Chip for purification

Abstract

The utility model relates to the technical field of exosome purification, in particular to a chip for purification, which comprises a chip body provided with a sample adding port for adding sample liquid and a negative pressure interface for discharging waste liquid, the sample adding port is communicated with a sample adding cavity, and the negative pressure interface is communicated with a negative pressure cavity; the filter membrane is mounted in the chip body and is used for separating the negative pressure cavity and the sample adding cavity so as to be used for purifying the sample liquid into waste liquid and target substances, the waste liquid enters the negative pressure cavity, and the target substances are left in the sample adding cavity; a liquid level identification area communicated with the inner bottom of the sample adding cavity is arranged in the chip body and is used for monitoring the liquid level of sample liquid in the sample adding cavity in real time by an external liquid level sensor; the method is used for solving the technical problems that in the prior art, when exosome liquid is purified, the application range is narrow, and automation cannot be achieved with low cost and a small machine.

Description

TECHNICAL FIELD

[0001] The utility model relates to exosome purification technical field, especially a chip for purification. BACKGROUND

[0002] The description in this section only provides background information related to the present disclosure and does not constitute prior art.

[0003] As an important intercellular communication carrier, the purification technology of exosomes is crucial for subsequent research and application. Several commonly used technologies include ultracentrifugation, ultrafiltration, chromatography, and microfluidic technology. Among them, ultrafiltration purification, as a highly efficient separation and purification technology, has many advantages such as efficient separation, normal temperature operation, energy saving and consumption reduction, simple operation, and health and safety, and is widely used.

[0004] A separation chip assembly is disclosed in the prior art, and the utility model patent with publication number CN221166537U discloses a filter membrane and a chip. The filter membrane is configured to prevent the target from passing through. The chip is provided with a separation chamber, a discharge chamber and a turbulent flow channel. The filter membrane is arranged between the separation chamber and the discharge chamber. The separation chamber and the discharge chamber are connected by the filter membrane. The separation chamber is configured to accommodate the sample liquid. The discharge chamber is configured to accommodate the liquid without the target. The turbulent flow channel is connected with the separation chamber. The turbulent flow channel is configured to communicate with the external driving pipeline to form a turbulent flow in the separation chamber. The related technology including the above technical solution still has many problems such as: generally relying on automatic sample addition, not applicable to manual sample addition in the laboratory; chip in place cannot be automatically monitored, manual confirmation and manual operation are required for next operation, the degree of automation is low, and the purification efficiency needs to be improved. UTILITY MODEL CONTENT

[0005] The utility model aims at providing a chip for purification, which solves the technical problems of narrow application range and inability to realize automation at low cost and with small machines when purifying exosome liquid in the prior art.

[0006] To achieve the above-mentioned purpose, the utility model provides the following technical scheme:

[0007] A chip for purification includes:

[0008] The chip body is provided with a sample adding port for adding sample liquid and a negative pressure interface for discharging waste liquid, wherein the sample adding port communicates with the sample adding chamber, and the negative pressure interface communicates with the negative pressure chamber;

[0009] The filter membrane is installed inside the chip body and separates the negative pressure chamber and the sample adding chamber to purify the sample liquid into waste liquid and target substance, wherein the waste liquid enters the negative pressure chamber, and the target substance remains in the sample adding chamber;

[0010] The chip body is internally provided with a liquid level identification area in communication with the bottom of the sample adding cavity, which is used for real-time monitoring of the liquid level of the sample liquid in the sample adding cavity by an external liquid level sensor.

[0011] Further, a to-position monitoring assembly is also included, which comprises a to-position feedback groove and a to-position identification groove. The to-position feedback groove is used to cooperate with a mechanical feedback structure on the purification equipment to realize mechanical feedback of the chip to position. The to-position identification groove is used to cooperate with a to-position sensor on the purification equipment to realize signal feedback of the chip to position.

[0012] Further, the chip body comprises:

[0013] The chip front shell comprises a front shell body and a front shell rib plate integrally formed with the front shell body. The front shell rib plate protrudes from the front shell body to form a front liquid level identification area, a front negative pressure cavity and a front sample adding cavity.

