CN113637637A - Method for efficiently separating, capturing and recovering rare cells in whole blood - Google Patents
Method for efficiently separating, capturing and recovering rare cells in whole blood Download PDFInfo
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Abstract
The invention discloses a method for efficiently separating, capturing and recovering rare cells in whole blood, which comprises the following steps: the channel pipe is provided with a first pipe orifice and a second pipe orifice; a first inlet in communication with the first nozzle; a second inlet in communication with the first nozzle; a third inlet in communication with the second nozzle; an outlet in communication with the second orifice; the target liquid channel is arranged in the channel tube and is communicated with the first tube opening, a lateral liquid channel is defined by the channel tube wall of the target liquid channel and the inner wall of the channel tube and is communicated with the second tube opening, a plurality of micropores communicated with the lateral liquid channel are arranged on the channel wall of the target liquid channel, and the aperture of each micropore is smaller than the volume of a target cell. Step S1, separating and enriching target cells; step S2, washing the target cells; step S3, recovery of target cells. The separation, capture and recovery of the target cells are completed rapidly.
Description
Technical Field
The invention relates to the technical field of cell separation, in particular to a method for efficiently separating, capturing and recovering rare cells in whole blood.
Background
The separation and enrichment of specific rare cells in blood have very important medical value, for example, the stem cells have great potential in the fields of treating different types of diseases, medical science and beauty and the like; the counting and characteristic analysis of Circulating Tumor Cells (CTCs) can be used as important basis for detecting the metastasis of the breast cancer, monitoring the recurrence, judging the curative effect and the personalized treatment prognosis, and the like. However, the content of stem cells and Circulating Tumor Cells (CTCs) in blood is very small, the content of CTCs is 1/100 ten thousand of that of blood cells, and the content of stem cells is only 0.01% of that of blood cells. In order to realize large-scale application of rare cells such as stem cells and CTCs, it is necessary to rapidly and efficiently separate the rare cells from whole blood.
At present, the separation of rare cells in blood is mainly divided into active separation and passive separation by adopting a microfluidic technology. Compared with an active separation mode for realizing cell separation by using an additional dynamic field (an electric field, a magnetic field, sound waves and light), the passive separation mode for realizing separation by depending on a design structure and fluid dynamics has the advantages of no need of an additional force field and an additional control system, easiness in manufacturing and assembling, simplicity and easiness in operating the system and the like, and is widely applied. Among them, the filter type microfluidic chip based on target cell size separation is the simplest in design and relatively flexible in use, and is a common separation method at present.
At present, the micro-fluidic chip based on filtration mainly has four modes of a weir, a column, cross flow and a membrane, but the micro-fluidic chip is easy to be blocked, and the subsequent separation efficiency can be influenced after the blockage, so that rare cells are difficult to capture and analyze, and meanwhile, the efficient recovery of target cells filtered in the chip is difficult to realize.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides a method for efficiently separating, capturing and recovering rare cells in whole blood, which can efficiently separate, capture and recover target cells in the whole blood.
According to a first aspect embodiment of the invention, a method for efficient separation, capture and recovery of rare cells in whole blood comprises:
the channel pipe is provided with a first pipe orifice and a second pipe orifice;
a first inlet in communication with the first nozzle;
a second inlet in communication with the first nozzle;
a third inlet in communication with the second nozzle;
an outlet in communication with the second orifice;
the target liquid channel is arranged in the channel tube, the target liquid channel is communicated with the first tube opening, a lateral liquid channel is defined by the channel tube wall of the target liquid channel and the inner wall of the channel tube, the lateral liquid channel is communicated with the second tube opening, a plurality of micropores communicated with the lateral liquid channel are arranged on the channel wall of the target liquid channel, and the aperture of each micropore is smaller than the volume of a target cell;
and the following steps:
step S1, separating and enriching target cells, wherein the second inlet and the third inlet are closed, the first inlet and the outlet are opened, sample liquid is injected from the first inlet, filtrate is discharged from the outlet, and the target cells are captured in the target liquid channel to obtain primary target cells;
step S2, flushing the target cells, wherein the first inlet and the third inlet are closed, the second inlet and the outlet are opened, flushing liquid is injected from the second inlet, and the flushing liquid is discharged from the outlet, so that the flushing of the target cells is completed;
and step S3, recovering the target cells, wherein the second inlet and the outlet are closed, the first inlet and the third inlet are opened, a back washing liquid is injected from the third inlet, and the back washing liquid is mixed with the target cells in the target liquid channel and flows out from the first inlet, so that the target cells are obtained.
