This application claims priority from prior Japanese Patent Application No. 2020-053892, filed on Mar. 25, 2020, entitled “MEASUREMENT APPARATUS”, the entire content of which is incorporated herein by reference.
The present invention relates to a measurement apparatus including a dispenser that dispenses a liquid.
Japanese Laid-Open Patent Publication No. 2006-300589 discloses a dispensing machine 900 as shown in
The scope of the present invention is defined solely by the appended claims, and is not affected to any degree by the statements within this summary.
In Japanese Laid-Open Patent Publication No. 2006-300589 above, with respect to the horizontal direction, the stage 902 is movable only in the Y1 direction and the Y2 direction, and the dispensing head 903 is movable only in the X1 direction and the X2 direction. Therefore, for example, when performing an operation of dispensing a reagent from a reagent container disposed in a region 912 on the stage 902 into each of the tubes 905 attached to the plurality of tube receiving holes 901 disposed in a region 911 on the stage 902, the stage 902 is moved in the Y1 direction first, and then the dispensing head 903 is moved in the X1 direction to suction a reagent from a reagent container disposed in the region 912. Then, the dispensing head 903 is moved in the X2 direction to dispense the reagent to a first tube 905 among the plurality of tubes 905 disposed in the region 911. Then, the dispensing head 903 is moved in the X1 direction to suction a reagent again from a reagent container disposed in the region 912, and the stage 902 is moved in the Y1 direction. Then, the dispensing head 903 is moved in the X2 direction to dispense the reagent into a second tube 905 among the plurality of tubes 905 disposed in the region 911. When a reagent is to be dispensed into a third tube 905 among the plurality of tubes 905, the stage 902 is moved in the Y2 direction, and then the dispensing head 903 is moved in the X1 direction to suction a reagent again from a reagent container disposed in the region 912. Then, the stage 902 is moved in the Y1 direction, and then the dispensing head 903 is moved in the X2 direction to dispense the reagent into the third tube 905 among the plurality of tubes 905 disposed in the region 911. Thus, performing an operation of dispensing a reagent from a reagent container disposed in the region 912 into each of the plurality of tubes 905 disposed in the region 911 requires a complicated operation in which the stage 902 and the dispensing head 903 are repeatedly reciprocated between the region 911 in which the plurality of tubes 905 are disposed and the region 912 in which reagent containers are disposed. When the total movement distance of the stage 902 and the dispensing head 903 is increased due to the reciprocating movement, the time required for the dispensing operation becomes longer.
As shown in
As described above, the measurement apparatus according to the present invention includes: the holding body (60) configured to hold the first setting base (10) and to hold the second setting base (21) so as to be movable relative to the first setting base (10); and the movement stopping unit (25) configured to, when the holding body (60) has been moved in the first direction (Y1) by the drive unit (50), stop movement in the first direction (Y1) of the second setting base (20) while the first setting base (10) is still allowed to be moved in the first direction (Y1). Accordingly, as shown in
Hereinafter, an embodiment will be described with reference to the drawings.
[Outline of Measurement Apparatus]
First, with reference to
The measurement apparatus 100 is an apparatus which measures a measurement sample created by adding a predetermined reagent to a specimen collected from a subject.
The subject is mainly a human, but may be an animal other than human. The measurement apparatus 100 performs measurement for a clinical test or a medical study of a specimen collected from a patient, for example. The specimen is a specimen derived from an organism. The specimen derived from an organism is, for example, blood (whole blood, serum, or plasma), urine, a liquid such as another body fluid each of which has been collected from the subject, a liquid obtained by subjecting a collected liquid to a predetermined pretreatment, or the like. The specimen may be, for example, a part of a tissue or cells of the subject, or the like, other than a liquid. The measurement apparatus 100 detects a predetermined analyte contained in the specimen. The analyte can include, for example, a predetermined component, a cell, or a particle in blood or a urine specimen. The analyte may be a nucleic acid such as DNA (deoxyribonucleic acid), a specific cell, an intracellular substance, an antigen, an antibody, a protein, a peptide, or the like. The measurement apparatus 100 may be a blood cell counter, a cell image analyzer, a blood coagulation measurement apparatus, an immunoassay apparatus, a urine particle measurement apparatus, or the like, or may be a measurement apparatus other than these.
As shown in
The first setting base 10 is configured such that a plurality of first storage portions 11 which each store a liquid can be set thereon in a first direction Y1. The first setting base 10 is configured such that one or a plurality of specimen containers can be set thereon.
Each first storage portion 11 is a recess capable of storing a liquid therein. The first storage portion 11 has an open top, an inner bottom face, and an inner side face. The open top serves as an inlet/outlet for a liquid. The first storage portion 11 can retain a predetermined amount of liquid. The first storage portion 11 can be an inner space of a liquid container. At least one first storage portion 11 is provided for one liquid container. A liquid container (hereinafter, referred to as a “single container”) having one first storage portion 11 formed therein is, for example, a test tube, a specimen container, a cuvette, a sample tube, a liquid bottle, or the like, as shown in
The first setting base 10 can have set thereon a plurality of first storage portions 11 as the single containers, shown in
The first setting base 10 has a plate-like shape, for example. In the first setting base 10, the upper face serves as a setting face for the first storage portions 11. The first setting base 10 supports a plurality of single containers or one or more multi-containers from below. The first setting base 10 can include, on the upper face, an insertion hole for inserting one first storage portion 11, or a recess for setting one multi-container 91. The first setting base 10 may indirectly support each first storage portion 11 via a member for holding the first storage portion 11. The member for holding the liquid container may be, for example, a rack capable of holding a plurality of single containers, a holder having a plurality of holding holes formed therein, or the like.
