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WO2025108320A1 - Dispositif de tri et d'enrichissement et son application - Google Patents

Dispositif de tri et d'enrichissement et son application Download PDF

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Publication number
WO2025108320A1
WO2025108320A1 PCT/CN2024/133271 CN2024133271W WO2025108320A1 WO 2025108320 A1 WO2025108320 A1 WO 2025108320A1 CN 2024133271 W CN2024133271 W CN 2024133271W WO 2025108320 A1 WO2025108320 A1 WO 2025108320A1
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WO
WIPO (PCT)
Prior art keywords
cavity
sorting
screening
chips
cell clusters
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Pending
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PCT/CN2024/133271
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English (en)
Chinese (zh)
Inventor
秦安妮
秦文彦
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Individual
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Individual
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Publication of WO2025108320A1 publication Critical patent/WO2025108320A1/fr
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors

Definitions

  • the present application relates to the field of biomedical technology, and in particular to a device for sorting and enrichment and its application.
  • cell sorting and/or enrichment methods are generally divided into two categories, one is sorting and/or enriching according to the physical properties of cells (cell size, density, motility, electrical properties, etc.), and the other is sorting and/or enriching according to the biochemical properties of cells (surface antigens, etc.).
  • Methods for sorting and/or enriching according to the physical properties of cells for example, according to the size of the cells, a sieve with a certain pore size is designed for filtration separation, and according to the different cell densities, sorting and/or enriching by density gradient centrifugation.
  • Methods for sorting and/or enriching according to the biochemical properties of cells for example, according to the different cell surface antigens, fluorescently labeled antibodies are used to bind to cells and sorting and/or enriching by flow cytometry.
  • the cell clusters formed by cell aggregation may be composed of cells of the same type or different types of cells. Different types of cells in the cell cluster may play different roles, so that the cell cluster has biological functions that a single cell does not have and realizes biological processes that a single cell cannot complete.
  • the size of the cell cluster is related to the number and type of cells.
  • Tumor cell clusters may contain tumor cells of different properties and may also contain non-tumor cells. The size of tumor cell clusters also varies, and the content in the blood circulation system is very low.
  • the number of tumor cell clusters in the blood is related to the patient's prognosis. Since tumor cell clusters are not easy to obtain in the blood circulation system, there are also technical solutions to obtain dispersed single cells by digesting tumor tissues, and then aggregate to form tumor cell clusters for scientific research and clinical testing. However, the size of the tumor cell clusters formed by this technical solution varies greatly, and it is necessary to sort and/or enrich tumor cell clusters containing a certain number of cells and uniform size. Tumor cell clusters can be used to obtain stable and accurate test results.
  • Existing cell sorting and/or enrichment methods are mainly used for sorting and/or enrichment of single cells, while methods and techniques for sorting and/or enrichment of cell clusters are seriously lacking. Due to differences in cell numbers and cell types, the size range of cell clusters is wide, and single cell sorting and/or enrichment techniques are mostly not suitable for sorting and/or enrichment of cell clusters.
  • Existing cell sieve sorting and/or enrichment methods mainly use mesh polymer membranes for filtration, which are mostly used for filtering and removing solid tissue blocks after shearing and digestion of small-volume solid tissues.
  • the pore size of the mesh polymer membranes used in cell sieves is mostly greater than 40 ⁇ m, which is not suitable for sorting and/or enriching free cell clusters in intracellular fluid samples.
  • Mesh polymer membranes are easily clogged and difficult to process large-volume samples. Cell clusters stuck in the mesh polymer membranes are also difficult to recover, with large losses, and cannot be used to separate circulating tumor cell clusters with rare contents.
  • the present application provides a device for sorting and enrichment and its application.
  • the technical solution of the present application is as follows:
  • a device for sorting and enrichment comprising:
  • N sorting chips each of which is provided with a screening hole, and the N sorting chips arranged in sequence divide the internal space of the housing into N+1 cavities, where N ⁇ 1;
  • a first cavity is formed between one side of the housing and the sorting chip adjacent thereto;
  • a second cavity is formed between the other side of the housing and the sorting chip adjacent thereto;
  • a first outlet and a first inlet connecting the first cavity with the outside are formed on the cavity wall of the first cavity;
  • a second outlet connecting the second cavity and the outside is formed on the cavity wall of the second cavity.
  • microcolumn is arranged on the shell; and/or the microcolumn is arranged on the surface of the sorting chip.
