JP2004093365A - Reagent temperature adjusting unit and sample analyzer using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reagent temperature adjusting unit simultaneously heating a reagent and removing bubbles. <P>SOLUTION: This reagent temperature adjusting unit comprises a metallic block for thermal storage, a heater for heating the metallic block, a bubble removing channel vertically formed in a state of being thermally kept into contact with the metallic block, first and second liquid discharge channels respectively connected to an upper end and a lower end of the bubble removing channel, a liquid supply passage connected to the bubble removing channel between the upper end and the lower end, and a liquid supply tube connected to the liquid supply passage at its one end and thermally kept into contact with the metallic block. The reagent to be heated is supplied from the other end of the liquid supply tube, the bubbles included in the reagent is discharged from the first liquid discharging passage, and the reagent after removing the bubbles is discharged from the second liquid discharge passage. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a reagent temperature control unit and a sample analyzer using the same.
[0002]
[Prior art]
As prior art related to the present invention, a plurality of metal pipe groups are buried facing each other at opposite positions on both sides of a constant temperature block made of a metal having high thermal conductivity, and ends of the metal pipes are connected to each other. To form a reagent flow path, a concave portion is provided at a substantially central portion between the metal pipe groups of the constant temperature block, and a linear control circuit portion and a power transistor are disposed in the concave portion. The power transistor and the linear control circuit portion There is known a reagent warming device in a sample analyzer, wherein the temperature detecting sensor is attached to a thermostatic block in a thermally conductive manner, and furthermore, these components are entirely covered with a heat insulating material ( For example, see Japanese Utility Model Publication No. 8-9773.
[0003]
[Problems to be solved by the invention]
By the way, in the conventional reagent temperature control unit, a bubble removing chamber is separately provided in order to remove bubbles generated in the heated reagent. However, when the bubble removing chamber is separately provided, not only does the configuration become more complicated, but also the reagent is cooled in the bubble removing chamber, so that it is difficult to maintain the heated reagent at a predetermined temperature. .
The present invention has been made in view of such circumstances, and provides a reagent temperature control unit capable of heating a reagent with a simple structure and simultaneously removing bubbles while having a bubble removing function therein. It is.
[0004]
[Means for Solving the Problems]
The present invention provides a metal block for heat storage, a heater for heating the metal block, a bubble removing channel formed in vertical contact with the metal block, and an upper end and a lower end of the bubble removing channel, respectively. A connected first and second drainage path, a liquid supply path connected between the upper end and the lower end to a bubble removing flow path, and one end connected to the liquid supply path and in thermal contact with the metal block. A supply tube provided so that the reagent to be heated is supplied from the other end of the supply tube, bubbles contained in the reagent are discharged from the first drainage path, and the reagent from which bubbles have been removed is removed. It is to provide a reagent temperature control unit discharged from the second drainage passage.
[0005]
According to this configuration, the reagent to be heated is heated by the heater via the metal block when passing through the liquid supply tube, and is heated and bubbles are removed when passing through the bubble removal channel. With a simple configuration, heating and air bubble removal can be performed simultaneously.
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
The metal block for heat storage can be manufactured using, for example, brass, copper, iron, aluminum, or the like. It is preferable that the air bubble removing channel is formed using a chemical resistant pipe (for example, a chemical resistant resin or stainless steel) so that the reagent can be isolated from the metal block. This prevents chemical corrosion of the metal block.
[0007]
Further, it is preferable to use a resin or metal (for example, FEP or stainless steel) having excellent chemical resistance as the liquid supply tube. Examples of the reagent to be heated include a sheath liquid for a sheath flow cell, a diluent, a stain, and a hemolytic agent.
[0008]
The liquid supply tube has flexibility and may be installed so as to be wound around the metal block.
Further, the metal block may have a plurality of holes penetrating in the horizontal direction, and the liquid supply tube may spirally penetrate the plurality of holes.
It is preferable that the air bubble removing channel is provided vertically penetrating the metal block and has an inner diameter larger than that of the liquid supply tube.
[0009]
The heater may be provided in a plate shape on the outer surface of the metal block.
This unit may further include a temperature control thermistor, or may further include a heat insulating material for preventing heat radiation of the metal block.
The present invention provides a sample analyzer using the above reagent temperature control unit.