The second setting base 20 shown in
The second storage portion 21 is a recess capable of storing a liquid therein. The second storage portion 21 has an open top, an inner bottom face, and an inner side face. The open top serves as an inlet/outlet for a liquid. The second storage portion 21 can retain a predetermined amount of liquid. At least one second storage portion 21 is provided for one liquid container. The second storage portion 21 can be a single container. The second storage portion 21 can be an individual well formed in the multi-container. The second setting base 20 can have set thereon at least one second storage portion 21. That is, the second setting base 20 may be able to have only one single container set thereon. Different from the first setting base 10, when a plurality of second storage portions 21 are set on the second setting base 20, the plurality of second storage portions 21 are set so as to be arranged in a second direction X1.
The second setting base 20 has a flat-plate shape or a rectangular parallelepiped shape, for example. In the second setting base 20, the upper face serves as a setting face for the second storage portion 21. The second setting base 20 supports, from below, a single container or a multi-container having the second storage portion 21 formed therein. The second setting base 20 can include, on the upper face, an insertion hole for inserting one second storage portion 21, or a recess for setting one multi-container.
The second setting base 20 is disposed, with respect to the first setting base 10, in the second direction X1 which crosses the first direction Y1. In addition, as described later, the second setting base 20 is configured to be movable relative to the first setting base 10 in a direction Y2 opposite to the first direction Y1.
The second direction X1 is one direction in a horizontal plane, and crosses the first direction Y1. In
The second setting base 20 is disposed at a position shifted in the second direction X1 with respect to the first setting base 10. In
The holding body 60 holds the first setting base 10 and the second setting base 20. The holding body 60 holds the first setting base 10 in a fixed manner, and holds the second setting base 20 so as to allow relative movement thereof in the direction Y2 opposite to the first direction Y1.
“Holding the first setting base 10 in a fixed manner” means that, when the holding body 60 is moved by the drive unit 50 described later, the first setting base 10 does not move with respect to the holding body 60. Therefore, the first setting base 10 need not be fixed to or integrated with the holding body 60. The holding body 60 detachably holds the first setting base 10. The holding body 60 may have an engagement portion that engages with the first setting base 10. The holding body 60 has a recess into which a lower portion of the first setting base 10 is fitted, for example.
Meanwhile, when moved by the drive unit 50, the holding body 60 holds the second setting base 20 in a state where the second setting base 20 is movable relative to the first setting base 10. That is, the holding body 60 holds the second setting base 20 in a state of being movable on the holding body 60. The holding body 60 may include a guide portion which guides movement of the second setting base 20 in the first direction Y1 and in the opposite direction Y2. The guide portion may include, for example, a rail, a groove, and a guide member that support the second setting base 20 so as to be able to slide in the first direction Y1 and the opposite direction Y2. The holding body 60 supports the second setting base 20 so as not to be able to move in the second direction X1 and the opposite direction X2, for example.
The drive unit 50 is configured to move the holding body 60. The drive unit 50 moves the holding body 60 holding the first setting base 10 and the second setting base 20, in the first direction Y1 toward a movement axis 31 of the dispenser 30. Hereinafter, with reference to the initial position shown in
The drive unit 50 includes an actuator for generating a driving force for moving the holding body 60. The actuator can include an electric (electromagnetic) actuator such as an electric motor, a linear motor, or a solenoid, a pressure actuator such as a pneumatic cylinder or a hydraulic cylinder, or the like. The drive unit 50 may include a linear motion mechanism for causing the holding body 60 to linearly move in the first direction Y1 and the opposite direction Y2. The drive unit 50 moves the holding body 60, thereby integrally moving both of the first setting base 10 and the second setting base 20 held by the holding body 60.
The movement stopping unit 25 is configured to stop, when the holding body 60 has been moved in the first direction Y1 by the drive unit 50, movement in the first direction Y1 of the second setting base 20 while the first setting base 10 is still allowed to move further in the first direction Y1, in a state where a first storage portion 11 and a second storage portion 21 are disposed on the movement axis 31 of the dispenser 30. Accordingly, with a simple configuration in which the second setting base 20 held by the holding body 60 is contacted, engaged, or fixed by the movement stopping unit 25, the second storage portion 21 on the second setting base 20 can be stopped at a position on the movement axis 31 at which liquid suction by the dispenser 30 is allowed, even when the first setting base 10 is moved in the first direction Y1.
The movement stopping unit 25 is disposed at a predetermined position in the first direction Y1 with respect to the second setting base 20. The movement stopping unit 25 is provided on the movement path of the second setting base 20. The movement stopping unit 25 is provided so as to come into contact with the second setting base 20 which moves together with the holding body 60 moved by the drive unit 50.
The movement stopping unit 25 is fixed to a housing or the like of the measurement apparatus 100. Accordingly, the movement stopping unit 25 stops movement of the second setting base 20. The movement stopping unit 25 is provided so as not to come into contact with the holding body 60 and the first setting base 10 (i.e., the portion that moves integrally with the first setting base 10). Accordingly, even in a state where the movement stopping unit 25 is in contact with the second setting base 20, the first setting base 10 can be moved further in the first direction Y1.
The dispenser 30 is configured to move along the movement axis 31 in the second direction X1 and the opposite direction X2. The dispenser 30 is configured to move along the movement axis 31, to suction a liquid in a second storage portion 21 on the second setting base 20 and dispense the liquid into a first storage portion 11 on the first setting base 10.
