WO2020135128A1 - Appareil de mélange d'échantillon, système d'analyse d'échantillon et procédé de mélange d'échantillon - Google Patents

Appareil de mélange d'échantillon, système d'analyse d'échantillon et procédé de mélange d'échantillon Download PDF

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Publication number
WO2020135128A1
WO2020135128A1 PCT/CN2019/125692 CN2019125692W WO2020135128A1 WO 2020135128 A1 WO2020135128 A1 WO 2020135128A1 CN 2019125692 W CN2019125692 W CN 2019125692W WO 2020135128 A1 WO2020135128 A1 WO 2020135128A1
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WIPO (PCT)
Prior art keywords
sample container
sample
rotation
axis
seat
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PCT/CN2019/125692
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English (en)
Chinese (zh)
Inventor
胡力坚
刘元幸
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深圳迈瑞生物医疗电子股份有限公司
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Application filed by 深圳迈瑞生物医疗电子股份有限公司 filed Critical 深圳迈瑞生物医疗电子股份有限公司
Priority to CN201980081120.XA priority Critical patent/CN113167805A/zh
Publication of WO2020135128A1 publication Critical patent/WO2020135128A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system

Definitions

  • the invention relates to the field of blood sample analysis, in particular to a sample mixing device, a sample analysis system, and a sample mixing method for mixing drawn blood samples, especially a trace amount of blood samples.
  • Blood sample measurement requires a certain amount of sample from the patient.
  • Blood collection methods are generally divided into collecting venous blood and collecting peripheral blood. For neonates, infants, intensive care patients and other patients who are not suitable for venous blood collection, peripheral blood is often collected.
  • blood collection tubes containing anticoagulants are usually used.
  • the blood is composed of blood cells and plasma. Due to the different specific gravity of blood cells and plasma, the anticoagulated blood will stratify after standing for a period of time, so the blood sample needs to be thoroughly mixed before measurement, otherwise the measurement results will have a large deviation .
  • the inverse mixing method is also used to mix the peripheral blood samples in the blood collection tube.
  • the characteristic of collecting the peripheral blood is that the blood collection volume is small (usually ⁇ 150uL), so the blood sample has poor fluidity and the blood collection tube is inverted Peripheral blood often adheres to the blood collection tube cap, the bottom of the blood collection tube or the wall of the tube, and the reverse mixing technique will cause blood sample loss and adversely affect the measurement, and it is still difficult to effectively solve the problem of peripheral blood mixing.
  • the first aspect of the present invention provides a sample mixing device including a container for containing a sample container A sample container seat and a driving mechanism for driving the sample container seat to rotate about its axis of rotation, wherein the sample container seat is configured such that when the sample container is fixedly received in the sample container seat, The central axis of the sample container and the rotation axis of the sample container seat form an acute angle.
  • the sample container holder may be configured such that when the sample container is fixedly received in the sample container holder, the central axis of the sample container and the rotation axis of the sample container holder are The intersection of the projection lines in the vertical plane is located above the bottom of the sample container containing the sample cavity.
  • the sample container holder may be configured such that when the sample container is fixedly received in the sample container holder, the central axis of the sample container and the axis of rotation of the sample container holder sample The container seats are located in the same plane, the central axis of the sample container intersects the rotation axis of the sample container seat, and the intersection point is located above the bottom of the cavity of the sample container.
  • the sample container holder may be configured such that when the sample container is fixedly received in the sample container holder, the central axis of the sample container and the sample container holder The rotation axes are located in different planes, and the intersection of the central axis of the sample container and the projection line of the rotation axis of the sample container seat in the vertical plane is above the bottom of the cavity of the sample container.
  • the sample container holder may have a sample container accommodating cavity capable of fixedly accommodating the sample container, the sample container accommodating cavity may be configured as an accommodating cavity in the form of a hole, or the sample container
  • the accommodating cavity is configured as a cavity surrounded by a plurality of cylinders, and the sample container can be fixedly accommodated in the cavity.
  • the sample container accommodating cavity may be configured such that when the sample container is fixedly accommodated in the sample container accommodating cavity, the central axis of the sample container and the rotation axis of the sample container seat are formed
  • the included angle of the acute angle preferably the intersection of the projection axis of the sample container center axis and the rotation axis of the sample container seat in the vertical plane is located above the bottom of the sample container containing cavity of the sample container.
  • an abutting portion may be provided in the sample container accommodating cavity, and the abutting portion is configured such that when the sample container is accommodated in the sample container accommodating cavity, the sample The container abuts on the abutting portion, so that the central axis of the sample container and the axis of rotation of the sample container seat form an acute angle, preferably the central axis of the sample container and the sample container seat rotate The intersection point of the projection line of the axis in the vertical plane is located above the bottom of the sample container containing the sample chamber.
  • the abutment portion may be integrally formed at the bottom of the sample container accommodating cavity of the sample container holder, or the abutment portion may be detachably fixed to the sample container container of the sample container holder Place the bottom of the cavity.
  • the sample container accommodating cavity is configured such that the central axis forms an acute angle with the rotation axis of the sample container seat, so that when the sample container is fixedly received in the sample
  • the central axis of the sample container and the rotation axis of the sample container seat form an acute angle
  • the central axis of the sample container and the rotation axis of the sample container seat are vertical
  • the intersection of the projection lines in the plane is located above the bottom of the sample container-containing cavity of the sample container.
  • the included angle between the central axis of the sample container and the axis of rotation of the sample container seat may be less than or equal to about 45°, preferably in the range of about 2° to about 15°.
