WO2017035875A1 - 一种细胞磁分选芯片及细胞磁分选装置 - Google Patents

一种细胞磁分选芯片及细胞磁分选装置 Download PDF

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WO2017035875A1
WO2017035875A1 PCT/CN2015/090028 CN2015090028W WO2017035875A1 WO 2017035875 A1 WO2017035875 A1 WO 2017035875A1 CN 2015090028 W CN2015090028 W CN 2015090028W WO 2017035875 A1 WO2017035875 A1 WO 2017035875A1
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port
outlet
cell
liquid
cell solution
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PCT/CN2015/090028
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English (en)
French (fr)
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张利峰
万书波
汪华
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深圳市赛特罗生物医疗技术有限公司
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Publication of WO2017035875A1 publication Critical patent/WO2017035875A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/42—Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
    • C12N2509/10—Mechanical dissociation

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  • the invention relates to a cell magnetic sorting chip and a cell magnetic sorting device.
  • Magnetic materials can specifically bind to target cells through biotechnology.
  • Using magnetically labeled target cells to magnetically classify highly specific target cells (target cells) is a critical step in cellular medical and cellular research activities.
  • the existing cell sorting scheme and cell sorting device have disadvantages such as complicated operation, low sorting efficiency, and low sorting purity.
  • the present invention provides a cell magnetic sorting chip and a cell magnetic sorting device which are simpler in structure and better in effect.
  • a cell magnetic sorting chip comprising a liquid line, the liquid line being in an involute shape, the liquid line comprising a first port, a second port, a third port and a fourth port, the a third port is located at an innermost end of the involute, the fourth port is located at an outermost end of the involute, and the first port and the second port are both at the third port and the fourth port And the first port is closer to the third port than the second port, the second port is for connecting a solution of a cell to be sorted, the first port is for connecting a rinsing liquid, the third port For collecting target cells, the fourth port is used to collect residual liquid.
  • the present invention also provides a cell magnetic sorting device comprising the cell magnetic sorting chip, further comprising a rotating magnetic field generator for applying a moving direction and a direction to the cell magnetic sorting chip A magnetic field in which the involute is unfolded in the opposite direction.
  • the velocity of the solution of the cell to be sorted injected from the second port is less than the velocity of the flow of the rinsing fluid injected from the first port to the fourth port, the sample to be sorted containing the magnetic marker Cells and cells that are not magnetically labeled.
  • the method further includes a source of the cell solution to be sorted, a source of the rinse solution, a constant flow syringe pump system for the cell solution, a constant flow syringe pump system for the flushing solution, and an inlet of the cell solution constant current syringe pump system
  • the sorting cell solution source is connected, and the outlet is connected to the second port, the inlet of the flushing fluid constant flow syringe pump system is connected to the flushing fluid source, and the outlet is connected to the first port.
  • the cell solution constant current syringe pump system comprises: a first solution of a cell solution, a second plunger pump of a cell solution, a first one-way valve of a cell solution, a second one-way valve of a cell solution, and a cell.
  • the sum of the liquid velocity of the outlet of the first plunger pump of the cell solution and the velocity of the liquid flowing out of the outlet of the second plunger pump of the cell solution is the first setting during the set period of time. Constant speed.
  • the liquid velocity of the outlet of the first plunger pump of the cell solution linearly decreases during a certain period of the set period of time, and the outlet of the second plunger pump of the cell solution flows out The liquid velocity increases linearly.
  • the first plunger pump including the rinsing liquid, the second plunger pump of the rinsing liquid, the first one-way valve of the rinsing liquid, the second one-way valve of the rinsing liquid, the third one-way valve of the rinsing liquid, and the rinsing liquid a four-way valve, a flushing liquid outlet pipe and a flushing liquid inlet pipe, wherein the outlet of the flushing liquid first plunger pump is respectively connected with an inlet of the first check valve of the flushing liquid and an outlet of the second check valve of the flushing liquid
  • the outlet of the first check valve of the flushing liquid is connected to the flushing liquid outlet pipe, and the flushing liquid inlet pipe is respectively connected with the inlet of the second check valve of the flushing liquid and the third of the flushing liquid
  • the outlet of the flushing liquid second plunger pump is respectively connected to the outlet of the third check valve of the flushing liquid and the inlet of the fourth check valve of
  • the sum of the speed of the liquid flowing out of the outlet of the first plunger pump of the flushing liquid and the speed of the liquid flowing out of the outlet of the second plunger pump of the flushing liquid is the first setting during the set period of time. Constant speed.
