Microfluidic separation structure, multi-channel separation tube and combined separation tube

Abstract

The utility model relates to a centrifugal separation tube, in particular to a microfluidic separation structure, a multi-channel separation tube and a combined type separation tube, the microfluidic separation structure comprises a body and a cavity which is arranged on the body and can contain liquid, at least one microfluidic channel is arranged on the body and located on the outer side of the cavity, and the multi-channel separation tube is arranged on the body. The inlet end of each micro-fluidic channel is communicated with the cavity, and when the separation structure works centrifugally, liquid in the cavity flows into the micro-fluidic channels from the inlet ends under the siphon action and then flows out from the outlet ends of the micro-fluidic channels. According to the separation structure disclosed by the utility model, the separation of layer liquid is realized by adopting the micro-fluidic channel, manual extraction is not needed, and the separation efficiency is improved on the basis of ensuring the separation and purification effects. Meanwhile, a multi-channel separation tube is provided by arranging a plurality of micro-fluidic channels, multi-channel separation can be carried out on layer liquid at the same time, and the separation efficiency is further improved.

Description

Technical Field

[0001] The utility model relates to a centrifugal separation tube, in particular to a microfluidic separation structure, a multi-channel separation tube and a combined separation tube. Background Art

[0002] Cell separation and purification generally adopts density gradient sedimentation method, which is based on the difference in cell density, with the help of separation fluid and centrifuge to achieve separation and purification. Since the cell gradient density separation fluid will produce a certain degree of density gradient, it is poured into the separation tube with anticoagulated whole blood, and the separation tube is driven by a centrifuge to perform centrifugal movement. Under the action of separation fluid and centrifugal force, the mixed liquid in the separation tube is layered, and the components are red blood cell layer, white film layer and plasma layer from bottom to top, and then the required layer liquid is extracted manually. At present, most of the peripheral blood mononuclear cells and white film layer (PBMC) are extracted, and then the proportion and status of different types of immune cells, such as T cells, B cells, natural killer (NK) cells and monocytes, are evaluated by flow cytometry analysis. This is very important for the diagnosis and monitoring of various immune-related diseases, such as leukemia, lymphoma and immunodeficiency diseases; PBMC can also be used to detect genetic mutations and gene polymorphisms, which is very useful for diagnosing genetic diseases and assessing genetic risks; PBMC can also be used to detect gene rearrangements, help diagnose and classify diseases, etc. It can be seen that PBMC is widely used, and its separation and purification are very important. However, the separation tube used in the existing technology for separation and purification only has a layering function, and the layer liquid must be manually extracted, which is time-consuming and labor-intensive, and inefficient. Although some biological separation chips have appeared on the market to achieve cell separation and purification, the effect of separation and purification using chips is not good enough. Utility Model Content

[0003] In view of the above technical problems, the utility model provides a microfluidic separation structure, a multi-channel separation tube and a combined separation tube with high separation efficiency and good effect.

[0004] The technical solution adopted by the utility model to solve the above-mentioned technical problems is: a microfluidic separation structure, which includes a main body and a cavity opened on the main body for holding liquid, at least one microfluidic channel is provided on the main body outside the cavity, and the inlet end of each microfluidic channel is connected to the cavity. When the separation structure is centrifuged, the liquid in the cavity flows into the microfluidic channel from the inlet end under the action of siphon, and then flows out from the outlet end of the microfluidic channel.

[0005] Preferably, the liquid in the cavity is stratified by centrifugation, and when multiple microfluidic channels are used, the stratified layer liquid flows from the inlet end of each microfluidic channel into the corresponding microfluidic channel.

[0006] Preferably, the inlet end of each microfluidic channel is distributed at the same height position of the cavity, and one of the layered liquids flows from the inlet end of each microfluidic channel into the corresponding microfluidic channel.

