Leukemia cell separation and extraction device

Abstract

The invention relates to the technical field of cell separation equipment, in particular to a leukemia cell separation and extraction device which comprises a fixed cylinder and a stratified sampling system for extracting leukemia cells, and a centrifugal cylinder is rotatably matched with the inner bottom wall of the fixed cylinder; a driving assembly for driving the centrifugal barrel to rotate is arranged on the outer bottom wall of the fixed barrel. The inner wall of the fixed cylinder is fixedly connected with a layering collector for acquiring layering information in the centrifugal cylinder; the outer wall of the fixed cylinder is fixedly connected with a telescopic piece; an output shaft of the telescopic piece is fixedly connected with a sampling pipe; the sampling pipe is in sliding fit with the top of the fixed cylinder; the stratified sampling system is used for controlling the telescopic part to operate based on stratified information; the sampling pipe is communicated with an adsorption part, and the stratified sampling system is used for controlling the operation of the adsorption part according to leukemia cell parameters required to be extracted. Through automatic layered detection and accurate sampling, the operation convenience and accuracy are improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of cell separation equipment, and in particular to a leukemia cell separation and extraction device. BACKGROUND

[0002] Leukemia is a malignant clonal disease of hematopoietic stem cells, and its treatment depends on the accurate identification and removal of abnormal leukemia cells. Traditional chemotherapy and radiotherapy can kill cancer cells, but lack of targeting and are easy to damage normal tissues. With the rise of cell therapy and precision medicine, efficient separation of leukemia cells from the blood or bone marrow of patients has become a key link.

[0003] In the prior art, for example, the Sepax 2 fully automatic cell separation system manufactured by Terumo BCT in Switzerland is suitable for separating stem cells in bone marrow, umbilical cord blood and peripheral blood. This system can also be used to separate other types of cells, including leukemia cells in some cases.

[0004] Although the above product can separate leukemia cells, it has weak dynamic extraction capability for key information after separation, insufficient full-process automatic control level, and lacks accurate analysis of cell layers, so that non-target layer cells may be extracted during extraction, thereby affecting the accuracy and stability of target cell extraction. Therefore, it is necessary to propose a leukemia cell separation and extraction device. SUMMARY

[0005] To solve the above problems, the present application provides a leukemia cell separation and extraction device, which acquires cell layering information in the centrifugal cylinder in real time through a layering collector, automatically analyzes and locates the leukemia cell layer position through a layering sampling system, and accurately controls the operation of the telescopic member to drive the sampling tube to insert into the target layer, thereby reducing the cumbersome steps and human errors of traditional manual measurement operation and reducing the dependence on the professional skills of the operator. At the same time, the accuracy and efficiency of sampling are improved; through automatic layering detection and accurate sampling, the operation convenience and accuracy are improved.

[0006] In order to achieve the above purpose, the technical scheme of the present application is as follows: a leukemia cell separation and extraction device, comprising a fixed cylinder and a layering sampling system for extracting leukemia cells, a centrifugal cylinder being rotatably connected to the inner bottom wall of the fixed cylinder; a driving assembly for driving the centrifugal cylinder to rotate is arranged on the outer bottom wall of the fixed cylinder.

[0007] A layering collector for acquiring layering information in the centrifugal cylinder is fixedly connected to the inner wall of the fixed cylinder; a telescopic member is fixedly connected to the outer wall of the fixed cylinder, and a sampling tube is fixedly connected to the output shaft of the telescopic member; the sampling tube is slidably connected to the top of the fixed cylinder, and the layering sampling system is used to control the operation of the telescopic member based on the layering information; the sampling tube is connected to a suction accessory, and the layering sampling system is used to control the operation of the suction accessory according to the leukemia cell parameters to be extracted.

[0008] The bottom of the fixed cylinder is provided with a cleaning assembly for cleaning the centrifugal cylinder; the driving assembly is also used for reverse rotation to drive the cleaning assembly to clean the centrifugal cylinder after the layered sampling system controls the sampling of the suction accessory to be completed.

[0009] The technical principle of the above scheme is as follows:

[0010] By adding the peripheral blood or bone marrow fluid of the patient into the centrifugal cylinder, adding the anticoagulant in a specific proportion, and sealing the centrifugal cylinder, the centrifugal cylinder is driven to rotate by the driving assembly, the centrifugal force of high-speed rotation is used to separate the cells, and the layered information in the centrifugal cylinder is obtained by the layered collector during the centrifugation. When the leukemia cell layer separation is completed, the driving assembly stops running, the sampling tube is accurately inserted into the leukemia cell layer through the telescopic piece, the leukemia cells are extracted and collected by the suction accessory, and the collection of the leukemia cells is completed. After the collection is completed, the driving assembly is reversed to drive the cleaning assembly to run, and the centrifugal cylinder is reversed synchronously, and the cleaning assembly is used to complete the cleaning of the centrifugal cylinder.

[0011] The above scheme has the following beneficial effects:

[0012] 1. The layered collector is used to obtain the cell layered information in the centrifugal cylinder in real time, the layered sampling system is used to automatically analyze and locate the leukemia cell layer position, the telescopic piece is accurately controlled to drive the sampling tube to be inserted into the target layer, the cumbersome steps of the traditional manual measurement operation and the human error are reduced, and the dependence on the professional skills of the operator is reduced. At the same time, the precision and efficiency of sampling are improved; through automatic layered detection and accurate sampling, the operation convenience and accuracy are improved.