  • the liquid velocity of the outlet of the first plunger pump of the rinse liquid linearly decreases during a certain period of the set period of time, and the outlet of the second plunger pump of the rinse liquid flows out The liquid velocity increases linearly.
  • the invention has the advantages of simple structure, high efficiency and reliability, and is suitable for continuous and large-capacity magnetic cell separation; the device integrates the target cell washing function, realizes sorting and rinsing once, and can realize high-quality continuous cell sorting.
  • the sorting device of the invention is carried out in a closed pipeline, and the cell solution driving device, the rinsing liquid driving device, the magnetic sorting chip, the connecting pipeline and the related container can all be designed for single use, which can avoid pollution of the operation process by environmental factors. High-volume and high-purity sorting cell products are available to facilitate the sorting of clinical grade cell preparations.
  • FIG. 1 is a schematic structural view of a cell magnetic sorting apparatus according to an embodiment of the present invention.
  • FIG. 2 is a schematic structural view of the cell magnetic sorting chip of FIG. 1;
  • Figure 3 is a schematic structural view of the rotating magnetic field generator of Figure 1;
  • Figure 4 is an assembled view of Figures 2 and 3;
  • Figure 5 is a schematic structural view of the cell magnetic sorting chip of Figure 2;
  • Figure 6 is a schematic view showing the equivalent structure of the cell magnetic sorting chip of Figure 5;
  • Figure 7 is a schematic structural view of the constant current syringe pump system of Figure 1;
  • Figure 8 is a schematic illustration of the flow rate of the constant current syringe pump system of Figure 7.
  • a cell magnetic sorting device includes a cell solution source 103 to be sorted, a cell solution constant current syringe pump system 106, a cell magnetic sorting chip 101, and a rotating magnetic field generator (end surface rotating magnetic field occurs). And a rinsing liquid constant current syringe pump system 111, a rinsing liquid source 108, a residual liquid collection container 104, and a target cell collection container 109.
  • the cell solution constant current syringe pump system 106 is configured to drive a cell solution containing the magnetic labeled target cells (target magnetic cells) to be inserted into the cell magnetic sorting chip 101; the flushing liquid constant current syringe pump system 111 is used for driving The rinsing liquid enters the cell magnetic sorting chip 101, so that the rinsing liquid rinses the target magnetic cells to remove the cells that have not been magnetically labeled; the cell magnetic sorting chip 101 is used for the magnetic force in the magnetic field and the magnetic cells and the fluid power of the rinsing liquid Next, the target magnetic cells are sorted and washed; the rotating magnetic field generator 112 is used to generate a rotating magnetic field to drag the target magnetic cells in the cell magnetic sorting chip 101 into the target cell collection container 109.
  • the cell solution constant current syringe pump system 106 may include: a first plunger pump 11, a second plunger pump 14, a first one-way valve 16, a second one-way valve 17, a third one-way valve 18, and a fourth one-way a valve 19, an outlet pipe 20 and an inlet pipe 21, the outlet 12 of the first plunger pump 11 being connected to an inlet of the first one-way valve 16 and an outlet of the second one-way valve 17, respectively, the first single The outlet of the valve 16 is connected to the outlet pipe 20, and the inlet pipe 21 is connected to the inlet of the second one-way valve 17 and the inlet of the third one-way valve 18, respectively, the second column
  • the outlet 15 of the plug pump 14 is connected to the outlet of the third check valve 18 and the inlet of the fourth check valve 19, respectively, and the outlet of the fourth check valve 19 is connected to the outlet pipe 20.
  • the inlet tube 21 is the line 105 and the outlet tube 20 is the line 102.
  • the outlet of the first plunger pump 11 pumps out the liquid, and when the first plunger 10 moves to the left, the first plunger pump 11 The outlet flows into the liquid (absorbs liquid).