[0010]
Embodiments The present invention will be described below in detail based on embodiments shown in the drawings. This does not limit the present invention.
Sample preparation device Fig. 1 is a front view showing a sample preparation device according to the present invention.
As shown in FIG. 1, the main frame 1 is provided with a sliding rail 2 in the horizontal direction, and the sliding rail 2 supports the slider 3 so as to be slidable in the horizontal direction.
[0011]
The main frame 1 supports a driving pulley 5 driven by a stepping motor 4 and rotatably supports a corresponding driven pulley 6. A timing belt 7 is suspended between the pulleys 5 and 6 in parallel with the slide rail 2. The slider 3 has a horizontal moving plate 8 mounted thereon, and the plate 8 is connected to the timing belt 7 by a connecting member 9. Here, when the stepping motor 4 rotates, the plate 8 moves in the arrow X1 or X2 direction according to the rotation direction.
[0012]
The plate 8 is provided with three sliding rails 10, 11, and 12 in the vertical direction, and the sliding rails 10, 11, and 12 respectively support the sliders 13, 14, and 15 so as to be slidable in the vertical direction. .
[0013]
The plate 8 supports driving pulleys 18 and 19 driven by stepping motors 16 and 17, respectively, and rotatably supports driven pulleys 20 and 21 corresponding thereto. Timing belts 22 and 23 are suspended vertically between the pulleys 18 and 20 and between the pulleys 19 and 21, respectively.
[0014]
The sliders 13 and 14 carry a first pipette 28 and a second pipette 29 via supporting members 24 and 25, respectively, and the slider 15 carries a catcher 27 via a supporting member 26. The first pipette 28 has a pipette heater 36 on the outer periphery and heats the sucked liquid to 42 ° C.
[0015]
The slider 13 is connected to the timing belt 22 by a connector 30, and the sliders 14 and 15 are connected to the timing belt 23 by connectors 31 and 32, respectively. Here, when the stepping motor 16 rotates, the first pipette 28 moves in the arrow Y1 or Y2 direction according to the rotation direction, and when the stepping motor 17 rotates, the second pipette 29 and the catcher 27 according to the rotation direction. Move in the directions of the arrows Y1 and Y2, respectively.
[0016]
On the other hand, the support frame 41 includes a turntable 42, a turntable rotating mechanism 43, a mixing vessel rotating mechanism 44, a stepping motor 45 as a rotation drive source, and a vessel discarding section 46. A third pipette 48 is fixed to the upper end of the support frame 47, and a slide rail 49 is fixed vertically. The sliding rail 49 supports the slider 50 so as to be slidable in the vertical direction.
[0017]
The slider 50 has a cleaning device 52 mounted thereon via a support member 51. Note that a stopper 53 is provided below the support frame 47, and the slider 50 is locked at the position shown in FIG. 1 by the stopper 53 so as not to separate downward from the slide rail 49. A mounting table 33 is provided on the right side of the support frame 41, and a diluent container 34 is mounted thereon.
[0018]
2 is a top view of the support frame 41, FIG. 3 is a longitudinal sectional view of the turntable rotating mechanism 43, and FIG. 4 is a longitudinal sectional view of the mixing vessel rotating mechanism 44.
[0019]
As shown in FIG. 4, a pulley 53 is coupled to the output shaft 40 of the stepping motor 45. As shown in FIG. 3, a pulley 56 is connected to a drive shaft 54 of the turntable 42 via a one-way clutch 55.
[0020]
As shown in FIG. 5, a sample container rotating mechanism 57 is provided between the turntable 42 and the support frame 41, and the pulley 58 is rotatably supported by the shaft 59 on the support frame 41. Having.
[0021]
Then, the pulleys 53, 56, 58 are connected by one timing belt 60 as shown in FIG. That is, the rotational force of the stepping motor 45 is transmitted to the mixing container rotating mechanism 44 (FIG. 4), and at the same time, the turntable rotating mechanism 43 (FIG. 3) via the timing belt 60 and the pulleys 53, 56, 58. Is transmitted to the sample container rotating mechanism 57 (FIG. 5).
