Circulating tumor cell screening and separating device

Abstract

The utility model provides a circulating tumor cell screening and separating device which is characterized in that the circulating tumor cell screening and separating device comprises a shell assembly, a mixing cavity, a screening cavity and a waste liquid cavity are formed in the shell assembly, and the bottom of the screening cavity is communicated with the top of the waste liquid cavity; the piston mechanism comprises a piston block, the piston block is movably installed in the mixing cavity and divides the mixing cavity into an upper cavity body and a lower cavity body, the upper cavity body and the lower cavity body are separated through the piston block, and the lower cavity body communicates with the top of the screening cavity; and the magnetic enrichment mechanism is mounted in the upper cavity. The device has the advantages that the piston block divides the mixing cavity into the upper cavity body and the lower cavity body, so that the mixing cavity has multiple functions, liquid discharging, cleaning, screening and separating steps are controlled through movement of the piston block, and the device is high in integration degree, compact and ingenious in structure, small in overall size and quite convenient to use.

Description

Technical Field

[0001] This utility model belongs to the field of medical testing technology and relates to a circulating tumor cell screening and separation device. Background Technology

[0002] Circulating tumor cells (CTCs) are tumor cells that detach from primary or metastatic tumors and enter the bloodstream. CTC detection is crucial for early cancer diagnosis, disease monitoring, treatment evaluation, and prognosis. CTCs are extremely rare in blood (only 0-100 CTCs per mL), making the enrichment and detection of CTCs from the blood a key challenge. Among various enrichment methods, immunomagnetic bead assays are widely used due to their rapid and non-destructive separation. This method relies on the binding of CTC surface-specific antigens to antibodies on magnetic beads, achieving enrichment through an external magnetic field, followed by detection using surface-enhanced Raman scattering (SERS) technology.

[0003] Previously, the screening and separation of circulating tumor cells (CTCs) in blood typically relied on manual operation, which was cumbersome and inefficient. To address these shortcomings, some devices based on SERS technology for CTC screening and separation exist. For example, a patent application (CN202211594054.6) entitled "A Circulating Tumor Cell Detection Device Based on SERS Technology" describes a device that achieves CTC detection throughout the entire process through a magnetic enrichment unit, a purification unit, and a detection unit. However, this device employs a segmented structural layout, with numerous components that cannot be integrated, resulting in a large device size and inconvenient operation. Utility Model Content

[0004] The purpose of this invention is to address the aforementioned problems in the existing technology by proposing a circulating tumor cell screening and separation device.

[0005] The objective of this utility model can be achieved through the following technical solution: a circulating tumor cell screening and separation device, comprising:

[0006] The housing assembly includes a mixing chamber, a screening chamber, and a waste liquid chamber, which are arranged sequentially from top to bottom. The bottom of the screening chamber is connected to the top of the waste liquid chamber.

[0007] A piston mechanism, comprising a piston block movably mounted within the mixing chamber and dividing the mixing chamber into an upper chamber and a lower chamber, wherein the upper chamber is configured as the portion between the top of the mixing chamber and the upper surface of the piston block, and the lower chamber is configured as the portion between the bottom of the mixing chamber and the lower surface of the piston block, the upper chamber and the lower chamber being isolated by the piston block, and the lower chamber communicating with the top of the screening chamber;

[0008] A magnetic enrichment mechanism is installed in the upper cavity;

[0009] When the piston block moves toward the top of the mixing chamber, the solution in the upper chamber is allowed to flow into the lower chamber; when the piston block moves toward the bottom of the mixing chamber, it applies pressure to the lower chamber.

[0010] Preferably, the housing assembly includes an upper housing, a screening base, and a lower housing. The screening base is detachably mounted on the lower housing, and the upper housing is detachably mounted on the screening base. The mixing chamber is disposed within the upper housing, the screening chamber is disposed within the screening base, and the waste liquid chamber is disposed within the lower housing.

[0011] Preferably, the screening base is provided with at least one set of fixing components, the fixing components including a filter membrane fixing ring and a window fixing ring, the filter membrane fixing ring being detachably connected to the screening base, a detachable filter membrane being installed between the screening base and the filter membrane fixing ring, the window fixing ring being detachably connected to the filter membrane fixing ring, and a gap being reserved between the window fixing ring and the filter membrane fixing ring for fixing a glass window.

[0012] Preferably, the screening base is provided with two sets of fixing components, the two sets of fixing components are respectively connected to the upper and lower ends of the screening base, and the filter membrane is provided between the filter membrane fixing ring of the two sets of fixing components and the screening base.