  • a device for sorting and enrichment comprising:
  • N sorting chips each of which is provided with a screening hole, and the N sorting chips arranged in sequence divide the internal space of the housing into N+1 cavities, where N ⁇ 2;
  • a first cavity is formed between one side of the housing and the sorting chip adjacent thereto;
  • a second cavity is formed between the other side of the housing and the sorting chip adjacent thereto;
  • a third cavity is formed between any two adjacent sorting chips
  • a first outlet connecting the first cavity with the outside is formed on the cavity wall of the first cavity
  • a second outlet connecting the second cavity and the outside is formed on the cavity wall of the second cavity
  • the third cavities are all provided with a third outlet on the cavity wall thereof, which connects the third cavity with the outside, and at least one of the third cavities is provided with a third outlet on the cavity wall thereof, which connects the third cavity with the outside. More than one third entrance.
  • the device further comprises a microcolumn, and at least one microcolumn is arranged in at least one of the first cavity, the second cavity, and the third cavity.
  • microcolumn is arranged on the shell; and/or the microcolumn is arranged on the surface of the sorting chip.
  • cell clusters in peripheral blood samples cell clusters in pleural effusions, ascites effusions, lymphatic fluid, urine or cerebrospinal fluid
  • cell clusters formed after enzymatic digestion of solid tissues cell clusters formed by reaggregation of single cells after solid tissues are digested into single cells
  • liposomes oil-in-water droplets or water-in-oil droplets.
  • the above-mentioned device for sorting and enrichment provided in the present application, through the following "movement direction 2", retains cells and/or cell clusters larger than the screening hole 34a in the corresponding cavity, and collects cells and/or cell clusters of the corresponding size range (larger size) through the corresponding outlet of the cavity, thereby screening and enriching the cells and/or cell clusters of the size range; through the following "movement direction 1", Cells and/or cell clusters with small screening holes enter the lower cavity through the screening holes, thereby further realizing the screening and enrichment of cells and/or cell clusters in the corresponding size range (smaller size); when an inlet for providing fluids such as buffer solutions is provided on the cavity, the fluid can, on the one hand, drive the flow of fluid samples in the corresponding cavity, reduce/prevent cells and/or cell clusters from clogging the screening holes, and at the same time, can directly collect cells and/or cell clusters suspended in the corresponding fluid, thereby directly obtaining a suspension of cells and/or cell
  • FIG1 is a schematic diagram of a device for separation and enrichment in one embodiment of the present application.
  • FIG2 is a schematic diagram of the inner structure of the upper shell in one embodiment of the present application.
  • FIG3 is a schematic diagram of the outer structure of the upper shell in one embodiment of the present application.
  • FIG4 is a schematic diagram of the upper structure of a first sorting chip in one embodiment of the present application.
  • FIG5 is a schematic diagram of the lower structure of a first sorting chip in one embodiment of the present application.
  • FIG6 is a schematic diagram of the inner structure of the lower housing in one embodiment of the present application.
  • FIG7 is a schematic diagram of the outer structure of the lower housing in one embodiment of the present application.
  • FIG8 is a schematic diagram of the upper structure of the sorting chip not adjacent to the upper housing in one embodiment of the present application.
  • FIG9 is a schematic diagram of the lower structure of the sorting chip not adjacent to the upper housing in one embodiment of the present application.
  • FIG. 10 is a schematic diagram showing a structure in which the screening holes of the sorting chip are hexagonal in one embodiment of the present application;
  • FIG. 11 In one embodiment of the present application, the screening holes of the sorting chip are rectangular and circular Schematic diagram of the combined setting structure
  • FIG. 12 is a schematic diagram showing a structure in which micro-pillars are arranged in an upper housing in one embodiment of the present application;
  • FIG. 13 is a schematic diagram showing a structure in which micro-pillars are arranged in a lower housing in one embodiment of the present application;
  • FIG. 14 is a schematic diagram showing a structure in which a microcolumn is arranged on a sorting chip in one embodiment of the present application;
  • FIG15 is a schematic diagram showing a wavy structure of a sorting chip in one embodiment of the present application.
  • Figure 16 is a schematic diagram of the structure of a device for sorting and enrichment in another embodiment of the present application.
  • This embodiment provides a device for sorting and enrichment, as shown in FIGS. 1 to 11 , comprising:
  • N sorting chips each of which is provided with a screening hole 34a, are sequentially provided with N
  • the sorting chip divides the internal space of the shell into N+1 cavities, N ⁇ 1.
