Biological tissue fractionating and sizing device

Abstract

This application relates to a biological tissue grading and screening device, comprising a mixed-flow screening module and a push pump assembly. The mixed-flow screening module further includes a first mixed-flow unit, at least one second mixed-flow unit and a third mixed-flow unit connected in series, and at least one grading filter. The push pump assembly includes a sample push pump and at least two collection push pumps. The sample push pump is connected to the inlet end of the first mixed-flow unit, and the first collection push pump of the at least two collection push pumps is connected to the outlet end of the third mixed-flow unit. The remaining collection push pumps are each connected to the outlet end of a grading filter. This biological tissue grading and screening device employs a purely physical separation technology of push-mixed flow and grading filtration. Different separation programs can be set for different biological tissues and cell types to obtain target samples of different grades. It not only achieves high cell recovery rate and cell purity but also improves the viable cell rate.

Description

Technical Field

[0001] This application relates to medical devices, and more specifically, to a biological tissue grading and screening device. Background Technology

[0002] Biological tissue and cell separation and extraction technologies are crucial cornerstones in life sciences, regenerative medicine, disease diagnosis, and new drug development. Obtaining high-yield, highly active, and highly pure target cells is a prerequisite for the success of downstream cell analysis, culture, therapy, and engineering applications. Currently, conventional biological tissue and cell separation and extraction methods mainly rely on principles such as biochemical digestion, centrifugation, and mechanical filtration. However, these methods often struggle to simultaneously achieve the core indicators of cell recovery rate and cell viability, exhibiting inherent limitations. For example, enzymatic chemical digestion, which uses enzymes such as trypsin and collagenase to dissociate the extracellular matrix in tissues, is widely used but has significant drawbacks. First, the non-specific action of enzymes may damage key proteins and receptors on the cell membrane surface, altering the cell's physiological state. Second, the digestion time and temperature are difficult to precisely control, easily leading to "over-digestion" of cells resulting in decreased activity, or "under-digestion" resulting in reduced recovery rate. Third, residual enzymes require multiple washings for removal, which is not only cumbersome but also causes secondary cell loss during the washing process. For example, centrifugation separates cells based on differences in cell density. Its main problem is that the enormous shear force and compression effect generated during centrifugation can cause significant physical damage or even rupture of cells, leading to reduced viability. Traditional filtration methods use mesh filters to screen cells based on size, but their most prominent problem is that the filters are prone to clogging, reducing recovery rates. Therefore, there is a long-standing unresolved contradiction in existing technologies: vigorous mechanical or chemical treatments aimed at improving cell recovery rates often come at the cost of sacrificing cell viability, while gentle treatments aimed at protecting cell viability often result in low recovery rates, lengthy processing times, or insufficient throughput. Summary of the Invention The technical problem to be solved by this application is to provide a biological tissue grading and screening device that can take into account both cell recovery rate and cell viability, in order to address the above-mentioned deficiencies of the prior art.

[0003] The technical solution adopted by this application to solve its technical problem is as follows: a biological tissue grading and screening device is proposed, comprising: a mixed-flow screening module, the mixed-flow screening module further comprising a first mixed-flow unit, at least one second mixed-flow unit and a third mixed-flow unit connected in series, and at least one grading filter, wherein the outlet end of the first mixed-flow unit is connected to the inlet end of the at least one second mixed-flow unit connected in series through a first three-way valve, the outlet end of the at least one second mixed-flow unit connected in series is connected to the inlet end of the third mixed-flow unit through a second three-way valve, the inlet end of the first grading filter of the at least one grading filter is connected to the third channel port of the second three-way valve, and the inlet ends of the remaining grading filters are respectively connected to the outlet end of the previous grading filter through a third three-way valve; and a push pump group, the push pump group comprising a sample push pump to be processed and at least two collection push pumps, the sample push pump to be processed being connected to the inlet end of the first mixed-flow unit, the first collection push pump of the at least two collection push pumps being connected to the outlet end of the third mixed-flow unit, and the remaining collection push pumps being respectively connected to the third channel port of the third three-way valve connected to the outlet end of a grading filter.

[0004] In one embodiment of the biological tissue grading and screening device described in this application, the at least one second mixing unit connected in series includes three second mixing units connected in series, and the three second mixing units are connected in sequence through a fourth three-way valve.