[0013] Preferably, the piston mechanism further includes a manual push rod, a portion of which is inserted into the upper cavity from the top of the housing assembly and fixedly connected to the piston block.

[0014] Preferably, the magnetic enrichment mechanism includes a glass tube and a built-in magnetic component. The top of the housing assembly is provided with an insertion hole, which communicates with the upper cavity. The glass tube is inserted into the upper cavity through the insertion hole, and the built-in magnetic component is disposed inside the glass tube and located in the upper cavity.

[0015] Preferably, the magnetic enrichment mechanism includes an external magnetic element, which is externally located on the outer wall of the housing assembly and close to the mixing chamber.

[0016] Preferably, the outer wall of the housing assembly is connected to a liquid guide tube, the two ends of which are respectively connected to two regions of the mixing chamber at different heights. The height of the upper chamber and the height of the lower chamber are determined by the stroke position of the piston block. When the piston block is in the liquid discharge stroke range, one end of the liquid guide tube is connected to the lower chamber and the other end is connected to the upper chamber. When the piston block is in the liquid discharge stroke range and moves toward the top of the mixing chamber, the solution in the upper chamber is allowed to enter the lower chamber through the liquid guide tube.

[0017] Preferably, the piston block has a valve hole, with its two ends located on the upper and lower surfaces of the piston block, respectively. A one-way valve is provided in the valve hole. When the piston block is stationary or moves toward the bottom of the mixing chamber, the one-way valve is in a closed state, and when the piston block moves toward the top of the mixing chamber, the one-way valve is in an open state.

[0018] Preferably, sealing rings are provided on the outer periphery of the piston block, at the junction of the screening base and the upper housing, and at the junction of the screening base and the lower housing.

[0019] Compared with the prior art, the beneficial effects of this utility model are as follows:

[0020] 1. The piston block divides the mixing chamber into an upper chamber and a lower chamber, enabling the mixing chamber to perform multiple functions. The movement of the piston block controls the drainage, washing, and screening separation steps. Therefore, this device has a high degree of integration and a compact and ingenious structure. Its overall size is small, making it easy to carry and use, and it is particularly suitable for applications in laboratory and clinical environments.

[0021] 2. Since the housing assembly consists of a detachable upper housing, a screening base, and a lower housing, it can be disassembled during operation. For example, the filter membrane can be left uninstalled in the screening base at the beginning, and then installed in the screening base before the cleaning step. After screening is completed, the screening base can be removed and taken to the Raman spectrometer for testing.

[0022] 3. The detachable design of the screening base enables in-situ detection. In-situ detection avoids loss and contamination during sample transfer, does not introduce other interfering substances or signals, ensures the accuracy of detection results, and reduces sample transfer time, thus improving detection efficiency. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the structure of Embodiment 1 of the device of this utility model.

[0024] Figure 2This is a schematic diagram of the structure of Embodiment 2 of the device of this utility model.

[0025] Figure 3 This is a schematic diagram of the structure of Embodiment 3 of the device of this utility model.

[0026] Figure 4 This is a schematic diagram of the structure of Embodiment 4 of the device of this utility model.

[0027] Figure 5 This is an exploded view of the screening and separation device of this utility model.

[0028] Figure 6 This is an isometric view of the screening and separation device of this utility model.

[0029] Figure 7 This is an exploded view of the screening base and fixing components of this utility model.

[0030] Figure 8 This is an axonometric view of the assembly structure of the screening base and fixing components of this utility model.

[0031] In the diagram, 100 is the upper shell; 110 is the mixing chamber; 111 is the upper cavity; 112 is the lower cavity; 120 is the liquid guide tube; 200 is the screening base; 210 is the screening chamber; 220 is the filter membrane fixing ring; 230 is the window fixing ring; 240 is the filter membrane; 250 is the glass window; 300 is the lower shell; 310 is the waste liquid chamber; 400 is the piston block; 410 is the manual push rod; 420 is the valve hole; 430 is the one-way valve; 500 is the glass tube; 600 is the built-in magnetic component; and 700 is the external magnetic component. Detailed Implementation

[0032] The following are specific embodiments of the present invention, which are described in conjunction with the accompanying drawings. However, the present invention is not limited to these embodiments.