  • the second plunger 13 operates on the same principle.
  • the liquid velocity of the outlet of the first plunger pump 11 and the velocity of the liquid flowing out of the outlet of the second plunger pump 14 during a set period of time eg, during the S2 period
  • the sum is the first set speed, thereby ensuring that the velocity of the liquid flowing out of the outlet pipe 20 is constant.
  • the liquid velocity of the outlet of the first plunger pump 11 decreases linearly during a certain period of the set period of time, and the outlet of the second plunger pump 14 flows out.
  • the liquid velocity increases linearly, which also ensures that the velocity of the liquid flowing out of the outlet pipe 20 is constant, and the speed of linear change is easily achieved.
  • the liquid velocity of the outlet of the first plunger pump 11 linearly increases during a certain period of the set period of time, and the liquid flows out of the outlet of the second plunger pump 14 The speed linearly decreases, so that the first plunger pump 11 and the second plunger pump 14 alternately draw and inject liquid, so that the liquid flow rate is constant and the flow rate is adjustable.
  • the liquid velocity of the outlet of the first plunger pump 11 linearly increases to the first set speed during a certain period of the set period of time, and then the setting is maintained. The speed then decreases linearly.
  • the liquid velocity of the outlet of the second plunger pump 14 linearly increases to the first set speed during a certain period of the set period of time, and then the setting is maintained. The speed then decreases linearly.
  • the liquid flows into the first column from the outlet of the first plunger pump at a second set speed.
  • the pump 11 is plugged, thereby enabling the first plunger pump 11 to draw liquid.
  • the liquid velocity of the outlet of the second plunger pump 14 is linearly reduced to zero, the liquid flows into the second column from the outlet of the second plunger pump at a second set speed. Plug pump 14.
  • the flushing fluid constant flow syringe pump system 111 can employ the same pump system.
  • FIG. 7 is the flushing fluid constant current syringe pump system 111
  • the inlet tube 21 is the line 110
  • the outlet tube 20 is the line 107.
  • a cell magnetic sorting chip 101 of an embodiment includes a liquid line 1011 having an involute shape, and the liquid line 1011 includes a port 1, a second port 2, a third port 3 and a fourth port 4, the third port 3 is located at the innermost end of the involute, and the fourth port 4 is located at the most inflection line An outer end, the first port 1 and the second port 2 are both between the third port 3 and the fourth port 4, and the first port 1 is closer to the third port 3 than the second port 2
  • the second port 2 is connected to the source of the solution to be sorted by a line 105, the first port 1 is connected to the rinse liquid source 108 via a line 110, and the third port 3 is connected to the target cell collection container 109.
  • Fourth port 4 connection residual liquid collection Container 104 is connected to the source of the solution to be sorted by a line 105, the first port 1 is connected to the rinse liquid source 108 via a line 110, and the third port 3 is connected to the target cell collection container 109.
  • FIG. 1 is connected to the flushing liquid source 108 to form two flow paths: a flushing liquid flow path of the first port 1 to the fourth port 4, and a flow path of the first port 1 to the third port 3; and a second port 2 injection
  • the cell solution is to be sorted, and the flow rate of the cell liquid to be sorted is smaller than the flow rate of the rinsing liquid of the first port 1 to the fourth port 4.
  • the magnetic field When the rotational direction of the rotating magnetic field generated by the rotating magnetic field generator 112 is opposite to the direction in which the involute is unfolded, when the rotating magnetic field is applied to the involute liquid line 1011, the magnetic field will drag the target magnetic cells from the outside to the inside (from the first The four-port 4 to the third port 3 direction, the direction of the reverse flushing liquid flow direction, prevents the target magnetic cells from being lost through the fourth port 4, and achieves the target magnetic cell flushing; when the target magnetic cell is dragged by the rotating magnetic field, the first port is passed. After 1 , the magnetic cells are collected by the rinsing liquid of the first port 1 to the third port 3 to the target cell collection container 109, and the cell sorting process is completed.