[0013] 2. After the sampling is completed, the driving assembly is reversed to drive the cleaning assembly to work synchronously, the centrifugal cylinder is reversed to cooperate with the cleaning assembly to automatically clean the inside of the centrifugal cylinder, manual disassembly or additional operation is not needed, the subsequent maintenance process is simplified, the cross contamination between different samples is effectively reduced, and the sanitary safety of the device and the reliability of subsequent sample processing are ensured.

[0014] 3. The centrifugal cylinder of the present application is made of transparent material, which facilitates the layered collector to obtain the layered information more clearly, provides a window for the operator to observe the cell separation process intuitively, can monitor the layered state in real time, and adjusts the parameters in time through the system, further improves the stability and practicability of the device.

[0015] Further, the driving assembly comprises a rotating piece fixedly connected to the outer bottom wall of the fixed cylinder, the layered sampling system is used to control the rotating piece to run according to the centrifugal parameters of the leukemia cells, and the output shaft of the rotating piece is coaxially fixedly connected with the centrifugal cylinder.

[0016] Beneficial effects: The rotation piece is coaxially fixedly connected with the centrifugal cylinder, stability and low loss of power transmission are realized, balance during high-speed rotation of the centrifugal cylinder is ensured, and uniformity and accuracy of cell stratification are guaranteed; the stratified sampling system controls the operation of the rotation piece, rotation speed and start-stop timing can be accurately adjusted, stratification damage caused by over centrifugation is reduced, and cell separation efficiency is improved.

[0017] Further, the cleaning assembly includes a piston cylinder fixedly connected to the outer bottom wall of the fixed cylinder, an activity plate is slidingly matched with the inner wall of the piston cylinder, and a piston rod is fixedly connected to the activity plate; one side of the piston cylinder away from the piston rod is communicated with an input pipe and an output pipe, and the connection parts of the input pipe and the output pipe with the piston cylinder are both communicated with one-way valves; one end of the input pipe away from the piston cylinder is communicated with a storage cylinder for storing cleaning liquid, and one end of the output pipe away from the piston cylinder is located at the top of the centrifugal cylinder; the bottom of the fixed cylinder is further provided with a transmission assembly for driving the piston rod to reciprocate.

[0018] Beneficial effects: Through cooperation of reciprocating movement of the piston rod and the one-way valve, automatic suction and discharge of the cleaning liquid are realized, the cleaning liquid is pressed into the top of the centrifugal cylinder without manual intervention, and the convenience of cleaning operation is improved. The piston rod is driven to reciprocate by the transmission assembly, the cleaning liquid is accurately delivered to the top of the centrifugal cylinder through the output pipe, and the cleaning liquid can flush the cylinder wall and the bottom in cooperation with the rotating force during reverse rotation of the centrifugal cylinder, so that residual cells or liquid are effectively removed, and cross contamination is reduced; the one-way valve design prevents backflow of the cleaning liquid, guarantees unidirectionality and stability of liquid flow, and improves reliability of the cleaning system.

[0019] Further, the transmission assembly includes a rotating shaft rotatably connected to the bottom of the fixed cylinder, a rotating wheel is coaxially fixedly connected to the bottom of the rotating shaft, and a connecting rod is eccentrically hinged to the bottom of the rotating wheel; one end of the connecting rod away from the rotating wheel is hinged to the piston rod; the rotation piece is provided with a reverse rotation assembly for driving the rotating wheel to rotate.

[0020] Beneficial effects: The reverse rotation power of the rotating wheel is converted into reciprocating linear motion of the piston rod through the hinged design of the rotating wheel and the eccentric connecting rod; when the rotating wheel rotates, the eccentric structure drives the connecting rod to push and pull the piston rod, so that automatic pumping of the cleaning liquid is realized. The power source relies on the reverse rotation function of the rotation piece, and no additional motor or power device is needed, which reduces the number of power components and energy consumption and cost.

[0021] Further, the reverse rotation assembly includes a gear coaxially fixedly connected to the output shaft of the rotation piece, and the gear is meshed with an external gear ring; the external gear ring is coaxially rotatably connected to the rotating shaft, a plurality of clamping teeth are fixedly connected to the inner wall of the external gear ring along the circumferential direction of the external gear ring; the outer wall of the rotating shaft is hinged to a clamping block oppositely arranged to the clamping teeth, and a torsional spring is arranged at the hinged part of the rotating shaft and the clamping block.

[0022] Beneficial effects: By the one-way engagement design of the clamping block and the clamping teeth, the utilization of the forward and reverse rotation function of the rotating part is realized. When the rotating part rotates forward (cell separation stage), the outer gear ring idles with the gear, the clamping teeth slide with the clamping block for one-way operation, and the rotating shaft is stationary, avoiding the interference of the cleaning assembly with the centrifugal process. When the rotating part rotates reversely (cleaning stage), the outer gear ring rotates reversely, the clamping block engages with the clamping teeth under the elastic force of the torsional spring, the outer gear ring drives the rotating shaft to rotate synchronously, and the rotating wheel rotates to complete the pumping of the cleaning liquid. This structure can realize function switching without additional power elements, ensuring the stability of cell separation; the elastic reset characteristic of the torsional spring ensures the reliable engagement and disengagement of the clamping block and the clamping teeth, improving the response sensitivity and long-term reliability of the device.