[0033] like Figures 1 to 8As shown, a circulating tumor cell screening and separation device includes: a housing assembly, within which a mixing chamber 110, a screening chamber 210, and a waste liquid chamber 310 are disposed, the mixing chamber 110, the screening chamber 210, and the waste liquid chamber 310 being distributed sequentially from top to bottom, the bottom of the screening chamber 210 communicating with the top of the waste liquid chamber 310; and a piston mechanism, including a piston block 400, the piston block 400 being movably installed within the mixing chamber 110 and dividing the mixing chamber 110 into an upper chamber 111 and a lower chamber 112, the upper chamber 111 being configured to be formed by the top of the mixing chamber 110. The lower cavity 112 is configured to extend from the bottom of the mixing chamber 110 to the lower surface of the piston block 400. The upper cavity 111 and the lower cavity 112 are isolated by the piston block 400, and the lower cavity 112 is in communication with the top of the screening chamber 210. A magnetic enrichment mechanism is installed in the upper cavity 111. When the piston block 400 moves toward the top of the mixing chamber 110, the solution in the upper cavity 111 is allowed to flow into the lower cavity 112. When the piston block 400 moves toward the bottom of the mixing chamber 110, it applies pressure to the lower cavity 112.

[0034] It should be noted that this screening and separation device is a device for screening and separating circulating tumor cells (CTCs) based on immunomagnetic bead separation (IMS) technology. It can efficiently separate and screen CTCs from blood samples. The target cells (circulating tumor cells) separated and screened by this device can be detected by surface-enhanced Raman scattering (SERS) technology. Structurally, the housing assembly is the housing part of the entire device. Its interior has a mixing chamber 110, a screening chamber 210, and a waste liquid chamber 310 arranged sequentially from top to bottom. The mixing chamber 110, the screening chamber 210, and the waste liquid chamber 310 are all chamber structures (i.e., cavity spaces). The mixing chamber 110 has multiple functions. It is connected to an inlet tube for blood samples and magnetic probes to enter. The mixing chamber 110, together with the piston block 400, can be used as a mixing space, a reaction incubation space, and a washing space. The mixing chamber 110 is used to mix blood samples with specific reagents or magnetic beads to label CTCs. This highly integrated design significantly reduces the size of the device, making the overall design more compact and convenient to use. The screening chamber 210 is equipped with a filter membrane 240 for sieving. The selection chamber 210 is located between the mixing chamber 110 and the waste liquid chamber 310, and the mixing chamber 110 and the waste liquid chamber 310 are connected through the selection chamber 210. The selection chamber 210 is used to install the filter membrane 240, which can block the marked CTCs. Then the selection chamber 210 and the filter membrane 240 can be removed together and placed under a Raman spectrometer for detection. The waste liquid chamber 310 is used to collect the waste liquid (i.e., excess reaction liquid or washing liquid) filtered out by the selection chamber 210. The waste liquid chamber 310 is connected to a drain pipe for discharging the waste liquid from the device.

[0035] The piston mechanism includes a piston block 400, which can move up and down within the mixing chamber 110, dividing the mixing chamber 110 into an upper chamber 111 and a lower chamber 112. When the piston block 400 moves upward, the volume of the upper chamber 111 decreases and the volume of the lower chamber 112 increases. When the piston block 400 moves downward, the volume of the upper chamber 111 increases and the volume of the lower chamber 112 decreases. The size of the upper chamber 111 and the lower chamber 112 can be controlled by the movement of the piston block 400. Its main functions are to discharge waste liquid, provide a cultivation environment, clean the inner wall of the mixing chamber 110, and assist the solution to pass through the filter membrane 240 under positive pressure. Specifically, the outer peripheral surface of the piston block 400 is tightly fitted and sealed to the inner wall of the mixing chamber 110. This means that the upper chamber 111 and the lower chamber 112 are isolated. After the blood sample and magnetic probe enter the upper chamber 111, they can react and be cultured fully within the upper chamber 111. After culture, they are enriched by a magnetic enrichment mechanism. Then, the piston block 400 discharges the liquid in the upper chamber 111 that does not contain the target cells into the lower chamber 112. The waste liquid enters the waste liquid chamber 310 through the lower chamber 112 and the screening chamber 210 for discharge. Then, the washing solution is introduced into the upper chamber 111 for washing. During the above process, the screening chamber 210 is not equipped with a filter membrane 240 and a glass window.

[0036] The magnetic enrichment mechanism can be a fixed or detachable structure, and can be a permanent magnet or an electromagnet. Magnetic nanoparticles or magnetic beads (magnetic probes) are added to the sample and bind to CTCs. Under the action of an external magnetic field, the CTCs-magnetic bead complex can be effectively separated from other cells. During washing, the magnetic field can be removed, and then washing solution is added. The washing solution is then driven from the upper chamber 111 to the lower chamber 112 by the piston block 400. The washing solution carries the CTCs-magnetic bead complex to the screening chamber 210, where the filter membrane 240 filters out the CTCs-magnetic bead complex.