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Abstract

一种细胞磁分选芯片及细胞磁分选装置，分选芯片（101）包括液体管路（1011），所述液体管路（1011）呈渐开线的形状，所述液体管路（1011）包括第一端口（1）、第二端口（2）、第三端口（3）和第四端口（4），所述第三端口（3）位于所述渐开线的最内端，所述第四端口（4）位于所述渐开线的最外端，所述第一端口（1）和第二端口（2）均在所述第三端口（3）与第四端口（4）之间，且所述第一端口（1）比第二端口（2）更靠近所述第三端口（3），所述第二端口（2）用于连接待分选细胞溶液，所述第一端口（1）用于连接冲洗液，所述第三端口（3）用于收集目标细胞，所述第四端口（4）用于收集残留液体。所述装置结构简单，高效可靠，适合连续、大容量磁性细胞分离；集成目标细胞冲洗功能，实现分选、冲洗一次完成，可实现高质量的连续细胞分选。

Description

一种细胞磁分选芯片及细胞磁分选装置 【技术领域】
本发明涉及一种细胞磁分选芯片及细胞磁分选装置。
【背景技术】
磁性材料通过生物技术可以与靶细胞特异性结合，利用磁标记的靶细胞的磁性，用电磁方法分选出高度特异性的靶细胞(目标细胞),是细胞医疗和细胞科研活动的关键性步骤。现有的细胞分选方案和细胞分选装置存在着操作较复杂、分选效率低、分选纯度不高等弊端。
【发明内容】
为了克服现有技术的不足，本发明提供了一种结构更加简单、效果更佳的细胞磁分选芯片及细胞磁分选装置。
一种细胞磁分选芯片，包括液体管路，所述液体管路呈渐开线的形状，所述液体管路包括第一端口、第二端口、第三端口和第四端口，所述第三端口位于所述渐开线的最内端，所述第四端口位于所述渐开线的最外端，所述第一端口和第二端口均在所述第三端口与第四端口之间，且所述第一端口比第二端口更靠近所述第三端口，所述第二端口用于连接待分选细胞溶液，所述第一端口用于连接冲洗液，所述第三端口用于收集目标细胞，所述第四端口用于收集残留液体。
本发明还提供了一种细胞磁分选装置，包括所述的细胞磁分选芯片，还包括旋转磁场发生器，所述旋转磁场发生器用于对所述细胞磁分选芯片施加运动方向与所述渐开线的展开方向相反的磁场。
在一个实施例中，从所述第二端口注入的待分选细胞溶液的速度小于从所述第一端口注入的冲洗液流到第四端口的速度，所述待分选细胞溶液含有磁标记细胞和未用磁标记细胞。
在一个实施例中，还包括待分选细胞溶液源、冲洗液源、细胞溶液恒流注射泵系统、冲洗液恒流注射泵系统，所述细胞溶液恒流注射泵系统的入口与所述待分选细胞溶液源连接、且出口与所述第二端口连接，所述冲洗液恒流注射泵系统的入口与所述冲洗液源连接、且出口与所述第一端口连接。
在一个实施例中，所述细胞溶液恒流注射泵系统包括：细胞溶液第一柱塞泵、细胞溶液第二柱塞泵、细胞溶液第一单向阀、细胞溶液第二单向阀、细胞溶液第三单向 阀、细胞溶液第四单向阀、细胞溶液出液管和细胞溶液进液管，所述细胞溶液第一柱塞泵的出口分别与细胞溶液第一单向阀的入口和细胞溶液第二单向阀的出口连接，所述细胞溶液第一单向阀的出口与所述细胞溶液出液管连接，所述细胞溶液进液管分别与所述细胞溶液第二单向阀的入口和所述细胞溶液第三单向阀的入口连接，所述细胞溶液第二柱塞泵的出口分别与所述细胞溶液第三单向阀的出口和细胞溶液第四单向阀的入口连接，所述细胞溶液第四单向阀的出口与所述细胞溶液出液管连接。
在一个实施例中，在设定时间段内，所述细胞溶液第一柱塞泵的出口流出的液体速度与所述细胞溶液第二柱塞泵的出口流出的液体速度之和为第一设定速度。