[0005] In one embodiment of the biological tissue grading and screening device described in this application, the at least one grading filter includes two grading filters, and the at least two collection push pumps include three collection push pumps, wherein the first collection push pump is connected to the outlet end of the third mixing unit, the second collection push pump is connected to the outlet end of the first grading filter through a third three-way valve, and the third collection push pump is connected to the outlet end of the second grading filter through another third three-way valve.

[0006] In one embodiment of the biological tissue grading and screening device described in this application, the biological tissue grading and screening device further includes a cleaning device connected to the third channel port of the first three-way valve.

[0007] In one embodiment of the biological tissue grading and screening device described in this application, the cleaning device is a replenishment pump connected to the third channel port of the first three-way valve.

[0008] In one embodiment of the biological tissue grading and screening device described in this application, the first mixing unit, at least one second mixing unit, and the third mixing unit are respectively selected from turbulent mixing units or vortex mixing units.

[0009] In one embodiment of the biological tissue grading and screening device described in this application, the turbulent mixed flow unit includes a mixed flow column, with an inlet and an outlet formed at both ends of the mixed flow column, and a jet cavity, a turbulent cavity, and a turbulent purification cavity arranged sequentially from the inlet to the outlet within the mixed flow column.

[0010] In one embodiment of the biological tissue grading and screening device described in this application, the jet cavity is a columnar flow channel formed in the middle of the mixed flow column and connected to the inlet. The turbulent flow cavity is arranged around the outlet end of the jet cavity. A screening baffle is provided at the outlet end of the turbulent flow cavity. A plurality of screening slits are formed in the middle of the turbulent flow cavity and connected to the outlet end. The turbulent flow purification cavity is connected to the outlet end of the turbulent flow cavity. A baffle is provided in the turbulent flow purification cavity to form an annular flow channel connected to the outlet.

[0011] In one embodiment of the biological tissue grading and screening device described in this application, the vortex-type mixing unit includes a mixing column, with an inlet and an outlet formed at both ends of the mixing column, and a vortex cavity connecting the inlet and the outlet is provided inside the mixing column.

[0012] In one embodiment of the biological tissue grading and screening device described in this application, the vortex cavity gradually narrows into a cone shape from the inlet end to the outlet end, and a spiral groove is formed on the inner wall of the vortex cavity.

[0013] The biological tissue grading and screening device of this application has the following beneficial effects: The biological tissue grading and screening device according to the embodiments of this application adopts a pure physical separation technology of push-in mixed flow and graded filtration. Different separation programs can be set for different biological tissues and cell types to obtain target samples of different grades. Not only is the cell recovery rate and cell purity high, but the influence of chemical reagents on cell activity is also avoided, the viable cell rate is improved, and the separated cells can be directly used for clinical treatment or scientific research experiments. Attached Figure Description

[0014] The present application will be further described below with reference to the accompanying drawings and embodiments. In the accompanying drawings: Figure 1 This is a schematic diagram of the structure of a biological tissue grading and screening device according to an embodiment of this application; Figure 2 This is a schematic diagram of the structure of a turbulent mixing unit according to an embodiment of this application; Figure 3 This is a schematic diagram of the structure of a vortex-type mixing unit according to an embodiment of this application.

[0015] Reference numerals: 100 - Biological tissue grading and sieving device; 10 - Mixed flow sieving module; 11 - First mixed flow unit; 12a, 12b, 12c - Second mixed flow unit; 13 - Third mixed flow unit; 14 - First grading filter; 15 - Second grading filter; 161 - First three-way valve; 162 - Second three-way valve; 163 - Third three-way valve; 164 - Fourth three-way valve; 20 - Pump assembly; 21 - Pump for sample to be processed; 22 - First collection pump; 23 - ... 24-Third collection and injection pump; 30-Cleaning module; 31-Replenishment injection pump; 40-Turbulent mixing unit; 41-Mixed column; 42-Inlet; 43-Outlet; 44-Jet cavity; 45-Turbulent cavity; 451-Sieve baffle; 452-Sieve slit; 46-Turbulent purification cavity; 461-Baffle; 462-Annular channel; 50-Vortex mixing unit; 51-Mixed column; 52-Inlet; 53-Outlet; 54-Vortex cavity; 541-Spiral groove. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application. Furthermore, the embodiments and features described herein can be combined with each other unless otherwise specified.