The chip for separating, capturing and recovering rare cells in whole blood provided by the embodiment of the invention has at least the following beneficial effects:
when the target cells are separated and enriched, the second inlet and the third inlet are closed, the sample liquid flows into the target liquid channel through the first inlet and the first pipe orifice, waste liquid (liquid, background cells with small size and the like) in the sample liquid flows into the side liquid channel through the micropores, and then flows out through the second pipe orifice and the outlet, so that the background cells in the sample are efficiently removed, the target cells are captured in the target liquid channel, and primary target cells are obtained.
And then the first inlet is closed, the second inlet is opened, forward flushing liquid flows into the target liquid channel through the first inlet and the first pipe orifice, primary target cells in the target liquid channel are flushed, flushing waste liquid flows into the lateral liquid channel through the micropores, and then flows out through the second pipe orifice and the outlet to obtain target cells.
When the target cells are recovered, the second inlet and the outlet are closed, the back washing liquid flows into the lateral liquid channel and the target liquid channel after passing through the third inlet and the second nozzle, the back washing liquid enters the target liquid channel through the micropores, and the target cells flow out through the first nozzle and the first inlet, so that the target cells are obtained.
According to some embodiments of the present invention, the target liquid channel includes a plurality of channel walls, a secondary target liquid channel is disposed between the channel walls, each of the channel walls has the micropores, and the size of the micropores in the secondary target liquid channel is equal to or smaller than the size of the micropores in the secondary target liquid channel in the previous stage, or is smaller than or equal to the size of the micropores in the target liquid channel in the previous stage.
According to some embodiments of the present invention, the channel wall is defined by a first micro-pillar array, the first micro-pillar array is composed of a plurality of micro-pillars arranged at intervals, and the micro-pores are formed between the micro-pillars arranged at intervals.
According to some embodiments of the present invention, the micro-column is a rounded square micro-column, an axis of the rounded square micro-column is perpendicular to a line connecting the first nozzle and the second nozzle, and an included angle between a bottom edge of the rounded square micro-column and the line connecting the first nozzle and the second nozzle is 45 degrees.
According to some embodiments of the present invention, a second micro-column array is disposed in the target fluid channel, and the second micro-column array is composed of a plurality of micro-columns arranged at intervals.
According to some embodiments of the invention, the target fluid channel and the secondary target fluid channel have a pipe diameter gradually decreasing from the first pipe orifice to the second pipe orifice.
According to some embodiments of the invention, the lateral liquid channel has a pipe diameter gradually decreasing from the first pipe orifice to the second pipe orifice.
According to some embodiments of the invention, the first orifice is connected with the inlet of the target fluid channel and the front end of the side fluid channel in a tangent curve;
the second pipe orifice is connected with the tail end of the target liquid channel and the outlet of the side liquid channel in a tangent curve mode.
According to some embodiments of the present invention, the number of the passage tubes is plural, the passage tubes are arranged side by side, and the target liquid passage and the side liquid passage are provided in each of the passage tubes.
According to some embodiments of the invention, the channel tube is made of polydimethylsiloxane or plexiglass.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a schematic diagram of a chip for efficient separation, capture and recovery of rare cells from whole blood according to an embodiment of the present invention;
FIG. 2 is a schematic view of a connection structure of a channel tube, a target fluid channel and a side fluid channel according to an embodiment of the present invention;
FIG. 3 is a schematic view of a connection structure of a channel tube and a multi-stage target fluid channel and a side fluid channel according to an embodiment of the present invention;
FIG. 4 is an enlarged schematic view of portion A of FIG. 2;
fig. 5 is an enlarged schematic view of a portion B in fig. 2.