  • the N sorting chips are three sorting chips arranged from top to bottom, namely, a first sorting chip 31a, a second sorting chip 32a, and a third sorting chip 33a; wherein,
  • a first cavity 41a is formed between one side of the housing (such as the inner side of the upper housing 10a) and the adjacent sorting chip (such as the first sorting chip 31a);
  • a second cavity 42a is formed between the other side of the housing (such as the inner side of the lower housing 20a) and the adjacent sorting chip (such as the third sorting chip 33a);
  • a first outlet 44a and a first inlet 47a connecting the first cavity 41a with the outside are formed on the cavity wall of the first cavity 41a;
  • a second outlet 45a connecting the second cavity 42a with the outside is formed on the cavity wall of the second cavity 42a.
  • composition structure of the shell of the present application can be a separate closed shell with each sorting chip arranged in sequence inside it. It can also be composed of an upper shell 10a, a lower shell 20a and the chip side walls 35a of N sorting chips 30a arranged therebetween, as in the present embodiment.
  • the present application has no specific restrictions.
  • the N sorting chips are arranged in sequence in a closed shell, the N sorting chips divide the internal space of the shell into N+1 cavities.
  • the upper shell 10a, the sorting chip 30a and/or the lower shell 20a are recessed, and N+1 cavities are formed by stacking the upper shell 10a, the lower shell 20a and the sorting chip 30a (refer to Figures 1 to 9).
  • each outlet such as the first outlet 44a, the second outlet 45a and the third outlet 46a described below
  • inlet the first inlet 47a and the second inlet, the third inlet 48a described below
  • an opening 50a is provided on the side wall of the upper shell 10a, the sorting chip 30a and/or the lower shell 20a, and the upper shell 10a, the lower shell 20a and the sorting chip 30a are stacked to obtain the corresponding inlet and/or outlet (refer to Figures 1 to 9).
  • each screening hole 34a As needed, and this application will not go into details. Specifically, multiple screening holes 34a are arranged in an array with a certain density.
  • the present application has no specific restrictions, as long as it can be applied to the screening of the corresponding cell clusters, such as the cross-sectional shape of the screening holes is circular or polygonal, as shown in FIG10, the cross-sectional shape of the screening holes is hexagonal, that is, an array or even multiple screening holes with hexagonal cross-sections.
  • the screening holes can be a combination of multiple shapes, such as in FIG11, the screening holes are a combination of rectangles and circles, that is, in at least one (such as one, part or all) of the sorting chips, at least two of the screening holes have different shapes and/or apertures.
  • the pore size of the screening hole is as small as 8 ⁇ m, that is, the pore size of the screening hole 34a in the present application is 8 ⁇ m or more, such as 9 ⁇ m, 10 ⁇ m, 12 ⁇ m, 15 ⁇ m, 18 ⁇ m, 20 ⁇ m, 25 ⁇ m, 30 ⁇ m, 35 ⁇ m, 50 ⁇ m, 75 ⁇ m, 100 ⁇ m, 200 ⁇ m or 500 ⁇ m or more.
  • the sorting chip is suitable for sorting and/or enriching free cell clusters present in the fluid sample.
  • the pore size refers to the diameter of the largest circle that can be accommodated by the cross-section of the screening hole.
  • the preparation method of the housing (such as the upper housing 10a, the lower housing 20a, etc.) and/or the sorting chip
  • it can be produced by existing and mature microfluidic chip processing technologies such as etching and injection molding.
  • the complete device for sorting and enrichment of the present application is formed by bonding and packaging.
  • the flow direction is mainly divided into: movement direction 1, for cells and/or cell clusters with a smaller aperture than the screening hole 34a of the sorting chip, they pass through the screening hole 34a and enter the lower cavity; movement direction 2, for cells and/or cell clusters with a larger aperture than the screening hole 34a of the sorting chip, they cannot pass through the screening hole 34a of the sorting chip, and can only flow to the outlet corresponding to the cavity where they are located. Then, as shown in FIG.
  • cell cluster refers to a cell cluster composed of two or more cells bound together by covalent and/or non-covalent interactions and moving in a fluid as a whole.
  • a third cavity 43a is formed between the sorting chips, and the third cavity 43a is formed with a third outlet 46a connecting the third cavity 43a with the outside world on its cavity wall.
