CN217367922U - Mixed flow channel for particle synthesis and mixed chip - Google Patents
Mixed flow channel for particle synthesis and mixed chip Download PDFInfo
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- CN217367922U CN217367922U CN202221417380.5U CN202221417380U CN217367922U CN 217367922 U CN217367922 U CN 217367922U CN 202221417380 U CN202221417380 U CN 202221417380U CN 217367922 U CN217367922 U CN 217367922U
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Abstract
A mixing flow channel and a mixing chip for particle synthesis relate to the field of micro-fluidic control; the mixing flow channel for particle synthesis comprises a first input flow channel, a second input flow channel, a mixing unit and a liquid outlet flow channel; the mixing unit comprises a mixing channel and two shunting channels; the input ends of the shunting channels are communicated with the output end of the mixing channel; the output end of the shunting channel of the previous mixing unit is communicated with the input end of the mixing channel of the next mixing unit along the flow direction of the fluid; the method is characterized in that: and the two flow dividing channels in the mixing unit form a circular ring or a regular polygon. A hybrid chip for particle synthesis includes a first substrate, a second substrate; it is characterized in that: the mixed flow channel for particle synthesis is adopted on the surface of the first substrate opposite to the second substrate; can prepare nano particles with high quality, high efficiency and stability continuously.
Description
Technical Field
The utility model relates to a micro-fluidic system field particularly, relates to a hybrid chip that is used for synthetic micro-fluidic mixing channel of particle and possesses micro-fluidic mixing channel.
Background
The micro-nanofluidics (Microfluidics) is a new scientific technology for researching and applying fluid characteristics at a microscale, and is applied to various fields such as chemistry, chemical engineering, biology, physics and the like, including aspects such as organic synthesis, inorganic particle synthesis, biological materials, drug synthesis and the like. The micro-fluidic chip can realize biochemical reactions of various different mechanisms and carry out analysis and research on molecules, cells and tissue layers. For example, the amplification and detection of specific nucleic acid sequences can be realized on a microfluidic chip by polymerase chain reaction; specific proteins were detected by enzyme linked immunosorbent assay on microfluidic chips. Microfluidic chips may also be used for cell culture to study the response of cells to different biochemical substances.
The micro-fluidic chip is applied to the preparation method of the medicine. Microfluidic chips typically have one or more fluid channels therein. Under the action of different action mechanisms such as external pressure, surface tension, capillary action and the like, the fluid can be mixed in the flow channel of the microfluidic chip so as to form the nano particles. The medicine carries small molecules, nucleic acid, protein and other substances into the body or lesion tissues through a nano medicine carrying system, is commonly used for treating cancers, infectious diseases, neurodegenerative diseases and the like, and is beneficial to improving the treatment effect and reducing the organ toxicity. In the aspect of micro-nano particle synthesis, the micro-fluidic technology adopted to replace the traditional synthesis mode has become a development trend in basic research and industrial application at present.
However, when the existing microfluidic mixing chip is used for preparing nano particles, the mixing effect is low, the blockage is easy to occur, and the quality of the final nano particle product is influenced.
SUMMERY OF THE UTILITY MODEL
The utility model provides a mixing flow channel and mixing chip for particle synthesis, which can ensure that liquid components can be fully mixed in the device, improve the mixing efficiency and stably produce uniform nano particles; the dead volume of the channel liquid is small, the loss of liquid components is effectively reduced, and the high-quality, high-efficiency, stable and continuous preparation of the nano particles is realized.
The utility model provides a technical scheme that its technical problem adopted is: a mixing flow channel for particle synthesis comprises a first input flow channel, a second input flow channel, a mixing unit and a liquid outlet flow channel; the mixing unit comprises a mixing channel and two shunting channels; the input ends of the flow dividing channels are communicated with the output end of the mixing channel; the output end of the shunting channel of the previous mixing unit is communicated with the input end of the mixing channel of the next mixing unit along the flow direction of the fluid; the method is characterized in that: and the two flow dividing channels in the mixing unit form a circular ring or a regular polygon.