[0017] Figure 1 A schematic diagram of a biological tissue grading and screening device 100 according to an embodiment of this application is shown. See also Figure 1 As shown, the biological tissue grading and screening device 100 mainly consists of a mixed-flow screening module 10 and a push pump group 20. The mixed-flow screening module 10 further includes a first mixed-flow unit 11, three second mixed-flow units 12a, 12b and 12c connected in series, a third mixed-flow unit 13, a first grading filter 14 and a second grading filter 15. The push pump group 20 further includes a sample push pump 21, a first collection push pump 22, a second collection push pump 23 and a third collection push pump 24.

[0018] See details Figure 1As shown, the sample injection pump 21 is connected to the inlet end of the first mixing unit 11. The outlet end of the first mixing unit 11 is connected to the inlet end of the second mixing unit 12a among the three second mixing units 12a, 12b and 12c connected in series through the first three-way valve 161. The outlet end of the second mixing unit 12c among the three second mixing units 12a, 12b and 12c connected in series is connected to the inlet end of the third mixing unit 13 through the second three-way valve 162. The outlet end of the third mixing unit 13 is connected to the first collecting injection pump 22. The three second mixing units 12a, 12b and 12c connected in series are connected to each other in sequence through the fourth three-way valve 164. Thus, by controlling the first three-way valve 161 to connect the outlet end of the first mixing unit 11 to the inlet end of the second mixing unit 12a, and controlling the second three-way valve 162 to connect the outlet end of the second mixing unit 12c to the inlet end of the third mixing unit 13, a first grading and screening channel can be formed from the sample injection pump 21 to the first collection injection pump 22 via the first mixing unit 11, the three second mixing units 12a, 12b and 12c connected in series and the third mixing unit 13, and the first collection injection pump 22 to obtain the first target sample.

[0019] See also Figure 1As shown, the inlet end of the first stage filter 14 is connected to the third channel port of the second three-way valve 162, and the inlet end of the second stage filter 15 is connected to the outlet end of the first stage filter 14 through the third three-way valve 163. Furthermore, the pore size of the second stage filter 15 is smaller than that of the first stage filter element 14. In a specific embodiment, the first stage filter 14 and the second stage filter 15 can be selectively switched between pore sizes of 20μm / 40μm / 70μm / 100μm / 200μm. The second collecting and injecting pump 23 is connected to the third channel port of the third three-way valve 163 connected to the outlet end of the first stage filter 14, and the third collecting and injecting pump 24 is connected to the third three-way valve 163 connected to the outlet end of the second stage filter 15. Thus, by controlling the first three-way valve 161 to connect the outlet end of the first mixing unit 11 to the inlet end of the second mixing unit 12a, controlling the second three-way valve 162 to connect the outlet end of the second mixing unit 12c to the inlet end of the first grading filter 14, and controlling the third three-way valve 163 to connect the outlet end of the first grading filter 14 to the second collection injection pump 23, a second grading sieving channel can be formed from the sample injection pump 21 to the second collection injection pump 23 via the first mixing unit 11, the three second mixing units 12a, 12b and 12c connected in series and the first grading filter 14, to the second collection injection pump 23, where the second target sample is obtained. Furthermore, by controlling the first three-way valve 161 to connect the outlet end of the first mixing unit 11 to the inlet end of the second mixing unit 12a, controlling the second three-way valve 162 to connect the outlet end of the second mixing unit 12c to the inlet end of the first grading filter 14, and controlling the third three-way valve 163 to connect the outlet end of the first grading filter 14 to the inlet end of the second grading filter 15, a third grading sieving channel can be formed from the sample injection pump 21 to the third collection injection pump 24 via the first mixing unit 11, the three second mixing units 12a, 12b and 12c connected in series, the first grading filter 14 and the second grading filter 15, and the sample to be collected. The third target sample is obtained in the third collection injection pump 24.