[0037] The piston block 400 divides the mixing chamber 110 into an upper chamber 111 and a lower chamber 112, enabling the mixing chamber 110 to perform multiple functions. The movement of the piston block 400 controls the drainage, washing, and screening separation steps. Therefore, this device has a high degree of integration and a compact and ingenious structure. Its overall size is small, making it easy to carry and use, and it is particularly suitable for applications in laboratory and clinical environments.

[0038] It should also be noted that in this device, the sample solution does not need to be drawn into other containers for transfer. The liquid transfer is achieved by the movement of the piston block 400, which is very convenient to operate. This allows the entire device to complete multiple steps within a limited space, reducing reliance on external equipment and improving operational convenience and efficiency. Through multiple up-and-down movements of the piston block 400, the mixing chamber 110 can be cleaned multiple times, ensuring that the CTCs-magnetic bead complex adhering to the inner wall of the mixing chamber 110 can be washed off by the cleaning solution, ensuring the accuracy of the detection.

[0039] like Figures 1 to 6 As shown, based on the above embodiment, the housing assembly includes an upper housing 100, a screening base 200, and a lower housing 300. The screening base 200 is detachably mounted on the lower housing 300, and the upper housing 100 is detachably mounted on the screening base 200. The mixing chamber 110 is disposed in the upper housing 100, the screening chamber 210 is disposed in the screening base 200, and the waste liquid chamber 310 is disposed in the lower housing 300.

[0040] The housing assembly is actually a detachable stacked structure. The lower housing 300 is located at the bottom of the housing assembly, and the waste liquid chamber 310 is disposed within the lower housing 300. A drain pipe communicating with the waste liquid chamber 310 is provided on the outer wall of the lower housing 300 for discharging waste liquid from the waste liquid chamber 310. The screening base 200 is a flange structure, and the screening chamber 210 is disposed within the screening base 200, which is stacked on the lower housing 300. The screening base 200 can be detached from the device, allowing the filter membrane 240 to be transferred to a Raman spectrometer for detection. This design achieves in-situ detection, improving accuracy. The upper housing 100 is disposed on the screening base 200, and the mixing chamber 110 is disposed within the upper housing 100. At least one inlet pipe is provided on the outer wall of the upper housing 100, communicating with the mixing chamber 110. Blood samples, nanomagnetic probes, and cleaning solutions can enter the mixing chamber 110 through the inlet pipe.

[0041] Since the housing assembly consists of a detachable upper housing 100, a screening base 200, and a lower housing 300, it can be disassembled during operation. For example, the filter membrane 240 can be left uninstalled in the screening base 200 initially, and then installed before the cleaning step. After screening is complete, the screening base 200 can be removed and taken to the Raman spectrometer for detection. Furthermore, specific components can be replaced according to different experimental needs, greatly improving the flexibility of the device. In particular, the detachable design of the screening base 200 enables in-situ detection, avoiding loss and contamination during sample transfer, preventing the introduction of other interfering substances or signals, ensuring the accuracy of the detection results, and reducing sample transfer time, thus improving detection efficiency.

[0042] Preferably, the lower part of the upper housing 100 and the screening base 200 are provided with internal threads on one and external threads on the other, and the upper housing 100 and the screening base 200 are connected by threads. The upper part of the lower housing 300 and the screening base 200 are provided with internal threads on one and external threads on the other, and the lower housing 300 and the screening base 200 are connected by threads. In actual assembly, the screening base 200 is first screwed into the upper part of the lower housing 300, and then the lower part of the upper housing 100 is screwed into the screening base 200, so that the upper housing 100, the screening base 200, and the lower housing 300 are detachably connected by the threaded structure.

[0043] Based on the above embodiments, at least one set of fixing components is provided on the screening base 200. The fixing components include a filter membrane fixing ring 220 and a window fixing ring 230. The filter membrane fixing ring 220 is detachably connected to the screening base 200. A detachable filter membrane 240 is installed between the screening base 200 and the filter membrane fixing ring 220. The window fixing ring 230 is detachably connected to the filter membrane fixing ring 220. A gap is reserved between the window fixing ring 230 and the filter membrane fixing ring 220 for fixing the glass window 250.