在一个实施例中，在所述设定时间段的某一段时间内，所述细胞溶液第一柱塞泵的出口流出的液体速度线性减小，所述细胞溶液第二柱塞泵的出口流出的液体速度线性增加。
在一个实施例中，包括冲洗液第一柱塞泵、冲洗液第二柱塞泵、冲洗液第一单向阀、冲洗液第二单向阀、冲洗液第三单向阀、冲洗液第四单向阀、冲洗液出液管和冲洗液进液管，所述冲洗液第一柱塞泵的出口分别与冲洗液第一单向阀的入口和冲洗液第二单向阀的出口连接，所述冲洗液第一单向阀的出口与所述冲洗液出液管连接，所述冲洗液进液管分别与所述冲洗液第二单向阀的入口和所述冲洗液第三单向阀的入口连接，所述冲洗液第二柱塞泵的出口分别与所述冲洗液第三单向阀的出口和冲洗液第四单向阀的入口连接，所述冲洗液第四单向阀的出口与所述冲洗液出液管连接。
在一个实施例中，在设定时间段内，所述冲洗液第一柱塞泵的出口流出的液体速度与所述冲洗液第二柱塞泵的出口流出的液体速度之和为第一设定速度。
在一个实施例中，在所述设定时间段的某一段时间内，所述冲洗液第一柱塞泵的出口流出的液体速度线性减小，所述冲洗液第二柱塞泵的出口流出的液体速度线性增加。
本发明的有益效果是：
本发明结构简单，高效可靠，适合连续、大容量磁性细胞分离；装置集成目标细胞冲洗功能，实现分选、冲洗一次完成，可实现高质量的连续细胞分选。
本发明分选处在密闭的管道中进行，细胞溶液驱动装置、冲洗液驱动装置、磁分选芯片、连接管路、相关容器可以全部为一次性使用设计，能避免环境因素对操作过程的污染，可获得高数量和高纯度的分选细胞产品，有利于分选临床级别的细胞制品。
【附图说明】
图1是本发明一种实施例的细胞磁分选装置的结构示意图；
图2是图1中的细胞磁分选芯片的结构示意图；
图3是图1中的旋转磁场发生器的结构示意图；
图4是图2和图3的组装示意图；
图5是图2的细胞磁分选芯片的结构示意图；
图6是图5的细胞磁分选芯片的等效结构示意图；
图7是图1的恒流注射泵系统的结构示意图；
图8是图7的恒流注射泵系统的流速示意图。
【具体实施方式】
以下对发明的较佳实施例作进一步详细说明。
如图1至8所示，一种细胞磁分选装置，包括待分选细胞溶液源103、细胞溶液恒流注射泵系统106、细胞磁分选芯片101、旋转磁场发生器(端面旋转磁场发生器)112、冲洗液恒流注射泵系统111、冲洗液源108、残留液体收集容器104、目标细胞收集容器109。
细胞溶液恒流注射泵系统106用于，驱动待分选的含有磁性标记的目标细胞(目标磁性细胞)的细胞溶液进入细胞磁分选芯片101；冲洗液恒流注射泵系统111用于，驱动冲洗液进入细胞磁分选芯片101，使冲洗液冲洗目标磁性细胞，去除未经过磁性标记的细胞；细胞磁分选芯片101用于，在磁场和磁性细胞的磁性作用力和冲洗液的流体动力下，目标磁性细胞被分选和冲洗；旋转磁场发生器112用于，产生旋转磁场拖动细胞磁分选芯片101中的目标磁性细胞进入目标细胞收集容器109。
细胞溶液恒流注射泵系统106可以包括：第一柱塞泵11、第二柱塞泵14、第一单向阀16、第二单向阀17、第三单向阀18、第四单向阀19、出液管20和进液管21，所述第一柱塞泵11的出口12分别与第一单向阀16的入口和第二单向阀17的出口连接，所述第一单向阀16的出口与所述出液管20连接，所述进液管21分别与所述第二单向阀17的入口和所述第三单向阀18的入口连接，所述第二柱塞泵14的出口15分别与所述第三单向阀18的出口和第四单向阀19的入口连接，所述第四单向阀19的出口与所述出液管20连接。在细胞溶液恒流注射泵系统106中，进液管21为管路105，出液管20为管路102。