As a further technical solution of the mixing flow channel for particle synthesis: the central line of the mixing channel in the mixing unit respectively passes through the central point of a circular ring or a regular polygon formed by the shunting channels of the mixing unit and the central point of a circular ring or a regular polygon formed by the shunting channels of the adjacent mixing units.
Further: the midline of the mixing channel in the former mixing unit and the midline of the mixing channel in the next mixing unit form an obtuse angle.
More preferably: the obtuse angle is 100-150 degrees.
Further technical difficulties as mixing flow channels for particle synthesis are: liquid inlet transition sections are arranged at the positions of the first input flow channel, the second input flow channel and the mixing channel of the first mixing unit, the width of each liquid inlet transition section is narrowed from wide to narrow along the flow direction of liquid, and the width of each liquid inlet transition section is finally equal to the width of the combined channel of the first mixing unit;
and a liquid outlet transition section is arranged between the liquid outlet flow channel and the outlet ends of the two flow dividing channels of the last mixing unit, the liquid outlet transition section is widened from narrow to narrow along the flow direction of liquid, and the width of the input end of the liquid outlet transition section is equal to that of one flow dividing channel of the mixing unit.
Further: the diameters of circular rings formed by two flow dividing channels in the plurality of mixing units are the same or the sizes and the number of sides of regular polygons are the same.
Further: the mixing unit is provided with 4.
Further: the first input flow channel and the second input flow channel are arc-shaped and are symmetrically arranged along the central line of the mixing channel of the first mixing unit.
A hybrid chip for particle synthesis includes a first substrate, a second substrate; it is characterized in that: the first substrate and the second substrate are provided with any one of the mixing flow channels for particle synthesis.
As a further technical scheme of the hybrid chip: the liquid inlets of the first input flow channel and the second input flow channel are through holes arranged on the first substrate, and the diameters of the two through holes are vertical to the plane of the first substrate; the liquid outlet of the liquid outlet runner is also a through hole arranged on the first substrate, and the diameter of the through hole is also vertical to the plane of the first substrate.
The utility model has the advantages that: the utility model provides a mixed runner and hybrid chip for particle synthesis makes liquid component can be in the device abundant mixing, and the material through hydrodynamics's method messenger input mixes passively to produce the nano-particle of size homogeneous, improved mixing efficiency, and produce the reliability of the nano-particle of homogeneous, stability is higher, this kind of hybrid chip simple structure in addition, the workable degree of difficulty, difficult jam washs convenient repeatedly usable.
Drawings
FIG. 1 is a schematic structural diagram of an embodiment of a mixing channel for particle synthesis according to the present invention;
FIG. 2 is an enlarged partial schematic view of one mixing unit of the embodiment of FIG. 1;
FIG. 3 is a schematic view showing the direction of flow of the liquid sample in the embodiment shown in FIG. 1;
FIG. 4 is a schematic diagram of a hybrid chip for particle synthesis according to the present invention;
FIG. 5 is a left side view of FIG. 4;
FIG. 6 is a schematic cross-sectional view of a first input flow channel;
FIG. 7 is a graph comparing the results of the preparation of nanoparticles of the hybrid chip of the present invention with those of the prior art fishbone chip;
the figure is as follows:
11 a first input flow channel, 12 a second input flow channel, 13 a mixing unit, 131 a mixing channel, 132 a first diversion channel, 133 a second diversion channel, 14 a liquid outlet flow channel, 15 a first liquid inlet, 16 a second liquid inlet and 17 a liquid outlet;
21 a first substrate, 22 a second substrate.