[0014] The chip rear shell comprises a rear shell body and a rear shell rib plate integrally formed with the rear shell body. The rear shell rib plate protrudes from the rear shell body to form a rear liquid level identification area, a rear negative pressure cavity and a rear sample adding cavity.

[0015] The chip front shell and the chip rear shell are bonded with the filter membrane. The front liquid level identification area and the rear liquid level identification area jointly form a liquid level identification area. The front sample adding cavity and the rear sample adding cavity jointly form a sample adding cavity. The front negative pressure cavity and the rear negative pressure cavity are both in communication with the sample adding cavity through the filter membrane. The top opening of the sample adding cavity facilitates manual sample adding operation.

[0016] Further, the to-position feedback groove is provided on the front shell body and is recessed inward on the side of the front shell body facing the rear shell body. The to-position identification groove is provided on the rear shell body and is a groove recessed inward on the side of the rear shell body facing away from the front shell body.

[0017] Further, the negative pressure interface comprises a front negative pressure interface and a rear negative pressure interface. The front negative pressure interface is in communication with the front negative pressure cavity. The rear negative pressure interface is in communication with the rear negative pressure cavity.

[0018] Further, the sample adding port is provided on the rear shell body and is in communication with the sample adding cavity through a flow guide groove formed by the front and rear shell rib plates. The rear shell rib plate forms a flow guide inclined surface as a transition surface between the flow guide groove and the filter membrane. The front shell rib plate forms a flow guide inclined surface symmetrically arranged with the rear shell rib plate.

[0019] Further, a communication groove is also provided on the rear shell body. One end of the communication groove is in communication with the rear sample adding cavity. The other end of the communication groove is in communication with the rear liquid level identification area.

[0020] Further, a circular shaft array of drainage rib strips is provided in the negative pressure cavity. The drainage rib strips are arranged as fan-shaped protrusions with the center of the negative pressure cavity as the center.

[0021] Further, the circumferential side wall of the negative pressure cavity is further provided with a plurality of support blocks, the height of the support blocks is consistent with the height of the drainage rib.

[0022] Further, the rear shell is further provided with a backflow pipeline, one end of the backflow pipeline is communicated with the sample adding cavity, and the other end is communicated with the inlet of the sample adding opening.

[0023] Further, the flow guide groove is inclined and the included angle between the flow guide groove and the horizontal plane is alpha, 10° < alpha < 90°, the liquid level identification area is a tapered groove with the upper part being wide and the lower part being narrow, and the taper is 1:beta, 6 < beta < 10, and the included angle between the flow guide inclined surface and the vertical plane is gamma, 10° < gamma < 30°.

[0024] Further, the edge of the rear shell or the front shell is provided with a handle which is integrally formed with the rear shell rib plate or the front shell rib plate.

[0025] Compared with the prior art, the technical scheme of the utility model has the following beneficial effects:

[0026] (1). The utility model discloses a liquid level identification area is arranged in the chip body, and the liquid level in the sample adding cavity can be monitored in real time by cooperating with the liquid level sensor, so that the liquid level in the sample adding cavity can be supplemented in real time, and the automatic monitoring and sample adding operation are realized, and the labor cost and labor intensity are reduced.

[0027] (2). The utility model discloses a position monitoring assembly, and the operator can be given mechanical feedback and automatic reminding whether the chip body is in place, and the automatic position monitoring is realized, so that the operator can quickly confirm whether the chip is installed in place when installing the chip body, and the purification efficiency is improved.