  • the aperture of the screening hole of each sorting chip gradually decreases. At this time, it is also possible to select to provide negative pressure through the third outlet 46a to provide power for the flow of the fluid sample.
  • the fluid sample flowing downward from the first cavity 41a into the third cavity 43a also has two flow directions.
  • the above-mentioned "movement direction 2” cells and/or cell clusters larger than the second sorting chip 32a flow into the third outlet 46a corresponding to the cavity, thereby screening and enriching cells and/or cell clusters in the corresponding size range
  • the above-mentioned "movement direction 1” cells and/or cell clusters smaller than the second sorting chip 32a enter the lower cavity through the screening hole 34a of the second sorting chip 32a, thereby screening and enriching cells and/or cell clusters in the corresponding size range.
  • each sorting chip realizes the step-by-step screening of cells and/or cell clusters of different sizes and performs corresponding enrichment.
  • first inlets 44a are formed on the wall of the first cavity 41a; and/or, at least one (such as one, part or all) of the third cavity is formed with a third inlet 48a connecting the third cavity 43a with the outside world on its wall.
  • a corresponding fluid such as a buffer solution and other components contained in the buffer solution
  • the corresponding fluid can be introduced through the extra first inlet 44a and/or third inlet 48a, and even positive pressure can be provided through the fluid.
  • the introduced fluid can drive the flow of the fluid sample in the corresponding cavity, reduce/prevent cells and/or cell clusters from clogging the screening holes, and at the same time, the cells and/or cell clusters suspended in the corresponding fluid can be directly collected, thereby directly obtaining the cells and/or cell clusters that can be used. A suspension of cells and/or cell clusters for subsequent use.
  • a corresponding second inlet may also be provided on the second cavity 42a to facilitate the above-mentioned effect of reducing/preventing cells and/or cell clusters from clogging the screening holes and directly collecting cells and/or cell clusters suspended in the corresponding fluid.
  • the device also includes a microcolumn 60a (also referred to as a "protrusion"), and at least one microcolumn 60a is arranged in at least one (such as one, part or all) of the first cavity 41a, the second cavity 42a, and the third cavity 43a. More preferably, the microcolumn 60a is arranged in all of the above cavities.
  • the microcolumn 60a can be arranged on the inner surface of the shell so that the microcolumn 60a extends toward the first cavity 41a, the second cavity 42a and/or the third cavity 43a.
  • FIG12 a schematic diagram of arranging the microcolumn 60a on the upper shell 10a is shown, which is arranged on the inner side of the upper shell 10a, such as being arranged on the inner side of the upper shell side wall 11a of the upper shell 10a and being arranged on the inner side of the upper shell 10a facing the adjacent sorting chip (the first sorting chip 31a).
  • FIG13 a schematic diagram of arranging the microcolumn 60a on the lower shell 20a is shown, which is arranged on the inner side of the lower shell 20a, such as being arranged on the inner side of the lower shell side wall 21a of the lower shell 20a and being arranged on the inner side of the lower shell 20a facing the adjacent sorting chip (the third sorting chip 33a).
  • FIG. 14 a schematic diagram of disposing a microcolumn 60 a on a sorting chip (specifically, a first sorting chip 31 a ) is shown, which is disposed on the inner side of the chip side wall 35 a .
  • the micro-pillar 60a can also be arranged on one side of the sorting chip facing the housing (such as the direction toward the upper housing 10a) and/or the other side of the housing (such as the direction toward the lower housing 20a). As shown in FIG14, a schematic diagram of setting the micro-pillar 60a on the sorting chip (specifically the first sorting chip 31a) is shown.
  • the micro-pillar 60a can be arranged on the upper side thereof, and of course, can also be arranged on the lower side thereof as required. That is, the micro-pillar 60a can be arranged in the area of the sorting chip for setting the screening hole 34a (i.e., the screening area described below).
  • each micro-pillar 60a a plurality of micro-pillars 60a are arrayed in at least one (such as one, part or all) of the first cavity 41a, the second cavity 42a, and the third cavity 43a.
  • FIGS. 12 to 14 exemplarily show examples where the cross-section of the microcolumn 60 a is hexagonal and trapezoidal.
  • the original flow velocity direction of the fluid in the cavity can be changed, and the chances of cells and/or cell clusters 70a in the fluid sample contacting the screening holes 34a of the sorting chip 30a are increased, so that cell clusters smaller than the screening holes 34a can flow to the next cavity through the screening holes 34a as much as possible, rather than directly flowing to the outlet corresponding to the cavity, thereby enhancing the screening and enrichment effects of the device of the present application.