  • the driving mechanism may have a driving shaft, and the sample container seat is directly fixed on the driving shaft or indirectly through a transmission mechanism, such as a belt, a timing belt, a gear set component, and the driving shaft Turn the connection.
  • a transmission mechanism such as a belt, a timing belt, a gear set component, and the driving shaft Turn the connection.
  • the driving mechanism may rotate the sample container seat by driving a rotating wheel with an elastic outer peripheral washer, and the outer peripheral washer contacts the outer periphery of the sample container seat to provide frictional force.
  • the sample container seat may include a rotating shaft fixing hole connected to the driving rotating shaft of the driving mechanism, and the driving rotating shaft of the driving mechanism is inserted into the rotating shaft fixing hole and fixed to the rotating shaft fixing hole Connected so that the sample container seat rotates as the drive shaft of the drive mechanism rotates.
  • the rotating shaft fixing hole may be coaxially arranged with the sample container accommodating cavity; or the rotating shaft fixing hole may also be eccentrically arranged with the sample container accommodating cavity, with an eccentricity of 0 mm to about 5 mm , Preferably it is about 1 mm to about 2 mm.
  • the driving mechanism may be configured as a motor, such as a stepper motor, or a DC motor, or a servo motor.
  • the sample mixing device may further include a sensor for detecting the rotation state of the sample container holder.
  • the sensor may be, for example, a through-beam photoelectric sensor, a reflection-type photoelectric sensor, a Hall sensor, or a capacitance sensor, and is preferably a through-beam photoelectric sensor.
  • the sample mixing device may be provided with a sensing portion and a notch in the sensing area of the sensor.
  • the sensing portion and the notch Enter the sensing area of the sensor alternately to generate the output pulse signal of the sensor for detecting the rotation state of the sample container seat.
  • a second aspect of the present invention provides a sample mixing system including a sample container for containing a sample and a sample mixing device for mixing the sample in the sample container, wherein the sample is mixed
  • the device is constructed according to one of the aforementioned sample mixing devices.
  • the sample container is configured as a micro blood collection tube for containing peripheral blood, and/or the sample container is configured as a closed container or an open container.
  • a third aspect of the present invention provides a sample analysis system, including:
  • the sample mixing device is configured to mix the sample in the sample container and includes a sample container holder for accommodating the sample container and a drive for driving the sample container holder around A driving mechanism whose rotation axis rotates, wherein the sample container seat is configured such that when the sample container is accommodated in the sample container seat, the central axis of the sample container and the rotation axis of the sample container seat Forming an acute angle;
  • the control device is configured to be communicatively connected with the driving mechanism to control the driving mechanism to drive the sample container holder to rotate around its rotation axis.
  • control device may be configured to control the driving mechanism in the following manner:
  • the driving mechanism drives the sample container seat to rotate alternately in a first direction and a second direction opposite to the first direction about its axis of rotation, preferably, the driving mechanism drives the sample container seat around it After the rotation axis rotates in the first direction for a predetermined period of time, the drive mechanism is stopped, and after the sample returns to the bottom of the cavity of the sample container, the drive mechanism is turned on to drive the sample container seat around its rotation axis Turn in a second direction opposite to the first direction.
  • the sample mixing device may further include a sensor for detecting the rotation state of the sample container holder, the sensor can be communicatively connected with the control device, so as to connect the detected sample container holder
  • the rotation state of is transmitted to the control device, the control device can adjust the driving parameters of the driving mechanism according to the rotation state of the sample container holder or can judge the sample container according to the rotation state of the sample container holder Whether the seat or the drive mechanism is malfunctioning.
  • the sample analysis system may further include:
  • a first conveying device configured to be communicatively connected to the control device and used to place the sample container into the sample container seat under the control of the control device;
  • the second transport device is configured to be communicatively connected to the control device and used to remove the sample container from the sample container seat under the control of the control device.
  • the first conveying device and the second conveying device may be configured as the same device or different devices.
  • the fourth aspect of the present invention provides a sample mixing method, including:
  • the sample container is fixedly placed in the rotatable sample container seat, so that the central axis of the sample container and the rotation axis of the sample container seat form an acute angle, preferably the central axis of the sample container and the The intersection point of the projection line of the rotation axis of the sample container seat in the vertical plane is located above the bottom of the sample container containing the sample container;
  • the sample container holder is driven by the driving mechanism to rotate the driving mechanism around its axis of rotation to perform the sample mixing operation.
  • the sample container can be fixedly placed in the rotatable sample container seat, so that the included angle between the central axis of the sample container and the axis of rotation of the sample container seat is less than or equal to about 45 °, preferably in the range of about 2° to about 15°.
  • the step of driving the sample container base to rotate about its rotation axis by the driving mechanism to perform the sample mixing operation may include:
  • the sample container holder is driven to rotate in the same direction around its axis of rotation by the drive mechanism, preferably the sample container holder is driven by the drive mechanism to periodically rotate in the same direction about its axis of rotation; or
  • the sample container holder is driven by the driving mechanism to rotate alternately in a first direction and a second direction opposite to the first direction around its axis of rotation.
  • the sample container holder is driven by the driving mechanism about its axis of rotation along the first After rotating in one direction for a predetermined period of time, stop the driving mechanism and wait for the sample to flow back to the bottom of the cavity of the sample container before turning on the driving mechanism to drive the sample container holder around its axis of rotation in the reverse direction
  • the second direction rotates in the first direction.