[0028] (3). The utility model discloses a front shell rib plate which is integrally formed with the front shell and a rear shell rib plate which is integrally formed with the rear shell, so that the strength of the chip body is improved, and the sealing property when installing the components is guaranteed, the flow guide inclined surface and the flow guide groove are arranged, so that the sample adding precision when adding the small volume sample liquid is guaranteed, and the influence of sample loss on the purification precision is prevented, the drainage rib and the backflow pipeline are arranged, so that the backflow and repeated purification operation when purifying the large volume sample liquid are realized, and then the purification efficiency and precision are improved. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 It is the front view of the utility model embodiment 1;

[0030] Figure 2 It is the three-dimensional structure schematic diagram of the rear shell of the utility model embodiment 1;

[0031] Figure 3It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 1;

[0032] Figure 4 It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 1;

[0033] Figure 5 It is Figure 1 It is the section structure schematic view of A-A in the middle;

[0034] Figure 6 It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 2;

[0035] Figure 7 It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 2;

[0036] Figure 8 It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 3;

[0037] Figure 9 It is the front shell body's three-dimensional structure schematic view of the utility model embodiment 3.

[0038] 100, chip front shell, 101, front negative pressure interface, 102, in place identification slot, 103, front negative pressure cavity, 107, front liquid level identification area, 109, front shell body, 110, front shell rib plate,

[0039] 200, chip rear shell, 201, lug, 202, sample addition port, 203, rear negative pressure interface, 204, pipe clamping groove, 205, flow guide inclined surface, 206, in place feedback slot, 207, rear liquid level identification area, 208, flow guide groove, 209, rear shell body, 210, rear shell rib plate, 211, communication groove, 212, rear negative pressure cavity, 2121, drainage rib, 213, support block, 214, backflow pipeline,

[0040] 300, filter membrane,

[0041] 400, sample addition cavity. DETAILED DESCRIPTION

[0042] The technical scheme in the utility model embodiments will be described clearly and completely below in conjunction with the drawings in the utility model embodiments. Obviously, the described embodiments are only part of the embodiments of the utility model and not all the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the utility model.

[0043] The drawings are only used for illustrative description and cannot be understood as limiting the patent;

[0044] The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in the description of the application and the appended claims, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It also will be understood that the term "and / or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.

[0045] The following description refers to the accompanying drawings. Unless otherwise noted, reference to a term in the "singular" includes a plural of the same meaning. Thus, for example, a reference to "a" entity includes embodiments having "one" entity or "more than one" entity. As used herein, the following terms have the following meanings.

[0046] In the description of the present application, it needs to be understood that the terms "first", "second", "third" and the like are only used to distinguish similar objects, and do not have to describe a specific order or sequence, nor can it be understood as indicating or implying relative importance. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0047] In addition, in the description of the present application, "a plurality of" means two or more, unless otherwise specified. The "and / or" describes the association relationship of the associated objects, which means that there can be three relationships, for example, A and / or B can represent: A exists alone, A and B exist together, and B exists alone. The character " / " generally represents that the associated objects before and after are in an "or" relationship. The utility model will be further described below in conjunction with the drawings and examples.

[0048] In order to solve the limitations of the prior art, the embodiment provides a technical scheme, and the technical scheme of the utility model will be further described below in conjunction with the drawings and examples.

[0049] The utility model is aimed at the optimization and improvement of the low purification efficiency and poor automation degree of the chip for exosome purification in the prior art. Through structural design, the liquid level in the sample adding cavity 400 is monitored in real time, so as to supplement the sample adding cavity 400 in real time, improve the automation degree of the purification operation, reduce the labor cost and labor intensity as a whole, and improve the purification efficiency.

[0050] Example 1

[0051] Referring to the drawings Figures 1-4A kind of purification chip, including chip body and filter membrane 300, wherein, chip body, the sample port 202 for adding sample liquid and the negative pressure interface for discharging waste liquid are arranged, wherein the sample port 202 is communicated with sample cavity 400, and the negative pressure interface is communicated with negative pressure cavity, here it can be understood that the sample cavity 400 contains sample liquid before purification, and the negative pressure cavity contains waste liquid after purification;Filter membrane 300, generally using nanometer ultrafiltration membrane 300, it is installed in the inside of chip body and is used to separate negative pressure cavity and sample cavity 400, to be used to purify sample liquid into waste liquid and target substance, wherein waste liquid enters negative pressure cavity, and target substance remains in sample cavity 400;The liquid level identification area that is communicated with the bottom of sample cavity 400 is arranged in the inside of chip body, and the liquid level identification area is used for the liquid level of sample liquid in sample cavity 400 to be monitored in real time by external liquid level sensor.It also includes in-place monitoring assembly, and the in-place monitoring assembly includes in-place feedback groove 206 and in-place identification groove 102, and the in-place identification groove 102 is used to cooperate with mechanical feedback structure on the purification equipment to realize the mechanical feedback of chip in place, and the in-place feedback groove 206 is used to cooperate with in-place sensor on the purification equipment to realize the signal feedback of chip in place.

