Separating chip

Abstract

The invention provides a separation chip which is used for separating a target object from a sample solution. The separation chip comprises a shell and a separation assembly; the shell is provided with a sample cavity and a collection cavity; the separation assembly at least comprises two separation membranes, the two separation membranes are inclined to each other, the sample cavity is at least partially located between the two separation membranes, and the collection cavities are formed in the sides, away from the sample cavity, of the two separation membranes; wherein the separation membrane is configured to prevent the target object from passing through, and the collection chamber is in fluid communication with the sample chamber through the separation membrane.

Description

Technical Field

[0001] This application relates to the field of biotechnology, and more particularly to a discrete chip. Background Technology

[0002] Most separation chips are equipped with two separation membranes to separate the target substances in the sample solution. The two separation membranes are set in parallel, and the rinsing area is limited when rinsing the separation membranes, resulting in low rinsing efficiency. Summary of the Invention

[0003] This application provides a separation chip to solve the problem of low separation membrane rinsing efficiency in known technologies.

[0004] This application provides a separation chip for separating a target analyte from a sample solution. The separation chip includes a housing and a separation assembly. The housing has a sample chamber and a collection chamber. The separation assembly includes at least two separation membranes, which are inclined relative to each other. The sample chamber is at least partially located between the two separation membranes, and the collection chamber is provided on the side of each separation membrane facing away from the sample chamber. The separation membranes are configured to prevent the target analyte from passing through, and the collection chambers are in fluid communication with the sample chamber through the separation membranes.

[0005] In one possible implementation, the two separation membranes are arranged at an angle to each other, and the angle is an acute angle.

[0006] In one possible implementation, the separation chip further includes a support located within the collection cavity, the support being configured to support the separation membrane on one side away from the other separation membrane.

[0007] In one possible implementation, the first bottom wall of the collection chamber near the separation membrane is provided with a plurality of first protrusions, the first protrusions being configured to support the support member away from the separation membrane, and forming a liquid passage between the first bottom wall of the collection chamber and the support member.

[0008] In one possible implementation, the support member has a liquid passage hole that connects to the liquid passage channel.

[0009] In one possible implementation, the outer peripheral surface of the support member is provided with a second protrusion, which abuts against the peripheral wall of the collection cavity to form an accommodating space between the outer peripheral surface of the support member and the peripheral wall of the collection cavity.

[0010] In one possible implementation, the outer contour of the separation membrane extends beyond the collection cavity to close the opening of the collection cavity.

[0011] In one possible implementation, the housing includes two shell portions arranged opposite each other along a first direction, and sample slots are provided on adjacent sides of the two shell portions; When the two shells are connected, the two sample slots are connected and together form the sample cavity.

[0012] In one possible implementation, the second bottom wall of the sample slot is provided with a mounting protrusion, and the collection cavity is provided on the side of the mounting protrusion away from the second bottom wall. The separation membrane is connected to the side of the mounting protrusion away from the second bottom wall.

[0013] In one possible implementation, the housing has a drainage channel, one end of which is connected to the collection chamber, and the other end is configured to be connected to a negative pressure generating device.

[0014] The separation chip of this application has two separation membranes arranged at an angle to each other, forming a sample cavity between the two membranes. When rinsing the surface of the separation membrane on the side forming the sample cavity, the angled separation membrane has a larger rinsing area, which improves the rinsing efficiency. In addition, the angled arrangement of the two separation membranes allows adjustment of the volume of the sample cavity and the pipette spacing by adjusting the relative angle between the two membranes, thus improving the adaptability of the separation chip. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the structure of the discrete chip in one embodiment of the present application.

[0016] Figure 2 for Figure 1 A magnified view of a portion of region A corresponding to the discrete chip in the diagram.

[0017] Figure 3 This is a schematic diagram of the shell portion of the discrete chip in one embodiment of this application.

[0018] Figure 4 This is a schematic diagram of the support structure of the discrete chip in one embodiment of this application.