  • the method may further include:
  • the sensor detects the rotation state of the sample container holder
  • Adjust the drive parameters of the drive mechanism such as the speed, according to the rotation state;
  • the rotation state it is determined whether the sample container holder or the driving mechanism is malfunctioning.
  • the method further includes stopping the driving mechanism after the sample mixing operation is completed, and after the sample returns to the bottom of the cavity of the sample container, taking out the sample container or directly performing a sample on the sample container Suck samples.
  • a fifth aspect of the present invention provides a control device for a sample analysis system, including:
  • At least one processor At least one processor
  • the memory stores instructions executable by the at least one processor, and when executed by the at least one processor, the instructions cause the sample analysis system to perform the steps of the foregoing sample mixing method.
  • a sixth aspect of the present invention provides a computer-readable storage medium that stores computer-executable instructions, which when executed by at least one processor of a sample analysis system, causes the sample analysis system to execute the foregoing Each step of the sample mixing method.
  • the sample container holder by tilting the central axis of the sample container contained in the sample container holder relative to the rotation axis of the sample container holder, the sample container holder can better meet the requirements of sample mixing when the sample container is driven to rotate
  • the liquid level of the sample to be mixed can be controlled by adjusting the inclination angle of the central axis of the sample container and the rotation axis of the sample container holder to prevent the sample to be mixed from overflowing the sample container. That is to say, by reasonably adjusting the rotation speed and the inclination angle, a dynamic balance can be finally achieved, that is, the sample to be mixed can not only make a circular rotation at a large angular velocity around the rotation axis, but also not cause the liquid surface to climb up. Too high, which can prevent the sample from overflowing the sample container, and by suppressing the height of the liquid surface when the sample is rotated, the residual amount of the sample hanging on the inner wall of the container cavity of the sample container is reduced, thereby reducing the sample loss.
  • FIG. 1 is a perspective view of a sample mixing device according to an embodiment of the present invention.
  • FIG. 2 is a perspective cross-sectional view of a sample container according to an embodiment of the present invention.
  • FIG. 3 is a perspective view of a sample container holder of a sample mixing device according to an embodiment of the present invention.
  • FIG. 4 is a schematic diagram of a sensor output signal of a sample mixing device according to an embodiment of the present invention.
  • FIG. 5 is a cross-sectional view of a first embodiment of a sample container holder of a sample mixing device of the present invention
  • FIG. 6 is a cross-sectional view of the sample container holder in FIG. 5 when it is at rest, together with the sample container accommodated in its sample container accommodating cavity, where the sample container is contained in the sample container;
  • FIG. 7 is a cross-sectional view of the sample container holder in FIG. 5 when it is rotated together with the sample container accommodated in its sample container accommodating cavity, where the sample container is contained in the sample container;
  • FIG. 8 is a perspective view of a second embodiment of the sample container holder of the sample mixing device of the present invention.
  • FIG. 9 is a schematic diagram of the force analysis of the sample in the sample container when the sample container holder according to the embodiment of the present invention rotates;
  • 10 to 12 are schematic diagrams of the intersection of the central axis of the sample container and the axis of rotation of the sample container holder according to an embodiment of the present invention
  • FIG. 13 is a cross-sectional view of a third embodiment of the sample container holder of the sample mixing device of the present invention.
  • FIG. 14 is a cross-sectional view of the sample container holder of FIG. 13 together with the sample container accommodated in its sample container accommodating cavity when it is at rest, in which a sample is contained in the sample container;
  • FIG. 15 is a cross-sectional view of a fourth embodiment of the sample container holder of the sample mixing device of the present invention.
  • FIG. 16 is a cross-sectional view of the sample container holder of FIG. 15 together with a sample container accommodated in its sample container accommodating cavity when it is at rest, in which a sample is contained in the sample container;
  • FIG. 17 is a schematic structural diagram of an embodiment of a sample mixing device of the present invention.
  • FIG. 18 is a schematic structural diagram of an embodiment of a sample analysis system of the present invention.
  • FIG. 19 is a schematic flowchart of a first embodiment of a sample mixing method of the present invention.
  • 20 is a schematic flowchart of a first mixing method of the sample mixing method of the present invention.
  • 21 is a schematic flowchart of a second mixing method of the sample mixing method of the present invention.
  • 22 is a schematic flowchart of a third mixing method of the sample mixing method of the present invention.
  • FIG. 23 is a schematic flowchart of a second embodiment of a sample mixing method of the present invention.
  • 24 is a schematic structural diagram of a control device according to an embodiment of the present invention.
  • FIG. 1 is a perspective view of a sample mixing device 1 according to an embodiment of the present invention.
  • the sample mixing device 1 of the embodiment of the present invention includes a sample container holder 12 for fixedly containing a sample container (not shown) and a drive for driving the sample container holder 12 to rotate about its rotation axis Mechanism 13, wherein the sample container holder 12 is configured such that when the sample container is fixedly received in the sample container holder 12, the central axis of the sample container and the axis of rotation of the sample container holder 12 An acute angle is formed, which is described in further detail below.
  • the sample container in the sample container fixing base 12 not only has the revolving motion around the rotation axis but also the self-rotating motion driven by the driving mechanism 13, and can achieve a better mixing effect.
  • the sample container 2 has a tube body 21 and an inner cavity 211 and is suitable for containing a micro blood sample.
  • the bottom 212 of the inner cavity 211 is higher than the bottom end of the tube body 21.
  • the rotation of the sample container 2 itself is particularly important for the mixing of the sample at a specific distance from the bottom of the inner cavity 212 to the tube 21 at a specific distance. Better mixing effect, so that the mixing device 1 has better adaptability to sample containers of different shapes.