[0022]
The third pipette 48, the cleaning device 52, the container disposal unit 46, the pulley 53, and the pulley 58 are arranged in a line on the straight line L shown in FIG. 2, and the first pipette 28, the second pipette 29, and the catcher 27 It is set to move on a straight line L by driving the stepping motor 4. The turntable 42 is configured such that five sample containers Ts and five empty mixing containers Tm can be installed at equal intervals on concentric circles having different diameters, and one sample container Ts and two The empty mixing container Tm can be arranged on the straight line L.
[0023]
As shown in FIGS. 2, 8, and 18, a photo interrupter 140 is installed on the support frame 1, and a light blocking piece 62a that protrudes downward and shields the photo interrupter 140 is provided on the turntable 42. . These are used for detecting a reference position (initial position) of the turntable 42 as described later.
[0024]
Hereinafter, the configuration of each unit will be described.
Turntable FIG. 6 is a configuration explanatory view showing a vertical cross section of the turntable 42.
As shown in the figure, the turntable 42 includes a disc-shaped container mounting portion 61 made of resin, and a rotating plate 62 made of a nonmagnetic material (made of stainless steel or aluminum) on which the container mounting portion 61 is detachably mounted. Consists of 7 and 8 are a side view and a top view of the turntable 42 showing a state in which the container mounting portion 61 is removed from the rotating plate 62.
[0025]
As shown in these figures, a guide block 63 for guiding the container mounting portion 61 at the time of mounting is provided on the upper surface of the rotating plate 62. The guide block 63 has a positioning pin 65 at a center position of the rotating plate 62, and the positioning pin 65 is urged upward by a compression spring 64. Further, the guide block 63 includes a protruding portion 66 that locks the container mounting portion 61 at a peripheral position of the rotating plate 62.
[0026]
9 is a top view of the container mounting portion 61 removed from the rotary plate 62, FIG. 10 is a cross-sectional view taken along the line AA of FIG. 9, FIG. 11 is a cross-sectional view taken along the line BB of FIG. 9, and FIG. It is a bottom view of the part 61. As shown in FIG. 9, the container mounting part 61 has five empty container accommodation holes 67 for accommodating an empty mixing container Tm (FIG. 2) and five empty container accommodation holes 67 for accommodating the sample container Ts (FIG. 2). The first holder 68 is provided at equal intervals on two concentric circles having different diameters.
[0027]
As shown in FIGS. 10 and 11, the container mounting portion 61 includes a groove 70 that fits into the guide block 63 when the container mounting portion 61 is mounted on the rotating plate 62 (FIG. 7). A positioning hole 69 for receiving the positioning pin 65 is provided at the position. Further, the container mounting portion 61 has a handle 71 on the upper surface used when attaching and detaching to and from the rotating plate 62.
[0028]
In the sample preparation apparatus of this embodiment, a sample container Ts for storing a sample collected from a subject and a mixing dissolution vessel Tm for mixing the sample with a predetermined solution to prepare a sample for analysis. Uses a disposable container (hereinafter referred to as a tube) T shown in FIG.
[0029]
The tube T is a cylindrical container made of a styrene (transparent) resin having a height H = 39,85 ± 0.1 mm, an outer diameter D _T = 7.6 to 8.2 mm, and a volume of about 0.7 mL. A flange F (outer diameter D _F = 10 mm) is provided on the upper peripheral edge to prevent the catcher 27 from slipping off when it is gripped by the catcher 27.
[0030]
As shown in FIG. 10, the first holder 68 is inserted from below into each of the five cylindrical through recesses 72 provided in the container mounting portion 61, and a bottom plate 73 made of a nonmagnetic material (stainless steel or aluminum) is provided. Supported by
[0031]
The first holder 68 has a hole 74 for receiving the sample container Ts at an upper portion, and is supported by the peripheral wall of the concave portion 72 so as to be rotatable around an axis. Further, the first holder 68 has a bar magnet 75 penetrating therethrough in a direction perpendicular to the axis, so that the first holder 68 rotates about the axis when receiving a rotating magnetic field from below the bottom plate 73 as described later. It has become.
[0032]
Turntable rotation mechanism As shown in FIG. 3, the drive shaft 54 of the turntable 42 has its base end fixed to the center of the back surface of the rotary plate 62 via a boss 78. The support frame 41 supports a bearing holder 76, and the drive shaft 54 is rotatably supported by the support frame 41 via a bearing 77 held by the bearing holder 76. The drive shaft 54 is fixed to a bearing holder 76 via a one-way clutch 79.