The dispenser 30 is configured to be able to suction and discharge a liquid. The dispenser 30 has one or more nozzles 32 that each suction and discharge a liquid. In
In
In a state where measurement is not started yet, the dispenser 30 is disposed at a position away from the first setting base 10 and the second setting base 20 in the first direction Y1. In the example in
The dispenser 30 moves the nozzle 32 downwardly from a position immediately above the second storage portion 21, thereby being able to suction the liquid stored in the second storage portion 21 into the nozzle 32. The dispenser 30 moves the nozzle 32 downwardly from a position immediately above a first storage portion 11, thereby being able to discharge the suctioned liquid into the first storage portion 11 from the tip of the nozzle 32. Accordingly, the dispenser 30 forms, in the first storage portion 11, a mixture of the liquid stored in the second storage portion 21 and the liquid stored in the first storage portion 11.
As an example, the first storage portion 11 stores a first liquid containing a specimen. The first liquid is a pretreated sample obtained through pretreatment on a specimen, for example. The second storage portion 21 stores a second liquid, which is a reagent. The reagent is a liquid to be used in measurement of an analyte. The reagent can contain a substance that reacts with a substance contained in the first liquid. The reagent may not necessarily react with a substance contained in the first liquid. The reagent may contain, in a state of being mixed with a sample, a substance measured separately from the analyte. A measurement result of such a substance can be used in calibration in measurement of the analyte, or operation control of the measurement apparatus 100, for example.
The measurement unit 40 is configured to measure a mixture dispensed in the first storage portion 11 by the dispenser 30. For example, the measurement unit 40 is in fluid connection with the dispenser 30, and obtains a mixture from the dispenser 30 having suctioned the mixture. The measurement unit 40 is set on the movement axis 31, for example, and the mixture is dispensed by the dispenser 30 having moved to a position immediately above the measurement unit 40.
The measurement unit 40 can be configured to measure the mixture and detect an analyte contained in the mixture. The method for detecting the analyte by the measurement unit 40 may be any method. The measurement unit 40 detects the analyte using a method suitable for the analyte, such as a chemical method, an optical method, an electromagnetics method, or the like. On the basis of the result of the detection by the measurement unit 40, the presence or absence of the analyte, the number or amount of the analyte, the concentration of the analyte, the presence ratio between the analyte and a substance other than the analyte, and the like are analyzed, for example.
Operation of the measurement apparatus 100 shown in
As shown in
Next, as shown in
Next, as shown in
In this manner, the measurement operation in the measurement apparatus 100 is performed.
The measurement apparatus 100 of the present embodiment includes: the holding body 60 which holds the first setting base 10 in a fixed manner and holds the second setting base 20 so as to allow relative movement thereof in the first direction Y1 and the opposite direction Y2; and the drive unit 50 which moves the holding body 60 holding the first setting base 10 and the second setting base 20, in the first direction Y1 toward the movement axis 31 of the dispenser 30. Accordingly, as shown in
<Position of Second Setting Base>
Preferably, the second setting base 20 is configured such that, in a state where the first storage portion 11 at the head in the first direction Y1 is disposed on the movement axis 31 of the dispenser 30, the second storage portion 21 is also disposed on the movement axis 31 of the dispenser 30. That is, preferably, as shown in
In
<The Number and Position of First Storage Portion and Second Storage Portion>
In the example in
Similarly, in the example in
<Stopper>
The stopper 26 is disposed at a predetermined position in the first direction Y1 with respect to the second setting base 20. The stopper 26 is provided on the movement path of the second setting base 20. The stopper 26 is provided so as to come into contact with the second setting base 20 moving together with the holding body 60 moved by the drive unit 50.
The stopper 26 has a contact face 26a that comes into contact with the second setting base 20. The structure of the stopper 26 is not limited in particular, as long as the stopper 26 has the contact face 26a. The stopper 26 can be a plate-like member or a block-like member, for example. The stopper 26 is fixed to the housing or the like of the measurement apparatus 100. Accordingly, the stopper 26 stops movement of the second setting base 20. The stopper 26 is provided so as not to come into contact with the holding body 60 and the first setting base 10 (i.e., the portion that moves integrally with the first setting base 10). Accordingly, even in a state where the stopper 26 is in contact with the second setting base 20, the first setting base 10 can be moved further in the first direction Y1.
The second setting base 20 is moved integrally with the first setting base 10 in the first direction Y1 from the initial position up to the position at which the second setting base 20 contacts the stopper 26. The first setting base 10 is moved in the first direction Y1 from the initial position up to a position on the first direction Y1 side with respect to the stopper 26, beyond the position where the stopper 26 is disposed. As a result, while the second storage portion 21 on the second setting base 20 remains held at the position on the movement axis 31 of the dispenser 30, a plurality of first storage portions 11 on the first setting base 10 are sequentially positioned at the position on the movement axis 31.
For the movement stopping unit 25 which holds, at a predetermined position in the first direction Y1, the second setting base 20 held by the holding body 60, a technique that causes the second setting base 20 to move relative to the holding body 60 by causing electric or magnetic force to act, can be adopted, other than the stopper 26. An example of a matter that causes magnetic force to act is a magnetic member 27 such as a magnet. As shown in
[Specific Configuration Example of Measurement Apparatus]
Next, with reference to
More specifically, the measurement apparatus 100 measures a sample prepared in pretreatment including a step of hybridizing a nucleic acid probe labeled with a fluorescent dye and a target site in a nucleic acid, thereby detecting, on the basis of a FISH method, a cell having an abnormality at the target site as an abnormal cell. The pretreatment includes, for example: a step of collecting nucleated cells as measurement target cells from a blood specimen collected from a subject; a step of labeling a target site in each cell with a fluorescent dye; and a step of staining the nucleus of each cell with a nucleus staining dye. The pretreatment includes, for example: a process of fixing cells so as to prevent the cells from contracting due to dehydration; a membrane permeation process of making, in the cells, holes having a size that allows introduction of a probe into the cells; a thermal denaturation process of applying heat to the cells; a process of hybridizing the target site and the probe; a washing process of removing unnecessary probes from the cells; and a process of staining the nuclei.