[0023] Further, the output pipe is communicated with a nozzle at the end away from the piston cylinder, and the nozzle forms a tangent angle with the inner wall of the centrifugal cylinder.

[0024] Beneficial effects: The design of the tangent angle between the nozzle and the inner wall of the centrifugal cylinder improves the cleaning efficiency and uniformity; when the cleaning liquid is sprayed along the tangent direction, it forms a synergistic effect with the rotation direction of the centrifugal cylinder, making the liquid flow diffuse along the cylinder wall, reducing local splashing or blind areas caused by misplacement of the spray. The tangent angle also enhances the scouring force of the cleaning liquid on the cylinder wall, making it easier to peel off stubborn residues; at the same time, the tangential path of the liquid flow can prolong the contact time with the cylinder wall, improve the cleaning effect of the spray, reduce the amount of cleaning liquid and the number of cycles, and reduce operating costs.

[0025] Further, the sampling tube is made of flexible material, and the bottom of the sampling tube is chamfered with a circular arc.

[0026] Beneficial effects: The sampling tube is made of flexible material and the bottom is chamfered with a circular arc, which reduces physical damage to fragile samples such as cells and tissues when inserting or extracting samples (such as avoiding piercing the cell membrane or tearing the tissue), while reducing the insertion resistance, making the operation smoother; the combination of the two protects the integrity of the sample (reduces sample loss), improves the controllability and reliability of the sampling process.

[0027] Further, the bottom of the sampling tube is also fixedly connected with a closure valve, and the closure valve is made of elastic material.

[0028] Beneficial effects: The design of the elastic valve can automatically open and close with the suction action of the sampling tube, reducing the invasion of external pollutants and ensuring the cleanliness of the cells. The elastic material is attached to the bottom of the sampling tube, reducing cell leakage; and the closure valve has little physical stimulation to the sample, reducing the risk of damage to fragile samples such as cells and tissues. In addition, the automatic closing function simplifies manual operation, improves sampling efficiency and operational convenience.

[0029] Further, the layered sampling system includes the following modules:

[0030] The hierarchical acquisition module is configured to acquire blood layering images inside the centrifuge cylinder in real time through a hierarchical acquisition device, and to pre-process the blood layering images, and transmit the pre-processed blood layering images to the recognition analysis module.

[0031] The recognition analysis module is configured to recognize the layering interfaces of the plasma layer, the leukemia cell layer and the red blood cell layer according to the blood layering images using a deep learning algorithm, calculate the thickness of each layer, and output the thickness analysis result.

[0032] The positioning control module is configured to calculate the insertion depth of the sampling tube according to the thickness analysis result, and to transport the bottom end of the sampling tube to the center plane of the leukemia cell layer by controlling the operation of the telescopic member.

[0033] The sample extraction module is configured to extract the leukemia cell layer by starting the suction member after the sampling tube reaches the center plane of the leukemia cell layer, and to adjust the insertion depth of the sampling tube and the output power of the suction member according to the thickness analysis result of the recognition analysis module during the extraction.

[0034] Beneficial effects: The modules work together to achieve precise and efficient separation of leukemia cells; the hierarchical acquisition module acquires and pre-processes blood layering images in real time, providing clear and reliable input data for subsequent analysis. The recognition analysis module locates the layering interfaces and calculates the thickness based on the deep learning algorithm. The positioning control module dynamically calculates the insertion depth of the sampling tube according to the thickness result, ensuring that it accurately reaches the center plane of the leukemia cell layer. The sample extraction module dynamically adjusts the sampling depth and suction power in combination with the thickness analysis result, which not only improves the efficiency of target cell collection, but also reduces interference with other layers and damage to fragile cells, ensuring sample purity and the accuracy of subsequent detection. At the same time, the automatic process reduces the complexity of operation and improves the overall separation efficiency.

[0035] Further, the operation steps of the recognition analysis module are as follows:

[0036] S1, receiving the blood layering images collected by the hierarchical acquisition device, using a filtering algorithm to perform noise reduction processing on the blood layering images, performing grayscale processing on the original images, and enhancing the contrast of the original images.

[0037] S2, using a pre-trained deep learning model to perform hierarchical segmentation on the processed blood layering images, and outputting a segmentation mask labeled with the plasma layer, the leukemia cell layer and the red blood cell layer.

[0038] S3, extracting the region of each layer and locating the pixel coordinates of the layering interface by connected region analysis, and converting the actual physical size in combination with the geometric parameters of the centrifuge cylinder.

[0039] S4, based on the mapping of the pixel coordinates and the actual physical size, calculating the upper and lower boundary heights of each layer, outputting the thickness values of each layer, and generating a visual report.

[0040] Beneficial effects: precise quantification analysis of blood stratification is realized through standardized process; image quality is improved by reducing noise, gray scale and contrast enhancement processing, effectively reducing bubbles, impurities and other interference in the centrifugation process. The deep learning model segmentation technology can automatically and accurately distinguish the plasma layer, leukemia cell layer and red blood cell layer, and improve the accuracy of stratification interface positioning. The image data is mapped to the actual device parameters through pixel and physical size conversion, ensuring the physical meaning of stratification height. Thickness calculation and visual report not only output specific values of key parameters such as leukemia cell layer, but also intuitively display the stratification state through labeled images, which is convenient for operators to monitor the separation effect in real time, reduce the risk of cross-layer pollution, and improve the overall separation reliability of the device.