[0033]
On the other hand, the one-way clutch 55 is interposed between the pulley 56 and the drive shaft 54 and connected to each other as described above. The spur gear 80 provided at the tip of the drive shaft 54 meshes with the spur gear 82 provided on the rotation shaft of the damper 81. The damper 81 always acts on the drive shaft 54, and operates to suppress the flywheel effect due to the inertia of the turntable 42, and particularly to reduce the excessive rotation of the turntable 42 when it is stopped.
[0034]
Here, the clutches 55 and 79 operate as follows.
When the stepping motor 45 (FIG. 2) rotates clockwise as viewed from the output shaft side, and thereby the pulley 56 rotates clockwise as viewed from above, the one-way clutch 55 is turned on (operated) and the one-way clutch 79 is turned on. It turns OFF (open), and the turntable 42 rotates clockwise as viewed from above while receiving the action of the damper 81.
[0035]
Conversely, when the stepping motor 45 rotates in the counterclockwise direction, the one-way clutch 55 is turned off and the one-way clutch 79 is turned on, whereby the drive shaft 54 is fixed to the bearing holder 76 and is prevented from rotating. 56 idles. That is, by the action of the one-way clutches 55 and 79, the turntable 42 can rotate in the same direction only when the stepping motor 45 rotates clockwise.
[0036]
Mixing container rotating mechanism As shown in FIG. 4, in the mixing container rotating mechanism 44, a cylindrical holding member 85 is fixed to a mounting plate 84 installed on the support frame 41. The holding member 85 is provided with a through hole at the center for receiving the second holder 86 from above, and a film heater 87 is wound around the outer periphery.
[0037]
The second holder 86 has a hole 88 at an upper portion for receiving and holding the mixing container Tm. The holding member 85 has a thin cylindrical oilless bush 89 fitted in the through hole, and the inner peripheral surface of the oilless bush 89 and the outer peripheral surface of the second holder 86 are slidably contacted with each other. 86 can rotate smoothly about the axis.
[0038]
On the other hand, a coupling 83 is fixed to an upper portion of the pulley 53, and the coupling 83 includes two pins 90 projecting upward. The second holder 86 has two holes on the bottom surface to receive two pins 90. Thereby, the second holder 86 is mechanically coupled to the pulley 53 so as to be detachable. Then, when the stepping motor 45 rotates either clockwise or counterclockwise, the second holder 86 smoothly rotates in the same direction as the stepping motor 45 around the axis by the action of the oilless bush 89.
[0039]
Sample container rotation mechanism As shown in FIG. 5, in the sample container rotation mechanism 57, a cylindrical magnet coupling 91 is fitted and fixed on the upper part of the pulley 58, and the pulley 58 is mounted on the upper surface of the magnet coupling 91. The two bar magnets 92 and 93 are vertically embedded symmetrically with respect to the axis 59 of FIG. The bar magnet 92 is disposed so that the N pole faces the turntable 42, and the bar magnet 93 is disposed such that the S pole faces the turntable 42.
[0040]
Since the bottom plate 73 and the rotating plate 62 are non-magnetic materials as described above, when the first holder 68 built in the turntable 42 faces the magnet coupling 91 as shown in FIG. The N pole is magnetically attracted to the S pole of the bar magnet 75, and the S pole of the bar magnet 93 is magnetically attracted to the N pole of the bar magnet 75. That is, the first holder 68 is magnetically coupled to the pulley 58 via the magnet coupling 91. Accordingly, in this state, when the pulley 58 is rotated clockwise or counterclockwise by the stepping motor 45, the first holder 68 is rotated in the same direction as the stepping motor 45 about the axis of the sample container Ts. .
[0041]
Catcher FIGS. 13 and 14 are a side view and a top view of the catcher 27, respectively. As shown in these figures, the catcher 27 includes a main body 98 and two fingers 94 and 95, and the two fingers 94 and 95 are opened by the pins 96 and 97 in the directions of arrows C and D, respectively. 98 supported. Then, the fingers 94 and 95 are urged by the tension spring 99 in the closing direction, and are held in the state shown in FIG.
[0042]
Then, when the catcher 27 approaches the fixed mixing container Tm in the direction of the arrow M in FIG. 13, the fingers 94 and 95 are engaged with the flange F across the side surface of the mixing container Tm. When the catcher 27 is moved to the arrow N in FIG. 13 with the mixing container Tm fixed, the catcher 27 is separated from the mixing container Tm.
