Flow type sample pretreatment system and flow cytometer
Technical Field
The invention relates to a flow sample pretreatment system and a flow cytometer, in particular to a high-efficiency, safe and accurate full-automatic flow sample pretreatment system and a flow cytometer.
Background
Flow cytometry and flow cytometry are quantitative analysis and sorting means for single cell and other biological particle, and can analyze thousands of cells in short time and in high speed and measure several parameters simultaneously. Flow cytometry is known as laboratory CT. The flow cytometer sample loading needs complex sample pretreatment, and usually needs a series of complex processing and separation processes such as manual sample loading, sample shaking, centrifugation and the like to obtain a prepared sample. Specifically, antibody screening in the research and development of biological drugs and sample preparation of in vitro cell drug toxicity screening are carried out; preparing a sample for detecting multi-drug resistant gene protein; sample preparation for large-scale detection of cell multifactorial; sample preparation for mass detection of TBNK; sample preparation for other fully automated tests in alternative clinical laboratory manual operations and in the context of biological contamination prevention, and the like. In the prior art, blood of a vacuum blood collection tube is added into a flow tube manually by a pipette (the vacuum blood collection tube needs to be opened in advance), a reagent and lysate are added into the flow tube by the pipette, the flow tube is centrifuged after being slowly vibrated, and then a supernatant is discarded by the pipette and added into PBS to prepare for loading.
With the popularization of human body immunity index detection (various immunodeficiency diseases) and cell multifactorial (cancer early screening and typing), the flow detection sample volume shows a growing trend, and simultaneously, the full-automatic popularization trend of clinical detection gradually increases. If pure manual sample preparation is continuously used, large-batch sample preparation cannot be realized, the error rate is increased along with the increase of the operation time, the consistency of processed samples cannot be fully ensured, and the sample processing rate is low. Meanwhile, the flow type pipe is manually transferred to the centrifugal machine by personnel, and certain hidden danger can be formed to the safety of the operating personnel. In summary, the detection demand for flow-type sample detection increases day by day, and a full-automatic flow-type sample pretreatment device replacing manual flow-type sample preparation is urgently needed, so that the error in sample treatment is zero, and the automatic and intelligent control management operation is realized from the treatment after sample collection.
Disclosure of Invention
Aiming at the technical problems, the invention provides a flow type sample pretreatment system and a flow cytometer, which automatically transfer a sample reagent, automatically carry out treatments such as uniform mixing, centrifugation and oscillation, realize a full-automatic flow type sample pretreatment process, greatly improve the test efficiency, reduce the test error and have high safety.
To achieve one of the above objects, the present invention provides a streaming sample preprocessing system, including:
a rack module;
a sample arm module movably mounted on the rack module;
the sample frame module is arranged below the sample arm module and is used for accommodating a plurality of sample containers and driving the sample containers to turn over;
a sample piercing module movably mounted on the sample arm module, the sample piercing module comprising a sample needle for piercing the sample container;
a reagent arm module movably mounted on the rack module and parallel to the sample arm module;
the reagent rack module is arranged below the reagent arm module and is used for accommodating at least one reagent container;
a reagent needle module movably mounted on the reagent arm module, the reagent needle module including a reagent needle for adding a reagent in the reagent container to the sample container to form a second generation sample container;
the centrifuge module is arranged beside the sample rack module and/or the reagent rack module and is used for accommodating the second-generation sample container and centrifuging the second-generation sample container;
the clamping module is movably arranged on the reagent arm module and is used for grabbing and transferring the second-generation sample container;
the oscillation vortex module is arranged beside the centrifuge module and is used for accommodating the second-generation sample container and carrying out oscillation treatment on the second-generation sample container; and
a control module for providing control and/or operation to all elements of the streaming sample pre-processing system to enable automation of the streaming sample pre-processing process.
As an optional technical solution, the flow-type sample pretreatment system further includes a needle washing pool module, and the needle washing pool module includes a sample needle washing pool and a reagent needle washing pool.
As an optional technical solution, the sample rack module includes:
a sample rack for holding a plurality of said sample containers;
the gear is connected with one end of the sample rack; and
the first motor is arranged below the gear to drive the sample rack to overturn.