Reference numerals:
100. a passage tube; 110. a first nozzle; 120. a second orifice; 200. a first inlet; 300. a second inlet; 400. a third inlet; 500. an outlet; 600. a target fluid channel; 610. a side fluid channel; 620. micropores; 630. a microcolumn; 640. a secondary target fluid channel; 700. a second micropillar array.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.
In the description of the present invention, it should be understood that the orientation or positional relationship referred to in the description of the orientation, such as the upper, lower, front, rear, left, right, etc., is based on the orientation or positional relationship shown in the drawings, and is only for convenience of description and simplification of description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.
In the description of the present invention, the meaning of a plurality of means is one or more, the meaning of a plurality of means is two or more, and larger, smaller, larger, etc. are understood as excluding the number, and larger, smaller, inner, etc. are understood as including the number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless otherwise explicitly limited, terms such as arrangement, installation, connection and the like should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above terms in the present invention in combination with the specific contents of the technical solutions.
In addition, the technical solutions in the embodiments of the present invention may be combined with each other, but it must be based on the realization of those skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination of technical solutions should not be considered to exist, and is not within the protection scope of the present invention.
As shown in fig. 1 and 2, the method for efficient separation, capture and recovery of rare cells in whole blood according to the embodiment of the present invention comprises:
a passage tube 100, the passage tube 100 being provided with a first orifice 110 and a second orifice 120;
a first inlet 200 communicating with the first nozzle 110;
a second inlet 300 communicating with the first nozzle 110;
a third inlet 400 communicating with the second nozzle 120;
an outlet 500 communicating with the second nozzle 120;
a target liquid channel 600, the target liquid channel 600 is arranged in the channel tube 100, the target liquid channel 600 is communicated with the first tube orifice 110, a side liquid channel 610 is enclosed between the channel tube wall of the target liquid channel 600 and the inner wall of the channel tube 100, the side liquid channel 610 is communicated with the second tube orifice 120, a plurality of micropores 620 communicated with the side liquid channel 610 are arranged on the channel wall of the target liquid channel 600, and the aperture of the micropores 620 is smaller than the volume of target cells;
and the following steps:
step S1, separating and enriching target cells, closing the second inlet 300 and the third inlet 400, opening the first inlet 200 and the outlet 500, injecting sample liquid from the first inlet 200, discharging filtrate from the outlet 500, capturing the target cells in the target liquid channel 600, and obtaining primary target cells;
step S2, flushing the target cells, wherein the first inlet 200 and the third inlet 400 are closed, the second inlet 300 and the outlet 500 are opened, the flushing liquid is injected from the second inlet 300 and discharged from the outlet 500, and the flushing of the target cells is completed;
step S3 is to collect the target cells, close the second inlet 300 and the outlet 500, open the first inlet 200 and the third inlet 400, inject the back washing solution from the third inlet 400, and mix the target cells in the target fluid channel 600 with the back washing solution and flow out from the first inlet 200, thereby obtaining the target cells.
Specifically, when the target cells are separated and enriched, the second inlet 300 and the third inlet 400 are closed, the sample liquid flows into the target liquid channel 600 through the first inlet 200 and the first nozzle 110, the waste liquid and the background cells with small size in the sample liquid flow into the lateral liquid channel 610 through the micropores 620, and then flow out through the second nozzle 120 and the outlet 500, so that the background cells in the sample are efficiently removed, and the target cells are captured in the target liquid channel 600 to obtain primary target cells.
Then the first inlet 200 is closed, the second inlet 300 is opened, the forward flushing liquid flows into the target liquid channel 600 through the second inlet 300 and the first nozzle 110, the primary target cells in the target liquid channel 600 are flushed, the flushing waste liquid flows into the lateral liquid channel 610 through the micropores 620, and then flows out through the second nozzle 120 and the outlet 500, and the flushing of the target cells is completed.