如图7所示，第一柱塞10向右运动挤压其内的液体时，第一柱塞泵11的出口泵出液体，第一柱塞10向左运动时第一柱塞泵11的出口流入液体(吸取液体)。第二柱塞13的工作原理相同。在一个实施例中，在设定时间段内(例如在S2时间段内)，所述第一柱塞泵11的出口流出的液体速度与所述第二柱塞泵14的出口流出的液体速度 之和为第一设定速度，从而保证了出液管20流出的液体的速度是恒速的。
在一个实施例中，在所述设定时间段的某一段时间内，所述第一柱塞泵11的出口流出的液体速度线性减小，而所述第二柱塞泵14的出口流出的液体速度线性增加，这样同样可以保证出液管20流出的液体的速度是恒速的，且线性变化的速度容易实现。
在一个实施例中，在所述设定时间段的某一段时间内，所述第一柱塞泵11的出口流出的液体速度线性增加，而所述第二柱塞泵14的出口流出的液体速度线性减小，从而，第一柱塞泵11和第二柱塞泵14交替吸取、注射液体，使液体流速恒流并流速可调。
在一个实施例中，在所述设定时间段的某一段时间内，所述第一柱塞泵11的出口流出的液体速度线性增加至所述第一设定速度，接着维持所述设定速度，然后线性减小。
在一个实施例中，在所述设定时间段的某一段时间内，所述第二柱塞泵14的出口流出的液体速度线性增加至所述第一设定速度，接着维持所述设定速度，然后线性减小。
在一个实施例中，所述第一柱塞泵11的出口流出的液体速度线性减小至零后，液体以第二设定速度从所述第一柱塞泵的出口流入所述第一柱塞泵11，从而实现第一柱塞泵11吸取液体。
在一个实施例中，所述第二柱塞泵14的出口流出的液体速度线性减小至零后，液体以第二设定速度从所述第二柱塞泵的出口流入所述第二柱塞泵14。
冲洗液恒流注射泵系统111可以采用相同的泵系统，图7为冲洗液恒流注射泵系统111时，进液管21为管线110，出液管20为管线107。
如图1、2、5和6所示，一种实施例的细胞磁分选芯片101，包括液体管路1011，所述液体管路呈渐开线的形状，所述液体管路1011包括第一端口1、第二端口2、第三端口3和第四端口4，所述第三端口3位于所述渐开线的最内端，所述第四端口4位于所述渐开线的最外端，所述第一端口1和第二端口2均在所述第三端口3与第四端口4之间，且所述第一端口1比第二端口2更靠近所述第三端口3，所述第二端口2通过管路105连接待分选细胞溶液源103，所述第一端口1通过管路110连接冲洗液源108，所述第三端口3连接目标细胞收集容器109，所述第四端口4连接残留液体收集 容器104。
如图1、5和6所示，其中图6是图5的等效原理图，图5和6中，实心圆点表示磁标记细胞，空心圆点表示未用磁标记细胞。第一端口1连接冲洗液源108，形成两条流路：第一端口1至第四端口4的冲洗液流路，以及第一端口1至第三端口3的流路；第二端口2注入待分选细胞溶液，且待分选细胞液流速小于第一端口1至第四端口4的冲洗液流速。
当旋转磁场发生器112产生的旋转磁场的旋转方向与渐开线展开方向相反时，该旋转磁场施加于渐开线液体管路1011上时，磁场会拖动目标磁性细胞由外向内(从第四端口4到第三端口3方向，逆冲洗液流速方向)运动，防止目标磁性细胞经由第四端口4流失，并实现目标磁性细胞冲洗；当目标磁性细胞在旋转磁场拖动下经过第一端口1后，磁性细胞被第一端口1至第三端口3的冲洗液收集至目标细胞收集容器109，完成细胞分选流程。
以上内容是结合具体的优选实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明由所提交的权利要求书确定的专利保护范围。

Claims (10)