[0052] Specifically, the chip body includes: chip front shell 100, see attached Figure 4 And 5 , including front shell body 109 and the front shell rib plate 110 integrally formed with it, the height of front shell rib plate 110 is projected from front shell body 109 to constitute front liquid level identification area 107, front negative pressure cavity 103 and front sample cavity 400;Chip rear shell 200, see attached Figure 2 、 Figure 3 And Figure 5, including the rear shell 209 and the rear shell rib plate 210 integrally formed with the rear shell 209, the height of the rear shell rib plate 210 protruding from the rear shell 209 constitutes the rear liquid level recognition area 207, the rear negative pressure cavity 212 and the rear sample adding cavity 400; the chip front shell 100 and the chip rear shell 200 and the filter membrane 300 are bonded and installed, the front liquid level recognition area 107 and the rear liquid level recognition area 207 jointly constitute the liquid level recognition area, the front sample adding cavity 400 and the rear sample adding cavity 400 jointly constitute the sample adding cavity 400, the front negative pressure cavity 103 and the rear negative pressure cavity 212 are both communicated with the sample adding cavity 400 through the filter membrane 300, the front negative pressure cavity 103 and the rear negative pressure cavity 212 are both set as circular grooves, the filter membrane 300 adopts a round shape matched with the circular groove for sealing, the sample adding cavity 400 is opened at the top for manual sample adding operation, at this point, it can be understood that the top of the front shell 109 and the rear shell 209 is set as open after bonding, that is, the top of the sample adding cavity 400 formed between the front shell 109, the rear shell 209 and the filter membrane 300 is set as open. The in-place feedback groove 206 is arranged on the front shell 109 and is arranged as a groove formed by inwardly recessing the side of the front shell 109 facing the rear shell 209, and the in-place recognition groove 102 is arranged on the rear shell 209 and is arranged as a groove formed by inwardly recessing the side of the rear shell 209 facing away from the front shell 109. The negative pressure interface includes the front negative pressure interface 101 and the rear negative pressure interface 203, wherein the front negative pressure interface 101 is communicated with the front negative pressure cavity 103, the rear negative pressure interface 203 is communicated with the rear negative pressure cavity 212, and the negative pressure interface and the rear negative pressure interface 203 are both communicated with the waste liquid recovery container of the external equipment. The sample adding port 202 is arranged on the rear shell 209, and the sample adding port 202 is communicated with the sample adding cavity 400 through the flow guide groove 208 formed by the rear shell rib plate 210, and the rear shell rib plate 210 constitutes the flow guide inclined surface 205 used as the transition surface between the flow guide groove 208 and the filter membrane 300, and the front shell rib plate 110 constitutes the flow guide inclined surface 205 symmetrically arranged with the rear shell rib plate 210, at this point, it can be understood that the flow guide inclined surface 205 on the front shell 109 and the flow guide inclined surface 205 on the rear shell 209 are symmetrically arranged, and the symmetry plane is the butt joint surface of the front shell 109 and the rear shell 209. The rear shell 209 is also provided with a communication groove 211, one end of the communication groove 211 is communicated with the bottom of the rear sample adding cavity 400, and the other end is communicated with the rear liquid level recognition area 207. In addition, the front shell 109 and the rear shell 209 are both provided with the pipe clamping groove 204, and the pipe clamping grooves 204 of the two are butted to clamp and limit the pipe output by the front negative pressure interface 101 and the rear negative pressure interface 203.