Detailed Description
As shown in fig. 1, 2 and 3, the mixing channel for particle synthesis includes a first input channel 11, a second input channel 12, a mixing unit 13 and a liquid outlet channel 14. The mixing unit 13 includes a mixing channel 131, two diversion channels, namely a first diversion channel 132 and a second diversion channel 133; the input ends of the two diversion channels are both communicated with the output end of the mixing channel 131.
In this embodiment, four mixing units are provided, and two flow dividing channels in the mixing units form a circular ring. Along the fluid circulation direction, the output end of the diversion channel of the previous mixing unit is communicated with the input end of the mixing channel of the next mixing unit.
In some other embodiments, three or five or more mixing units may be provided, and four of the embodiments are preferred embodiments, so as to simplify the structure as much as possible based on the mixing requirement. Secondly, in some other embodiments, the two diversion channels may be formed in a regular polygon. The diversion channel is arranged so as to divide the mixed liquid after the first-stage mixing into two parts, and the two parts finally enter the mixing channel of the next-stage mixing unit under the guidance of the two diversion channels. The arrangement of the flow dividing channels is preferably designed in the form of a circular ring, since the mixing homogeneity and the flow of the liquid are to be minimized to avoid dead corners or dead volumes.
The central line of the mixing channel 131 in the mixing unit passes through the center of a circular ring formed by the shunt channels of the mixing unit and the center of a circular ring formed by the shunt channels of the adjacent mixing units respectively. The median line refers to the median line of the width of the mixing channel as shown in fig. 1, and when the mixing channel is a solid with a long width and a high height, the median line actually refers to a plane perpendicular to the bottom surface (i.e. the surface showing the width) of the mixing channel and intersecting the bottom surface at the middle position of the width, and the projection to the bottom surface of the mixing channel is a line.
If the two branch channels form a regular polygon, the center line of the mixing channel 131 in the mixing unit passes through the center point of the regular polygon formed by the branch channels of the mixing unit.
Further: the midline of the mixing channel in the former mixing unit and the midline of the mixing channel in the next mixing unit form an obtuse angle. More preferably: the obtuse angle is 100-150 degrees. The setting of angle is to final mixed effect production influence, because set up the angle, the collision that produces when the path total length of two reposition of redundant personnel passageways and intersect all can change thereupon. The obtuse angle is preferably 100-150 degrees. Specifically, the number of the first through third embodiments may be 100 °, 110 °, 120 °, 130 °, 140 °, and 150 °, but is not limited to the 6 embodiments described above.
Further technical difficulties as mixing flow channels for particle synthesis are: liquid inlet transition sections are arranged at the positions of the first input flow channel, the second input flow channel and the mixing channel of the first mixing unit, the width of each liquid inlet transition section is narrowed from wide to narrow along the flow direction of liquid, and the width of each liquid inlet transition section is finally equal to the width of the combined channel of the first mixing unit;
and a liquid outlet transition section is arranged between the liquid outlet flow channel and the outlet ends of the two flow dividing channels of the last mixing unit, the liquid outlet transition section is widened from narrow to narrow along the flow direction of liquid, and the width of the input end of the liquid outlet transition section is equal to that of one flow dividing channel of the mixing unit.
In the embodiment shown in fig. 1-3, the diameters of the circular rings formed by the two flow dividing channels in the plurality of mixing units are the same. Therefore, the mixing effect area of the liquid in each stage of mixing unit is uniform, so that the prepared nano-sample is stable and uniform.
The first and second inlet channels 11, 12 are arc-shaped and symmetrically arranged along the center line of the mixing channel of the first mixing unit. This allows the first stage to be mixed more uniformly and without creating dead volumes.
A hybrid chip for particle synthesis as shown in fig. 4 and 5, comprising a first substrate 21, a second substrate 22; wherein a mixing channel for particle synthesis as shown in fig. 1-3 is used on the side of the first substrate 21 opposite to the second substrate 22.