  • the area where the screening hole 34a is set in the sorting chip 30a forms a screening area; a part or all of at least one surface of the screening area of at least one (such as one, part or all) of the sorting chips is a non-planar structure, preferably, a part or all of the surface of the screening area of at least one of the sorting chips facing the first cavity is a non-planar structure, and further preferably, a part or all of the two surfaces of the screening area of the sorting chip are non-planar structures.
  • Figure 15 exemplarily shows an example in which both surfaces of the screening area are curved surfaces (specifically wavy structures).
  • the original flow velocity direction of the fluid in the cavity can be changed, thereby increasing the chance of the cell cluster 70a contacting the screening hole 34a of the sorting chip 30a, and allowing the cell clusters smaller than the screening hole 34a to flow to the next cavity through the screening hole 34a as much as possible, rather than directly flowing to the outlet corresponding to the cavity, thereby enhancing the screening and enrichment effects of the device of the present application.
  • FIG16 another device for sorting and enrichment is provided, as shown in FIG16 , comprising:
  • N sorting chips each of which is provided with a screening hole 34b, and the N sorting chips arranged in sequence divide the internal space of the shell into N+1 cavities, N ⁇ 2, as shown in FIG16 , in this embodiment, the N sorting chips are two sorting chips arranged from top to bottom - a first sorting chip 31b and a second sorting chip 32b; wherein,
  • a first cavity 41b is formed between one side of the housing (such as the inner side of the upper housing 10b) and the sorting chip adjacent thereto (ie, the first sorting chip 31b);
  • a second cavity 42b is formed between the other side of the housing (such as the inner side of the lower housing 20b) and the adjacent sorting chip (such as the second sorting chip 32b);
  • a third cavity 43b is formed between two adjacent sorting chips (such as between the first sorting chip 31b and the second sorting chip 32b);
  • a first outlet 44b is formed on the cavity wall of the first cavity 41b, connecting the first cavity 41b with the outside;
  • a second outlet 45b is formed on the cavity wall of the second cavity 42b, connecting the second cavity 42b with the outside.
  • the third cavities 43b are all provided with a third outlet 46b connecting the third cavities 43b with the outside world on their cavity walls, and at least one (such as one, part or all) of the third cavities 43b are provided with one or more third inlets 48b connecting the third cavities 43b with the outside world on their cavity walls.
  • composition structure of the shell; the specific implementation method of the N sorting chips arranged in sequence to divide the internal space of the shell into N+1 cavities; the specific implementation method of each outlet and/or inlet; the number and density of screening holes; the shape and aperture of the screening holes; the preparation method and material of the shell and/or sorting chip; the setting position, size, density and shape of the microcolumns; the surface form of the screening area of the sorting chip, etc. all refer to the previous embodiment, and those skilled in the art know that the same corresponding effects can be brought about, and they will not be repeated here.
  • the third inlet 48b supplies a fluid sample (here, a fluid sample containing a cell cluster is used as an example, and the principle of other fluid samples is the same).
  • a fluid sample here, a fluid sample containing a cell cluster is used as an example, and the principle of other fluid samples is the same.
  • the flow direction is mainly divided into: movement direction 1, for cells and/or cell clusters with a smaller aperture than the screening hole 34b of the sorting chip, they pass through the screening hole 34b and enter the adjacent cavity; movement direction 2, for cells and/or cell clusters with a larger aperture than the screening hole 34b of the sorting chip, they cannot pass through the screening hole 34b of the sorting chip and can only flow to the outlet (third outlet 46b) corresponding to the cavity where they are located.
  • the fluid sample is supplied from the third inlet 48b, and through the above-mentioned “movement direction 2” in the third cavity 43b, cells and/or cell clusters larger than the screening holes 34b of the sorting chips on both sides of the third cavity 43b (such as the first sorting chip 31b and the second sorting chip 32b) flow into the third outlet 46b, thereby screening and enriching cells and/or cell clusters in the corresponding size range (larger size); through the above-mentioned “movement direction 1”, cells and/or cell clusters smaller than the screening holes 34b of the sorting chips on both sides of the third cavity 43b (such as the first sorting chip 31b and the second sorting chip 32b) flow into the third outlet 46b.