[0007] Preferably, at least one inlet port is provided at a different height position of the cavity, and each layer of liquid after stratification flows into the corresponding microfluidic channel from the inlet port at a different height position.

[0008] Preferably, each microfluidic channel includes a first section and a last section arranged axially along the cavity, the first section is connected to the cavity through the inlet end, the last section is provided with the outlet end, and the first section and the last section are connected through a middle section in an upward convex arc shape.

[0009] Preferably, a spiral flow channel is provided on the inner wall of the cavity.

[0010] Preferably, the liquid is blood, and the layered liquid after the blood is stratified includes a buffy coat layer, the upper layer of the buffy coat layer is a plasma layer, and the lower layer of the buffy coat layer is a red blood cell layer.

[0011] The utility model also provides a multi-channel separation tube, which includes at least two microfluidic channels. The separation structure and the separation tube are an integrally formed structure. The separation structure is the upper structure of the separation tube, and the lower inner cavity of the separation tube is formed with a collection cavity connected to each outlet end.

[0012] The utility model further provides a combined separation tube, which comprises a sleeve that can be installed on a centrifuge, wherein the separation structure is installed at the upper part of the inner cavity of the sleeve, and the liquid flowing out from the outlet end of the separation structure flows into the lower part of the inner cavity of the sleeve.

[0013] Preferably, the body is connected to the upper portion of the sleeve by means of a hook, a thread or a plunger.

[0014] From the above technical solutions, it can be seen that the separation structure of the utility model uses microfluidic channels to achieve separation of layer liquids, without the need for artificial extraction, and improves the separation efficiency on the basis of ensuring the separation and purification effect. At the same time, by setting up multiple microfluidic channels, a multi-channel separation tube is provided, which can simultaneously perform multi-channel separation on the layer liquids, further improving the separation efficiency. In addition, the separation structure of the utility model and the sleeve adopt a combined structure, which not only improves the adaptability of the separation structure, but also is easy to install and low in cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 It is a schematic cross-sectional structural diagram of the separation structure of the utility model.

[0016] Figure 2 yes Figure 1 Schematic diagram of the top view structure.

[0017] Figure 3 It is a structural schematic diagram of a preferred embodiment of the multi-channel separation tube of the utility model.

[0018] Figure 4 It is a structural schematic diagram of a preferred embodiment of the combined separation tube of the utility model. DETAILED DESCRIPTION

[0019] The present invention will be described in detail below in conjunction with the accompanying drawings. The illustrative embodiments and descriptions of the present invention are used to explain the present invention but are not intended to limit the present invention.

[0020] like Figure 1 and Figure 2 The utility model provides a microfluidic separation structure, which includes a main body 1 and a cavity 11 opened on the main body for holding liquid, at least one microfluidic channel 2 is provided on the main body on the outside of the cavity, and the inlet end 21 of each microfluidic channel is connected to the cavity; during implementation, when the separation structure is centrifuged under the driving action of a centrifuge, the liquid in the cavity flows from the inlet end into the microfluidic channel under the action of a siphon, and then flows out from the outlet end 22 of the microfluidic channel. By designing the shape of the microfluidic channel and coordinating the speed at which the centrifuge drives the separation structure to perform centrifugal motion, the microfluidic channel can produce a siphon effect, thereby realizing automatic separation of the liquid without manual extraction, thereby improving efficiency. The following is a detailed description using blood as an example of the liquid in the cavity:

[0021] During the implementation process, the separation structure is first placed on a centrifuge, and blood and separation liquid are injected into the cavity. Then the centrifuge is started to drive the separation structure to perform centrifugal motion, so that the blood is stratified under the action of centrifugation. The stratified layer liquid includes a white film layer, the upper layer liquid of the white film layer is the plasma layer, and the lower layer liquid is the red blood cell layer. When multiple microfluidic channels are used, the stratified layer liquid flows from the inlet end of each microfluidic channel into the corresponding microfluidic channel, and then multiple microfluidic channels are used for simultaneous separation, further improving the separation efficiency.