When the target cells are recovered, the second inlet 300 and the outlet 500 are closed, the back washing liquid flows into the lateral liquid channel 610 through the third inlet 400 and the second nozzle 120, and the back washing liquid enters the target liquid channel 600 through the micropores 620, so that the target cells in the target liquid channel 600 flow out through the first nozzle 110 and the first inlet 200, and the target cells are obtained.
Specifically, the chip of the present embodiment includes a first chip plate and a second chip plate, wherein the surface of the first chip plate is a groove having a pattern identical to that of the channel tube 100 and the target fluid channel 600, and one surface of the second chip plate is a smooth surface, and the second chip plate is covered on the groove of the first chip plate to jointly enclose the closed channel tube 100 and the target fluid channel 600.
In one embodiment, a concentration of mouse embryonic fibroblast cell line 3T3 is introduced at a rate of 0.2mL/hr from the first inlet 200, the second inlet 300 is closed, the sample fluid fills the target fluid channel 600, and the fluid is subsequently drained through the pores 620. In this process, a single 3T3 cell is gradually trapped at microwell 620. Subsequently, when all microwells 620 capture single cells, 3T3 cells gradually accumulate at microwell 620, gradually capturing target cells with a capture effect of greater than 80%.
When the target liquid channel is two-stage, the separation effect is more than 90%. Subsequently, 3T3 cells were rapidly recovered, up to 90%, by passing a backwash through the third inlet at a rate of 0.2 mL/hr.
Mouse whole blood is passed through the first inlet 200 at a rate of 0.2mL/hr, the second inlet 300 is closed, the target fluid channel 600 is first filled with sample fluid, and then the fluid seeps out through the micropores 620. In the process, more than 99% of the blood cells seep out of the micro-column array, and only very individual larger cells are captured to the micro-wells 620.
Compared with the existing micro-fluidic blood rare cell separation and filtration platform, the micro-fluidic blood rare cell separation and filtration platform has the separation and capture rate as high as 90 percent and the recovery rate of 90 percent. The single cell can be captured for subsequent single cell analysis, the separation efficiency is 72% compared with the existing microfluidic filtering platform, and the single cell capture and the online processing and analysis of rear-end target cells cannot be realized. The recovery efficiency is obviously improved, and single cells can be captured for subsequent on-line analysis.
As shown in fig. 3, in some embodiments of the present invention, the target liquid channel 600 includes a plurality of channel walls, a secondary target liquid channel 640 is disposed between the channel walls, each channel wall has micropores 620, and the size of the micropores in the secondary target liquid channel 640 is equal to or smaller than that of the micropores in the secondary target liquid channel 640 of the previous stage, or is smaller than or equal to that of the micropores in the target liquid channel 600 of the previous stage.
Specifically, when the chip has only one secondary target fluid channel 640, the secondary target fluid channel 640 of the next stage is smaller than or equal to the size of the micro-pores in the target fluid channel 600 of the previous stage. When a plurality of secondary fluidic channels 640 are included, the first secondary fluidic channel 640 adjacent to the fluidic channel 600 is smaller than or equal to the size of the micro-wells in the fluidic channel 600. And the subsequent secondary target fluid passage 640 has a pore size smaller than or equal to that of the previous secondary target fluid passage 640.
The channel walls of the target solution channel may be replaced by 2 or more layers, the channel walls enclosing the target solution channel, the second channel wall and the first channel wall enclosing the secondary target solution channel 640, and the nth channel wall and the nth-1 channel wall enclosing the (n-1) th channel wall.
When the target cells are separated and enriched, the second inlet 300 and the third inlet 400 are closed, the sample liquid flows into the target liquid channel 600 through the first inlet 200 and the first nozzle 110, the waste liquid and the background cells with small size in the sample liquid flow into the lateral liquid channel 610 through the micropores 620, and then flow out through the second nozzle 120 and the outlet 500, so that the background cells in the sample are efficiently removed, and the target cells are captured in the target liquid channel 600 to obtain primary target cells.
Flows into the next secondary target fluid channel 640 through the pores 620 on the channel wall, further capturing the overflowing target cells until the waste fluid flows into the lateral fluid channel 610 through the last channel wall, and the primary target cells are obtained. And then repeating the washing and the back washing to finally obtain the target cells.