In some other embodiments, the mixing channel on the upper substrate 21 may be other forms of mixing channels listed above, such as polygonal, for example, three or five or more mixing units are provided, and the description in the embodiment section of the mixing channel is not repeated in this embodiment section of the chip.
As a further technical scheme of the hybrid chip: the liquid inlets of the first input flow channel 11 and the second input flow channel 12 are through holes arranged on the first substrate 21, and are respectively a first liquid inlet 15 and a second liquid inlet 16, and the diameters of the two through holes are both vertical to the plane of the first substrate 21; the liquid outlet 17 of the liquid outlet channel 14 is also a through hole provided on the first substrate 21, and the diameter of the through hole is also perpendicular to the plane of the first substrate 21.
As a more specific embodiment, in order to further optimize the structural configuration, in some embodiments, the first inlet flow channel, the second inlet flow channel, the liquid outlet flow channel, and each mixing unit have a depth of 1 to 1000 micrometers.
Preferably, the size parameters include sizes of channels at different positions of the channel, and when the cross section of the channel is a cuboid (as shown in fig. 6), the depth of the channel is 10 to 2000 micrometers, and the width of the channel is 10 to 1000 micrometers; the width range refers to the width of the shunting channel in the mixing unit 13, but the width of the mixing channel is generally the same as or slightly larger than the width of the shunting channel, and as for the widths of the widest first input flow channel 11, second input flow channel 12 and liquid outlet flow channel 14 in the channel, the maximum width does not exceed 1000 micrometers.
The utility model provides a pair of a mix chip for particle synthesis uses the utility model discloses a micro-fluidic chip and commercial fishbone chip carry out the preparation of lipid nanoparticle, investigate different chips and to the influence of lipid nanoparticle particle diameter, concrete step is: an appropriate amount of lipid solution (ionizable lipid MC3, DSPC, cholesterol, mPEG2000-DMG prepared as a 10mg/ml lipid solution at a molar ratio of 50: 10: 38.5: 1.5) was mixed with mRNA (citric acid-sodium citrate buffer solution at pH 4) at a flow rate of 20ml/min, at a test temperature of 25 ℃, at a N/P ratio of 6:1, at a flow rate of 3(mRNA solution): 1 (lipid solution), lipid nanoparticles were obtained by mixing, and the particle size was measured by a dynamic light scattering particle sizer, the results are shown in table 1:
TABLE 1 comparison of particle size of lipid nanoparticles prepared from different chips
It can be seen from table 1 and fig. 7, the utility model provides a particle diameter result of the lipid nanoparticle that the micro-fluidic chip structure made compares with the chip of selling, the utility model provides a continuous stability of chip structure is good as a result, and the particle diameter result that the chip obtained after continuously operating 40 minutes is equivalent with initial value, and overall stability is higher, and the lipid nanoparticle particle diameter PDI that makes is less than 0.1, can prove the utility model provides a to hitting the nanometer particle homogeneous stability that the stream mixing arrangement made, mixing efficiency is high, and the effect is obviously superior to current micro-fluidic chip.
As shown in figures 1-3 the utility model discloses a whole pipeline design of hybrid channel contains linear type/curved type mixing path, and the hybrid channel who comprises four circular mixing units compares in the mixed chip of common fishbone type and improves mixing efficiency, has reduced the flow resistance simultaneously, and the performance is more stable, is applicable to the production of liposome nanometer particle. When the liquid stream flows through during the hybrid tube, receive the asymmetric shearing force of passageway both sides, can select the big little main entrance of flow resistance of velocity of flow to continue to advance, and partial liquid then can get into branching branch road channel, the utility model provides a micro-fluidic chip can realize the high-efficient mixture of liquid through the micro-fluidic chip that branching branch road structure found.