[0020] The biological tissue grading and screening device 100 according to the above embodiments of this application adopts a purely physical method, combining push-mixing with graded filtration. Different separation programs can be set for different tissue types such as tissue homogenates, cell suspensions, and matrix cells. By controlling the opening and closing of the first three-way valve 161, the second three-way valve 162, and the third three-way valve 163, different grades of target samples can be selectively obtained from the first collection push pump 22, the second collection push pump 23, and the third collection push pump 24. In different embodiments of this application, the number of second mixing units connected between the first mixing unit 11 and the third mixing unit 13 via the first three-way valve 161 and the second three-way valve 162 can be selected differently depending on the sample to be processed and the target sample, and is not limited to the illustrated embodiment. Similarly, in different embodiments of this application, the number of graded filters and collection push pumps can also be expanded as needed, and is not limited to the illustrated embodiment. See also... Figure 1 As shown, the biological tissue grading and screening device 100 may also be equipped with a cleaning device 30. The cleaning device 30 may be connected to the third channel of the first three-way valve 161 via a replenishment pump 31. When the first three-way valve 161 is controlled to connect the replenishment pump 31 to the inlet of the second mixing unit 12a, the cleaning solution can be pushed by the replenishment pump 31 through the three second mixing units 12a, 12b and 12c connected in series, and then selectively passed through the third mixing unit 13, the first grading filter 14 and the second grading filter 15 by the opening and closing of the second three-way valve 162 and the third three-way valve 163, in order to improve the cell recovery rate of the aforementioned first grading screening channel, second grading screening channel and third grading screening channel. The first mixing unit 11, the three second mixing units 12a, 12b and 12c, and the third mixing unit 13 in the biological tissue grading and screening device 100 according to the above embodiments of this application can be either turbulent mixing units or vortex mixing units. That is, the first mixing unit 11, the second mixing units 12a, 12b and 12c, and the third mixing unit 13 can all be turbulent mixing units, or all be vortex mixing units, or various combinations of turbulent mixing units and vortex mixing units. The turbulent mixing units and vortex mixing units respectively utilize the principles of turbulence / vortex mechanics to design fluid channels, inducing the fluid to generate controllable microscale turbulence or vortices, efficiently and relatively gently mixing the samples to be processed, gently "tearing" or "washing" loosened cells at the edges of tissue fragments, or breaking up small cell clumps, keeping the cells in suspension and avoiding cell damage caused by large-scale violent agitation.

[0021] Figure 2 A schematic diagram of the structure of a turbulent mixing unit 40 according to a specific embodiment of this application is shown. See also Figure 2As shown, the turbulent mixing unit 40 includes a mixing column 41, with an inlet 42 and an outlet 43 formed at its two ends. Within the mixing column 41, a jet chamber 44, a turbulence chamber 45, and a turbulent purification chamber 46 are sequentially connected from the inlet 42 to the outlet 43. See details... Figure 2 As shown, the jet cavity 44 is a columnar flow channel formed in the middle of the mixing column 41 and connected to the inlet 42. A turbulent flow cavity 45 is arranged around the outlet end of the jet cavity 44, and a screening baffle 451 is provided at the outlet end of the turbulent flow cavity 45. A ring of multiple screening slits 452 is formed in the middle of the turbulent flow cavity 45, connecting to the outlet end. A turbulent purification cavity 46 is connected to the outlet end of the turbulent flow cavity 45, and a baffle 461 is provided inside the turbulent purification cavity 46 to form an annular flow channel 462 connected to the outlet 43. The mixed liquid undergoes preliminary screening, stripping, and homogenization in the jet cavity 44 using the opposing force generated by the high-speed jet, and then enters the turbulent flow cavity 45 for fine dissociation using lower energy density but more uniform microturbulence. After the mixture enters the turbulent cavity 45, it first encounters the sieving baffle 451. Larger tissue fragments are trapped in front of the sieving baffle 451 due to inertia. The fluid bypassing the sieving baffle 451 continues to mix and dissociate under the action of controlled turbulence in the turbulent cavity 45. Then it enters the turbulent purification cavity 46 through the sieving slit 452, and then flows into the outlet 43 from the annular flow channel 462 of the turbulent purification cavity 46. Figure 2 The turbulent mixing unit 40 shown transforms the original tissue into a highly active, high-purity target suspension with the highest efficiency and lowest damage through the stepwise processing of the jet cavity 44, turbulent cavity 45 and turbulent purification cavity 46.

[0022] Figure 3 A schematic diagram of the structure of a vortex-type mixing unit 50 according to a specific embodiment of this application is shown. See also Figure 3 As shown, the vortex-type mixing unit 50 includes a mixing column 51, with an inlet 52 and an outlet 53 formed at both ends of the mixing column 51. A vortex cavity 54 communicating with the inlet 52 and the outlet 53 is provided inside the mixing column 51. See details. Figure 3 As shown, the vortex cavity 54 gradually narrows into a cone shape from the inlet end to the outlet end, and a spiral groove 541 is formed on the inner wall of the vortex cavity 54. In this way, the mixture entering the vortex cavity 54 from the inlet 52 can generate a vortex under the guidance of the gradually narrowing spiral groove 541. The rotational centrifugal force generated by the vortex is used to gently and uniformly screen, peel off and fully mix the tissue fragments or cell clumps in the mixture.