[0043]
Sample analyzer FIG. 16 is an explanatory diagram showing an optical system and a fluid system of a sample analyzer using the sample preparation device shown in FIG. 1, and FIG. 17 is a block diagram showing a control system thereof.
[0044]
Optical system and fluid system As shown in FIG. 16, the sheath flow cell 107 includes a nozzle 113 for injecting the analysis sample upward toward the orifice 111, a sheath liquid supply port 110, and a drain port 114. Prepare. In the vicinity of the sheath flow cell 107, a laser light source 117, a condenser lens 118, a beam stopper 119, a collector lens 120, a light shielding plate 130 having a pinhole 121, a dichroic mirror 122, a filter 123, a photomultiplier tube 124, and a photodiode 125 are provided. Has been.
[0045]
A sheath liquid container 109 pressurized with positive pressure is connected to the sheath liquid supply port 110 via a temperature control unit 115 and a valve 105. The drain port 114 is connected to a waste liquid chamber (not shown). The third pipette 48 of the sample preparation device (FIG. 1) is connected to the nozzle 113 via the valve 101, and a negative pressure source is connected via the flow path 139 and the valve 102. The syringe pump 133 is connected to the side. The temperature control unit 115 is connected to a waste liquid chamber (not shown) via a valve 106 so that air bubbles stored inside can be appropriately removed.
[0046]
The first pipette 28 of the sample preparation device (FIG. 1) is connected to the syringe pump 131, and the second pipette 29 is connected to the syringe pump 132 via the valve 103. The syringe pump 132 is further connected to the staining liquid container 112 via the valve 104.
[0047]
Temperature control unit FIG. 20 is a top view of the temperature control unit 115, FIG. 21 is a cross-sectional view taken along the line EE of FIG. 20, FIG. 22 is a cross-sectional view taken along the line FF of FIG. 20, and FIG. It is GG arrow sectional drawing of 22.
[0048]
As shown in FIG. 21, a metal block (made of brass) 149 for heat storage is provided at the center of the temperature control unit 115, and a disc-shaped heat insulating block (made of polyacetal resin) 150 is provided on the upper and lower surfaces of the metal block 149. , 151 are fitted respectively. At the center of the metal block 149, a bubble removal flow path (inner diameter 3.2 mm) 152 extending vertically from the heat insulating block 150 to 151 is formed.
[0049]
The heat insulating blocks 150 and 151 have first and second drainage paths (inner diameter 1 mm) 153 and 154 in the horizontal direction, respectively. The first drainage passage 153 is connected to an external tube connection nipple (inner diameter 1.5 mm, made of stainless steel) 155 having one end connected to the upper end of the air bubble removal channel 152 and the other end horizontally projecting from the heat insulating block 150. Connected.
[0050]
The second drainage passage 154 has one end connected to the lower end of the air bubble removal channel 152 and the other end protruding horizontally from the heat insulating block 151 for connecting an external tube (inner diameter 1.5 mm, made of stainless steel). 156.
[0051]
Further, the heat insulating block 150 horizontally has a liquid supply path connected between the upper end and the lower end of the bubble removing flow path 152, and a nipple (inner diameter 0.9 mm) 157 is fitted into the liquid supply path. I have.
[0052]
In addition, a pipe (made of stainless steel) 159 is attached to the inner wall of the air-bubble removing channel 152, and the upper end of the pipe 159 is press-fitted into the heat-insulating block 150, and the lower end thereof is watertight through the O-ring 158 to the heat-insulating block 151. Is inserted. This prevents the liquid flowing through the bubble removal flow channel 152 from coming into contact with the metal block 149. That is, corrosion of the metal block 149 by the liquid is prevented.
[0053]
As shown in FIGS. 22 and 23, the metal block 149 includes a total of eight through holes 160 provided in parallel four by four in a left-right symmetry with respect to the bubble removing passage 152. One liquid supply tube (made of FEP having an inner diameter of 0.8 mm) 161 sequentially penetrates from the lower through-hole 160 to the upper through-hole 160, and is arranged in a spiral shape around the bubble removing channel 152.
