid discharge pipe is 0.25 mm; the total flow rate was 8 ml to 20 ml/min, yielding 65 nm liposome particles with a Polymer Dispersion Index (PDI) of 0.17 and a nucleic acid encapsulation efficiency of 82%.

In another specific embodiment, the inlet fitting 300 is T-shaped with an inner diameter of 0.5 mm; the inner diameter of the mixing tube 110 is 1mm, the specification of the embedded spiral spring of the mixing tube 110 is 0.18mm (wire diameter) x1mm (outer diameter) x35mm (length), and the diameter of the embedded steel ball of the spiral spring is 0.5 mm; the inner diameter of drain 150 is 0.5 mm; the total flow rate was 40 ml to 100 ml/min, yielding 65 nm liposome particles with a Polymer Dispersion Index (PDI) of 0.15 and a nucleic acid encapsulation efficiency of 83%.

In the present disclosure, the first liquid inlet pipe 400 and/or the second liquid inlet pipe 500 are provided with a buffer device to reduce pressure fluctuation of the first liquid in the first liquid inlet pipe 400 and reduce pressure fluctuation of the second liquid in the second liquid inlet pipe 500, thereby enabling smooth flow after the first liquid and the second liquid enter the mixing pipe 110.

In one example, the cushioning device may include a fluid pulse damper 200, and fig. 3 is a schematic structural view of the fluid pulse damper according to one embodiment of the present disclosure.

As shown in fig. 3, the fluid pulse dampener 200 of the present disclosure may include: a fluid distribution portion 210, a fluid junction portion 220, at least two connecting conduits 230, and the like.

The fluid distribution part 210 is capable of receiving fluid and outputting the received fluid after distribution; in one embodiment, the material of the fluid distribution portion 210 is plastic or metal; more preferably, the material of the fluid distribution portion 210 is PEEK material or stainless steel material, etc.

The fluid distribution portion 210 has at least one fluid inlet and at least two fluid outlets, and in a preferred embodiment, the fluid distribution portion 210 includes one fluid inlet and three fluid outlets, i.e., is formed in a four-way structure; more preferably, the fluid outlet and the fluid inlet are arranged in a cross shape, i.e. formed as a cross-shaped four-way.

The fluid distribution portion 210 has a fluid distribution center that is a point or area located inside the fluid distribution portion 210 and at approximately the same distance as three fluid outlets, for example, the fluid distribution center may be a geometric center point or an area near the geometric center point of the four-way, wherein the fluid outlets are the starting points of the liquid located inside the fluid distribution portion 210 flowing out of the fluid distribution portion 210.

Whereby fluid received through the fluid inlet passes through the fluid distribution center and is discharged through the fluid outlet.

Similarly, the fluid junction 220 is capable of receiving fluid and outputting the received fluid outwardly after the received fluid is joined. In one embodiment, the material of the fluid junction 220 is plastic or metal; more preferably, the material of the fluid junction 220 is a PEEK material or a stainless steel material.

The fluid junction 220 has at least two fluid inlet ports and at least one fluid outlet port, and in a preferred embodiment, the fluid junction 220 includes three fluid inlet ports and one fluid outlet port, i.e., can be formed in a four-way configuration; more preferably, the fluid inlet and the fluid outlet are arranged in a cross shape, i.e. formed as a cross-shaped four-way.

The fluid junction 220 has a fluid junction center that is located inside the fluid junction 220 and is at approximately the same point or region as the distance of the three fluid inlet ports, which may be, for example, the geometric center point or region near the geometric center point of the four-way, wherein the fluid inlet ports are the end points at which liquid located inside the fluid junction 220 enters the fluid junction 220.

Thus, the fluid received through the fluid inlet port is discharged from the fluid outlet port after being joined at the fluid joining center.

The connection pipe 230 is used to connect the fluid distribution portion 210 and the fluid junction portion 220, thereby enabling fluid communication between the fluid distribution portion 210 and the fluid junction portion 220; in one embodiment, the connecting tube 230 may be made of plastic or metal; more preferably, the material of the connection pipe 230 is PEEK material or stainless steel material.

Each of the at least two connection pipes 230 is connected to the fluid outlet of the fluid distribution portion 210 and the fluid inlet of the fluid junction 220, and causes a different fluid flow path to be formed between the fluid distribution center and the fluid junction center through different connection pipes 230.

Those skilled in the art will appreciate that different connecting conduits 230 each connect different fluid outlets and different fluid inlets of the fluid distribution portion 210.

In a preferred embodiment, the number of the connecting pipes 230 is three, which is referred to herein as: the first connecting pipeline, the second connecting pipeline and the third connecting pipeline; accordingly, a first fluid flow path is formed through the first connection pipe, a second fluid flow path is formed through the second connection pipe, and a third fluid flow path is formed through the third connection pipe; in the present disclosure, the fluid flow path is a path that starts from the fluid distribution center, ends from the fluid junction center, and ends from the connecting pipe as a fluid channel.