[0022] As a preferred embodiment, the inlet of each microfluidic channel is distributed at the same height position of the cavity, such as Figure 4, one of the layers of liquid after stratification flows into the corresponding microfluidic channel from the inlet end of each microfluidic channel. Specifically, at least one of the plasma layer, the buffy coat layer and the red blood cell layer can be separated simultaneously through the inlet ends of multiple microfluidic channels. As another preferred embodiment, at least one inlet end is provided at different height positions of the cavity, and each layer of liquid after stratification flows into the corresponding microfluidic channel from the inlet ends at different height positions. If three microfluidic channels are set, the inlet end of the first one is set at the plasma layer, the inlet end of the second one is set at the buffy coat layer, and the inlet end of the third one is set at the red blood cell layer. In this way, the three layers of liquid can be separated simultaneously and separately, and any layer needed can be collected at any time, which improves convenience.

[0023] Each microfluidic channel 2 of the utility model includes a first section 23 and a last section 24 arranged along the axial direction of the cavity, the first section is connected to the cavity through the inlet end 21, the last section is provided with the outlet end 22, and the first section and the last section are connected through an intermediate section 25 in the shape of an upper convex arc. Whether the first section and the last section are inclined, the inclination angle, the curvature of the arc, the length of each section, the cross-sectional diameter, etc. are all obtained by calculation, so that the microfluidic channel has the effect of a capillary, thereby realizing the automatic separation of the layer liquid under the action of siphon. Preferably, the inner wall of the cavity is provided with a spiral flow channel 12, and when blood is injected into the cavity, it flows into the cavity along the spiral flow channel to prevent damage to the cells in the blood.

[0024] like Figure 3 As shown, the utility model provides a multi-channel separation tube 3, which is made based on the above-mentioned separation structure, and includes at least two microfluidic channels 2. At least two microfluidic channels can separate one layer of liquid at the same time. For example, when extracting the white film layer, two microfluidic channels are used for separation at the same time to improve the separation efficiency. The separation structure and the separation tube of the utility model are an integrally formed structure, and the separation structure is the upper structure of the separation tube, that is, the above-mentioned separation structure is directly processed on a solid separation tube, and the lower inner cavity of the separation tube is formed with a collection chamber 31 connected to each outlet end. During implementation, multiple microfluidic channels used in each layer of liquid can flow into one collection chamber at the same time, and different layers of liquid should adopt different collection chambers, so that different layers of liquid can be collected separately. Figure 3 In the embodiment of the present invention, one of the two collection chambers can collect the plasma layer and the other can collect the buffy coat layer. At the same time, an opening should be provided at the bottom or top of each collection chamber so that the collected layer liquid can be extracted from the opening.

[0025] like Figure 4As shown, the utility model also provides a combined separation tube, which includes a sleeve 4 that can be installed on a centrifuge, so that the centrifuge drives the sleeve and the separation structure to perform centrifugal motion. During the implementation process, the separation structure is installed on the upper part of the inner cavity of the sleeve, and the liquid flowing out from the outlet end of the separation structure flows into the lower part of the inner cavity of the sleeve, that is, the lower part of the inner cavity of the sleeve is directly used as the collection chamber 31, so that the layer liquid separated by the microfluidic channel directly flows into the collection chamber of the sleeve. It can be seen that the utility model adopts a split-type setting for the separation structure and the sleeve, which is not only easy to process, low in cost, but also easy to use and install. As a preference, the peripheral wall of the body can be provided with several hooks 13 that can be buckled on the mouth of the sleeve, so as to facilitate the installation and disassembly of the separation structure; the body can also be directly inserted into the upper part of the sleeve by setting a plunger, and can also be directly screwed on the upper part of the sleeve by setting a thread, so as to realize the combination of the separation structure and the sleeve in a variety of ways, thereby improving the adaptability of the separation structure. When only a single layer of liquid is to be separated, such as a white film layer, the combined separation tube can use the existing separation tube as a sleeve, and the separation structure can be directly hung on the sleeve, or inserted into the sleeve by setting a plunger, or directly screwed on the sleeve by setting a thread, so as to form a combined automatic separation tube, which greatly saves costs and improves separation efficiency. When extracting the separated layer liquid, the separation structure can be directly dismantled and then the layer liquid can be poured out; or an extraction port can be opened on the separation structure to extract the layer liquid through the extraction port. When multiple layers of liquid need to be extracted, different collection chambers should be separated in the lower inner cavity of the sleeve.