The waste liquid containing a few exuded target cells is further captured by adopting a multi-stage channel filtration mode. The waste liquid is filtered, the target cells seeped out by the upper-level target liquid channel due to overlarge pressure are captured, the capture efficiency is improved, and furthermore, the pore diameter of the micropore 620 of the next-layer channel wall is smaller than that of the micropore 620 of the previous-layer channel wall between the adjacent channel walls, so that the capture efficiency can be further improved.
As shown in fig. 3 in conjunction with fig. 4 and 5, in some embodiments of the present invention, the channel wall is defined by a first micro-pillar array, the first micro-pillar array is composed of a plurality of micro-pillars 630 arranged at intervals, and micro-pores 620 are formed between the micro-pillars 630 arranged at intervals.
Further, the microcolumn 630 is a rounded square microcolumn, the axis of the rounded square microcolumn is perpendicular to the line connecting the first nozzle 110 and the second nozzle 120, and the included angle between the bottom edge of the rounded square microcolumn and the line connecting the first nozzle 110 and the second nozzle 120 is 45 degrees.
The width and length between the two microcolumns 630 and the gap are smaller, and the liquid with low width-length ratio is easier to enter the side liquid channel through the target liquid channel (according to the infiltration and hysteresis phenomenon of the fluid on the rough solid surface), so the design can avoid the problem that the liquid is difficult to seep out due to the larger width-length ratio (relative to the fluid direction). The square distance of the round corners can be adjusted according to the size of target cells, and the size of the square and the size of the round corners can be adjusted according to the processing precision.
In some embodiments of the present invention, a second micro-column array 700 is disposed in the target fluid channel 600, and the second micro-column array 700 is composed of a plurality of micro-columns 630 arranged at intervals.
The second microcolumn arrays 700 having the same size and the same pitch are disposed at the middle of the target fluid channel 600 to prevent the supporting function of the target fluid channel 600. And changing the direction of the fluid in the target fluid channel 600, which facilitates the leakage of the waste fluid from the gap of the microcolumn 630.
In some embodiments of the present invention, the diameters of the target fluid channel 600 and the secondary target fluid channel 640 gradually decrease from the first nozzle 110 to the second nozzle 120.
The target fluid channel 600 has a smaller tube diameter and an increased tube pressure, which helps to increase the seepage rate of the pores 620 and the back washing fluid entering the target fluid channel 600 through the gap. Specifically, the target liquid channel 600 is formed by surrounding a micro-column array into a pipeline with a reduced pipe diameter.
In some embodiments of the present invention, the lateral fluid channel 610 has a pipe diameter that gradually decreases from the first nozzle 110 to the second nozzle 120. Also, the side fluid channel 610 has a smaller diameter, which helps to increase the seepage rate of the pores 620 and the back flushing fluid entering the target fluid channel 600 through the gap.
In some embodiments of the present invention, the first nozzle 110 is connected to the inlet of the target fluid channel 600 and the front end of the side fluid channel 610 in a tangent curve;
the second nozzle 120 is connected to the trailing end of the target fluid channel 600 and the outlet 500 of the side fluid channel 610 in a tangential curve. The resistance to the inflow of liquid can be reduced, which facilitates the leakage of waste liquid out of the gap between the microcolumns and the entry of backwash liquid into the target liquid channel 600 through the gap.
As shown in fig. 1, the number of the passage tubes 100 is plural, the passage tubes 100 are arranged side by side, and a target liquid passage 600 and a side liquid passage 610 are provided in each passage tube 100.
In the present embodiment, a plurality of channel tubes 100 are provided, the channel tubes 100 are arranged side by side, a target fluid channel 600 and a side fluid channel 610 are provided in each channel tube 100, and the first inlet 200, the second inlet 300, the third inlet 400, the outlet 500 and each channel tube 100 are communicated, so that the separation efficiency is improved geometrically.