[0041] Additional aspects and advantages of the application will be set forth in part in the following description, will become apparent from the following description, or will be learned by practice of the application. BRIEF DESCRIPTION OF DRAWINGS

[0042] Figure 1 A perspective view of the blood cell separation device according to the present application.

[0043] Figure 2 A perspective view of the blood cell separation device according to the present application. Figure 1 A perspective view of the blood cell separation device according to the present application.

[0044] Figure 3 A perspective view of the blood cell separation device according to the present application. Figure 2 A perspective view of the blood cell separation device according to the present application.

[0045] Figure 4 A perspective view of the blood cell separation device according to the present application. Figure 2 A perspective view of the blood cell separation device according to the present application.

[0046] Figure 5 A perspective view of the blood cell separation device according to the present application. Figure 2 A perspective view of the blood cell separation device according to the present application.

[0047] Figure 6 A perspective view of the blood cell separation device according to the present application. Figure 2 A perspective view of the blood cell separation device according to the present application.

[0048] Figure 7 A perspective view of the blood cell separation device according to the present application.

[0049] The reference signs in the drawings of the specification include: 1, fixed cylinder; 2, centrifugal cylinder; 3, stratification collector; 4, telescopic part; 5, suction accessory; 6, rotating part; 7, piston cylinder; 8, movable plate; 9, piston rod; 10, rotating shaft; 11, rotating wheel; 12, connecting rod; 13, gear; 14, outer gear ring; 15, clamping tooth; 16, clamping block; 17, nozzle; 18, sampling tube; 19, closing valve. DETAILED DESCRIPTION

[0050] The specific embodiments are further described in detail below:

[0051] Embodiment 1:

[0052] As shown in Figure 1 and Figure 2 : a leukemia cell separation and extraction device, comprising a fixed cylinder 1 and a layered sampling system for extracting leukemia cells, in this embodiment, a top cover is detachably connected to the top of the fixed cylinder 1 to ensure the sealing of the internal environment; the inner bottom wall of the fixed cylinder 1 is rotationally fitted with a centrifugal cylinder 2; the outer bottom wall of the fixed cylinder 1 is provided with a driving assembly for driving the centrifugal cylinder 2 to rotate.

[0053] In this embodiment, the centrifugal cylinder 2 is made of transparent material, PC material is used; the inner wall of the fixed cylinder 1 is screw-fixedly connected with a layered collector 3 for obtaining layered information in the centrifugal cylinder 2, in this embodiment, the layered collector 3 is an industrial camera; the outer wall of the fixed cylinder 1 is screw-fixedly connected with an extension piece 4, in this embodiment, the extension piece 4 is an electric push rod, and the output shaft of the extension piece 4 is fixedly connected with a sampling tube 18; the sampling tube 18 is slidingly fitted on the top of the fixed cylinder 1, and the layered sampling system is used to control the extension piece 4 to operate based on the layered information; the sampling tube 18 is communicated with a suction accessory 5, in this embodiment, the suction accessory 5 is a micro flow pump, and the layered sampling system is used to control the suction accessory 5 to operate according to the required leukemia cell parameters.

[0054] The bottom of the fixed cylinder 1 is provided with a cleaning assembly for cleaning the centrifugal cylinder 2; the driving assembly is also used to reverse the rotation to drive the cleaning assembly to clean the centrifugal cylinder 2 after the layered sampling system controls the suction accessory 5 to complete sampling.

[0055] The driving assembly comprises a rotating member 6 screw-fixedly connected to the outer bottom wall of the fixed cylinder 1, in this embodiment, the rotating member 6 is an electric motor, the layered sampling system is used to control the rotating member 6 to operate according to the centrifugal parameters of the leukemia cells, and the output shaft of the rotating member 6 is coaxially fixedly connected with the centrifugal cylinder 2 through the fixed cylinder 1.

[0056] As shown in Figure 3 and Figure 5 , the cleaning assembly comprises a piston cylinder 7 screw-fixedly connected to the outer bottom wall of the fixed cylinder 1, the inner wall of the piston cylinder 7 is slidingly fitted with a movable plate 8, and the movable plate 8 is fixedly bonded with a piston rod 9; the side of the piston cylinder 7 away from the piston rod 9 is communicated with an input pipe and an output pipe, the connection parts of the input pipe and the output pipe with the piston cylinder 7 are both communicated with a one-way valve, in this embodiment, the one-way valve is used to guide the fluid to flow from the input pipe into the output pipe; the end of the input pipe away from the piston cylinder 7 is communicated with a storage cylinder for storing cleaning liquid, in this embodiment, the cleaning liquid uses 0.9% physiological saline and 0.1% peracetic acid; the end of the output pipe away from the piston cylinder 7 is located at the top of the centrifugal cylinder 2; the bottom of the fixed cylinder 1 is also provided with a transmission assembly for driving the piston rod 9 to reciprocate.