[0053] Specifically, the flow guide groove 208 is obliquely arranged and has an angle of a with the horizontal plane, 10°<a<90°, preferably a=15°, the liquid level recognition area is arranged as a tapered groove with a width decreasing from top to bottom, and the taper is 1:β, 6<β<10, preferably β=9.5, the flow guide slope 205 has an angle of γ with the vertical plane, 10°<γ<30°, preferably γ=15°. The edge of the rear shell 209 or the front shell 109 is arranged with a handle 201 integrally formed with the rear shell rib plate 210 or the front shell rib plate 110. The handle 201 is arranged to facilitate the gripping of the chip body, and is arranged in a shape with a width decreasing from top to bottom, and the corners are all arranged with rounded corners to facilitate the gripping and improve the comfort of the gripping. Further, anti-slip protrusions can be arranged on the handle 201 to improve the stability during the gripping.

[0054] Embodiment 2

[0055] Referring to the accompanying Figure 6 and the accompanying Figure 7 Different from embodiment 1, the negative pressure cavity is arranged with a drainage rib plate 2121 of an array of circular shafts, which is arranged as a fan-shaped protrusion with the center of the negative pressure cavity as the center. The drainage rib plate 2121 is arranged to facilitate the formation of turbulent flow during the purification and improve the purification efficiency.

[0056] When the exosome is purified by using the embodiment 1 of the utility model, first, the sample adding port 202 and the negative pressure interface are connected to the liquid path system of the machine, the pipeline connected to the negative pressure interface is clamped into the clamping groove 204, the chip is inserted into the clamping groove of the chip working position, after the chip is in place, the elastic beads of the mechanical feedback structure of the working position perform in-place feedback through the in-place feedback groove 206, and the photoelectric sensor of the machine detects the in-place recognition groove 102, which automatically reminds the operator whether it is installed in place. A small amount of sample liquid enters the sample adding cavity 400 through the opening above the chip, and when the sample liquid is more, it enters the sample adding cavity 400 through the sample adding port 202. The ultrasonic head of the machine acts on the chip body, the machine starts the exosome purification operation, and during the purification process, the machine monitors the liquid level in the sample adding cavity 400 in real time through the liquid level recognition area, adds sample when the liquid level is low, and after the purification is completed, the operator takes out the target substance from the opening at the top of the sample adding cavity 400 by using the pipette, and completes the purification operation.

[0057] Embodiment 3

[0058] Referring to the accompanying Figure 8 and the accompanying Figure 9The sample adding port 202 directly communicates with the negative pressure cavity and does not have the flow guide slope 205, the negative pressure cavity is provided with the drainage rib array 2121 of the circular shaft, and the drainage rib 2121 is provided as a fan-shaped convex with the center of the negative pressure cavity as the center. The circumferential side wall of the negative pressure cavity is further provided with a plurality of support blocks 213, the height of the support block 213 is consistent with the height of the drainage rib 2121. The back shell 209 is further provided with the backflow pipeline 214, one end of the backflow pipeline 214 communicates with the negative pressure cavity, and the other end communicates with the inlet of the sample adding port 202 through the peristaltic pump. The embodiment is suitable for large-volume sample purification operation.

[0059] When the purification operation is performed by using the embodiment 3 of the utility model, the difference from the purification operation of the embodiment 1 is that when the liquid in the sample adding cavity 400 needs to be repeatedly purified, the valve on the backflow pipeline 214 can be opened, and the sample adding valve of the sample adding port 202 is closed, at this time, the sample adding port 202, the sample adding cavity 400 and the backflow pipeline 214 form a closed loop, so as to realize the repeated purification of the liquid in the sample adding cavity 400 and improve the purification effect.

[0060] The above description of the disclosed embodiments enables those skilled in the art to implement or use the utility model. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the utility model. Therefore, the utility model will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

[0061] The above description is only the preferred embodiment of the utility model, and does not limit the utility model, any modification, equivalent replacement and improvement made within the spirit and principle of the utility model should be included in the protection scope of the utility model.