[0019] Key component symbols: 100, Separation chip; Y, First direction; X, Second direction; Z, Third direction; P1, First bottom wall; P2, Second bottom wall; P3, Guide surface; 10, Housing; 11, Shell portion; 12, Sample chamber; 121, Sample slot; 13, Limiting groove; 14, Liquid passage; 15, Drainage passage; 16, Mounting protrusion; 160, Collection chamber; 1601, First protrusion; 161, Mounting portion; 162, Guide portion; 17, Receiving space; 20, Separation membrane; 30, Support; 31, Liquid passage hole; 32, Second protrusion; 33, Support rib; 40, Pipette needle; 50, Negative pressure generating device.

[0020] The following detailed description, in conjunction with the accompanying drawings, will further illustrate this application. Detailed Implementation

[0021] The following description will refer to the accompanying drawings to provide a more complete picture of the present application. The drawings illustrate exemplary embodiments of the present application. However, the present application may be implemented in many different forms and should not be construed as limited to the exemplary embodiments set forth herein. These exemplary embodiments are provided to make the present application thorough and complete, and to fully convey the scope of the present application to those skilled in the art. The same reference numerals denote the same or similar components.

[0022] The terminology used herein is for the purpose of describing particular exemplary embodiments only and is not intended to limit the application. As used herein, unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” are intended to also include the plural forms. Furthermore, when used herein, “comprising” and / or “including” and / or “having,” integers, steps, operations, components, and / or components, but does not exclude the presence or addition of one or more other features, regions, integers, steps, operations, components, and / or groups thereof.

[0023] Unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains. Furthermore, unless expressly defined herein, terms such as those defined in a general dictionary should be interpreted as having the same meaning as they have in the relevant art and in the content of this application, and will not be interpreted as having an idealized or overly formal meaning.

[0024] The specific embodiments of this application will be further described in detail below with reference to the accompanying drawings.

[0025] like Figures 1 to 2 As shown, this embodiment provides a separation chip 100 for separating target analytes from sample fluids. The sample fluid can be any liquid sample requiring analysis, such as plasma, serum, cerebrospinal fluid, saliva, urine, or gastric juice. The target analyte is particulate matter, and can be exosomes or circulating tumor cells, among other particulate matter.

[0026] The separation chip 100 includes a housing 10 and a separation assembly. The housing 10 has a sample chamber 12 and a collection chamber 160. The separation assembly includes at least two separation membranes 20. The separation membranes 20 can be polymer filter membranes or inorganic alumina membranes. The molecular weight or particle size of the target analyte to be retained can be controlled by controlling the pore size of the membrane material of the separation membranes 20.

[0027] Two separation membranes 20 are spaced apart and inclined relative to each other. A sample chamber 12 is at least partially located between the two separation membranes 20, and each of the two separation membranes 20 has a collection chamber 160 on its side opposite to the sample chamber 12. The separation membranes 20 are configured to prevent the passage of target substances, and the collection chambers 160 are in fluid communication with the sample chamber 12 through the separation membranes 20. The sample chamber 12 is used to contain the sample solution, and the collection chambers 160 are used to collect liquid from the sample solution that can pass through the separation membranes 20, thereby intercepting and separating or purifying the target substances in the sample solution through the separation membranes 20.

[0028] In this embodiment, the two separation membranes 20 are arranged at an angle to each other, and the angle is an acute angle. The angle can be 20°, 25°, 30°, etc. The specific angle can be selected according to actual needs and is not limited in this application.

[0029] Thus, in the separation chip 100 of this application, the two separation membranes 20 are arranged at an angle to each other, forming a sample cavity 12 between the two separation membranes 20. When rinsing the surface of the separation membrane 20 on the side forming the sample cavity 12, the angled separation membrane 20 has a larger rinsing area, which can improve the rinsing efficiency of the separation membrane 20. In addition, the angled arrangement of the two separation membranes 20 allows adjustment of the volume of the sample cavity 12 and the spacing between the pipettes 40 by adjusting the relative inclination between the two separation membranes 20, thereby improving the adaptability of the separation chip 100.