In the FISH method, the target site on the chromosome is detected by using one or more fluorescent dyes. Preferably, in the FISH method, a first target site and a second target site are detected by using two or more fluorescent dyes. The first target site is hybridized with a probe labeled with a first fluorescent dye that generates a first fluorescence having a wavelength λ21, by being irradiated with a light having a wavelength λ11. The second target site is hybridized with a probe labeled with a second fluorescent dye that generates a second fluorescence having a wavelength λ22, by being irradiated with a light having a wavelength λ12. The nucleus is stained by a nucleus staining dye that generates a third fluorescence having a wavelength λ23, by being irradiated with a light having a wavelength λ13. The lights having the wavelength λ11, the wavelength λ12, and the wavelength λ13 are so-called excitation light. A pretreated sample is stored as the first liquid in the first storage portion 11.
As shown in
The housing 101 includes a container setting part 102 and a body part 103.
The container setting part 102 is a part on the Y2 direction side of the housing 101, and has a table-like flat upper face portion. The container setting part 102 is provided with a setting work position P1 for the first storage portion 11 and the second storage portion 21. At the setting work position P1 of the container setting part 102, the first setting base 10 and the second setting base 20 can be exposed to the outside of the housing 101.
The body part 103 is a part on the Y1 direction side of the housing 101, and has a box-like shape in which an inner space separated from the outside is formed. The body part 103 houses, in the inner space, the dispenser 30, the measurement unit 40, the fluid circuit unit 110, and the controller 120. The drive unit 50 (see
The measurement apparatus 100 includes a separation wall 104 which provides separation between the setting work position P1 and the dispenser 30. The separation wall 104 is provided so as to provide partition that passes at least a position between the setting work position P1 and the dispenser 30. In the example in
The holding body 60 is configured to be movable in a reciprocating manner in the Y1 direction and the Y2 direction between the setting work position P1 and the movement axis 31 of the dispenser 30. The first setting base 10 and the second setting base 20 are provided so as to pass below (see
The holding body 60 is disposed in a recess 105 formed in the upper face of the table-like container setting part 102. The first setting base 10 is set on the upper face of the holding body 60. A plurality of first storage portions 11 can be set on the upper face of the first setting base 10. One second storage portion 21 can be set on the upper face of the second setting base 20.
The holding body 60 is provided so as to be linearly movable in the first direction Y1 and the opposite direction Y2. The holding body 60 is provided so as not to be able to move except in the first direction Y1 and the opposite direction Y2. The first setting base 10 and the second setting base 20 held by the holding body 60 are integrally moved in the first direction Y1 by the drive unit 50 (see
The dispenser 30 is set in the body part 103, and is movable in a reciprocating manner in the second direction X1 and the opposite direction X2 along the movement axis 31 in the second direction X1. The dispenser 30 includes: the nozzle 32; a nozzle drive unit 33 and a linear motion mechanism 34 for moving the nozzle 32; a raising/lowering mechanism 35; and an origin sensor 36.
As shown in
The origin sensor 36 is set at one end portion of the movement axis 31, and detects the origin position in the horizontal direction of the nozzle 32.
In
The washing port 130 (see
The dispenser 30 can move the nozzle 32 to a plurality of discharge positions P2 and one suction position P3 on the movement axis 31, other than the origin position. The plurality of discharge positions P2 are positions at which a liquid is discharged into individual first storage portions 11 set on the first setting base 10. The suction position P3 is a position at which a liquid is suctioned from the second storage portion 21 set on the second setting base 20.
With reference to
The fluid circuit unit 110 includes a chamber, a flow path, a valve, a pump, and the like. The fluid circuit unit 110 is in fluid connection with the nozzle 32 of the dispenser 30, and is in fluid connection with the flow cell of the measurement unit 40. The fluid circuit unit 110 is in fluid connection with the washing port 130. The fluid circuit unit 110 includes: a dispensing pump for dispensing a liquid by the nozzle 32; a liquid sending pump for sending a liquid suctioned from the nozzle 32 to the flow cell; a sheath liquid pump for supplying a sheath liquid to the flow cell; a sheath liquid retaining chamber; and the like. The dispensing pump, the liquid sending pump, and the sheath liquid pump are syringe pumps, for example.
The controller 120 includes a processor such as a CPU, an FPGA, or the like. The controller 120 performs operation control of each component of the drive unit 50, the dispenser 30, the fluid circuit unit 110, and the measurement unit 40.
<Holding Body, First Setting Base, Second Setting Base, and Drive Unit>
In the configuration example in
The first storage portion 11 is a tubular sample container capable of storing a specimen, and corresponds to the single container described above. The first storage portion 11 is a PCR tube, for example.