[0057] Specifically, when the transmission assembly is started, the piston rod 9 is driven to reciprocate, and the piston rod 9 synchronously drives the movable plate 8 to reciprocate to generate negative pressure or positive pressure. When negative pressure is generated, the one-way valve (only allowing liquid to flow from the storage cylinder to the piston cylinder 7) at the connection between the input pipe and the piston cylinder 7 is opened under the action of the pressure difference, and the cleaning liquid in the storage cylinder is sucked into the piston cylinder 7 through the input pipe. When positive pressure is generated, the one-way valve of the output pipe is opened, and the one-way valve of the input pipe is closed; the cleaning liquid in the piston cylinder 7 is pressed into the top of the centrifugal cylinder 2 through the output pipe, and the delivery of the cleaning liquid to the centrifugal cylinder 2 is completed.

[0058] The transmission assembly includes a rotating shaft 10 rotatably connected to the bottom of the fixed cylinder 1, the rotating shaft 10 is coaxially and fixedly connected with a rotating wheel 11 at the bottom, and the rotating wheel 11 is eccentrically hinged with a connecting rod 12 at the bottom; one end of the connecting rod 12 away from the rotating wheel 11 is hinged with the piston rod 9; the rotating member 6 is provided with a reverse rotation assembly for driving the rotating wheel 11 to rotate.

[0059] Specifically, taking Figure 3 as an example, since the hinged point of the connecting rod 12 and the rotating wheel 11 is eccentric, when the rotating wheel 11 rotates, the hinged point will make a circular motion with the rotating wheel 11. At this time, the connecting rod 12 acts as a connecting rod, one end of the connecting rod 12 is hinged with the rotating wheel 11 and makes a circular motion with the rotating wheel 11, and the other end of the connecting rod 12 is hinged with the piston rod 9, so that it is constrained to move only in the axial direction of the piston rod 9 (i.e. the axial direction of the piston cylinder 7).

[0060] When the rotating wheel 11 rotates to the side away from the piston cylinder 7, the connecting rod 12 is pulled away from the piston cylinder 7, driving the piston rod 9 to slide away from the piston cylinder 7, and at this time the movable plate 8 moves out with the piston rod 9; when the rotating wheel 11 rotates to the side close to the piston cylinder 7, the connecting rod 12 is pushed close to the piston cylinder 7, driving the piston rod 9 to slide into the piston cylinder 7, and the movable plate 8 moves in with the piston rod 9.

[0061] As shown in Figure 4 , the reverse rotation assembly includes a gear 13 coaxially and fixedly connected to the output shaft of the rotating member 6, the gear 13 is engaged with an external gear ring 14; the external gear ring 14 is coaxially and rotatably connected to the rotating shaft 10, and a plurality of clamping teeth 15 are integrally formed on the inner wall of the external gear ring 14 along the circumferential direction; the rotating shaft 10 is hinged with a clamping block 16 opposite to the clamping teeth 15, and a torsional spring is further arranged at the hinged position of the rotating shaft 10 and the clamping block 16.

[0062] Specifically, the output shaft of the rotating member 6 rotates forward (e.g. clockwise), driving the coaxially fixed gear 13 to synchronously rotate clockwise; since the gear 13 is engaged with the external gear ring 14, Figure 4For example, the outer gear ring 14 is driven by the gear 13 to rotate reversely (counterclockwise), at this time the clamping block 16 is hinged to the outer wall of the rotating shaft 10 and is pushed by the clamping tooth 15. When the clamping block 16 is in contact with the clamping tooth 15, the movement direction of the clamping tooth 15 is consistent with the hinging direction of the clamping block 16, and the clamping block 16 swings (i.e. retracts) to the rotating shaft 10 direction under the pushing force of the clamping tooth 15, and is disengaged from the engagement of the clamping tooth 15.

[0063] Since the clamping block 16 is not engaged with the clamping tooth 15, the rotation of the outer gear ring 14 cannot be transmitted to the rotating shaft 10, and the rotating shaft 10 remains stationary; the rotating wheel 11 is coaxially fixed to the bottom of the rotating shaft 10 and thus does not rotate, the piston rod 9 does not reciprocate, and the cleaning assembly does not work, thereby avoiding interference with the stability of the centrifugal process.

[0064] When the output shaft of the rotating member 6 rotates reversely (e.g. counterclockwise), it drives the gear 13 to rotate synchronously counterclockwise; the outer gear ring 14 is driven to rotate clockwise due to the engagement with the gear 13. The clamping tooth 15 on the inner wall of the outer gear ring 14 rotates with the outer gear ring 14, at this time the clamping block 16 swings away from the rotating shaft 10 direction (i.e. pops out) under the action of the torsional spring force, and is clamped into the tooth groove of the clamping tooth 15; the clamping block 16 is engaged with the clamping tooth 15, and the outer gear ring 14 is connected with the rotating shaft 10 through the structure of the clamping block 16 and the clamping tooth 15.

[0065] The rotation of the outer gear ring 14 is transmitted to the rotating shaft 10 through the engaged clamping block 16 and clamping tooth 15, driving the rotating shaft 10 to rotate synchronously; the rotating wheel 11 (coaxially fixed to the bottom of the rotating shaft 10) rotates with it, driving the piston rod 9 to reciprocate through the eccentrically hinged connecting rod 12, realizing the delivery of cleaning liquid and completing the cleaning operation of the centrifugal cylinder 2.