[0030] For ease of reading, this application introduces the terms first direction Y, second direction X, and third direction Z to describe embodiments of the application. The first direction Y, second direction X, and third direction Z can be three non-parallel straight lines in space; further, the first direction Y, second direction X, and third direction Z can be three mutually perpendicular directions in a three-dimensional coordinate system (a three-dimensional Cartesian coordinate system). In subsequent embodiments, the first direction Y is described as the Y-axis direction of the three-dimensional coordinate system, the second direction X as the X-axis direction of the three-dimensional coordinate system, and the third direction Z as the Z-axis direction of the three-dimensional coordinate system.

[0031] Please combine Figures 1 to 3 In one embodiment, the housing 10 includes two housing portions 11 arranged opposite each other along a first direction Y, and sample slots 121 are formed on adjacent sides of the two housing portions 11. When the two housing portions 11 are connected, the two sample slots 121 are connected and together form a sample cavity 12.

[0032] The two shell parts 11 have the same structure and are symmetrically arranged. Along the first direction Y, the opposite sides of the two shell parts 11 are attached to each other, and the two shell parts 11 can be connected to each other by means of bonding, ultrasonic welding or fusion, and the two sample slots 121 are connected to form a closed cavity structure.

[0033] Along the first direction Y, the sample groove 121 is formed by recessing inward from the side of the shell 11 near the other shell 11, and along the second direction X, one end of the sample groove 121 extends upward to penetrate the shell 11, so that after the two shells 11 are connected, the top of the sample cavity 12 formed between them is set with an opening so that the sample liquid can enter the sample cavity 12 from the opening.

[0034] Furthermore, the outer contour of the separation membrane 20 extends beyond the collection chamber 160 to close the opening of the collection chamber 160.

[0035] In this embodiment, along the first direction Y, the side of the sample tank 121 away from the other shell portion 11 is designated as a second bottom wall P2. A mounting protrusion 16 protrudes from the second bottom wall P2 of the sample tank 121. A collection cavity 160 is provided on the side of the mounting protrusion 16 away from the second bottom wall P2. The collection cavity 160 is formed by indentation from the side of the mounting protrusion 16 away from the second bottom wall P2. A separation membrane 20 is connected to the side of the mounting protrusion 16 away from the second bottom wall P2, and the outer contour of the separation membrane 20 extends beyond the edge of the collection cavity 160, thereby sealing the opening formed in the collection cavity 160 at the surface of the mounting protrusion 16. Furthermore, the portion of the separation membrane 20 extending beyond the edge of the collection cavity 160 is fitted to the mounting protrusion 16 to ensure that the sample liquid in the sample tank 12 must pass through the separation membrane 20 before flowing into the collection cavity 160.

[0036] Along the second direction X, the opposite sides of the mounting protrusion 16 and the opposite sides of the sample tank 121 are spaced apart to form a liquid addition chamber between the mounting protrusion 16 and the sample tank 121 in the second direction X. This liquid addition chamber can be part of the sample chamber 12, so that sample liquid can be added into the sample chamber 12 through the liquid addition chamber. In addition, the amount of sample liquid added to the sample chamber 12 at one time can be controlled by controlling the volume of the liquid addition chamber to ensure that the separation membrane 20 is always in the best working condition.

[0037] Furthermore, when the two shells 11 are connected, the surfaces of the two shells 11 on the adjacent side are attached to each other and are surrounded by two separation membranes 20 to form a sample cavity 12. The sample liquid in the cavity between the two separation membranes 20 can flow to the collection cavity 160 through the separation membranes 20, and then the separation membranes 20 block the target substances in the sample liquid, thereby achieving the function of separation and purification.

[0038] In this embodiment, the housing 10 has a drain channel 15, one end of which is connected to the collection chamber 160, and the other end is configured to be connected to a negative pressure generating device 50.

[0039] Along the first direction Y, each of the two shell portions 11 has a drain channel 15 on its opposite side. The drain channel 15 extends inward from the surface of the opposite side of the two shell portions 11 to the connecting collection chamber 160, so that the liquid entering the collection chamber 160 can be discharged from the drain channel 15 under negative pressure and then collected. The negative pressure generating device 50 can be a vacuum device or the like, which is used to create a pressure difference to drive the liquid flow.