In the configuration example in
Specifically, as shown in
In the configuration example in
A detection piece 15 for detecting the presence or absence of a container holder 12 is provided to the inner bottom face of the recess 14. One detection piece 15 is provided to the setting position of each of the six container holders 12. The detection piece 15 is a rod protruding upward from the inner bottom face of the recess 14. When a container holder 12 is set from above, the detection piece 15 is moved so as to protrude to the lower side (i.e., the holding body 60 side) of the first setting base 10. The detection piece 15 protruding to the lower side blocks the optical axis of a holder sensor 124 shown in
The second setting base 20 is arranged with an interval in the second direction X1 from the first setting base 10. The second setting base 20 has a substantially square shape in a plan view. In the configuration example in
As shown in
An inner diameter D2 (see
In the example in
The holding body 60 is configured to hold the second setting base 20 so as to allow relative movement thereof in the first direction Y1 and the opposite direction Y2, and is configured to move integrally with the first setting base 10. As shown in
A plurality of through-holes 62a penetrating the peripheral wall portion 62 in the second direction X1 and the opposite direction X2 are formed in the peripheral wall portion 62. The plurality of through-holes 62a are provided so as to correspond to the positions of the six detection pieces 15 when protruding, and the optical axis of the holder sensor 124 shown in
The holding body 60 includes the frame-shaped portion 64 surrounding the second setting base 20, and holds the second setting base 20 on the inner side of the frame-shaped portion 64 such that the second setting base 20 is movable in the first direction Y1 and the opposite direction Y2. The second setting base 20 is provided so as to be movable, on the inner side of the frame-shaped portion 64, in the first direction Y1 and the opposite direction Y2 relative to the frame-shaped portion 64, within a range St (see
Accordingly, the range St in which the second setting base 20 can move in the first direction Y1 can be assuredly restricted. Therefore, when the second setting base 20 moves in the holding body 60 due to contact with the stopper 26, it is possible to inhibit the second setting base 20 from unintentionally falling off from the holding body 60 or from being unintentionally shifted in position along the second direction X1.
The frame-shaped portion 64 has a rectangular outer shape extending in the first direction Y1. The frame-shaped portion 64 has a length corresponding to the range St. As shown in
The holding body 60 includes a biasing member 65 which biases the second setting base 20 in the first direction Y1 toward the movement axis 31 of the dispenser 30. The biasing member 65 is disposed, on the inner periphery side of the frame-shaped portion 64, on the side (Y2 direction side) opposite to the movement axis 31 of the dispenser 30 with respect to the second setting base 20. By being positioned, by the biasing member 65, to an end portion in the first direction Y1 in the movement range in the holding body 60 thereby contacting the stopper 26, the second setting base 20 moves to the opposite side (Y2 direction side) relative to the holding body 60 which moves in the first direction Y1 while compressing the biasing member 65.
Thus, the position of the second setting base 20 in a state of not contacting the stopper 26 can be fixed to an end portion on the dispenser 30 side in the holding body 60. Therefore, when the drive unit 50 moves the first setting base 10 and the second setting base 20 in the first direction Y1 from the setting work position P1 toward the movement axis 31 of the dispenser 30, it is not necessary for the user to move the second setting base 20 in advance to the position of the end portion on the dispenser 30 side in the holding body 60. Thus, convenience for the user can be improved.
In addition to the biasing member 65, a guide 66 extending in the first direction Y1 is disposed on the inner periphery side of the frame-shaped portion 64. The guide 66 guides linear movement of the second setting base 20. In the configuration example in
The numbers of the guide 66 and the biasing member 65 may each be one. The guide 66 may be a guide groove engaged by the second setting base 20, or a guide rail that engages with a groove of the second setting base 20. The biasing member 65 may be a tension spring that biases the second setting base 20 to the movement axis 31 side (Y1 direction side) of the dispenser 30.
In
The stopper 26 is disposed below (see
As shown in
Accordingly, when a liquid is dispensed into the first storage portions 11 at the head (Row A), the second storage portion 21 is in a state of being stopped at the position on the movement axis 31 at which liquid suction can be performed. In addition, when all of the first storage portions 11 at the second order (Row B) and thereafter are moved in the first direction Y1 to positions on the movement axis 31, the second storage portion 21 can be caused to remain stopped at the position on the movement axis 31 at which liquid suction can be performed. Therefore, dispensing operation to all of the first storage portions 11 can be performed only through one-direction movement in the first direction Y1. Thus, operation of each setting base at the time of dispensing can be simplified as much as possible, and the total movement distance can be shortened.
As shown in
(Measurement Unit)
Next, a configuration example of the measurement unit 40 is described with reference to
The measurement unit 40 includes a flow cell 150, light sources 151 to 154, a light guiding section 160, and the imaging section 165. The measurement unit 40 applies light to a measurement sample 73 including a plurality of kinds of target sites labeled with fluorescences, and detects a plurality of kinds of fluorescences having different wavelengths. The measurement sample 73 is a mixture of the first liquid 71 (see
The measurement unit 40 is configured to measure a particle in the specimen contained in the mixture, on the basis of a measurement result of each bead contained in the mixture. Accordingly, measurement of a particle in the specimen can be optimized or corrected by using measurement results of the beads which have less variation than an organism substance in the specimen. Thus, the particle that is the analyte can be accurately measured.
A measurement sample 73 sent from the dispenser 30 is caused to flow in the flow path of the flow cell 150 by the fluid circuit unit 110. In
The light sources 151 to 154 each apply a light to the measurement sample 73 flowing in the flow cell 150. The light sources 151 to 154 are each implemented as a semiconductor laser light source. The lights emitted from the light sources 151 to 154 are laser lights having different wavelengths λ11 to λ14, respectively.
The light guiding section 160 includes condenser lenses, dichroic mirrors, and a spectroscopic optical unit. The light guiding section 160 guides, through a combination of condenser lenses and dichroic mirrors, lights emitted from the light sources 151 to 154, to the flow path of the flow cell 150. Then, lights having the wavelengths λ11 to λ14 are applied to the measurement sample 73 flowing in the flow path of the flow cell 150, in a direction orthogonal thereto.