  • the axis of rotation of the sample container holder is the axis of rotation of the sample container or the sample contained in the sample container.
  • the driving mechanism 13 may be configured as a motor to drive the sample container holder 12 to rotate clockwise and/or counterclockwise.
  • the motor may be, for example, a stepper motor, a DC motor, a servo motor, or other device that can provide rotational power.
  • the drive mechanism 13 configured as a stepper motor is a preferred embodiment of the present invention.
  • the sample container holder 12 is rotatably connected with a driving mechanism 13, especially a motor, so that the sample container holder 12 rotates about the axis of rotation together with the sample container fixedly accommodated in the sample container holder 12.
  • the sample container holder 12 can be directly fixed on the driving shaft of the motor 13, or can be indirectly connected to the driving shaft of the motor 13 through a transmission mechanism, such as a belt, a timing belt, a gear set component, and the like.
  • the driving mechanism 13 may rotate the sample container seat 12 by driving a runner with an elastic outer peripheral washer to provide frictional force through the outer peripheral washer contacting the outer periphery of the sample container seat 12.
  • directly fixing the sample container base 12 on the rotating shaft of the motor 13 is a preferred embodiment of the present invention, because this connection method has a more compact structure, uses fewer components, and has advantages of miniaturization and low cost.
  • the driving mechanism 13 may be communicatively connected with a control device (not shown), which is configured to control the startup, shutdown, and rotation speed of the driving mechanism 13.
  • the sample mixing device 1 further includes a sensor 14 configured to detect the rotation state of the sample container holder 12, for example, to detect whether the sample container holder 12 rotates and its rotation speed, etc. .
  • the sensor 14 may be an epi-photoelectric sensor, a reflective photoelectric sensor, a Hall sensor, a capacitive sensor, or the like.
  • the sensor 14 is a through-beam photoelectric sensor is a preferred embodiment of the present invention.
  • the senor 14 can also be communicatively connected with the above-mentioned control device, so as to transmit the rotation state of the sample container holder 12 to the control device.
  • the control device can adjust the rotation speed of the driving mechanism 13 according to the rotation state of the sample container holder 12 or Further, according to the rotation state of the sample container holder 12, it is determined whether the sample mixing device 1 is malfunctioning, for example, whether the sample container holder is stuck.
  • the control device may determine that the sample mixing device 1 has failed, for example, there may be a failure of the control device to open the driving mechanism 13 or the sample container base 12 Failure condition that the connection to the drive mechanism 13 is broken or the sample container holder is stuck.
  • the control device may also determine that the sample mixing device 1 has failed, for example, the connection between the sample container seat 12 and the drive mechanism 13 is loose and causes slippage, thereby The speed drops.
  • the sample mixing device 1 further includes a bracket 11 for fixing the driving mechanism 13 and the sensor 14.
  • FIG. 3 shows a perspective view of the sample container holder 12 of the sample mixing device 1 according to the embodiment of the present invention.
  • the sample container holder 12 has a sample container accommodating chamber 121 that can fixedly receive the sample container.
  • the sample container accommodating cavity 121 is provided above the sample container seat.
  • a sensing portion 124 and a notch 125 are provided below the sample container holder 12.
  • the driving mechanism 13 drives the sample container holder 12 to rotate, the sensing portion 124 and the notch 125 will alternately pass through the sensing area of the sensor 14, that is, the sensing area of the sensor 14 will alternately switch between the blocked state and the unblocked state.
  • the sensor 14 The pulse signal as shown in (a) or (b) of FIG.
  • the pulse signal output by the sensor 14 can be used to determine whether the sample container holder 12 rotates and the rotation speed. For example, by calculating the number of pulse signals output by the sensor 14, the number of rotations of the sample container holder 12 can be determined, so that the control device connected to the sensor 14 can determine whether the number of rotations is as expected. By calculating the signal period T of the pulse signal shown in FIG. 4, the rotation speed of the sample container holder 12 can be calculated, so that the control device connected to the sensor 14 can determine whether the rotation speed is in line with expectations.
  • FIG. 5 is a cross-sectional view of the first embodiment of the sample container holder 12 of the sample mixing device 1 of the present invention
  • FIG. 6 is FIG. 5
  • FIG. 7 is the sample container holder in FIG. 5 12 is a cross-sectional view of the sample container 2 accommodated in the sample container accommodating cavity 121 during rotation, in which the sample 3 is accommodated.
  • the sample container holder 12 has a sample container accommodating cavity 121, and the diameter at the entrance of the sample container accommodating cavity 121 is slightly larger than the outer diameter of the sample container.
  • An abutting portion 122 is provided at the bottom of the sample container accommodating chamber 121, and the abutting portion 122 is configured such that when the sample container 2 is accommodated in the sample container accommodating chamber 121, the sample container 2 Abutting on the abutting portion 122, so that the central axis A3 of the sample container 2 and the rotation axis A1 of the sample container holder 12 or the rotation axis A1 of the sample container 2 form an acute angle, especially The intersection of the central axis A3 of the sample container and the projection line of the rotation axis A1 of the sample container holder 12 in the vertical plane is located above the bottom of the cavity of the sample container 2 that contains the sample 3.
  • the abutment portion 122 is integrally formed on the bottom of the sample container accommodating chamber 121 of the sample container holder 12.
  • the abutment portion 122 may be detachably fixed to the bottom of the sample container accommodating chamber 121 of the sample container holder 12, such a structure can facilitate replacement of the abutment To accommodate different sample containers.