As an optional technical solution, the flow sample preprocessing system further includes an identification module, and the identification module is disposed at the other end of the sample rack and is configured to read a barcode on the sample container and/or the second-generation sample container.
As an optional technical solution, the sample puncturing module further includes:
a grip portion;
the second motor is used for driving the holding part to move so as to hold the sample container; and
a third motor for driving the sample needle to puncture the sample container when the sample container is gripped by the grip portion.
As an optional technical solution, the centrifuge module includes:
the centrifuge comprises a cover body and a corner rotor, wherein a plurality of container jacks for inserting the second-generation sample containers are formed in the annular surface of the corner rotor;
the thickened base plate is used for bearing the centrifuge; and
an imbalance protection module for gradually slowing down when the centrifuge reaches an imbalance critical point.
As an optional technical solution, the clamping module includes:
a plurality of clamping jaws, which form an automatically adjustable gripping space around to grip the second generation sample container; and
and the fourth motor is used for driving the clamping jaws to move and rotate.
As an optional technical solution, the oscillating vortex module includes:
an oscillating device;
a clamping device, the clamping device comprising:
a chassis;
the lantern ring is movably hinged on the chassis through a hinge;
an annular gasket secured to the collar such that the second generation sample container passes through the annular gasket and the collar in sequence; and
and the oscillation vortex motor is used for driving the oscillation device to oscillate vortexes of the second-generation sample container and driving the lantern ring to rotate so as to drive the annular gasket to contract, so that the second-generation sample container is clamped and loosened.
As an optional technical solution, the reagent needle module further includes a fifth motor, and the fifth motor is used for driving the reagent needle to move.
In order to achieve one of the above objects, the present invention further provides a flow cytometer including the flow sample pretreatment system as described above, and a fully automatic test analysis system.
Compared with the prior art, the flow type sample pretreatment system comprises a rack module, a sample arm module, a sample frame module, a sample puncture module, a reagent arm module, a reagent frame module, a reagent needle module, a centrifuge module, a clamping module, a vibration vortex module and a control module, wherein the sample puncture module is used for puncturing a sample container, the reagent needle module is used for adding a reagent in the reagent container into the sample container to form a second-generation sample container, the centrifuge module performs centrifugal treatment, the vibration vortex module performs vibration treatment, and the control module is used for controlling and/or operating all elements of the flow type sample pretreatment system, so that the full-automatic flow type sample pretreatment process is realized by automatically transferring the sample reagent, automatically performing treatments such as uniform mixing, centrifugation, vibration and the like, the test efficiency is greatly improved, and the test error is reduced, meanwhile, the safety is high.
Drawings
The invention is further illustrated with reference to the following figures and examples.
Fig. 1 is a schematic view of a perspective of a streaming sample pre-processing system in accordance with an embodiment of the present invention.
Fig. 2 is a top view of the streaming sample pretreatment system of fig. 1.
Fig. 3 is a schematic diagram of another perspective of the streaming sample pre-processing system of fig. 1.
Fig. 4 is a schematic diagram of a sample rack module in the streaming sample pre-processing system of fig. 1.
Fig. 5 is a schematic diagram of a first state of a sample puncturing module in the streaming sample pretreatment system of fig. 1.
Fig. 6 is a schematic view of the sample piercing module of fig. 5 from another perspective.
Fig. 7 is a schematic diagram of a second state of the sample piercing module in the streaming sample pretreatment system of fig. 1.
Fig. 8 is a schematic view of the sample piercing module of fig. 7 from another perspective.
Fig. 9 is a schematic diagram of a third state of the sample piercing module in the streaming sample pretreatment system of fig. 1.
Fig. 10 is a schematic view of the sample piercing module of fig. 9 from another perspective.
FIG. 11 is a schematic diagram of a cover for a centrifuge of the centrifuge module in the flow sample pretreatment system of FIG. 1.
FIG. 12 is a schematic view of a corner rotor of a centrifuge module in the flow sample pretreatment system of FIG. 1.
FIG. 13 is a partial schematic view of a corner rotor of a centrifuge module in the flow sample pretreatment system of FIG. 1.