The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. The present invention can be modified in many ways without departing from the spirit and scope of the present invention, and those skilled in the art can modify or change the embodiments described above without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which may be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
The drawings in the specification show the structure, ratio, size, etc. only for the purpose of matching with the content disclosed in the specification, so as to be known and read by those skilled in the art, and not for the purpose of limiting the present invention, so the present invention does not have the essential meaning in the art, and any structure modification, ratio relationship change or size adjustment should still fall within the scope covered by the technical content disclosed in the present invention without affecting the function and achievable purpose of the present invention. Meanwhile, the terms "upper", "lower", "front", "rear", "middle", and the like used in the present specification are for the sake of clarity only, and are not intended to limit the scope of the present invention, and changes or adjustments of the relative relationship thereof are also considered to be the scope of the present invention without substantial changes in the technical content.
Claims (10)
1. A mixing flow channel for particle synthesis comprises a first input flow channel, a second input flow channel, a mixing unit and a liquid outlet flow channel; the mixing unit comprises a mixing channel and two flow dividing channels; the input ends of the shunting channels are communicated with the output end of the mixing channel; the output end of the shunting channel of the previous mixing unit is communicated with the input end of the mixing channel of the next mixing unit along the flow direction of the fluid; the method is characterized in that: and the two flow dividing channels in the mixing unit form a circular ring or a regular polygon.
2. A mixing channel for particle synthesis as claimed in claim 1, wherein: the central line of the mixing channel in the mixing unit respectively passes through the central point of a circular ring or a regular polygon formed by the shunting channels of the mixing unit and the central point of a circular ring or a regular polygon formed by the shunting channels of the adjacent mixing units.
3. A mixing channel for particle synthesis as claimed in claim 2, wherein: the midline of the mixing channel in the former mixing unit and the midline of the mixing channel in the next mixing unit form an obtuse angle.
4. A mixing channel for particle synthesis as claimed in claim 3, wherein: the obtuse angle is 100-150 degrees.
5. A mixing channel for particle synthesis as claimed in claim 1, wherein: liquid inlet transition sections are arranged at the positions of the first input flow channel, the second input flow channel and the mixing channel of the first mixing unit, the width of each liquid inlet transition section is narrowed from wide to narrow along the flow direction of liquid, and the width of each liquid inlet transition section is finally equal to the width of the combined channel of the first mixing unit;
and a liquid outlet transition section is arranged between the liquid outlet flow channel and the outlet ends of the two flow dividing channels of the last mixing unit, the liquid outlet transition section is widened from narrow to narrow along the flow direction of liquid, and the width of the input end of the liquid outlet transition section is equal to that of one flow dividing channel of the mixing unit.
6. A mixing channel for particle synthesis as claimed in claim 1, wherein: the diameters of circular rings formed by two flow dividing channels in the plurality of mixing units are the same or the sizes and the number of edges of regular polygons are the same.
7. A mixing channel for particle synthesis as claimed in claim 1, wherein: the mixing unit is provided with 4.
8. A mixing channel for particle synthesis as claimed in claim 1, wherein: the first input flow channel and the second input flow channel are arc-shaped and are symmetrically arranged along the central line of the mixing channel of the first mixing unit.
9. A hybrid chip for particle synthesis includes a first substrate, a second substrate; it is characterized in that: the first substrate having a surface opposite to the second substrate, in which the mixing channel for particle synthesis according to any one of claims 1 to 8 is used.
10. A hybrid chip for particle synthesis according to claim 9, characterized in that: the liquid inlets of the first input flow channel and the second input flow channel are through holes arranged on the first substrate, and the diameters of the two through holes are vertical to the plane of the first substrate; the liquid outlet of the liquid outlet runner is also a through hole arranged on the first substrate, and the diameter of the through hole is also vertical to the plane of the first substrate.
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| CN202221417380.5U CN217367922U (en) | 2022-06-08 | 2022-06-08 | Mixed flow channel for particle synthesis and mixed chip |
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| CN202221417380.5U CN217367922U (en) | 2022-06-08 | 2022-06-08 | Mixed flow channel for particle synthesis and mixed chip |
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