  • the sample container seat 12 is configured as a receiving cavity in the form of a hole, but the present invention is not limited thereto.
  • the sample container holder 12 can also be configured as a cavity 121 surrounded by a plurality of (three or more) cylinders, and the sample container 12 can be fixedly accommodated in the cavity 121.
  • FIG. 8 In the embodiment of FIG.
  • the bottom of the cavity 121 is also provided with an abutment portion 122 configured such that when the sample container 2 is accommodated in the cavity 121, the sample The container 2 abuts on the abutment portion 122 so that the central axis of the sample container 2 forms an acute angle with the rotation axis of the sample container holder 12 or the rotation axis of the sample container 2.
  • FIG. 8 For other features in the embodiment of FIG. 8, refer to the description of the embodiments shown in FIGS. 5 to 7, and details are not described herein again.
  • the sample container seat 12 further includes a rotating shaft fixing hole 123 below, and the driving rotating shaft of the driving mechanism 13 is inserted into the rotating shaft fixing hole 13 and fixed to the rotating shaft fixing hole 13 Connected so that the sample container seat 12 rotates as the drive shaft of the drive mechanism 13 rotates.
  • the axis A1 of the rotation shaft fixing hole 123 is the rotation axis of the sample container holder 12.
  • the axis A1 of the rotating shaft fixing hole 123 and the central axis A2 of the sample container accommodating cavity 121 may not coincide, that is, the sample container accommodating cavity 121 may be eccentrically disposed relative to the rotation axis of the sample container holder 12,
  • the eccentricity d may be, for example, 0 mm to 5 mm, and the preferred range is 1 mm to 2 mm.
  • the sensor 14 can also be used to locate the initial position of the sample container holder 12.
  • the role of the abutting portion 122 is to keep the sample container 2 inclined relative to the sample container accommodating cavity 121 when being put into the sample container accommodating cavity 121, that is, to make the sample container 2 be put into the sample container accommodating cavity 121 when the sample
  • the central axis A3 of the container 2 and the rotation axis A1 of the sample container holder 12 form an acute angle ⁇ , as shown in FIG. 6.
  • the central axis A3 of the sample container 2 and the rotation axis A1 of the sample container holder 12 are in the same plane, that is, the central axis of the sample container 2 A3 intersects the axis of rotation A1 of the sample container holder 12.
  • the included angle ⁇ of the acute angle may be less than or equal to about 45°, and preferably may be about 2° to about 15°.
  • intersection point P of the central axis A3 of the sample container 2 and the rotation axis A1 of the sample container holder 12 is located above the bottom of the sample chamber of the sample container 2.
  • the intersection point P between the rotation axis A1 of the sample container holder 12 and the central axis A3 of the sample container 2 may be located above the entrance of the sample chamber of the sample container 2, as shown in FIG. 10; or as shown in FIG. 11,
  • the intersection point P between the axis of rotation A1 of the sample container holder 12 and the central axis A3 of the sample container 2 is located between the inlet of the sample container 2 and the bottom of the sample container 2.
  • the driving mechanism 13 drives the sample container holder 12 to rotate about its rotation axis A1
  • the sample (such as a blood sample) 3 in the sample container 2 changes from the state shown in FIG. 6 to the state shown in FIG. 7.
  • the sample 3 is thrown away from the rotation axis A1 of the sample container seat 12 and rises along the inner wall of the cavity of the sample container 2.
  • the force analysis of the sample on the inner wall of the sample container 2 is as follows:
  • the sample unit S on the inner wall of the sample container 2 is subjected to
  • the force F1 provides a centripetal force for the sample unit S to rotate about the rotation axis A1, and the force F2 can prevent the sample unit S from rising along the inner wall of the cavity of the sample container 2.
  • the mass, ⁇ is the angular velocity of the sample unit S around the axis of rotation A1
  • r is the radius of the sample unit S around the axis of rotation A1.
  • the sample unit S can rotate around the rotation axis A1 at a larger angular velocity ⁇ , and It does not cause the liquid level to climb too high, and thus can prevent the sample from overflowing the sample container 2.
  • the residual amount of the hanging liquid of the sample 3 on the inner wall of the chamber of the sample container 2 is reduced, thereby reducing the sample loss.
  • the center axis A3 of the sample container 2 relative to the axis of rotation of the sample container base 12 when the sample container 2 is placed in the sample container base 12 A1 is inclined, that is, by staggering the rotation axis A1 of the sample container holder 12 and the central axis A3 of the sample container 2, ie forming an acute angle, it is preferable that the rotation axis A1 of the sample container holder 12 and the central axis A3 of the sample container 2
  • the intersection point is located above the bottom of the sample chamber of the sample container 2, which can not only prevent the sample from spilling, but also reduce the wall loss when the sample 2 is mixed. This is especially true for samples with a small sample volume. For example, peripheral blood samples are extremely important, because excessive wall loss will affect the reliability of sample aspiration after mixing.
  • the mixing device 1 proposed in the embodiment of the present invention can also be used to mix a sample container containing a larger sample volume. Therefore, the sample container 2 that can be placed in the sample container accommodating cavity 121 of the sample container holder 12 is not limited to a small amount of blood collection tube containing a small amount of sample, such as a small amount of peripheral blood, or a vacuum containing more venous blood Blood collection tubes can also be other types of sample containers, such as sample containers used to contain urine, ascites, cerebral spinal cord, pleural effusion, etc. However, for a micro blood collection tube containing a small amount of samples, such as peripheral blood, the mixing device of the embodiment of the present invention has obvious advantages.