Wherein, in the fluid flow paths, at least one fluid flow path has a length different from that of the remaining fluid flow paths.

Thus, the fluid pulse dampener 200 of the present disclosure produces different wavelength phase shifts through different length fluid flow paths, i.e., different channel lengths, that cancel each other out in the fluid junction 220, producing a pressure-smoothed fluid output.

Moreover, the fluid pulse damper 200 of the present disclosure is easy to process, is suitable for flow rates ranging from 40 ml per minute to 1000 ml per minute, and experimental results show that the effect of suppressing fluid pulsation to 95% or more is achieved.

In the present disclosure, the connecting tube 230 and other components may be connected by a luer fitting, which is a 1/4-28 english thread, flat bottom geometry; 1/4 refers to the outside diameter of the thread, in inches, of about 6.35 millimeters; 28 means 28 threads per inch, i.e., 28 teeth/inch.

In a preferred embodiment, the fluid enters the fluid distribution portion 210 with pulses having a pulse wavelength, at least one of the fluid flow paths having a length of M times the pulse wavelength plus one quarter to one eighth times the pulse wavelength; and/or at least one of the fluid flow paths has a length of N times the pulse wavelength plus one half to one fifth times the pulse wavelength; and/or at least one of the fluid flow paths has a length of an integer multiple of the pulse wavelength plus one-half to one-time the pulse wavelength, where M and N are integers. Where M and N are integers, more preferably M and N may take values of 10 or 20, etc.

Specifically, the length of the first fluid flow path is M times the pulse wavelength plus one sixth times the pulse wavelength; and/or the second fluid flow path has a length of N times the pulse wavelength plus one third times the pulse wavelength; and/or the length of the third fluid flow path is an integer multiple of the pulse wavelength.

Accordingly, one end of the first liquid inlet pipe 400 or the second liquid inlet pipe 500 is connected to the liquid phase pump, and the other end is connected to the fluid inlet of the fluid distribution part 210; in one specific example, the first inlet tube 400 or the second inlet tube 500 employs a standard 1/16 inch outer diameter catheter with an inner diameter of 0.2mm-1mm; the selection of the inner diameter of the first liquid inlet pipe 400 or the second liquid inlet pipe 500 may be determined according to specific usage situations, such as the type and flow rate of the fluid.

Thus, the fluid inputted from the first fluid intake pipe 400 or the second fluid intake pipe 500 has a pressure pulse with a wavelength λ, the fluid is divided into three streams and is transferred through the first fluid flow path, the second fluid flow path and the third fluid flow path, respectively, at this time, the fluid pressure pulse in the first fluid flow path is delayed by a sixth wavelength due to the length setting of the first fluid flow path, the second fluid flow path and the third fluid flow path, and accordingly, the fluid pressure pulse in the second fluid flow path is delayed by a third wavelength, the fluid pressure pulse in the third fluid flow path is delayed by a half wavelength, and after the three streams of fluid are combined in the fluid combining part 220, the pressure pulses are mutually offset by phases, are combined into a smooth fluid, and are discharged outwards.

The connecting tubing 230 is a standard 1/16 inch outer diameter catheter with an inner diameter of 0.2mm-1mm; the selection of the inner diameter of the connection pipe 230 may be determined according to specific use situations, such as the type and flow rate of the fluid.

The fluid pulse dampener 200 of the present disclosure may be directly connected to the distributor 600 through the back pressure line 800 and thereby indirectly connected to the inlet fitting 300; or may be directly connected to the inlet fitting 300 through a back pressure line 800.

In one embodiment, the back pressure pipe 800 may be connected to a fluid discharge port of the fluid junction 220, thereby enabling smooth fluid output of the pressure generated by the fluid junction 220. In another embodiment, the back pressure pipe 800 can be further connected to the damper 260, for example, the fluid flow pipe 261 connected to the damper 260, so that the fluid having a smooth pressure generated from the fluid junction 220 is buffered again and then is output to the outside, whereby the pressure of the fluid can be smoother.

In one specific example, the back pressure tube 800 employs a standard 1/16 inch outer diameter conduit with an inner diameter of 0.2mm-1mm; the selection of the inner diameter of the back pressure pipe 800 may be determined according to a specific use situation, such as the type and flow rate of the fluid.

In the present disclosure, the fluid pulse dampener 200 further includes: a damper 260, the damper 260 being connected to the fluid discharge port of the fluid junction 220 for damping the flowing fluid.

In a specific embodiment, the buffer 260 includes: a fluid flow tube 261, a buffer 262, and the like.