[0054]
Then, as shown in FIG. 21, the lower end 161a of the liquid supply tube 161 projects downward from the heat insulating block 151, and the upper end 161b is connected to the nipple 157. As shown in FIG. 23, concave portions 162 are formed in the metal block 149 at both ends of the through hole 160, and the curved portion of the liquid supply tube 161 extending in a spiral shape is accommodated in the concave portion 162.
[0055]
Therefore, a plate-shaped sheath liquid heater 148 is installed so as to cover the side surface of the metal block 149. Further, as shown in FIGS. 21 and 22, a heat insulating material (made of polyethylene foam) 163 is provided between the heat insulating blocks 150 and 151 so as to cover the sheath liquid heater 148.
[0056]
Further, a heat insulating material (made of foamed polyethylene) 164 is provided so as to cover the side surfaces of the heat insulating blocks 150 and 151 and the heat insulating material 163. As shown in FIG. 22, the metal block 149 is provided with a temperature sensor (thermistor) 146 and a thermal protector (switching element) 147. In such a configuration, when the sheath liquid is supplied from the lower end 161a of the liquid supply tube 161 shown in FIG. 21, if the nipples 155 and 156 are opened, the sheath liquid is heated in the liquid supply tube 161 and the nipple 155 Outflow from 156.
[0057]
Next, when the nipple 155 is closed, the heated sheath liquid flows out only from the nipple 156, and the bubbles in the sheath liquid sequentially rise in the bubble removing channel 152 and stay near the upper end thereof. In other words, the flow rate of the sheath liquid flowing from the nipple 156 into the bubble removing channel 152 decreases, so that the bubbles are removed upward when descending the bubble removing channel 152.
[0058]
The bubbles remaining near the upper end of the bubble removing channel 152 are discharged from the nipple 155 by closing the nipple 156 and opening the nipple 155 as necessary and supplying the sheath liquid from the liquid supply tube 161. Together with the sheath fluid.
[0059]
The temperature of the metal block 149 is detected by the temperature sensor 146, and the sheath liquid heater 148 heats the metal block 149 so that the metal block 149 is maintained at a temperature of 42 ° C. When the metal block 149 is overheated, the thermal protector 147 operates to cut off the power supply to the sheath liquid heater 148.
[0060]
First pipette FIG. 24 is a longitudinal sectional view of the first pipette 28. As shown in the figure, the first pipette 28 has a hollow elongated cylindrical shape extending from the distal end 165 to the proximal end 166, and is made of stainless steel. The first pipette 28 includes, in order from the distal end 165 to the proximal end 166, a suction unit 167 having a length L0 and an inside diameter D0, a sample accommodation unit 168 having a length L1 and an inside diameter D1, and a reagent accommodation unit having a length L2 and an inside diameter D2. A portion 169.
[0061]
Here, D0 <D1 <D2, and in this embodiment, D0 = 0.6 mm, D1 = 1.5 mm, D2 = 2.1 mm, L0 = 3 mm, L1 = 45 mm, and L2 = 150 mm. Therefore, the volumes of the sample storage section 168 and the reagent storage section 169 are 79.5 μL and 520 μL, respectively.
The suction unit 167 is formed to be thin in order to suck the sample and the reagent without excess or shortage. The sample storage section 168 stores a sample and a reagent. The reagent storage section 169 stores only the reagent, and does not store the sample.
[0062]
The suction unit 167 and the sample storage unit 168, and the sample storage unit 168 and the reagent storage unit 169 are connected by connection units 170 and 171 each having a tapered hole. The reagent storage section 169 includes a copper heat storage pipe 172 on the outer wall, and the pipette heater 36 on the outer wall of the heat storage pipe 172.
[0063]
The pipette heater 36 is made of a coated nichrome wire, and is wound around the outer wall of the heat storage pipe 172 in a coil shape. Further, a temperature sensor (thermistor) 144 is provided on a part of the outer wall of the heat storage pipe 172. Further, the reagent container 169 includes a stainless steel protective cover 173 that covers the pipette heater 36 and the temperature sensor 144.
[0064]
Control system The control unit 134 shown in FIG. 17 includes an operation unit 134a and a storage unit 134b, receives outputs from the input unit 135, the photomultiplier tube 124, and the photodiode 125, and analyzes analysis conditions and analysis results. Output to the output unit 138.