[0026] The microfluidic channel of the utility model can be set up with only one, and only separate layers of liquid, such as the white film layer, and can be used Figure 1 The structure shown in the figure; the microfluidic channel is also provided with two or three channels, and the layer liquids of different layers are separated at the same time, such as setting one channel to separate the buffy coat layer and another channel to separate the plasma layer, such as Figure 3 As shown; the microfluidic channel can also be set up with two or more channels to separate layers of liquid at the same time, such as Figure 4 The number combination of the microfluidic channels of the present invention is not limited to the above-mentioned manner, and other combinations are within the protection scope of the present invention.

Claims

1. A microfluidic separation structure, comprising a body and a cavity for holding a liquid provided on the body, characterized in that: At least one microfluidic channel is provided on the main body at the outside of the cavity, and the inlet end of each microfluidic channel is connected to the cavity. When the separation structure is centrifugally working, the liquid in the cavity flows into the microfluidic channel from the inlet end under the action of siphon, and then flows out from the outlet end of the microfluidic channel; each microfluidic channel includes a first section and a last section arranged along the axial direction of the cavity, the first section is connected to the cavity through the inlet end, and the outlet end is arranged on the last section, and the first section and the last section are connected through a middle section in the shape of an upward convex arc.

2. The microfluidic separation structure according to claim 1, characterized in that: The liquid in the cavity is stratified by centrifugation. When multiple microfluidic channels are used, the stratified layer liquid flows into the corresponding microfluidic channel from the inlet end of each microfluidic channel.

3. The microfluidic separation structure according to claim 2, characterized in that: The inlet end of each microfluidic channel is distributed at the same height position of the cavity, and one of the layered liquids flows into the corresponding microfluidic channel from the inlet end of each microfluidic channel.

4. The microfluidic separation structure according to claim 2, characterized in that: The cavity is provided with at least one inlet end at different height positions, and each layer of liquid after stratification flows into the corresponding microfluidic channel from the inlet end at different height positions.

5. The microfluidic separation structure according to any one of claims 1 to 4, characterized in that: The inner wall of the cavity is provided with a spiral flow channel.

6. The microfluidic separation structure according to any one of claims 1 to 4, characterized in that: The liquid is blood, and the layered liquid after the blood is stratified includes a buffy coat layer, the upper layer of the buffy coat layer is a plasma layer, and the lower layer of the buffy coat layer is a red blood cell layer.

7. A multi-channel separation tube made according to the microfluidic separation structure according to any one of claims 1 to 6, comprising at least two microfluidic channels, characterized in that: The separation structure and the separation tube are integrally formed structures. The separation structure is the upper structure of the separation tube, and the lower inner cavity of the separation tube is formed with a collecting cavity connected to each outlet end.

8. A combined separation tube made of the microfluidic separation structure according to any one of claims 1 to 6, comprising a sleeve that can be installed on a centrifuge, characterized in that: The separation structure is installed at the upper part of the inner cavity of the sleeve, and the liquid flowing out from the outlet end of the separation structure flows into the lower part of the inner cavity of the sleeve.

9. The combined separation tube according to claim 8, characterized in that: The body is connected to the upper part of the sleeve by arranging a hook, a thread or a plunger.

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