  • the cell clusters enter the cavities on both sides (such as the first cavity 41b or the second cavity 42b) through the screening holes 34b of the first sorting chip 31b or the second sorting chip 32b, thereby further screening and enriching cells and/or cell clusters in the corresponding size range (smaller size).
  • the aperture of the screening holes 34b between the sorting chips can be gradually reduced in the direction away from the third inlet 48b for introducing fluid samples as in the previous embodiment, thereby being similar to the previous embodiment, cells and/or cell clusters of different sizes can be screened step by step and enriched accordingly.
  • At least one of the third cavities 43b is formed with two or more third inlets 48b connecting the third cavity with the outside world on the cavity wall.
  • the cells and/or cell clusters after screening and enrichment need to be suspended in a corresponding fluid (such as a buffer solution and other costs contained in the buffer solution) to obtain a suspension of cells and/or cell clusters for subsequent use.
  • a corresponding fluid such as a buffer solution and other costs contained in the buffer solution
  • one of the two or more third inlets 48b is used to introduce a fluid sample, and the extra third inlet 48b is used to introduce a corresponding fluid, and even provide positive pressure through the fluid.
  • the fluid introduced can drive the flow of the fluid sample in the corresponding cavity, reduce/prevent cells and/or cell clusters from clogging the screening holes, and at the same time, cells and/or cell clusters suspended in the corresponding fluid can be directly collected, thereby directly obtaining a suspension of cells and/or cell clusters that can be used for subsequent use.
  • corresponding inlets are set on other cavities (such as the first cavity 41b, the second cavity 42b and/or other third cavities 43b) (such as setting a first inlet on the first cavity; setting a second inlet on the second cavity; and/or, a third inlet is also set in at least one (such as one, part or all) of the other third cavities), so that the corresponding fluid is introduced through the corresponding inlet, so as to achieve the above-mentioned effect of reducing/preventing cells and/or cell clusters from clogging the screening holes and directly collecting the cells and/or cell clusters suspended in the corresponding fluid.
  • N 2
  • the pore size of the screening holes 34b between the sorting chips (the first sorting chip 31b and the second sorting chip 32b) on both sides of the third cavity 43b is the same.
  • cells and/or cell clusters with a smaller pore size than the screening hole 34b enter the first cavity and the second cavity through the screening hole 34b of the sorting chip, and flow out and are collected through the corresponding first outlet 44b and second outlet 45b; cells and/or cell clusters with a larger pore size than the screening hole 34b will be retained in the third cavity by the sorting chip, and flow out and are collected through the corresponding third outlet 46b.
  • the device After the cells and/or cell clusters in the fluid sample are sorted by the device, two cell and/or cell cluster components with different size ranges are obtained.
  • the cells and/or cell clusters sorted by the sorting chip The cells and/or cell clusters trapped by the chip can easily flow out of the device directly through the third outlet along with the solvent, and are not likely to clog the screening holes 34b of the sorting chip, thereby improving the sorting and/or enrichment efficiency of the device; and the device has two sorting chips with the same aperture of the screening holes 34b, which is also conducive to improving the sorting and enrichment efficiency of the device, making the device suitable for processing large-volume samples.
  • it can also be used to sort and enrich mixtures of particles of different sizes containing other biological molecules, such as (5) liposomes, oil-in-water droplets or water-in-oil droplets.
  • the present application also provides the use of the above-mentioned device in sorting and enriching the above-mentioned fluid samples.

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Abstract

L'invention concerne un dispositif de tri et d'enrichissement et son application. Le dispositif comporte un boîtier et N puces de tri, des criblages étant constitués dans les puces de tri, et les N puces de tri agencées successivement divisant l'espace interne du boîtier en N + 1 cavités, où N ≥ 1. Une première cavité est formée entre un côté du boîtier et une puce de tri adjacente ; une deuxième cavité est formée entre l'autre côté du boîtier et une puce de tri adjacente ; une première sortie et une première admission qui relient la première cavité à l'extérieur sont constituées dans la paroi de la première cavité ; et une deuxième sortie qui relie la deuxième cavité à l'extérieur est constituée dans la paroi de la deuxième cavité.
PCT/CN2024/133271 2023-11-24 2024-11-20 Dispositif de tri et d'enrichissement et son application Pending WO2025108320A1 (fr)

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CN202311586278 2023-11-24
CN202311586278.7 2023-11-24
CN202323186250 2023-11-24
CN202323186250.2 2023-11-24

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Citations (9)

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