[0044] A filter membrane 240 and a glass window 250 (i.e., a glass slide) can be mounted on the screening base 200 via a fixing assembly. The screening base 200 has a through hole with internal threads on its inner wall. A filter membrane retaining ring 220 is used to fix the filter membrane 240. The filter membrane retaining ring 220 has external threads and is threadedly connected to the screening base 200 via both internal and external threads. The filter membrane 240 is detachably mounted between the screening base 200 and the filter membrane retaining ring 220 to intercept CTCs-magnetic bead complexes during the cleaning step, while allowing cleaning fluid to pass through. The window retaining ring 230 has external threads, and the inner wall of the filter membrane retaining ring 220 has internal threads. The window retaining ring 230 is threadedly connected to the filter membrane retaining ring 220 via both internal and external threads. After collecting the CTCs-magnetic bead complex, the screening base 200 is removed, and then the glass window 250 is installed in the gap between the window fixing ring 230 and the filter membrane fixing ring 220. The glass window 250 provides a transparent observation window, which is convenient for detection under Raman spectroscopy.

[0045] In its initial state, the filter membrane 240 and glass window 250 can be omitted. When collecting CTCs-magnetic bead complexes after cleaning, the screening base 200 can be detached separately. Then, the filter membrane retaining ring 220 is unscrewed, and the filter membrane 240 is inserted, sealing the through-hole of the screening base 200. The filter membrane retaining ring 220 is then screwed back in to restrain the filter membrane 240. The screening base 200 is then installed between the upper housing 100 and the lower housing 300. The size of the filter membrane 240 is sufficient to intercept CTCs-magnetic bead complexes while allowing the cleaning solution to pass through. During the detection step, the screening base 200 can be removed, and the window retaining ring 230 is unscrewed. Then, the glass window 250 is inserted and the window retaining ring 230 is screwed back in. The screening base 200 is then placed under a Raman spectrometer for in-situ detection, avoiding loss and contamination during sample transfer, ensuring the accuracy of the detection results, and the entire operation is very convenient.

[0046] Based on the above embodiments, two sets of fixing components are provided on the screening base 200. The two sets of fixing components are respectively connected to the upper and lower ends of the screening base 200, and a filter membrane 240 is provided between the filter membrane fixing ring 220 of the two sets of fixing components and the screening base 200.

[0047] In this embodiment, two sets of filter membranes 240 are designed to collect CTCs-magnetic bead complexes. The double-layer filter membrane 240 can form multiple barriers, which improves the collection effect of CTCs-magnetic bead complexes and further improves the detection accuracy.

[0048] like Figures 1 to 6 As shown, based on the above embodiment, the piston mechanism also includes a manual push rod 410. A portion of the manual push rod 410 is inserted into the upper cavity 111 from the top of the housing assembly and is fixedly connected to the piston block 400. By moving the manual push rod 410 up and down, the movement of the piston block 400 within the mixing chamber 110 can be controlled. This design is intuitive and simple to operate, requiring no complex mechanical or electric devices, making the device more compact and portable.

[0049] The operating steps of this device are as follows: The piston block 400 is positioned at the bottom of the mixing chamber 110, thus sealing the connection channel between the mixing chamber 110 and the screening chamber 210. The filter membrane 240 and glass window 250 are not installed in the screening base 200 initially, and the valve on the drain pipe is closed. Then, a blood sample and a nano-magnetic probe (magnetic SERS probe) are added to the upper chamber 111 of the mixing chamber 110 through the inlet pipe. The blood sample and the nano-magnetic probe react and incubate in the upper chamber 111 for a certain period, allowing the nano-magnetic probe to combine with CTCs to form a CTCs-magnetic bead complex. Next, the magnetic enrichment mechanism is installed or activated. The CTCs-magnetic bead complex is captured by the magnetic field of the magnetic enrichment mechanism. Then, the piston block 400 and glass tube 500 are moved upwards by the manual push rod 410, discharging the liquid in the upper chamber 111 into the lower chamber 112. At this time, the liquid enters the waste liquid chamber 310 from the screening chamber 210. Finally, the upper shell 100 and the magnetic enrichment mechanism remain stationary. Remove the screening base 200, then unscrew the filter membrane retaining ring 220 and insert the filter membrane 240. Next, tighten the filter membrane retaining ring 220 and reinstall the screening base 200 between the upper housing 100 and the lower housing 300. Then, add washing solution (PBS buffer) to the upper chamber 111 and remove the magnetic field of the magnetic enrichment mechanism. At this point, the CTCs-magnetic bead complex is collected in the washing solution. Then, allow the washing solution to enter the lower chamber 112 (this step can be achieved by...). (The stopper 400 moves down), the cleaning fluid carrying the CTCs-magnetic bead complex enters the screening chamber 210, the CTCs-magnetic bead complex is blocked by the filter membrane 240, thereby transferring the CTCs-magnetic bead complex onto the filter membrane 240; the screening base 200 is disassembled, the window fixing ring 230 is unscrewed and the glass window 250 is installed, then the window fixing ring 230 is tightened to fix the glass window 250, and finally the screening base 200 is placed under the Raman spectrometer for detection.