FIG. 14 is another partial schematic view of a corner rotor of a centrifuge module in the flow sample pretreatment system of FIG. 1.
Fig. 15 is a schematic diagram of a clamping module and a reagent needle module in the flow sample pretreatment system of fig. 1.
Fig. 16 is a schematic diagram of a clamping module in the streaming sample pretreatment system of fig. 1.
Fig. 17 is a partial schematic view of a reagent needle module in the flow sample pretreatment system of fig. 1.
Fig. 18 is a schematic diagram of an oscillating vortex module in the flow sample pretreatment system of fig. 1.
Fig. 19 is a schematic partial cross-sectional view of an oscillating vortex module in the flow sample pretreatment system of fig. 1.
Fig. 20 is a partial cross-sectional view along the parting line AA of fig. 19.
Fig. 21 is a simplified schematic of fig. 20.
Detailed Description
The present invention will be further described with reference to the accompanying drawings and the detailed description, and it should be noted that any combination of the embodiments or technical features described below can be used to form a new embodiment without conflict.
Referring to fig. 1 to 21, a flow sample preprocessing system according to the present invention will be described.
As shown in fig. 1 to 3, the flow sample preprocessing system includes a rack module 11, a sample arm module 12, a sample rack module 13, a sample puncturing module 14, a reagent arm module 15, a reagent rack module 16, a reagent needle module 17, a centrifuge module 18, a clamping module 19, an oscillation vortex module 20, and a control module. The sample arm module 12 is movably mounted on the rack module 11, the sample rack module 13 is disposed below the sample arm module 12 and configured to accommodate a plurality of sample containers 21 and drive the plurality of sample containers 21 to turn over, the sample puncturing module 14 is movably mounted on the sample arm module 12, the sample puncturing module 14 includes a sample needle 22, and the sample needle 22 is configured to puncture the sample containers 21. The reagent arm module 15 is also movably mounted on the rack module 11 in parallel with the sample arm module 12, the reagent rack module 16 is disposed below the reagent arm module 15 for accommodating at least one reagent container 23, the reagent needle module 17 is movably mounted on the reagent arm module 15, the reagent needle module 17 includes a reagent needle 24, the reagent needle 24 is used for adding a reagent in the reagent container 23 to the sample container 21 to form a second-generation sample container 25, and the grip module 19 is also movably mounted on the reagent arm module 15 for gripping and transferring the second-generation sample container 25.
The centrifuge module 18 is disposed near the sample rack module 13 and/or the reagent rack module 16, and is configured to receive the second-generation sample container 25 and centrifuge the second-generation sample container 25. The oscillation vortex module 20 is disposed beside the centrifuge module 18, and is configured to accommodate the second-generation sample container 25 and oscillate the second-generation sample container 25. The control module is used for providing control and/or operation for all elements of the flow type sample pretreatment system, so as to realize full automation of the flow type sample pretreatment process.
As described above, the flow sample pretreatment system automatically transfers the sample reagent, automatically performs treatments such as uniform mixing, centrifugation and oscillation, realizes a full-automatic flow sample pretreatment process, greatly improves the test efficiency, reduces the test error and has high safety.
In the embodiment of the invention, the frame module 11 adopts a portal frame structure, so that the deformation of the arm group when the cantilever structure of the arm group is loaded greatly is avoided, and the service life of the X-direction guide rail of the arm group is ensured. Preferably, a slide rail structure is disposed on a cantilever on one side of the rack module 11 for sliding the sample arm module 12 and the reagent arm module 15, meanwhile, a slide rail is also disposed on the sample arm module 12 for sliding the sample puncturing module 14, and a slide rail is also disposed on the reagent arm module 15 for sliding the reagent needle module 17 and the holding module 19, because the slide rail structure is simple and can facilitate movement, but the present invention is not limited thereto, and other ways that can achieve movable installation are also applicable.
The flow type sample pretreatment system further comprises a needle washing pool module, wherein the needle washing pool module comprises a sample needle washing pool 26 and a reagent needle washing pool 27, the sample needle washing pool 26 is used for cleaning the sample needle 22, the reagent needle washing pool 27 is used for cleaning the reagent needle 24, and the two needle washing pools can be arranged nearby in corresponding active areas, for example, the sample needle washing pool 26 is arranged beside the centrifuge module 18, and the reagent needle washing pool 27 is arranged beside the oscillation vortex module 20. The provision of two separate wash reservoirs avoids cross-contamination of the sample needle 22 and reagent needle 24 for mixed cleaning.