One end of the fluid flow tube 261 is connected to a fluid discharge port of the fluid junction 220 for receiving a fluid; the buffer portion 262 is connected to the fluid flow tube 261, and is used for buffering the fluid in the fluid flow tube 261.

For example, the buffer 262 includes a buffer tube that communicates with the fluid flow tube 261, and when fluid flows in the fluid flow tube 261, fluid is present in an end of the buffer tube that is connected to the fluid flow tube 261, and gas is present in an end of the buffer tube that is remote from the fluid flow tube 261.

In the present disclosure, regarding the wavelength λ of the fluid pulse, it can be calculated by the following formula:

wherein V represents the flow rate of the fluid in milliliters per minute, which can be obtained according to the flow rate parameter displayed by the reciprocating liquid phase pump; f represents the pulse frequency of the fluid, the pulse times per minute per unit time, and the parameter is determined by the frequency of the reciprocating liquid phase pump for alternately sucking and discharging liquid; pi is the circumference ratio and r is the inner radius of the first inlet pipe.

In a preferred embodiment, a conduit with a smaller inner diameter is selected at low flow rates and a conduit with a larger inner diameter is selected at high flow rates.

For example: the flow rate is 10 ml/min to 40 ml/min, and the inner diameter of the catheter is 0.25 mm; the flow rate is 40 ml/min to 200 ml/min, and the inner diameter of the catheter is 0.5 mm; the flow rate was between 200 ml per minute and 1000 ml per minute, and the catheter inner diameter was 1 mm.

When the fluid pulse damper is used, the fluid pulse damper is connected into an Shimadzu LC-20AP reciprocating liquid pump, the flow speed is 40 milliliters per minute, the outer diameters of a first inlet pipe and an outlet pipe are 1/16 inch PEEK pipes, and the inner diameter is 0.5 millimeter; the fluid distribution portion 210 and the fluid junction portion 220 are made of PEEK, and have an inner diameter of 0.5 mm; the connecting tube 230 has an outer diameter of 1/16 inch PEEK tubing and an inner diameter of 0.3 millimeter, wherein the length of the first connecting tube is 100mm; the length of the second connecting pipeline is 200mm; the length of the third connecting pipe is 300mm.

As shown in FIG. 4, the pressure (intensity of pressure) of the output fluid is almost in a straight line, and the pressure pulsation suppression rate is more than 95%. By way of comparison, fig. 5 is the effect of not using a fluid pulse dampener.

Fig. 6 is a schematic structural view of a fluid pulse damper 200 according to another embodiment of the present disclosure.

As shown in fig. 6, the fluid pulse dampener 200 of the present disclosure may include: a fluid distribution portion 210, a fluid junction portion 220, at least two connecting conduits 230, and the like.

The fluid distribution portion 210 has at least one fluid inlet and at least two fluid outlets, and in a preferred embodiment, the fluid distribution portion 210 includes one fluid inlet and two fluid outlets, i.e., is formed in a three-way structure; more preferably, the fluid outlet and the fluid inlet are arranged in a T-shape, i.e. formed as a T-tee. Whereby a fluid flow received through the fluid inlet is discharged through the fluid outlet.

The fluid junction 220 has at least two fluid inlet ports and at least one fluid outlet port, and in a preferred embodiment, the fluid junction 220 includes two fluid inlet ports and one fluid outlet port, i.e., can be formed in a three-way configuration; more preferably, the fluid inlet and the fluid outlet are arranged in a T-shape, i.e. formed as a T-tee. Whereby fluid received through the fluid inlet port is discharged from the fluid outlet port.

In a preferred embodiment, the number of the connecting pipes 230 is at least two, namely, includes: a first connecting pipe and a second connecting pipe; accordingly, a first fluid flow path is formed through the first connection pipe, and a second fluid flow path is formed through the second connection pipe. Of course, it should be understood by those skilled in the art that the connection pipe 230 may further include a third connection pipe or the like, and a third fluid flow path or the like is formed through the third connection pipe or the like.

Wherein, in the fluid flow paths, the flow rate of the fluid flowing in at least one fluid flow path is different from the flow rate of the fluid flowing in the remaining fluid flow paths; that is, there is a difference in the volume of the fluid delivered through the different fluid flow paths per unit time, whereby a pressure-smoothed fluid output can be produced.

In one embodiment, at least one of the connection pipes 230 has an inner diameter that is different from the inner diameter of the remaining connection pipes 230, and thus the flow rate of the fluid through the different connection pipes 230 is different.

In another embodiment, at least one of the connection pipes 230 is provided with a flow restriction device 231, and the flow rate of the fluid flowing in that connection pipe 230 is reduced by the flow restriction device 231, and thus the flow rates of the fluid through the different connection pipes 230 are made different.

As one implementation of the flow restriction 231, the flow restriction 231 comprises a throttle valve and the flow rate of the fluid in the connection pipe 230 is varied by the throttle valve; of course, the flow restriction 231 may be implemented by other valves capable of reducing the flow rate.