[0050] Example 1:

[0051] like Figure 1 , Figure 5 , Figure 6 As shown, the magnetic enrichment mechanism includes a glass tube 500 and a built-in magnetic component 600. The top of the housing assembly is provided with an insertion hole, which is connected to the upper cavity 111. The glass tube 500 is inserted into the upper cavity 111 through the insertion hole, and the built-in magnetic component 600 is disposed in the glass tube 500 and located in the upper cavity 111.

[0052] In this embodiment, a built-in magnetic element 600 is installed inside the glass tube 500. The built-in magnetic element 600 can generate a magnetic field to adsorb the CTCs-magnetic bead complex in the sample onto the smooth outer wall surface of the glass tube 500. During drainage, the CTCs-magnetic bead complex will not leave the upper cavity 111 with the waste liquid. This method of inserting the glass tube 500 with the built-in magnetic element 600 into the upper cavity 111 can significantly improve the magnetic enrichment effect. During cleaning, the built-in magnetic element 600 can be removed, or the CTCs-magnetic bead complex on the outer wall surface of the glass tube 500 can be rinsed off with cleaning fluid before removing the glass tube 500.

[0053] Example 2:

[0054] like Figures 2 to 4 As shown, the magnetic enrichment mechanism includes an external magnetic component 700, which is located outside the outer wall of the housing assembly and close to the mixing chamber 110. In this embodiment, the external magnetic component 700 is not inserted into the upper cavity 111, but rather enriches the CTCs-magnetic bead composite through the outer wall of the upper housing 100, thereby adsorbing the CTCs-magnetic bead composite onto the inner wall surface of the upper cavity 111. The advantage of this design is that, since the external magnetic component 700 is outside the upper cavity 111, the piston block 400 will not interfere with or collide with the external magnetic component 700 during movement.

[0055] Example 3:

[0056] like Figure 2 , Figure 3 , Figure 5 , Figure 6 As shown, the outer wall of the housing assembly is connected to a liquid guide pipe 120. The two ends of the liquid guide pipe 120 are respectively connected to two regions of the mixing chamber 110 at different heights. The height of the upper chamber 111 and the height of the lower chamber 112 are determined by the stroke position of the piston block 400. When the piston block 400 is in the liquid discharge stroke range, one end of the liquid guide pipe 120 is connected to the lower chamber 112 and the other end is connected to the upper chamber 111. When the piston block 400 is in the liquid discharge stroke range and moves toward the top of the mixing chamber 110, the solution in the upper chamber 111 is allowed to enter the lower chamber 112 through the liquid guide pipe 120.

[0057] In this embodiment, conduit connectors are provided on the outer wall of the upper housing 100 near the upper and lower parts of the mixing chamber 110. The conduit connectors are connected to the mixing chamber 110, and the two ends of the liquid guide tube 120 are connected to two conduit valves respectively. The advantage of this design is that the flow direction of the liquid is controlled by the movement of the piston block 400, realizing the transfer of liquid between the upper chamber 111 and the lower chamber 112, and the liquid transfer purpose can be achieved without removing the sample (reaction liquid).

[0058] The specific principle of this embodiment is as follows: In the initial state, the piston block 400 is at the bottom of the mixing chamber 110, that is, the piston block 400 seals the interface between the mixing chamber 110 and the screening chamber 210. At this time, the upper chamber 111 has the largest volume and the lower chamber 112 has the smallest volume. At this time, neither end of the liquid guide tube 120 is connected to the lower chamber 112. When the piston block 400 moves upward, the volume of the upper chamber 111 decreases and the volume of the lower chamber 112 increases. When the piston block 400 is at the beginning of the liquid discharge stroke range, one end of the liquid guide tube 120 is connected to the upper chamber 111 and the other end is connected to the lower chamber 112. As the piston block 400 continues to move upward, the liquid in the upper chamber 111 enters the lower chamber 112 along the liquid guide tube 120, thereby achieving the purpose of liquid transfer. As the piston block 400 moves downward, it can apply pressure to the lower chamber 112, thereby assisting in passing the liquid through the screening chamber 210. In addition, during the cleaning process, the piston block 400 can move repeatedly to clean the mixing chamber 110 multiple times, ensuring that all CTCs-magnetic bead complexes are collected onto the filter membrane 240.