[0066] The specific implementation process is as follows:

[0067] First, the peripheral blood or bone marrow fluid of the patient is added to the centrifugal cylinder 2, and an anticoagulant of a specific ratio is added, and the centrifugal cylinder 2 is sealed. When centrifugal separation is needed, the rotating member 6 (motor) is controlled to rotate forward (e.g. clockwise) through the layered sampling system, and its output shaft directly drives the centrifugal cylinder 2 (PC transparent material) to rotate synchronously at high speed, and the blood sample is stratified by density (e.g. plasma layer, leukemia cell layer and red blood cell layer) under the action of centrifugal force. The plasma layer after centrifugation is generally light yellow or transparent, the leukemia cell layer is gray or translucent, and the red blood cell layer is dark red or opaque.

[0068] The layered image of the sample in the centrifugal cylinder 2 is taken by the layered collector 3 (industrial camera), and the layered information (such as the position and thickness of each layer) is transmitted to the layered sampling system. The layered sampling system controls the extension member 4 (electric push rod) to operate according to the layered information, and its output shaft pushes the sampling tube 18 to slide along the top of the fixed cylinder 1 and position to the leukemia cell layer; then the suction accessory 5 (micro flow pump) is controlled to operate, and the target layer cells are sucked through the sampling tube 18, and the sample extraction is completed.

[0069] After sampling is completed, the layered sampling system controls the reverse rotation (e.g., counterclockwise) of the rotating member 6, the output shaft of which drives the gear 13 to rotate synchronously counterclockwise, and the gear 13 meshes with the driving outer ring gear 14 to rotate clockwise. The clamping teeth 15 on the inner wall of the outer ring gear 14 rotate clockwise with the outer ring gear 14, and the clamping block 16 swings (pops out) away from the rotating shaft 10 under the action of the torsion spring, and is clamped into the tooth groove of the clamping teeth 15. The outer ring gear 14 is connected to the rotating shaft 10 through the structure of the clamping block 16 and the clamping teeth 15, and drives the rotating shaft 10 to rotate synchronously. The rotating wheel 11 (fixed coaxially at the bottom of the rotating shaft 10) rotates with the rotating shaft 10.

[0070] The eccentric hinge point at the bottom of the rotating wheel 11 rotates with the rotating wheel 11 to convert the rotary motion into the reciprocating linear motion of the piston rod 9 through the connecting rod 12; the cleaning liquid in the storage cylinder is delivered to the centrifugal cylinder 2, and the cleaning liquid is used to clean the centrifugal cylinder 2 synchronously through the rotation of the centrifugal cylinder 2; so as to reduce cross contamination.

[0071] The embodiment realizes that the cleaning liquid is not delivered during cell separation, and actively works to clean the centrifugal cylinder 2 after sampling is completed through the forward and reverse rotation switching of the motor and the meshing design of the clamping block 16 and the clamping teeth 15. No external power element is needed, the efficiency is improved by 60% compared with the traditional manual operation (about 30 minutes), the cleanliness (residual ≤0.1%), the overall structure is compact, the reliability is high, and it is suitable for automatic separation and extraction of leukemia cells.

[0072] Embodiment 2:

[0073] As shown in the accompanying drawings, Figure 5 The difference from the above embodiment is that the output pipe is communicated with a nozzle 17 away from the piston cylinder 7, and the nozzle 17 forms a tangent angle with the inner wall of the centrifugal cylinder 2. In this embodiment, the tangent angle is 22°.

[0074] The specific implementation process is as follows: the design of the tangent angle between the nozzle 17 and the inner wall of the centrifugal cylinder 2 improves the cleaning efficiency and uniformity; when the cleaning liquid is sprayed out along the tangent direction, it forms a synergistic effect with the rotation direction of the centrifugal cylinder 2, so that the liquid flow diffuses along the cylinder wall, reducing local splashing or blind area caused by misplacement of the spray. The tangent angle also enhances the scouring force of the cleaning liquid on the cylinder wall, making it easier to peel off stubborn residues; at the same time, the liquid flow along the tangent path can prolong the contact time with the cylinder wall, improve the cleaning effect of the spray, reduce the amount of cleaning liquid and the number of cycles, and reduce the operating cost.

[0075] Embodiment 3:

[0076] As shown in the accompanying drawings, Figure 6As shown, unlike the above embodiments, the sampling tube 18 is made of flexible material, and the bottom of the sampling tube 18 is arc chamfered. The bottom of the sampling tube 18 is also fixedly bonded with a closing valve 19 made of elastic material.

[0077] The specific implementation process is as follows: the sampling tube 18 is made of flexible material and the bottom is arc chamfered, so that the sampling tube 18 reduces the physical damage to fragile samples such as cells and tissues when inserting or extracting samples (such as avoiding piercing the cell membrane or tearing the tissue), while reducing the insertion resistance, making the operation more smooth; the combination of the two protects the integrity of the sample (reduces sample loss), improves the controllability and reliability of the sampling process.

[0078] The design of the elastic valve can be automatically opened and closed with the suction action of the sampling tube 18. When suctioning, the suction pressure pushes away the closing valve 19 to allow entry; after the suction is completed, the closing valve 19 is closed under the action of its own elasticity, effectively reducing the internal extraction cell dripping loss, while reducing the invasion of external pollutants, protecting the cleanliness of the cells. The elastic material is in close contact with the bottom of the sampling tube 18, reducing cell leakage; and the closing valve 19 has little physical stimulation to the sample, reducing the risk of damage to fragile samples such as cells and tissues. In addition, the automatic closing function simplifies manual operation, improves sampling efficiency and operational convenience.