When lights having the wavelengths λ11 to λ13 are applied to the measurement sample 73 flowing in the flow cell 150, fluorescence is generated from the fluorescent dye staining each cell. When a light having the wavelength λ11 is applied to a first fluorescent dye staining a first target site, a first fluorescence having a wavelength λ21 is generated from the first fluorescent dye. When a light having the wavelength λ12 is applied to a second fluorescent dye staining a second target site, a second fluorescence having the wavelength λ22 is generated from the second fluorescent dye. When a light having the wavelength λ13 is applied to a third fluorescent dye staining a nucleus, a third fluorescence having the wavelength λ23 is generated from the third fluorescent dye. Images of the fluorescences having the wavelengths λ21 to λ23 are respectively captured, whereby fluorescence images regarding the nucleus and two genes as the target sites can be obtained.
When a light having the wavelength λ14 is applied to the measurement sample 73 flowing in the flow cell 150, a scattered light is generated from each bead contained in the mixture flowing in the flow cell 150. An image of the scattered light of the light having the wavelength λ14 is captured by the imaging section 165, whereby a scattered light image of the bead is obtained. Each bead has a size about 1/10 of the average diameter of cells, for example, and can be easily and accurately identified on the basis of the difference in size. Other than these, the measurement unit 40 may be further provided with a light source that enables a bright field image to be captured.
In the light guiding section 160, the fluorescences having the wavelengths λ21 to λ23 generated from the measurement sample 73 and the scattered light scattered by each bead are condensed by a condenser lens. In the light guiding section 160, the fluorescences having the wavelengths λ21 to λ23 and the scattered light having the wavelength λ14 are reflected at angles slightly different from each other by using the spectroscopic optical unit, and are separated, through a condenser lens, on the light receiving surface of the imaging section 165.
The imaging section 165 is implemented as a TDI (Time Delay Integration) camera. The TDI camera includes a plurality of rows of line sensors. In the TDI camera, electric charges accumulated in the line sensors are sequentially transferred, and the electric charges are integrated, whereby high sensitivity imaging is performed. The imaging section 165 captures images of the fluorescences having the wavelengths λ21 to λ23 and the scattered light having the wavelength λ14, and generates fluorescence images respectively corresponding to the fluorescences having the wavelengths λ21 to λ23, and a flow image of each bead. Under control of the controller 120, the imaging section 165 integrates the received signals of fluorescences to generate a fluorescence image. Through the integration, the quality of the fluorescence image of the cell is enhanced. The fluorescence image is obtained for each individual cell separated while flowing in the flow cell 150. The controller 120 transmits the fluorescence image generated by the imaging section 165 to the control apparatus 300 (see
Here, the controller 120 is configured to perform processing of controlling the measurement operation of the measurement unit 40 on the basis of the measurement result of the reagent stored in the second storage portion 21. The controller 120 obtains the moving speed of the bead from the flow image by the imaging section 165, to generate speed information 166 of the speed in the flow cell 150. The controller 120 outputs the speed information 166 to the imaging section 165, thereby performing a feed-back control of the electric charge transfer speed in the TDI camera. Accordingly, electric charge transfer is performed at a speed accurately matched with the actual moving speed of the cell in the captured field of view, and thus, a non-blurred high-definition continuous image (moving image) can be obtained. As a result, in the fluorescence image, a bright point due to the label contained in the cell can be accurately detected.
<Controller and Control Apparatus>
As shown in
The controller 120 performs various processes on the basis of a program stored in the storage unit 121. The controller 120 performs operation control of the dispenser 30 and the drive unit 50. On the basis of an output signal from an encoder provided to the drive unit 50, the controller 120 obtains and controls the positions of the first setting base 10 and the second setting base 20 in the first direction Y1 and the opposite direction Y2. On the basis of an output signal from an encoder provided to the dispenser 30, the controller 120 obtains and controls the positions of the nozzle 32 in the second direction λ1 and the opposite direction λ2. The controller 120 controls suctioning/discharging operation of the dispenser 30, supplying operation of a sheath liquid to the measurement unit 40, washing operation on components of the fluid circuit unit 110 and the washing port 130, and the like, which are performed by the fluid circuit unit 110. The controller 120 controls measurement operation of the measurement unit 40. The communication unit 123 is communicably connected to a communication unit 330 of the control apparatus 300. The communication unit 123 includes a communication interface and performs information communication in a wired or wireless manner. The controller 120 transmits data of fluorescence images obtained by the measurement unit 40 to the control apparatus 300 via the communication unit 123.
As shown in
The container sensor 125 is an optical sensor in which the optical axis between a light transmitter and a light receiver is provided so as to extend across the second holding hole 22 of the second setting base 20. As shown in
The control apparatus 300 includes a controller 310, a storage unit 320, and the communication unit 330. The controller 310 is implemented by a processor such as a CPU. The storage unit 320 is implemented by a RAM, a ROM, a hard disk, and the like. The communication unit 330 includes a communication interface. The control apparatus 300 is a PC (personal computer) in which the controller 310 performs various processes on the basis of a program stored in the storage unit 320. The control apparatus 300 includes a display unit 340 and an input unit 350. The display unit 340 and the input unit 350 may be connected to the control apparatus 300 from outside, or may be of a built-in type incorporated in the control apparatus 300. The display unit 340 is a display device such as a liquid crystal display or an EL display. The input unit 350 is an input device such as a keyboard, a mouse, or a touch panel. As an example, the control apparatus 300 includes a touch panel-type display in which the display unit 340 and the input unit 350 are integrated.