  • sample container 2 that can be put into the sample container accommodating chamber 121 of the sample container holder 12 may be either a closed lid container or an open lid container. Since the mixing device 1 proposed in the embodiment of the present invention can effectively prevent the sample in the sample container 2 from flowing toward the opening of the cavity of the sample container 2 when the sample 3 in the sample container 2 is mixed, even if the lid is opened There is no need to worry about the risk of spilling when mixing the container.
  • the embodiment of the present invention achieves better mixing by tilting the central axis of the sample container 2 relative to the axis of rotation of the sample container holder 12 when the sample container 2 is contained in the sample container holder 12
  • the effect especially to prevent the sample from overflowing the sample container 2 and to suppress the liquid level height when the sample rotates, therefore, it is best to make the intersection point of the rotation axis of the sample container 2 (that is, the rotation axis of the sample container holder 12) and the central axis of the sample container 2 P is located above the bottom of the sample chamber of the sample container 2, as shown in FIGS. 10 and 11.
  • the central axis of the sample container 2 and the rotation axis of the sample container holder 12 may also lie in different planes, in this case
  • the central axis of the sample container 2 and the projection line of the rotation axis of the sample container holder 12 in the vertical plane form an angle ⁇ of an acute angle, preferably the center axis of the sample container 2 and the rotation axis of the sample container holder 12 are in the vertical plane
  • the intersection of the projection lines in is located above the bottom of the sample chamber of the sample container 2.
  • the rotation axis A1 of the sample container holder 12 and the central axis A3 of the sample container 2 may be two straight lines that are neither parallel nor intersecting ,
  • the intersection point of the projection line of the axis A1 and the axis A3 in the vertical plane is located above the bottom of the sample chamber of the sample container 2, so that when the driving mechanism 13 drives the sample container holder 12 to rotate around the rotation axis A1, the sample container
  • the sample 3 in 2 is subjected to the component force of the side wall of the sample container 2 toward the bottom of the cavity of the sample container 2, and then the angular velocity ⁇ of the sample container base 12 rotating around the rotation axis A1 and the sample container 2 are set by reasonably setting To adjust the mixing effect and the height of the sample liquid level in the sample container 2 during mixing.
  • FIG. 13 is a cross-sectional view of the second embodiment of the sample container holder 12 of the sample mixing device 1 of the present invention
  • FIG. 14 It is a cross-sectional view of the sample container holder 12 in FIG. 13 together with the sample container 2 accommodated in its sample container accommodating cavity when it is at rest, in which the sample container 2 contains a sample.
  • This second embodiment is different from the first embodiment shown in FIGS.
  • the sample container 2 is also inclined by providing the contact portion 122 in the sample container accommodating chamber 121.
  • the rotation axis A1 of the sample container holder 12 and the sample The intersection point P of the central axis A3 of the container 2 is also located above the bottom of the sample chamber of the sample container 2.
  • FIG. 15 is a cross-sectional view of the third embodiment of the sample container holder 12 of the sample mixing device 1 of the present invention
  • FIG. 16 is a cross-sectional view of the sample container holder 12 in FIG. 15 together with the sample container 2 accommodated in its sample container accommodating cavity when at rest, in which the sample container 2 contains a sample.
  • This third embodiment differs from the first embodiment shown in FIGS. 5 to 7 or the second embodiment shown in FIGS.
  • the sample container holder 12 is provided There is a sample container accommodating cavity 121 and a motor shaft fixing hole 123, but the sample container accommodating cavity 121 is not provided with an abutting portion 122 for abutting the sample container 2.
  • the sample container accommodating chamber 121 is constructed such that the central axis A2 and the rotation axis of the sample container holder 12 (in this embodiment, the axis line A1 of the shaft fixing hole 123)
  • the acute angle ⁇ is formed so that when the sample container 2 is accommodated in the sample container accommodating chamber 121, the central axis A3 of the sample container 2 and the rotation axis A1 of the sample container seat form an acute angle
  • the angle ⁇ is preferably such that the intersection point P of the projection line of the central axis A3 of the sample container 2 and the rotation axis A1 of the sample container seat in the vertical plane is located above the bottom of the sample chamber of the sample container 2.
  • the included angle ⁇ of the acute angle may be less than or equal to about 45°, preferably from about 2° to about 15°.
  • the inlet of the sample container fixing hole 121 of the sample container fixing base 12 of the mixing device 1 is set into a tooth shape, for example, a dentate shape, and the inner diameter of the tooth shape is larger than that of the sample container 2 Diameter, so that when the barcode label of the sample container 2 is not firmly adhered and the edge of the barcode label paper is opened, when the sample container is transported to the sample container holder 12, the sample container can not be placed in the sample container of the sample container holder 12 Probability of fixing hole 121.
  • the present invention also describes a sample analysis system 100, especially an automatic blood analysis system with a peripheral blood measurement mode, such as a single automatic blood analyzer or one or more blood Automatic analyzer blood analysis pipeline system.
  • the sample analysis system includes:
  • the sample mixing device 110 is configured to mix the sample in the sample container and includes a sample container seat for accommodating the sample container and a driving mechanism for driving the sample container seat to rotate about its rotation axis, wherein,
  • the sample container holder is configured such that when the sample container is accommodated in the sample container holder, the central axis of the sample container forms an acute angle with the rotation axis of the sample container holder;
  • a control device (not shown) is configured to communicate with the drive mechanism to control the drive mechanism to drive the sample container holder to rotate about its axis of rotation.
  • the structure of the sample mixing device 110 may be completely the same as the structure of the mixing device shown in FIGS. 1 to 17 of the foregoing embodiment, and details are not described herein again.