[0040] Thus, the negative pressure generating device 50 creates a transmembrane pressure difference across the separation membrane 20, allowing substances in the sample solution smaller than the pore size of the separation membrane 20 to pass through the separation membrane 20 and flow into the collection chamber 160, thereby achieving the separation, purification, or concentration of the sample solution.

[0041] In some implementations, the negative pressure generating device 50 generates negative pressure in a collection chamber 160 connected to it via a drain channel 15. Under the influence of this negative pressure in the collection chamber 160, components in the sample liquid in the sample chamber 12 with a size smaller than the pore size of the separation membrane 20 move toward the collection chamber 160 where negative pressure is generated. Similarly, when the negative pressure generating device 50 generates negative pressure in another collection chamber 160 connected to it via another drain channel 15, components in the sample liquid in the sample chamber 12 with a size smaller than the pore size of the separation membrane 20 move toward the collection chamber 160 where negative pressure is generated. Simultaneously, the sample liquid in the sample chamber 12 experiences a backflow effect at the previously used separation membrane 20, thereby reducing or cleaning components adhering to the previously used separation membrane 20 and preventing clogging of the separation membrane 20 during the separation process. In this way, the negative pressure device repeatedly and alternately controls the negative pressure generated in the two collection chambers 160, which can effectively make the sample liquid flow to the two separation membranes 20 alternately. This allows the components blocked by the separation membranes 20 to fall off the surface of the separation membranes 20 during the separation process, thus avoiding the clogging of the separation membranes 20 and improving the recovery rate of the target analyte.

[0042] Please combine Figures 1 to 3 In one embodiment, the mounting protrusion 16 includes a flow guide 162 and a mounting portion 161. Along the third direction Z, the mounting portion 161 is integrally formed on the side of the flow guide 162 away from the top opening of the sample chamber 12. Along the first direction Y, the surface of the flow guide 162 away from the second bottom wall P2 is designated as a flow guide surface P3. The flow guide surface P3 is inclined and can be an inclined plane, a curved surface, or a slope, etc. The two flow guide surfaces P3, together with the two separation membranes 20, form the sample chamber 12. The two flow guide surfaces P3 are inclined inwards and towards the mounting portion 161 to form a flushing slope. When the pipette 40 performs membrane washing operations, it expands the flushing area through the two flow guide surfaces P3 to maximize the flushing of the target material on the separation membranes 20, thereby improving the recovery rate of the target material.

[0043] Specifically, along the first direction Y, the surface of the mounting portion 161 on the side away from the second bottom wall P2 can also be inclined, and this surface is smoothly connected to the guide surface P3, so that the separation membrane 20 connected to the surface of the mounting portion 161 on the side away from the second bottom wall P2 is in an inclined state. In addition, along the first direction Y, a limiting groove 13 can be provided on the surface of the mounting portion 161 on the side away from the second bottom wall P2. The limiting groove 13 connects the sample tank 121 and the collection chamber 160. The separation membrane 20 is fixed in the limiting groove 13 to ensure that the surfaces of the two separation membranes 20 on adjacent sides can be smoothly connected to the two guide surfaces P3 respectively.

[0044] It is understood that, in some implementations, the inclination of the separation membrane 20 supported by the mounting protrusion 16 can be changed by adjusting the inclination of the surface on the side away from the second bottom wall P2.

[0045] Please combine Figures 1 to 4 In one embodiment, the separation chip 100 further includes a support 30 located within the collection cavity 160 and configured to support the side of the separation membrane 20 away from the other separation membrane 20.

[0046] Two support members 30 are provided, each located within a separate collection chamber 160. The two support members 30 are inclined relative to each other, and the surfaces of the two support members 30 on their adjacent sides support two separation membranes 20 respectively. The cross-sectional shape of the collection chamber 160 is approximately circular, and the shape of the support member 30 is adapted to the shape of the collection chamber 160, that is, the support member 30 is approximately cylindrical.