Next, each module will be explained in detail with reference to the drawings.
As shown in fig. 4, the sample rack module 13 includes a sample rack 28, a gear 29, and a first motor 30, wherein the sample rack 28 is used for holding a plurality of sample containers 21, the gear 29 is connected to one end of the sample rack 28, and the first motor 30 is disposed below the gear 29 to drive the gear 29 to turn the sample rack 28 integrally. Compared with the time-consuming disadvantage of the conventional U-shaped sample rack that the single tubes are shaken up one by one, the sample rack 28 provided by the invention adopts the integral shaking-up type sample rack, so that the time is saved and the efficiency is high. In a more preferred embodiment, the gear 29 is driven by a POM gear, thereby reducing the abnormal rotating sound.
In addition, as shown in fig. 3, the flow sample preprocessing system further includes an identification module 31, and the identification module 31 is disposed at the other end of the sample rack 28 and is used for reading the bar code on the sample container 21 and/or the second-generation sample container 25. In other words, when the user loads different containers, the identification module 31 automatically reads the bar codes on the containers, identifies the sample information, saves the time for manually inputting the samples, and thus realizes the automatic sample information input of the streaming sample preprocessing system. Preferably, the identification module 31 is a barcode scanner.
With reference to fig. 5 to 10, the sample puncturing module 14 further includes a holding portion 32, a second motor 33 and a third motor 34, the second motor 33 is used for driving the holding portion 32 to move so as to hold the sample container 21, the third motor 34 is used for driving the sample needle 22 to puncture the sample container 21 when the holding portion 32 holds the sample container 21, wherein the second motor 33 and the third motor 34 are arranged in parallel, the moving directions of the holding portion 32 and the sample needle 22 are the same, and the sample needle 22 is disposed right above the holding portion 32. Specifically, as shown in fig. 5 and 6, when sample piercing is performed, the sample piercing module 14 is moved above the sample container 21 to be pierced so that the grip portion 32 is aligned with the nozzle of the sample container 21; as shown in fig. 7 and 8, the second motor 33 drives the holding portion 32 to move down to hold the nozzle of the sample container 21; at this time, as shown in fig. 9 and 10, the third motor 34 drives the sample needle 22 to move downward to puncture the sample container 21, that is, the holding design in the sample puncturing module 14 of the present embodiment not only prevents the sample container 21 from shifting during puncturing, but also ensures that the sample needle 22 is not bent when being stressed, and the holding and puncturing adopt a dual-motor driving method to ensure that the sample container 21 is not taken out during the pushing back process of the sample needle 22 after the puncturing is finished.
Referring to fig. 11 to 14, the centrifuge module 18 includes a centrifuge 35, a thickened chassis 36 and an unbalance protection module, wherein the thickened chassis 36 is used for carrying the centrifuge 35, so as to ensure the stability of the centrifuge 35 during operation, and the addition of the unbalance protection module ensures that the centrifuge 35 gradually slows down when reaching an unbalance critical point, thereby further ensuring the service life of the centrifuge 35 and the safety of related operators. The centrifuge 35 includes a lid body 37 and a corner rotor 38, the lid body 37 is provided with an openable lid 39 and a motor for driving the lid 39 to open and close, a plurality of container insertion holes 40 for inserting a plurality of second-generation sample containers 25 are provided on a ring surface of the corner rotor 38, and the plurality of container insertion holes 40 are hinged and fixed to form a ring shape. The centrifuge 35 of the invention adopts the self-switching angle rotor, when the centrifuge 35 reaches a certain rotating speed, the centrifuge 35 is automatically switched to the angle rotor 38, after the centrifugation is finished, the vertical state is recovered due to the self gravity of the container retainer, so that the clamping module 19 can conveniently transfer the second-generation sample container 25 in the centrifuge 35, and the centrifuge balancing algorithm of the whole machine ensures that the centrifugation experiment can be stably carried out under the state of odd number of samples.