  • the control device may be any device capable of issuing control commands, such as a microcontroller or the like.
  • the communication connection includes a wireless communication connection, such as a WIFI connection, and a wired communication connection, such as a direct connection through a USB interface or a network port.
  • control device may be configured to control the driving mechanism in the following manner:
  • the driving mechanism drives the sample container seat to rotate alternately in a first direction and a second direction opposite to the first direction about its axis of rotation, preferably, the driving mechanism drives the sample container seat around it After the rotation axis rotates in the first direction for a predetermined period of time, the drive mechanism is stopped, and after the sample returns to the bottom of the cavity of the sample container, the drive mechanism is turned on to drive the sample container seat around its rotation axis Turn in a second direction opposite to the first direction.
  • the sample mixing device further includes a sensor for detecting the rotation state of the sample container holder, the sensor is in communication connection with the control device, so as to transmit the detected rotation state of the sample container holder to
  • the control device which can adjust the driving parameters of the driving mechanism according to the rotation state of the sample container seat or can determine the sample container seat or the drive according to the rotation state of the sample container seat Whether the organization is malfunctioning.
  • the sensor may be used to determine whether the sample container base is rotated, so that the control device can determine whether the drive mechanism or the sample container base is damaged based on this.
  • the sensor can also be used to determine whether the rotation speed of the base of the sample container is as expected. If the predetermined rotation speed is not reached, it will affect the mixing effect.
  • sample analysis system further includes:
  • a first conveying device configured to be communicatively connected with the control device and used to place the sample container into the sample container seat under the control of the control device;
  • the second transport device is configured to be communicatively connected to the control device and used to remove the sample container from the sample container seat under the control of the control device.
  • the first conveying device is to place the sample container to be mixed in the sample container seat, so as to mix the sample in the sample container
  • the second conveying device is to mix the sample container after mixing Remove from the sample container holder so that the next sample to be mixed is contained in the sample container holder.
  • first conveying device and the second conveying device may be configured as the same device or different devices.
  • the first transport device and the second transport device are configured as the same sample container transport device 120.
  • sample analysis system 100 may further include a sample suction device 130 configured to communicate with the control device and draw the sample mixed through the sample mixing device 110 under the control of the control device.
  • sample analysis system 100 may further include a sample rack transport device 140 configured to transport a sample rack 150 that can load at least one sample container 2.
  • the working process of the sample analysis system 100 is as follows: the sample rack transport device 140 transports the sample rack 150 loaded with the sample container 2 to the mixing position of the sample analysis system 100, and then the sample container handling device 120 transfers the sample container 2 from The sample rack 150 is transported to the sample mixing device 110, the sample mixing device 110 mixes the sample 3 in the sample container 2, and then the sample container transport device 120 transfers the sample container 2 from the sample mixing device 110 back The sample rack 150, and finally the sample rack conveying device 140 further sends the sample rack 150 where the sample container 2 loaded with the mixed sample is located to the sample suction position of the sample analysis system 100, and the sample suction device 130 performs sample suction to perform sample Detection.
  • the present invention also describes a sample mixing method, especially the sample mixing method implemented by the above-mentioned sample mixing device 1.
  • FIG. 19 shows a schematic flowchart of a first embodiment of a sample mixing method 200 of the present invention.
  • the sample mixing method 200 includes:
  • the sample container into the rotatable sample container seat (using a manipulator or manual) so that the central axis of the sample container and the rotation axis of the sample container seat form an acute angle, preferably such that The intersection of the central axis of the sample container and the projection line of the rotation axis of the sample container seat in the vertical plane is located above the bottom of the sample container cavity of the sample container, and it is more preferable that the central axis of the sample container and the The acute angle formed by the axis of rotation of the sample container holder is less than or equal to about 45°, preferably in the range of about 2° to about 15°.
  • the driving mechanism drives the sample container base to rotate around its rotation axis to perform sample mixing operation.
  • the driving mechanism is stopped, especially after the sample is returned to the bottom of the cavity of the sample container, the sample container is taken out, and then the sample container The sample is sucked, or the sample in the sample container is directly sucked by the sampling device.
  • the embodiment of the present invention drives the sample container holder to drive the sample container containing the sample to rotate around the rotation axis by the driving mechanism, so that the sample in the sample container is uniformly mixed, wherein the central axis of the sample container is inclined with respect to the rotation axis of the sample container holder.
  • the driving mechanism drives the sample container holder to rotate
  • the sample in the sample container rotates along the inner wall of the sample container cavity and climbs toward the sample container cavity opening of the sample container, and when the sample container holder stops rotating, it faces the inner wall of the sample container cavity
  • the sample cavity opening of the sample container climbs a certain distance and the sample flows back to the bottom of the sample container cavity. Therefore, in the embodiment of the present invention, the sample 3 in the sample container is rotated and climbed and refluxed to achieve uniform mixing of the sample.
  • FIG. 20 shows a schematic flowchart of the first mixing method in step 202 of the sample mixing method 200, where step 202 includes:
  • the sample container holder is driven by the driving mechanism to rotate around the axis of rotation in the first direction;
  • the sample container holder is driven by the driving mechanism to rotate in a second direction opposite to the first direction about its axis of rotation.
  • step 202 includes:
  • the sample container holder is driven to rotate around its axis of rotation by the driving mechanism;
  • step 202 includes:
  • the driving mechanism drives the sample container base to rotate in a first direction around its axis of rotation
  • the sample container holder is driven by the driving mechanism to rotate around its axis of rotation in a second direction opposite to the first direction;
  • 2023a to 2023d can also be repeated multiple times.