[0023] According to different embodiments of this application, the first mixing unit 11, the second mixing units 12a, 12b and 12c, and the third mixing unit 13 in the biological tissue grading and screening device 100 can be combined in various ways using the aforementioned turbulent mixing unit 40 and vortex mixing unit 50. However, those skilled in the art will understand that the specific structure of the turbulent mixing unit or vortex mixing unit that can be used in the biological tissue grading and screening device according to different embodiments of this application is not limited to... Figure 2 and Figure 3 The specific embodiments shown can also be implemented using various existing suitable turbulence structures or vortex structures.

[0024] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A biological tissue fractionating and sizing device, characterized by, include: The mixed-flow screening module further includes a first mixed-flow unit, at least one second mixed-flow unit and a third mixed-flow unit connected in series, and at least one graded filter. The outlet end of the first mixed-flow unit is connected to the inlet end of the at least one second mixed-flow unit connected in series via a first three-way valve. The outlet end of the at least one second mixed-flow unit connected in series is connected to the inlet end of the third mixed-flow unit via a second three-way valve. The inlet end of the first graded filter in the at least one graded filter is connected to the third channel of the second three-way valve, and the inlet ends of the remaining graded filters are respectively connected to the outlet end of the previous graded filter via a third three-way valve. The injection pump assembly includes a sample injection pump and at least two collection injection pumps. The sample injection pump is connected to the inlet end of the first mixing unit. The first collection injection pump of the at least two collection injection pumps is connected to the outlet end of the third mixing unit. The remaining collection injection pumps are respectively connected to the third channel port of a third three-way valve connected to the outlet end of a graded filter.

2. The biological tissue fractionating screening device according to claim 1, characterized in that, The at least one second mixing unit connected in series includes three second mixing units connected in series, and the three second mixing units are connected in sequence through a fourth three-way valve.

3. The biological tissue fractionating screening device according to claim 1, wherein, The at least one graded filter includes two graded filters, and the at least two collection pumps include three collection pumps, wherein the first collection pump is connected to the outlet end of the third mixing unit, the second collection pump is connected to the outlet end of the first graded filter through a third three-way valve, and the third collection pump is connected to the outlet end of the second graded filter through another third three-way valve.

4. The biological tissue fractionating screening device according to claim 1, wherein, The biological tissue grading and screening device also includes a cleaning device connected to the third channel port of the first three-way valve.

5. The biological tissue fractionating screening device according to claim 4, wherein, The cleaning device is a replenishing pump connected to the third port of the first three-way valve.

6. The biological tissue and biological tissue fractionation device of claim 1, wherein, The first mixing unit, at least one second mixing unit, and the third mixing unit are respectively selected from turbulent mixing units or vortex mixing units.

7. The biological tissue fractionating screening device according to claim 6, wherein, The turbulent mixing unit includes a mixing column, with an inlet and an outlet formed at both ends of the mixing column. The mixing column is provided with a jet cavity, a turbulent cavity, and a turbulent purification cavity connected sequentially from the inlet to the outlet.

8. The biological tissue fractionating screening device according to claim 7, characterized in that, The jet cavity is a columnar flow channel formed in the middle of the mixed flow column and connected to the inlet. The turbulent flow cavity is arranged around the outlet end of the jet cavity. A screening baffle is provided at the outlet end of the turbulent flow cavity. A ring of multiple screening slits is formed in the middle of the turbulent flow cavity, which is connected to the outlet end. The turbulent flow purification cavity is connected to the outlet end of the turbulent flow cavity. A baffle is provided in the turbulent flow purification cavity to form an annular flow channel connected to the outlet.

9. The biological tissue fractionating screening device according to claim 6, wherein, The vortex-type mixing unit includes a mixing column, with an inlet and an outlet formed at both ends of the mixing column, and a vortex cavity connecting the inlet and the outlet is provided inside the mixing column.

10. The biological tissue fractionating screening device according to claim 9, wherein, The vortex cavity gradually narrows into a cone shape from the inlet end to the outlet end, and the inner wall of the vortex cavity is provided with spiral grooves.

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