[0079] Embodiment 4:

[0080] As shown in the accompanying drawings, Figure 7 The difference from the above embodiments is that the layered sampling system includes a layered collection module for collecting blood layering images, an identification analysis module for identifying layer interfaces, a positioning control module for transporting the sampling tube 18 to the accurate position, and a sample extraction module for sucking leukemia cell layers.

[0081] The functions of each module are as follows:

[0082] The layered collection module is used to acquire blood layering images inside the centrifugal cylinder 2 in real time through the layered collector 3 (industrial camera), and to pre-process the blood layering images, and to transmit the pre-processed blood layering images to the identification analysis module. In this embodiment, the layered collector 3 adopts a Basler acA2440-35um industrial camera with a resolution of 2448×2048 pixels and a frame rate of 35fps, and is matched with a fixed-focus lens (focal length 35mm, aperture F2.8) to ensure full field coverage of the centrifugal cylinder 2; and an infrared cutoff filter (to avoid environmental red light interference) and a polarizer (to reduce the surface reflection of PC material) are installed in front of the lens.

[0083] The identification analysis module is used to identify the layering interfaces of the plasma layer, leukemia cell layer and red blood cell layer according to the blood layering images using a deep learning algorithm, calculate the thickness of each layer, and output the thickness analysis result.

[0084] Specifically, the operation steps of the recognition analysis module are as follows:

[0085] S1, receiving the blood layering image collected by the layered collector 3, using a median filter algorithm to perform noise reduction processing (such as the micro-bubbles or impurity shadows generated in the centrifugation process) on the blood layering image, performing grayscale processing (reducing color interference and highlighting the brightness difference of the layering boundary) on the original image, and using CLAHE (Contrast Limited Adaptive Histogram Equalization) to enhance the contrast of the original image.

[0086] S2, using a pre-trained deep learning model to perform layering segmentation on the processed blood layering image, and outputting a segmentation mask labeled with the plasma layer, the leukemia cell layer and the red blood cell layer. In this embodiment, the deep learning model is based on the semantic segmentation network of U-Net or DeepLabv3+, and the model has been trained through a large number of blood layering sample images. The label includes four categories: "plasma layer", "leukemia cell layer", "red blood cell layer" and "background".

[0087] S3, extracting the region of each layer and locating the pixel coordinates of the layering interface through connected region analysis (for example, the lower boundary of the plasma layer is the lowest row of pixels in its region, the upper boundary of the leukemia cell layer is the highest row of pixels in its region, and the overlapping line of the two is the plasma-leukemia cell layering interface), and converting it into actual physical size (through the pixel-to-millimeter conversion coefficient obtained by pre-calibration) combined with the geometric parameters (such as inner diameter and height) of the centrifugal cylinder 2.

[0088] S4, based on the mapping of pixel coordinates and actual physical size, calculating the upper and lower boundary heights of each layer (such as the lower interface height of the plasma layer h1, the lower interface height of the leukemia cell layer h2, the upper interface height of the red blood cell layer h2, and the lower interface height h3), and outputting the thickness values of each layer; and generating a visual report (such as the original image with layering interface labels superimposed, and a thickness value chart).

[0089] The positioning control module is used to calculate the insertion depth of the sampling tube 18 according to the thickness analysis result, and to deliver the bottom end of the sampling tube 18 to the center plane of the leukemia cell layer by controlling the operation of the telescopic part 4. In this embodiment, the positioning control module selects a PLC controller based on the PID algorithm control.

[0090] The sample extraction module is used to start the suction accessory 5 (micro-flow pump) to extract the leukemia cell layer after the sampling tube 18 reaches the center plane of the leukemia cell layer; and to adjust the insertion depth of the sampling tube 18 and the output power of the suction accessory 5 according to the thickness analysis result of the recognition analysis module during extraction, and to adjust the micro-flow pump power by PID (flow rate reduced to 0.3 mL / min) to avoid excessive suction.

[0091] Obviously, the above embodiments are merely example for clearly illustrating but not limitation to the embodiments. Based on the above description, other different forms of changes or variations can be made by those skilled in the art. Here, all the embodiments need not and can not be enumerated. The obvious changes or variations derived from the above description are still within the protection scope of the present application.

Claims

1. A leukemia cell separation and extraction device, comprising a fixed cylinder (1), wherein the inner bottom wall of the fixed cylinder (1) is rotatably matched with a centrifugal cylinder (2), characterized in that: It also includes a layered sampling system for extracting leukemia cells; the outer bottom wall of the fixed cylinder (1) is provided with a driving assembly for driving the centrifugal cylinder (2) to rotate; The inner wall of the fixed cylinder (1) is fixedly connected to a stratification collector (3) for obtaining stratification information in the centrifugal cylinder (2); the outer wall of the fixed cylinder (1) is fixedly connected to a telescopic member (4), and the output shaft of the telescopic member (4) is fixedly connected to a sampling tube (18); the sampling tube (18) is slidably fitted on the top of the fixed cylinder (1), and the stratification sampling system is used to control the operation of the telescopic member (4) based on the stratification information; the sampling tube (18) is connected to an adsorption member (5), and the stratification sampling system is used to control the operation of the adsorption member (5) according to the leukemia cell parameters to be extracted; A cleaning assembly for cleaning the centrifugal cylinder (2) is provided at the bottom of the fixed cylinder (1); the driving assembly is also used to reversely operate after the stratified sampling system controls the adsorption component (5) to complete sampling, so as to drive the cleaning assembly to clean the centrifugal cylinder (2).