[0047] In this embodiment, along the first direction Y, the cavity wall of the collecting cavity 160 near the separation membrane 20 is designated as a first bottom wall P1, and the first bottom wall P1 of the collecting cavity 160 near the separation membrane 20 is provided with a plurality of first protrusions 1601. The protrusion direction of the first protrusions 1601 is inclined to both the first direction Y and the second direction X. The plurality of first protrusions 1601 are arranged in a ring array, and any two adjacent first protrusions 1601 are spaced apart. The first protrusions 1601 are configured to support the side of the support member 30 away from the separation membrane 20, so that a liquid passage 14 is formed between the first bottom wall P1 of the collecting cavity 160 and the support member 30, avoiding the support member 30 from sticking to the first bottom wall P1, which would block the liquid passing through the support member 30 and prevent it from flowing to the drain channel 15.

[0048] In addition, when supporting the separation membrane 20, the support member 30 needs to control the gap between the support member 30 and the side of the separation membrane 20 that is in contact with it, so as to prevent the support member 30 from lifting the separation membrane 20 off the mounting protrusion 16 and affecting the working state of the separation membrane 20.

[0049] In some implementation methods, the protrusion lengths of the multiple first protrusions 1601 are the same, and the first bottom wall P1 is inclined, and the degree of inclination of the first bottom wall P1 is the same as the degree of inclination of the separation membrane 20, thereby ensuring that the degree of inclination of the separation membrane 20 supported by the support member 30 is within the expected range.

[0050] In other embodiments, the inclination of the first bottom wall P1 may differ from that of the separation membrane 20, or the normal direction of the first bottom wall P1 may be parallel to the first direction Y. In this case, the protrusion lengths of the plurality of first protrusions 1601 are different, so that the inclination of the support member 30 supported by the plurality of first protrusions 1601 can be the same as the desired inclination of the separation membrane 20, thereby ensuring that the inclination of the separation membrane 20 supported by the support member 30 is at the expected level.

[0051] In other embodiments, the inclination of the surface of the support member 30 away from the first bottom wall P1 along the first direction Y is different from the inclination of the surface of the support member 30 close to the first bottom wall P1. This allows the support member 30 to be shaped in a specific way so that the surface of the support member 30 supporting the separation membrane 20 can support the separation membrane 20, thus ensuring that the inclination of the separation membrane 20 meets the desired degree. In this way, the inclination angle of the separation membrane 20 can be adjusted by replacing different support members 30, as long as the bottom edge of the separation membrane 20 extending beyond the lower edge of the collection cavity 160 can fit against the wall of the sample groove 121, ensuring that the opening of the sample cavity 12 is completely sealed by the separation membrane 20.

[0052] In this embodiment, the outer peripheral surface of the support member 30 is provided with a second protrusion 32, which abuts against the peripheral wall of the collection cavity 160 to form an accommodating space 17 between the outer peripheral surface of the support member 30 and the peripheral wall of the collection cavity 160.

[0053] The number of second protrusions 32 is set to be multiple. The multiple second protrusions 32 are arranged sequentially and spaced apart around the outer peripheral surface of the support member 30. Thus, the arrangement of the multiple second protrusions 32 forms a receiving space 17 between the outer peripheral surface of the support member 30 and the peripheral wall of the collecting cavity 160. The receiving space 17 can accommodate the overflow of glue when the separation membrane 20 is bonded to the mounting protrusion 16 or the overflow of substances during ultrasonic welding or fusion, so as to avoid the overflow of glue or overflow of substances affecting the effective working area of ​​the separation membrane 20.

[0054] In this embodiment, the support member 30 has a liquid passage hole 31, which is connected to the liquid passage channel 14, so that the liquid passing through the separation membrane 20 flows from the liquid passage hole 31 through the support member 30 into the liquid passage channel 14, and then enters the drain channel 15 connected to it from the liquid passage channel 14.