The controller 310 transmits to the measurement apparatus 100 various types of information such as a start instruction and a stop instruction of measurement operation for the measurement apparatus 100, and measurement information 170 (see
<Input of Setting Position>
In the configuration example in
When inputting a setting position, a screen 180 (see
Accordingly, even in a case where the number of setting positions at which first storage portions 11 are disposed on the first setting base 10 is large, the user can input the setting position of each first storage portion 11 as the measurement target, while visually confirming each setting position on the screen 180. As a result, inputting work of the setting position of each first storage portion 11 can be facilitated, and occurrence of erroneous input can be inhibited.
In the example in
When the user has set a first storage portion 11 to a first holding hole 13 of the first setting base 10, the user selects and inputs (i.e., touch operation) a
The setting position of a first storage portion 11 can be represented by a combination of a row number and a column number, for example. In the example in
For example, in
As shown in
<Movement of Setting Base>
Next, with reference to
The drive unit 50 is configured to, when the measurement is started, move the first setting base 10 having set thereon a plurality of first storage portions 11 and the second setting base 20 having set thereon the second storage portion 21, in the first direction Y1 from the setting work position P1 toward the movement axis 31 of the dispenser 30.
Accordingly, the work of setting a plurality of first storage portions 11 to the first setting base 10 and the work of setting the second storage portion 21 to the second setting base 20, which are performed by the user, can be performed at the setting work position P1 away from the movement axis 31 of the dispenser 30. Therefore, the movement mechanism and the like of the dispenser 30 does not obstruct the setting work, and the setting work can be efficiently performed.
During the measurement, the controller 120 of the measurement apparatus 100 controls the drive unit 50 on the basis of the information 171 of the setting positions of the first storage portions 11 as the measurement targets.
The controller 120 positions (see
More specifically, the controller 120 controls the drive unit 50 so as to position a plurality of first storage portions 11 set on the first setting base 10, to positions on the movement axis 31 of the dispenser 30, from the first storage portions 11 at the head in the first direction Y1 in order. Accordingly, simply by the first setting base 10 and the second setting base 20 being moved by the drive unit 50 in one direction, i.e., in the first direction Y1, dispensing work to the plurality of first storage portions 11 set in the first direction Y1 on the first setting base 10 can be completed. Therefore, operation of the drive unit 50 of moving the first setting base 10 and the second setting base 20 can be simplified.
The drive unit 50 moves the first setting base 10 and the holding body 60 in the first direction Y1, thereby moving the second setting base 20 held by the holding body 60 in the first direction Y1, and moves the first setting base 10 and the holding body 60 in the first direction Y1 while the second setting base 20 is caused to remain stopped in a state where the second setting base 20 is in contact with the movement stopping unit 25 (i.e., the stopper 26). Accordingly, while the second setting base 20 remains positioned on the movement axis 31, dispensing operation to a plurality of first storage portions 11 can be sequentially performed.
The controller 120 of the measurement apparatus 100 controls the dispenser 30 and the drive unit 50 such that dispensing operation is performed for the first storage portions 11 set at the setting positions obtained via the input unit 350, and dispensing operation is not performed for first storage portions 11 at setting positions other than the setting positions obtained via the input unit 350. Accordingly, it is possible to skip the operation of moving, among a plurality of setting positions at which a plurality of first storage portions 11 are disposed in the first setting base 10, the setting positions other than the setting positions as the measurement targets, to dispensing positions on the movement axis 31 of the dispenser 30. That is, operation of the drive unit 50 can be further simplified because the dispensing operation is completed simply by moving only the setting positions of the first storage portions 11 as the measurement targets to dispensing positions on the movement axis 31.
Here, for convenience, an example case where six positions of A-1, A-2, A-3, A-5, B-1, and E-1 as in
As shown in
When the measurement ends, as shown in
Accordingly, the user can perform collecting work of the first storage portions 11 and the second storage portion 21 having been subjected to the measurement and the next setting work of storage portions, at the setting work position P1 which is the same place where the setting work of the first storage portions 11 and the second storage portion 21 is performed. Therefore, the measurement apparatus 100 can be downsized, and convenience for the user can be improved. In addition, the drive unit 50 can move both of the first storage portions 11 and the second storage portion 21 to the setting work position P1 simply by moving, in the Y2 direction, the first setting base 10 and the second setting base 20 of which movement has been stopped by the stopper 26. That is, it is not necessary to provide movement mechanisms separately for the first setting base 10 and the second setting base 20, and thus, the structure and operation of the drive unit 50 can be simplified.
(Description of Measurement Process Operation)
Next, the measurement process operation of the measurement apparatus 100 shown in
As preparation work before the flow below, the user sets first storage portions 11 to the first setting base 10 of the measurement apparatus 100 and sets the second storage portion 21 to the second setting base 20. Before the start of measurement, the first setting base 10 and the second setting base 20 are disposed at the setting work position P1 by the drive unit 50. A first liquid 71 being a pretreated sample is stored in advance in each first storage portion 11. The user sets, one by one, the first storage portions 11 to first holding holes 13 of the first setting base 10, by the number of the first liquids 71 (i.e., first storage portions 11) to be measured. The second liquid 72 being a liquid reagent containing beads is stored in advance in the second storage portion 21.