Claims

1. A purification chip, characterized in that, include: The chip body is provided with a sample inlet (202) for adding sample liquid and a negative pressure interface for discharging waste liquid, wherein the sample inlet (202) is connected to the sample dispensing chamber (400) and the negative pressure interface is connected to the negative pressure chamber; A filter membrane (300) is installed inside the chip body and is used to separate the negative pressure chamber and the sample dispensing chamber (400) for purifying the sample liquid into waste liquid and target substance, wherein the waste liquid enters the negative pressure chamber and the target substance remains in the sample dispensing chamber (400); a liquid level recognition area is provided inside the chip body and communicates with the bottom of the sample dispensing chamber (400), which is used for an external liquid level sensor to monitor the liquid level of the sample liquid in the sample dispensing chamber (400) in real time.

2. The purification chip according to claim 1, characterized in that, It also includes a position monitoring component, which includes a position feedback slot (206) and a position recognition slot (102). The position feedback slot (206) is used to cooperate with the mechanical feedback structure on the purification device to realize the mechanical feedback of chip position, and the position recognition slot (102) is used to cooperate with the position sensor on the purification device to realize the signal feedback of chip position.

3. The purification chip according to claim 2, characterized in that, The chip body includes: The chip front shell (100) includes a front shell (109) and a front shell rib (110) integrally formed therewith. The height of the front shell rib (110) protrudes from the front shell (109) to form a front liquid level identification area (107), a front negative pressure chamber (103), and a front sample loading chamber (400). The chip back shell (200) includes a back shell (209) and a back shell rib (210) integrally formed therewith. The height of the back shell rib (210) protrudes from the back shell (209) to form a rear liquid level recognition area (207), a rear negative pressure chamber (212) and a rear sample addition chamber (400). The chip front shell (100), chip rear shell (200), and filter membrane (300) are bonded together. The front liquid level recognition area (107) and the rear liquid level recognition area (207) together constitute the liquid level recognition area. The front sample loading chamber (400) and the rear sample loading chamber (400) together constitute the sample loading chamber (400). The front negative pressure chamber (103) and the rear negative pressure chamber (212) are respectively connected to the sample loading chamber (400) through the filter membrane (300). The top opening of the sample loading chamber (400) facilitates manual sample loading operation.

4. A purification chip according to claim 3, characterized in that, The positioning recognition groove (102) is provided on the front housing (109) and is formed by the front housing (109) being recessed inward on the side facing the rear housing (209). The positioning feedback groove (206) is provided on the rear housing (209) and is formed by the rear housing (209) being recessed inward on the side facing away from the front housing (109).

5. A purification chip according to claim 4, characterized in that, The negative pressure interface includes a front negative pressure interface (101) and a rear negative pressure interface (203), wherein the front negative pressure interface (101) is connected to the front negative pressure chamber (103), and the rear negative pressure interface (203) is connected to the rear negative pressure chamber (212).

6. A purification chip according to claim 5, characterized in that, The sample inlet (202) is located on the rear shell (209), and the sample inlet (202) is connected to the sample filling chamber (400) through the guide groove (208) formed by the front and rear shell ribs (210). The rear shell rib (210) forms a guide slope (205) to serve as a transition surface between the guide groove (208) and the filter membrane (300). The front shell rib (110) forms a guide slope (205) symmetrically arranged with the rear shell rib (210).

7. A purification chip according to claim 6, characterized in that, The rear housing (209) is also provided with a connecting groove (211), one end of which is connected to the sample addition chamber (400) and the other end is connected to the rear liquid level identification area (207).

8. A purification chip according to claim 7, characterized in that, The negative pressure cavity is provided with a circular shaft array of drainage ribs (2121), which are configured as fan-shaped protrusions with the center of the negative pressure cavity as the center.

9. A purification chip according to claim 8, characterized in that, The circumferential sidewall of the negative pressure chamber is also provided with several support blocks (213), the height of which is consistent with the height of the drainage ribs (2121).

10. A purification chip according to claim 9, characterized in that, The rear housing (209) is also equipped with a reflux pipe (214), one end of which is connected to the sample dispensing chamber (400) and the other end is connected to the inlet of the sample dispensing port (202).

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