In some embodiments of the invention, the channel tube 100 is made of polydimethylsiloxane or plexiglass. Polydimethylsiloxane (PDMS) is a high molecular organosilicon compound, commonly referred to as silicone. It has the features of optical transparency, inertness, no toxicity and non-inflammability. The organic glass has the advantages of good transparency, chemical stability, mechanical property and weather resistance, easy dyeing, easy processing, beautiful appearance and the like.
The device for separating, capturing and recovering the rare cells in the whole blood can efficiently and quickly complete the separation, capture and recovery of the target cells, and has high recovery rate.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example" or "some examples" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims (10)
1. A method for efficient separation, capture and recovery of rare cells from whole blood, comprising:
the channel pipe is provided with a first pipe orifice and a second pipe orifice;
a first inlet in communication with the first nozzle;
a second inlet in communication with the first nozzle;
a third inlet in communication with the second nozzle;
an outlet in communication with the second orifice;
the target liquid channel is arranged in the channel tube, the target liquid channel is communicated with the first tube opening, a lateral liquid channel is defined by the channel tube wall of the target liquid channel and the inner wall of the channel tube, the lateral liquid channel is communicated with the second tube opening, a plurality of micropores communicated with the lateral liquid channel are arranged on the channel wall of the target liquid channel, and the aperture of each micropore is smaller than the volume of a target cell;
and the following steps:
step S1, separating and enriching target cells, wherein the second inlet and the third inlet are closed, the first inlet and the outlet are opened, sample liquid is injected from the first inlet, filtrate is discharged from the outlet, and the target cells are captured in the target liquid channel to obtain primary target cells;
step S2, flushing the target cells, wherein the first inlet and the third inlet are closed, the second inlet and the outlet are opened, flushing liquid is injected from the second inlet, and the flushing liquid is discharged from the outlet, so that the flushing of the target cells is completed;
and step S3, recovering the target cells, wherein the second inlet and the outlet are closed, the first inlet and the third inlet are opened, a back washing liquid is injected from the third inlet, and the back washing liquid is mixed with the target cells in the target liquid channel and flows out from the first inlet, so that the target cells are obtained.
2. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1, wherein: the target liquid channel comprises a plurality of layers of channel walls, secondary target liquid channels are arranged between the channel walls, the micropores are arranged on each layer of the channel walls, and the size of the micropores on the secondary target liquid channels is equal to or smaller than that of the micropores on the secondary target liquid channels of the previous stage, or is smaller than or equal to that of the micropores on the target liquid channels of the previous stage.
3. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1 or 2, characterized in that: the channel wall is surrounded by a first micro-column array, the first micro-column array is formed by a plurality of micro-columns which are arranged at intervals, and the micro-pores are formed among the micro-columns which are arranged at intervals.
4. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 3, wherein: the microcolumn is a round corner square microcolumn, the axis of the round corner square microcolumn is perpendicular to the line connecting the first pipe orifice and the second pipe orifice, and the included angle between the bottom edge of the round corner square microcolumn and the line connecting the first pipe orifice and the second pipe orifice is 45 degrees.
5. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 3, wherein: and a second micro-column array is arranged in the target liquid channel and consists of a plurality of micro-columns which are arranged at intervals.
6. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 2, wherein: the pipe diameters of the target liquid channel and the secondary target liquid channel are gradually reduced from the first pipe orifice to the second pipe orifice.
7. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1, wherein: the pipe diameter of the lateral liquid channel is gradually reduced from the first pipe orifice to the second pipe orifice.
8. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1, wherein: the first pipe orifice is connected with the inlet of the target liquid channel and the front end of the side liquid channel in a tangent curve manner;
the second pipe orifice is connected with the tail end of the target liquid channel and the outlet of the side liquid channel in a tangent curve mode.
9. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1, wherein: the number of the channel pipes is multiple, the channel pipes are arranged side by side, and the target liquid channel and the side liquid channel are arranged in each channel pipe.
10. The method for efficient separation, capture and recovery of rare cells in whole blood according to claim 1, wherein: the channel tube is made of polydimethylsiloxane or organic glass.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110788130.6A CN113637637B (en) | 2021-07-13 | 2021-07-13 | Method for efficiently separating, capturing and recovering rare cells in whole blood |
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