First, operation of the control apparatus 300 is described. In step S1 in
In step S2, the controller 310 receives an input of the measurement information 170 (see
In step S3, the controller 310 receives an input operation of measurement start via the input unit 350 by the user. Upon reception of the input operation of measurement start, the controller 310 transmits, in step S4, the measurement information 170 obtained in step S2 and a measurement start instruction to the measurement apparatus 100 via the communication unit 330. On the basis of the measurement start instruction, measurement operation of the measurement apparatus 100 shown in
In step S5, the controller 310 receives fluorescence images from the measurement apparatus 100 via the communication unit 330. On the basis of the received fluorescence image, the controller 310 performs analysis for each sample (for each piece of specimen information 172) stored in each first storage portion 11.
Next, operation of the measurement apparatus 100 is described.
In step S11 in
In step S12, the controller 120 determines whether or not the second storage portion 21 is set on the second setting base 20. The controller 120 determines the presence or absence of the second storage portion 21 on the basis of an output signal of the container sensor 125 disposed at a side position of the second setting base 20 at the setting work position P1. When the second storage portion 21 is not detected, the controller 120 performs an error process of step S23 described later.
When the second storage portion 21 has been detected, the controller 120 causes, in step S13, the drive unit 50 to move the holding body 60 (the first setting base 10 and the second setting base 20) in the first direction Y1. At this time, the controller 120 causes the first setting base 10 to be moved to the holder monitoring position P4 (see
In step S14, the controller 120 determines whether or not a container holder 12 has been normally detected by the holder sensor 124. The controller 120 determines it to be normal when, for example, all of six container holders 12 that can be set in the recess 14 have been detected. In order to complete the measurement, it is sufficient that at least each container holder 12 that includes the setting positions of the first storage portions 11 as the measurement targets is set on the first setting base 10. For example, in a case where measurement is performed for the first storage portions 11 at six positions of A-1, A-2, A-3, A-5, B-1, and E-1 as shown in
When the container holder 12 is not detected normally, the controller 120 causes, in step S22, the drive unit 50 to return the holding body 60 to the setting work position P1. Then, in step S23, the controller 120 performs a predetermined error process. For example, the controller 120 transmits an error signal and the content of the error to the control apparatus 300, thereby causing the display unit 340 to display a screen including a message indicating the content of the error.
When the container holder 12 has been normally detected, the controller 120 causes, in step S15, the drive unit 50 to dispose first storage portions 11 at the head in the first direction Y1 onto dispensing positions on the movement axis 31 of the dispenser 30. In the example shown in
As shown in
In step S16, the controller 120 causes the dispenser 30 to be moved to the suction position P3 of the second storage portion 21, and causes the dispenser 30 to suction the second liquid 72. Specifically, under control of the controller 120, the dispenser 30 (see
In step S17, the controller 120 causes the dispenser 30 to move to a discharge position P2 of a first storage portion 11, and causes the dispenser 30 to discharge the suctioned second liquid 72 and perform stirring operation. In the configuration example shown in
In step S18, the controller 120 causes measurement operation on the measurement sample 73 (see
The controller 120 causes lights from the light sources 151 to 154 to be applied to the flow cell 150, and causes the imaging section 165 to capture images of generated fluorescences and scattered light. Then, the controller 120 calculates speed information 166 from the result of captured images of beads, and performs feed-back control of imaging process of the imaging section 165. Acquisition of the speed information 166 and the feed-back control are continuously performed while the measurement sample 73 is sent. Upon completion of the sending of the measurement sample 73, the measurement operation on the sample ends.
In step S19, after the measurement operation has ended, the controller 120 causes washing operation of the nozzle to be performed. First, the controller 120 causes the nozzle 32 (see
Through the above operation, measurement operation on a sample (the first sample) stored in the first storage portion 11 at the first order ends. When fluorescence images have been obtained by the measurement unit 40, the controller 120 transmits data of the fluorescence images to the control apparatus 300 via the communication unit 123. The controller 120 sets, as a measured position, the setting position (e.g., A-1) of the first storage portion 11 for which the measurement has been completed.
In step S20, with reference to the measurement information 170, the controller 120 determines whether or not there is a setting position for which measurement has not been performed. When there is a setting position for which measurement has not been performed, the controller 120 returns the process to step S15.
At this time, when there is a setting position (e.g., A-2) of another first storage portion 11 as the measurement target in the same row (Row A) as that of the setting position (e.g., A-1) of the first storage portion 11 measured in the previous time, the first setting base 10 is not moved in step S15. Then, in steps S16 to S19, suctioning and discharging of the second liquid 72, the measurement operation, and the washing operation of the nozzle 32 are performed for the first storage portion 11 at the next setting position. In the example shown in
When there is no setting position of another first storage portion 11 as the measurement target in the same row, the first holding holes 13 in Row B, which becomes the head row next are positioned at dispensing positions on the movement axis 31 of the dispenser 30 in step S15 (see
The controller 120 performs the measurement operation, for each row in order, from the row that becomes the head row. In the example in
When the controller 120 has determined, in step S20, that there is no sample for which the measurement has not been performed, the controller 120 causes the measurement process to be completed, and advances to step S21. In step S21, the controller 120 controls the drive unit 50 such that the first setting base 10 and the second setting base 20 are returned to the setting work position P1 (see
Then, the operation of the measurement apparatus 100 is completed.
In the flow described above, when a plurality of first storage portions 11 as the measurement targets are set in the same row (e.g., Row A in
It should be noted that the embodiment disclosed herein is merely illustrative in all aspects and should not be considered as being restrictive. The scope of the present disclosure is not defined by the description of the above embodiment but by the scope of the claims, and further includes meaning equivalent to the scope of the claims and all modifications within the scope of the claims.
Number | Date | Country | Kind |
---|---|---|---|
2020-053892 | Mar 2020 | JP | national |