  1. 一种细胞磁分选芯片，其特征是，包括液体管路，所述液体管路呈渐开线的形状，所述液体管路包括第一端口、第二端口、第三端口和第四端口，所述第三端口位于所述渐开线的最内端，所述第四端口位于所述渐开线的最外端，所述第一端口和第二端口均在所述第三端口与第四端口之间，且所述第一端口比第二端口更靠近所述第三端口，所述第二端口用于连接待分选细胞溶液，所述第一端口用于连接冲洗液，所述第三端口用于收集目标细胞，所述第四端口用于收集残留液体。
  2. 一种细胞磁分选装置，其特征是，包括如权利要求1所述的细胞磁分选芯片，还包括旋转磁场发生器，所述旋转磁场发生器用于对所述细胞磁分选芯片施加运动方向与所述渐开线的展开方向相反的磁场。
  3. 如权利要求2所述的细胞磁分选装置，其特征是，从所述第二端口注入的待分选细胞溶液的速度小于从所述第一端口注入的冲洗液流到第四端口的速度，所述待分选细胞溶液含有磁标记细胞和未用磁标记细胞。
  4. 如权利要求2所述的细胞磁分选装置，其特征是，还包括待分选细胞溶液源、冲洗液源、细胞溶液恒流注射泵系统、冲洗液恒流注射泵系统，所述细胞溶液恒流注射泵系统的入口与所述待分选细胞溶液源连接、且出口与所述第二端口连接，所述冲洗液恒流注射泵系统的入口与所述冲洗液源连接、且出口与所述第一端口连接。
  5. 如权利要求4所述的细胞磁分选装置，其特征是，所述细胞溶液恒流注射泵系统包括：细胞溶液第一柱塞泵、细胞溶液第二柱塞泵、细胞溶液第一单向阀、细胞溶液第二单向阀、细胞溶液第三单向阀、细胞溶液第四单向阀、细胞溶液出液管和细胞溶液进液管，所述细胞溶液第一柱塞泵的出口分别与细胞溶液第一单向阀的入口和细胞溶液第二单向阀的出口连接，所述细胞溶液第一单向阀的出口与所述细胞溶液出液管连接，所述细胞溶液进液管分别与所述细胞溶液第二单向阀的入口和所述细胞溶液第三单向阀的入口连接，所述细胞溶液第二柱塞泵的出口分别与所述细胞溶液第三单向阀的出口和细胞溶液第四单向阀的入口连接，所述细胞溶液第四单向阀的出口与所述细胞溶液出液管连接。
  6. 如权利要求5所述的细胞磁分选装置，其特征是，在设定时间段内，所述细胞溶液第一柱塞泵的出口流出的液体速度与所述细胞溶液第二柱塞泵的出口流出的液体速度之和为第一设定速度。
  7. 如权利要求5所述的细胞磁分选装置，其特征是，在所述设定时间段的某一段时间内，所述细胞溶液第一柱塞泵的出口流出的液体速度线性减小，所述细胞溶液第 二柱塞泵的出口流出的液体速度线性增加。
  8. 如权利要求4所述的细胞磁分选装置，其特征是，包括冲洗液第一柱塞泵、冲洗液第二柱塞泵、冲洗液第一单向阀、冲洗液第二单向阀、冲洗液第三单向阀、冲洗液第四单向阀、冲洗液出液管和冲洗液进液管，所述冲洗液第一柱塞泵的出口分别与冲洗液第一单向阀的入口和冲洗液第二单向阀的出口连接，所述冲洗液第一单向阀的出口与所述冲洗液出液管连接，所述冲洗液进液管分别与所述冲洗液第二单向阀的入口和所述冲洗液第三单向阀的入口连接，所述冲洗液第二柱塞泵的出口分别与所述冲洗液第三单向阀的出口和冲洗液第四单向阀的入口连接，所述冲洗液第四单向阀的出口与所述冲洗液出液管连接。
  9. 如权利要求8所述的细胞磁分选装置，其特征是，在设定时间段内，所述冲洗液第一柱塞泵的出口流出的液体速度与所述冲洗液第二柱塞泵的出口流出的液体速度之和为第一设定速度。
  10. 如权利要求8所述的细胞磁分选装置，其特征是，在所述设定时间段的某一段时间内，所述冲洗液第一柱塞泵的出口流出的液体速度线性减小，所述冲洗液第二柱塞泵的出口流出的液体速度线性增加。
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