As another implementation form of the flow limiting device 231, the flow limiting device 231 comprises a flow limiting pipe having an inner diameter smaller than the inner diameter of the current connecting pipe in which the flow limiting device 231 is installed, or the connecting pipe 230 comprises a portion having a tapered inner diameter, i.e. formed as the flow limiting device 231 described above.

For example: the flow rate is 10 ml/min to 40 ml/min, and the inner diameter of the catheter is about 0.25 mm; the flow rate is 40 ml/min to 200 ml/min, and the inner diameter of the catheter is about 0.5 mm; the flow rate is between 200 ml per minute and 1000 ml per minute, and the inner diameter of the catheter is about 1 mm.

In the example shown in fig. 6, the same contents as those of the example shown in fig. 3 are not repeated here.

In a preferred embodiment, as shown in fig. 7, the buffering device may be a fluid pulse buffer, the fluid pulse buffer includes a three-way connection member 270, two interfaces of the three-way connection member 270 are respectively connected to the first liquid inlet pipe 400 or the second liquid inlet pipe 500, another interface of the three-way connection member 270 is connected to the back pressure pipe 800, and a third interface of the three-way connection member 270 is connected to the air damper 280, so as to buffer pressure fluctuation of the fluid flowing in the three-way connection member 270 through the air damper 280.

According to another aspect of the present disclosure, a stopper 700 is further disposed between the mixing pipe 110 and the drain pipe 150, and an inner diameter of the stopper 700 is smaller than a diameter of the ball, so that the ball can be prevented from entering the finished product by the arrangement of the stopper 700.

In the description of the present specification, reference to the terms "one embodiment/manner," "some embodiments/manner," "example," "specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment/manner or example is included in at least one embodiment/manner or example of the present application. In this specification, the schematic representations of the above terms are not necessarily for the same embodiment/manner or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments/modes or examples. Furthermore, the various embodiments/modes or examples described in this specification and the features of the various embodiments/modes or examples can be combined and combined by persons skilled in the art without contradiction.

Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" is at least two, such as two, three, etc., unless explicitly defined otherwise.

It will be appreciated by those skilled in the art that the above-described embodiments are merely for clarity of illustration of the disclosure, and are not intended to limit the scope of the disclosure. Other variations or modifications will be apparent to persons skilled in the art from the foregoing disclosure, and such variations or modifications are intended to be within the scope of the present disclosure.

Claims

1. A mixing device, comprising:

a mixing tube having a liquid inlet and a liquid outlet;

a second mixing part provided in the accommodation space;

2. The mixing device of claim 1, wherein the first mixing section comprises a coil spring having an outer diameter that is less than or equal to an inner diameter of the mixing tube.

3. The mixing device of claim 2, wherein the second mixing section comprises a plurality of spheres arranged in a flow direction of the liquid, the spheres having a diameter smaller than an inner diameter of the coil spring, whereby there is a gap between the spheres and the coil spring.

4. A mixing device according to claim 3, wherein the liquid to be mixed flows at least along the outer surface of the sphere.

5. The mixing device of claim 1, wherein the gap has a size of 0.005-10mm; preferably 0.01-1mm; preferably 0.02-0.5mm.

6. The mixing device of claim 1, wherein at least one end of the mixing tube is provided with a click-through double-pass joint for limiting the first mixing section and the second mixing section.

7. The mixing device of claim 6, wherein the snap-fit two-way fitting has a flow passage therein, the flow passage of the snap-fit two-way fitting having a cross-sectional area substantially the same as an effective cross-sectional area of the mixing device.

8. The mixing device of claim 6, further comprising:

9. A mixing system comprising a mixing device according to any one of claims 1-8.

10. The mixing system of claim 9, further comprising:

a first liquid inlet pipe for providing a first liquid to the mixing pipe; and

a second liquid inlet pipe for supplying a second liquid to the mixing pipe so that the first liquid and the second liquid can be mixed in the mixing pipe;

optionally, the first liquid inlet pipe and/or the second liquid inlet pipe are/is provided with a buffer device;

optionally, the damping device comprises a fluid pulse damper and/or a fluid pulse buffer;

optionally, the first liquid inlet pipe is connected to a distributor, and the distributor is used for dividing the liquid entering the first liquid inlet pipe into at least two paths;

optionally, the method further comprises:

an inlet fitting comprising a plurality of liquid inlets and at least one liquid outlet, wherein a first liquid of the at least two paths enters the inlet fitting from a different liquid inlet, a second liquid enters the inlet fitting from a separate liquid inlet, and the mixing tube is connected to the liquid outlet of the inlet fitting;

Optionally, a bit inhibitor is further arranged between the mixing pipe and the liquid discharge pipe.