[0055] Multiple liquid passage holes 31 are provided, extending through the support member 30 along its axis. The multiple liquid passage holes 31 form an array of honeycomb holes, and the support member 30 can be manufactured using injection molding or foam metal. Along the first direction Y, a support rib 33 protrudes from the side of the support member 30 closest to the separation membrane 20. The support rib 33 is formed between any two adjacent liquid passage holes 31, supporting the separation membrane 20. The support rib 33 controls the deformation of the separation membrane 20 under negative pressure, preventing excessive deformation that could affect its service life and efficiency. Furthermore, the liquid passage holes 31 prevent the separation membrane 20 from excessively adhering to the support member 30 under the influence of the support rib 33, thus avoiding blockages and ensuring proper liquid flow.

[0056] In particular, the edge of the liquid passage 31 is provided with a chamfer structure so that the liquid passage 31 is recessed relative to the support rib 33, and the support rib 33 protrudes from the surface of the support member 30 relative to the liquid passage 31.

[0057] In summary, the support member 30 not only works with the inclined separation membrane 20 to maintain its tilt, but also ensures that the inclined separation membrane 20 is effectively supported, preventing it from undergoing significant deformation under negative pressure and affecting its service life. Furthermore, the first protrusion 1601 not only maintains the tilt of the support member 30, keeping the supported separation membrane 20 in an inclined state, but also ensures that the liquid passage 14 between the support member 30 and the first bottom wall P1 is not affected by the support member 30, preventing liquid passing through the separation membrane 20 from entering the drain channel 15. The second protrusion 32 further ensures that the effective working area of ​​the separation membrane 20 is not affected, further improving its service life. Therefore, the combined effect of the shell 11 and the support member 30 in this application not only maintains the tilt of the separation membrane 20 but also significantly improves its service life and separation effect.

[0058] The specific embodiments of this application have been described above with reference to the accompanying drawings. However, those skilled in the art will understand that various changes and substitutions can be made to the specific embodiments of this application without departing from the scope of this application. All such changes and substitutions fall within the scope defined by this application.

Claims

1. A separation chip for separating a target analyte from a sample solution; characterized in that, The separation chip includes: The shell has a sample chamber and a collection chamber; A separation assembly includes at least two separation membranes, the two separation membranes being arranged at an angle to each other, and the sample cavity being at least partially located between the two separation membranes, with the collection cavity provided on the side of each separation membrane facing away from the sample cavity; The separation membrane is configured to prevent the target object from passing through, and the collection chamber is in fluid communication with the sample chamber through the separation membrane.

2. The discrete chip as described in claim 1, characterized in that, The two separation membranes are arranged at an angle to each other, and the angle is an acute angle.

3. The discrete chip as described in claim 1, characterized in that, The separation chip also includes a support located within the collection chamber and configured to support the separation membrane on one side away from the other separation membrane.

4. The discrete chip as described in claim 3, characterized in that, The first bottom wall of the collection chamber near the separation membrane has a plurality of first protrusions. The first protrusions are configured to support the support member away from the separation membrane and to form a liquid passage between the first bottom wall of the collection chamber and the support member.

5. The discrete chip as described in claim 4, characterized in that, The support member has a liquid passage hole, which is connected to the liquid passage channel.

6. The discrete chip as described in claim 3, characterized in that, The outer peripheral surface of the support member is provided with a second protrusion, which abuts against the peripheral wall of the collection cavity to form an accommodating space between the outer peripheral surface of the support member and the peripheral wall of the collection cavity.

7. The discrete chip as described in claim 3, characterized in that, The outer contour of the separation membrane extends beyond the collection cavity, serving to close the opening of the collection cavity.

8. The discrete chip as described in claim 1, characterized in that, The housing includes two shell sections, which are arranged opposite to each other along a first direction, and sample slots are provided on the adjacent sides of the two shell sections. When the two shells are connected, the two sample slots are connected and together form the sample cavity.

9. The discrete chip as described in claim 8, characterized in that, The second bottom wall of the sample slot is provided with an installation protrusion, and the collection cavity is provided on the side of the installation protrusion away from the second bottom wall. The separation membrane is connected to the side of the installation protrusion away from the second bottom wall.

10. The discrete chip as described in claim 1, characterized in that, The housing has a drainage channel, one end of which is connected to the collection chamber, and the other end is configured to be connected to a negative pressure generating device.

Images