[0059] The device in this embodiment can complete multiple steps such as mixing, draining and cleaning through simple manual operation, reducing the complexity of the operation process.

[0060] Example 4:

[0061] like Figure 4 As shown, the piston block 400 has a valve hole 420. The two ends of the valve hole 420 are located on the upper and lower surfaces of the piston block 400, respectively. A one-way valve 430 is provided in the valve hole 420. When the piston block 400 is stationary or moves toward the bottom of the mixing chamber 110, the one-way valve 430 is in the closed state. When the piston block 400 moves toward the top of the mixing chamber 110, the one-way valve 430 is in the open state.

[0062] In this embodiment, a valve hole 420 is provided in the piston block 400 and a one-way valve 430 is provided. The flow of liquid is then controlled by the direction of movement of the piston block 400. Specifically, the upper cavity 111 and the lower cavity 112 can be connected through the valve hole 420, and the one-way valve 430 controls the unidirectional flow of liquid, ensuring that under specific conditions, liquid can only flow from the upper cavity 111 to the lower cavity 112.

[0063] It should be further noted that, in the embodiment, the top of the upper housing 100 has a top cover, thereby sealing the upper cavity 111. Therefore, when the piston block 400 moves toward the top of the mixing chamber 110 (i.e., when the piston block 400 moves upward), the liquid will not leak from the top of the upper cavity 111 (because the top cover seals the top of the upper cavity 111).

[0064] However, when the piston block 400 moves downward, the volume of the upper cavity 111 increases, which can cause a vacuum, preventing the piston block 400 from moving downward. To solve this problem, an air vent is opened inside the top cover, and another one-way valve is installed inside the air vent. When the piston block 400 moves upward, the one-way valve in the air vent closes, thus keeping the upper cavity 111 sealed; when the piston block 400 moves downward, the air pressure inside the upper cavity 111 is lower than the external air pressure, the one-way valve in the air vent opens, allowing external gas to enter the upper cavity 111, thus enabling the piston block 400 to move downward.

[0065] like Figures 1 to 8 As shown, the specific principle of this embodiment is as follows: In the initial state, the piston block 400 is at the bottom of the mixing chamber 110, that is, the piston block 400 seals the interface between the mixing chamber 110 and the screening chamber 210. When the piston block 400 moves upward, the one-way valve 430 opens, allowing the liquid in the upper chamber 111 to enter the lower chamber 112 through the valve hole 420, thereby achieving the purpose of liquid transfer. When the piston block 400 is stationary, the one-way valve 430 is closed, at which time the upper chamber 111 and the lower chamber 112 are isolated. When the piston block 400 moves downward, the one-way valve 430 closes, at which time the lower surface of the piston block 400 applies pressure to the lower chamber 112, thereby assisting in passing the liquid through the screening chamber 210. In addition, during the cleaning process, the piston block 400 can move repeatedly to clean the mixing chamber 110 multiple times, ensuring that all CTCs-magnetic bead complexes are collected on the filter membrane 240. The device in this embodiment can complete multiple steps such as mixing, draining and cleaning through simple manual operation, reducing the complexity of the operation process.

[0066] like Figures 1 to 4 As shown, based on the above embodiments, sealing rings are provided on the outer periphery of the piston block 400, at the junction of the screening base 200 and the upper housing 100, and at the junction of the screening base 200 and the lower housing 300.

[0067] The sealing ring on the outer periphery of the piston block 400 ensures a seal between the upper cavity 111 and the lower cavity 112 when the piston block 400 moves up and down, preventing liquid leakage. The sealing ring at the junction of the screening base 200 and the upper housing 100 ensures a seal between the mixing chamber 110 and the screening chamber 210, preventing liquid leakage between them. The sealing ring at the junction of the screening base 200 and the lower housing 300 ensures a seal between the screening chamber 210 and the waste liquid chamber 310, preventing liquid leakage between them.

[0068] It should be noted that all directional indicators (such as up, down, left, right, front, back, etc.) in this utility model embodiment are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indicator will also change accordingly.

[0069] Furthermore, in this utility model, the use of terms such as "first," "second," and "a" is for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this utility model, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0070] In this utility model, unless otherwise explicitly specified and limited, the terms "connection," "fixing," etc., should be interpreted broadly. For example, "fixing" can mean a fixed connection, a detachable connection, or an integral part; it can mean a mechanical connection or an electrical connection; it can mean a direct connection or an indirect connection through an intermediate medium; it can mean the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this utility model according to the specific circumstances.

[0071] Furthermore, the technical solutions of the various embodiments of this utility model can be combined with each other, but only if they are based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by this utility model.