  • FIG. 23 shows a schematic flowchart of a second embodiment of a sample mixing method 300 of the present invention. Steps 301 and 302 of the sample mixing method 300 and steps 201 and 302 of the sample mixing method 200 shown in FIG. 19 Same as 202, the sample mixing method 300 further includes:
  • the sensor detects the rotation state of the sample container holder
  • Adjust the driving parameters of the driving mechanism such as the rotation speed, according to the rotation state; and/or determine whether the sample container holder or the driving mechanism fails according to the rotation state.
  • An embodiment of the present invention also describes a control device for a sample analysis system having the above-mentioned sample mixing device, and the control device is in communication connection with a driving mechanism and a sensor (if any) of the sample mixing device .
  • the control device 400 includes at least one processor 401 and a memory 402.
  • the memory 402 stores instructions executable by the at least one processor 401.
  • the sample analysis system executes the steps of the above sample mixing method.
  • control device 400 may further include at least one network interface 404 and user interface 403.
  • the various components in the control device 400 are coupled together via a bus system 405. Understandably, the bus system 405 is used to implement connection and communication between these components.
  • the bus system 405 also includes a power bus, a control bus, and a status signal bus. However, for the sake of clarity, various buses are marked as the bus system 405 in FIG. 24.
  • the user interface 403 may include a display, a keyboard, a mouse, a trackball, a click wheel, buttons, buttons, a touch panel, or a touch screen.
  • the memory 402 may be a volatile memory or a non-volatile memory, and may also include both volatile and non-volatile memory.
  • the non-volatile memory can be read-only memory (ROM, Read Only Memory), programmable read-only memory (PROM, Programmable Read-Only Memory), erasable programmable read-only memory (EPROM, Erasable Programmable Read- Only Memory), Electrically Erasable Programmable Read Only Memory (EEPROM, Electrically Erasable Programmable Read-Only Memory), Magnetic Random Access Memory (FRAM, Ferromagnetic Random Access Memory), Flash Memory (Flash) Memory, Magnetic Surface Memory , Compact disc, or read-only compact disc (CD-ROM, Compact, Read-Only Memory); the magnetic surface memory can be a disk storage or a tape storage.
  • the volatile memory may be a random access memory (RAM, Random Access Memory), which is used as an external cache.
  • RAM random access memory
  • SRAM static random access memory
  • SSRAM synchronous static random access memory
  • DRAM Dynamic Random Access Memory
  • SDRAM Synchronous Dynamic Random Access Memory
  • DDRSDRAM Double Data Rate Synchronous Dynamic Random Access Memory
  • ESDRAM Double Data Rate Synchronous Dynamic Random Access Memory
  • ESDRAM Double Data Rate Synchronous Dynamic Random Access Memory
  • ESDRAM Enhanced Synchronous Dynamic Random Access Memory
  • SLDRAM SyncLink Dynamic Random Access Memory
  • DRRAM Direct Rambus Random Access Random Access Memory
  • the memory 402 described in the embodiments of the present invention is intended to include these and any other suitable types of memory.
  • the memory 402 in the embodiment of the present invention includes, but is not limited to: tri-state content addressable memory, static random access memory capable of storing various types of data such as received sensor signals to support the operation of the control device 400.
  • the processor 401 in the embodiment of the present invention may be a central processing unit (Central Processing Unit, CPU), or other general-purpose processors, digital signal processors (Digital Signal Processor, DSP), application specific integrated circuits (Application Specific Integrated Circuit, ASIC ), off-the-shelf programmable gate array (Field-Programmable Gate Array, FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc.
  • a general-purpose processor can be a microprocessor or the processor can also be Any conventional processor, etc.
  • Embodiments of the present invention also provide a computer-readable storage medium, for example, a memory 402 including a computer program, which can be executed by the processor 401 of the controller 400, so that the sample analysis system executes the steps of the sample mixing method .
  • the computer-readable storage medium may be a memory such as FRAM, ROM, PROM, EPROM, EEPROM, Flash Memory, magnetic surface memory, optical disk, or CD-ROM; it may also be various devices including one or any combination of the foregoing memories.

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Abstract

L'invention concerne un appareil de mélange d'échantillon (1), un système de mélange d'échantillon et un système d'analyse d'échantillon de sang comprenant l'appareil de mélange d'échantillon (1), un procédé de mélange d'échantillon correspondant, un appareil de commande pour un système d'analyse d'échantillon et un support de stockage lisible par ordinateur. L'appareil de mélange d'échantillon (1) comprend une base de récipient d'échantillon (12) dans laquelle un récipient d'échantillon (2) est reçu, et un mécanisme d'entraînement (13) pour entraîner la base de récipient d'échantillon (12) à tourner autour de son axe de rotation. La base de récipient d'échantillon (12) est configurée, lorsque le récipient d'échantillon (2) est reçu dans la base de récipient d'échantillon (12), de telle sorte qu'un angle inclus aigu (α) est formé entre un axe central du récipient d'échantillon (2) et l'arbre de rotation de la base de récipient d'échantillon (12).
PCT/CN2019/125692 2018-12-28 2019-12-16 Appareil de mélange d'échantillon, système d'analyse d'échantillon et procédé de mélange d'échantillon WO2020135128A1 (fr)

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PCT/CN2018/124757 WO2020133182A1 (fr) 2018-12-28 2018-12-28 Appareil de mélange d'échantillon, système d'analyse d'échantillon et procédé de mélange d'échantillon
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