2. The leukemia cell separation and extraction device according to claim 1, characterized in that: The driving assembly includes a rotating member (6) fixedly connected to the outer bottom wall of the fixed cylinder (1); the layered sampling system is used to control the operation of the rotating member (6) according to the centrifugal parameters of the leukemia cells; the output shaft of the rotating member (6) passes through the fixed cylinder (1) and is coaxially fixedly connected to the centrifugal cylinder (2).

3. The leukemia cell separation and extraction device according to claim 1, characterized in that: The cleaning assembly comprises a piston cylinder (7) fixedly connected to the outer bottom wall of a fixed cylinder (1); a movable plate (8) is slidably fitted on the inner wall of the piston cylinder (7); a piston rod (9) is fixedly connected to the movable plate (8); an input pipe and an output pipe are connected to the side of the piston cylinder (7) away from the piston rod (9); the connection points of the input pipe and the output pipe with the piston cylinder (7) are both connected to a one-way valve; the end of the input pipe away from the piston cylinder (7) is connected to a storage cylinder for storing cleaning liquid, and the end of the output pipe away from the piston cylinder (7) is located at the top of the centrifugal cylinder (2); The bottom of the fixed cylinder (1) is also provided with a transmission assembly for driving the piston rod (9) to perform reciprocating motion.

4. The leukemia cell separation and extraction device according to claim 3, characterized in that: The transmission assembly comprises a rotating shaft (10) rotatably connected to the bottom of the fixed cylinder (1); the bottom of the rotating shaft (10) is coaxially fixedly connected to a rotating wheel (11); the bottom of the rotating wheel (11) is eccentrically hinged to a connecting rod (12); one end of the connecting rod (12) away from the rotating wheel (11) is hinged to the piston rod (9); and a reversing assembly for driving the rotating wheel (11) to rotate is provided on the rotating member (6).

5. The leukemia cell separation and extraction device according to claim 4, characterized in that: The reversing assembly comprises a gear (13) coaxially fixedly connected to the output shaft of the rotating member (6), the gear (13) being meshed with an outer gear ring (14); the outer gear ring (14) being coaxially rotatably connected to the rotating shaft (10), the inner wall of the outer gear ring (14) being fixedly connected with a plurality of latching teeth (15) along its circumference; a latching block (16) being hingedly connected to the outer wall of the rotating shaft (10) and being arranged opposite to the latching teeth (15), and a torsion spring being further provided at the hinged joint between the rotating shaft (10) and the latching block (16).

6. The leukemia cell separation and extraction device according to claim 3, characterized in that: One end of the output tube away from the piston cylinder (7) is connected to a nozzle (17), and the nozzle (17) forms a tangent angle with the inner wall of the centrifugal cylinder (2) in the axial direction.

7. The leukemia cell separation and extraction device according to claim 1, characterized in that: The sampling tube (18) is made of flexible material, and the bottom of the sampling tube (18) is chamfered in an arc shape.

8. The leukemia cell separation and extraction device according to claim 7, characterized in that: The bottom of the sampling tube (18) is also fixedly connected with a closed valve (19), which is made of elastic material.

9. The leukemia cell separation and extraction device according to claim 1, characterized in that: The stratified sampling system includes the following modules: A layered acquisition module is used to acquire a blood layered image inside the centrifuge tube (2) in real time through a layered acquisition device (3), pre-process the blood layered image, and transmit the pre-processed blood layered image to the recognition and analysis module; The recognition and analysis module is used to identify the layered interfaces of the plasma layer, leukemia cell layer, and red blood cell layer based on the blood layer image using a deep learning algorithm, calculate the thickness of each layer, and output the thickness analysis results; A positioning control module is used to calculate the insertion depth of the sampling tube (18) according to the thickness analysis result, and to transport the bottom end of the sampling tube (18) to the center plane of the leukemia cell layer by controlling the operation of the telescopic member (4); The sample extraction module is used to start the adsorption component (5) to extract the leukemia cell layer after the sampling tube (18) reaches the center plane of the leukemia cell layer; and during the extraction, the insertion depth of the sampling tube (18) and the output power of the adsorption component (5) are adjusted according to the thickness analysis result of the identification and analysis module.

10. The leukemia cell separation and extraction device according to claim 9, characterized in that: The operation steps of the identification and analysis module are as follows: S1, receiving the blood layer image collected by the layer collector (3), using a filtering algorithm to reduce noise on the blood layer image, graying the original image, and enhancing the contrast of the original image; S2. Use the pre-trained deep learning model to perform hierarchical segmentation on the processed blood layer image and output a segmentation mask marked with the plasma layer, leukemia cell layer, and red blood cell layer; S3, extracting the regions of each layer through connected region analysis and locating the pixel coordinates of the layer interface, and converting them into actual physical dimensions in combination with the geometric parameters of the centrifugal cylinder (2); S4. Based on the mapping between pixel coordinates and actual physical dimensions, the upper and lower boundary heights of each layer are calculated, and the thickness values ​​of each layer are output; and a visual report is generated.

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