Claims

1. A circulating tumor cell screening and separation device, characterized in that, include: The housing assembly includes a mixing chamber (110), a screening chamber (210), and a waste liquid chamber (310) arranged inside the housing assembly. The mixing chamber (110), the screening chamber (210), and the waste liquid chamber (310) are distributed sequentially from top to bottom. The bottom of the screening chamber (210) is connected to the top of the waste liquid chamber (310). A piston mechanism comprising a piston block (400) movably mounted within a mixing chamber (110) and dividing the mixing chamber (110) into an upper chamber (111) and a lower chamber (112). The upper chamber (111) is configured to extend from the top of the mixing chamber (110) to the upper surface of the piston block (400), and the lower chamber (112) is configured to extend from the bottom of the mixing chamber (110) to the lower surface of the piston block (400). The upper chamber (111) and the lower chamber (112) are separated by the piston block (400), and the lower chamber (112) communicates with the top of the screening chamber (210). A magnetic enrichment mechanism is installed inside the upper cavity (111); When the piston block (400) moves toward the top of the mixing chamber (110), the solution in the upper chamber (111) is allowed to flow to the lower chamber (112); when the piston block (400) moves toward the bottom of the mixing chamber (110), it applies pressure to the lower chamber (112).

2. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The housing assembly includes an upper housing (100), a screening base (200), and a lower housing (300). The screening base (200) is detachably mounted on the lower housing (300), and the upper housing (100) is detachably mounted on the screening base (200). The mixing chamber (110) is disposed within the upper housing (100), the screening chamber (210) is disposed within the screening base (200), and the waste liquid chamber (310) is disposed within the lower housing (300).

3. The circulating tumor cell screening and separation device as described in claim 2, characterized in that: At least one set of fixing components is provided on the screening base (200). The fixing components include a filter membrane fixing ring (220) and a window fixing ring (230). The filter membrane fixing ring (220) is detachably connected to the screening base (200). A detachable filter membrane (240) is installed between the screening base (200) and the filter membrane fixing ring (220). The window fixing ring (230) is detachably connected to the filter membrane fixing ring (220). A gap is reserved between the window fixing ring (230) and the filter membrane fixing ring (220) for fixing the glass window (250).

4. The circulating tumor cell screening and separation device as described in claim 3, characterized in that: The screening base (200) is provided with two sets of fixing components. The two sets of fixing components are respectively connected to the upper and lower ends of the screening base (200), and the filter membrane (240) is provided between the filter membrane fixing ring (220) of the two sets of fixing components and the screening base (200).

5. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The piston mechanism also includes a manual push rod (410), a portion of which is inserted from the top of the housing assembly into the upper cavity (111) and fixedly connected to the piston block (400).

6. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The magnetic enrichment mechanism includes a glass tube (500) and a built-in magnetic component (600). The top of the housing assembly is provided with an insertion hole, which communicates with the upper cavity (111). The glass tube (500) is inserted into the upper cavity (111) through the insertion hole. The built-in magnetic component (600) is disposed in the glass tube (500) and located in the upper cavity (111).

7. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The magnetic enrichment mechanism includes an external magnetic component (700) which is externally located on the outer wall of the housing assembly and close to the mixing chamber (110).

8. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The outer wall of the housing assembly is connected to a liquid guide tube (120). The two ends of the liquid guide tube (120) are respectively connected to two regions of the mixing chamber (110) at different heights. The height of the upper chamber (111) and the height of the lower chamber (112) are determined by the stroke position of the piston block (400). When the piston block (400) is in the liquid discharge stroke range, one end of the liquid guide tube (120) is connected to the lower chamber (112) and the other end is connected to the upper chamber (111). When the piston block (400) is in the liquid discharge stroke range and moves toward the top of the mixing chamber (110), the solution in the upper chamber (111) is allowed to enter the lower chamber (112) through the liquid guide tube (120).

9. The circulating tumor cell screening and separation device as described in claim 1, characterized in that: The piston block (400) has a valve hole (420). The two ends of the valve hole (420) are located on the upper and lower surfaces of the piston block (400), respectively. A one-way valve (430) is provided in the valve hole (420). When the piston block (400) is stationary or moves toward the bottom of the mixing chamber (110), the one-way valve (430) is in a closed state. When the piston block (400) moves toward the top of the mixing chamber (110), the one-way valve (430) is in an open state.

10. The circulating tumor cell screening and separation device as described in claim 2, characterized in that: Sealing rings are provided on the outer periphery of the piston block (400), at the junction of the screening base (200) and the upper housing (100), and at the junction of the screening base (200) and the lower housing (300).

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