Referring to fig. 15 and 16, the holding module 19 includes a plurality of holding jaws 41 and a fourth motor 42, the plurality of holding jaws 41 form an automatically adjustable holding space around to hold the second-generation sample container 25, and the fourth motor 42 is used for driving the plurality of holding jaws 41 to move up, down, left, right, back, forth, and rotate. Specifically, the clamping jaw 41 is a 360-degree self-rotating electric clamping jaw with automatically adjusted torsion force, and can be used for grabbing different reaction containers, such as a flow tube, an EP tube and a vacuum blood collection tube, and meanwhile, the clamping force is adjusted according to the different containers to be grabbed, and the containers can be automatically rotated after being grabbed, so that the code scanning is performed by the identification module 31. Referring to fig. 15 and 17, the reagent needle module 17 further includes a fifth motor 43, and the fifth motor 43 is used for driving the reagent needle 24 to add the reagent in the reagent container 23 into the sample container 21 to form the second-generation sample container 25. As shown in fig. 17, in the present embodiment, the reagent needle module 17 includes two reagent needles and two corresponding motors, and the reagent needle module can be designed by considering the efficiency and the type difference of reagent addition, which is not limited in the present invention. Preferably, the clamping module 19 and the reagent needle module 17 are connected in one piece, for example, disposed on both sides of the reagent arm module 15, respectively, and move simultaneously.
Referring to fig. 18 to 21, the oscillating vortex module 20 includes an oscillating device 44, a clamping device 45 and an oscillating vortex motor, and the oscillating vortex motor is used for driving the oscillating device 44 to oscillate and vortex the second-generation sample container 25 and driving the clamping device 45 to clamp and unclamp the second-generation sample container. In particular, the clamping device 45 comprises a base plate 46, a collar 47 and a ring-shaped gasket 48, the collar 47 being movably hinged on the base plate 46 by a hinge 49, the end of the hinge 49 being, for example, designed with a spring 50, the ring-shaped gasket 48 being fixed on the collar 47 so as to allow the second-generation sample container 25 to pass through the ring-shaped gasket 48 and the collar 47 in succession. As the plurality of jaws 41 displace the second generation sample container 25 into collar 47, the oscillating scroll motor drives collar 47 to rotate to retract annular gasket 48, thereby clamping and unclamping the second generation sample container 25. The oscillation vortex module 20 of this embodiment adopts single motor drive to vibrate the vortex to have the self-holding function, but whole module pull, convenience of customers changes the consumptive material.
The invention also provides a flow cytometer, which comprises the flow sample pretreatment system and a full-automatic test analysis system. The sample processed by the flow sample preprocessing system is placed on a sample rack 51 to be loaded, and then transferred to a test analysis system for automatic analysis and test, so that the full automation of the whole flow cytometer is realized.
In summary, the flow sample pretreatment system of the present invention comprises a rack module, a sample arm module, a sample rack module, a sample puncturing module, a reagent arm module, a reagent rack module, a reagent needle module, a centrifuge module, a clamping module, a vibration vortex module and a control module, wherein the sample puncturing module is used for puncturing a sample container, the reagent needle module is used for adding a reagent in the reagent container into the sample container to form a second-generation sample container, the centrifuge module performs centrifugation, the vibration vortex module performs vibration, and the control module is used for providing control and/or operation for all elements of the flow sample pretreatment system of the present invention, such that automatic sample reagent transfer is adopted to automatically perform treatments such as uniform mixing, centrifugation and vibration, thereby realizing a fully automated flow sample pretreatment process, greatly improving test efficiency, and reducing test errors, meanwhile, the safety is high.
It should be understood that although the present description refers to embodiments, not every embodiment contains only a single technical solution, and such description is for clarity only, and those skilled in the art should make the description as a whole, and the technical solutions in the embodiments can also be combined appropriately to form other embodiments understood by those skilled in the art.
The present invention has been described in terms of its practical and advantageous aspects, such as its performance, efficiency, progress, and novelty, which are determined by the requirements of the patent laws, functional improvements and operational requirements, and it is understood that the above description and drawings are merely exemplary embodiments of the invention and are not intended to limit the invention thereto.