[0065]
The photo interrupter 140 detects the initial position of the turntable 42 as described above, and the position sensors 141 to 143 respectively determine the horizontal position of the horizontal moving plate 8 and the vertical positions of the first pipette 28, the second pipette 29 and the catcher 27. It is a sensor to detect.
[0066]
The temperature sensors 144 to 146 are sensors (thermistors) that detect the temperatures of the first pipette 28, the second holder 86, and the temperature adjustment unit 115, respectively. The thermal protector 147 is a switching element for preventing the temperature control unit 115 from overheating as described above.
[0067]
Therefore, the control unit 134 controls the drive circuit unit 137 by receiving outputs from the photo interrupter 140, the position sensors 141 to 143, the temperature sensors 144 to 146, and the thermal protector 147. Here, the control unit 134 is configured by a microcomputer, and the input unit 135 and the output unit 138 are integrally configured by a touch panel LCD.
[0068]
The drive circuit section 137 includes a stepping motor drive circuit, a syringe pump drive circuit, a valve drive circuit, a heater drive circuit, and a laser drive circuit, and receives outputs from the control section 134 and receives stepping motors 4, 16, and 17 shown in FIG. , 45, the syringe pumps 131 to 133 and the valves 101 to 106, the heaters 36, 87, 148, and the laser light source 117 shown in FIG.
[0069]
Preparation operation of analysis sample Next , preparation operation of the analysis sample will be described.
(A) Initialization of Turntable First, FIG. 19 shows an initialization operation for determining the number Nb of drive pulses of the stepping motor 45 necessary for rotating the sample container Ts on the turntable 42 by one pitch. This will be described with reference to a flowchart.
[0070]
First, when the power of the control system shown in FIG. 17 is turned on, a drive pulse is applied to the stepping motor 45, and the turntable 42 rotates clockwise (step S1). Then, when the light shielding piece 62a shields the photo interrupter 140 (hereinafter, referred to as a sensor ON) (step S2), counting of the driving pulse applied to the stepping motor 45 is started (step S3), and the driving of the motor is continued. (Step S4) Next, when the sensor is turned on (Step S5), the application of the driving pulse to the stepping motor 45 is stopped, the counting of the driving pulse number N required for one rotation of the turntable 42 is completed, and the stepping is performed. The motor 45 stops (step S6).
[0071]
Therefore, Na = N / 5 is calculated as the number of drive pulses required for rotation of the turntable 45 for one pitch (step S7). Here, Na is a value that ignores excessive rotation due to inertia.
Next, a drive pulse is repeatedly applied to the stepping motor 45 by Na, and the turntable 42 repeatedly rotates and stops (steps S8, S9, S10).
[0072]
At this time, since the turntable 42 rotates while accumulating an excessive amount of rotation due to inertia every stop, the sensor is turned on during the fifth application of the Na drive pulses while all of the Na drive pulses are not applied (step S11). ), ΔN drive pulses are left. Then, the remaining pulse number ΔN is calculated as the accumulated overrun amount (step S12).
[0073]
Therefore, the Na calculated in step S7 is corrected as Nb = (N−ΔN) / 5 in consideration of the excessive rotation amount (step S13), and the storage unit stores the correct number of drive pulses for rotating the turntable 42 by one pitch. 134b (FIG. 17) (step S14).
[0074]
On the other hand, after the sensor is turned on in step S11, a predetermined number of drive pulses are further applied to the stepping motor 45, and the position where the user can most easily remove the container mounting portion 61 from the rotating plate 62, that is, the guide block 63 When the turntable 42 reaches a position that intersects the straight line L at right angles, the stepping motor 45 stops, and the initialization operation of the turntable ends (steps S15, S16, and S17).
[0075]
(B) Installation of Sample Container and Mixing Container Next, the user grips the handle 71 shown in FIG. 6 and pulls it toward the user, and slides the container mounting portion 61 on the rotating plate 62 toward the user. The mounting unit 61 is removed from the rotating plate 62. Therefore, the user loads the sample containers Ts containing 300 μL of different samples (for example, urine) into each of the holes 74 of the five first holders 68 of the container mounting portion 61 shown in FIG. Each of the container receiving holes 67 is loaded with an empty mixing container Tm.
[0076]
Next, the user grips the handle 71 and places the container mounting portion 61 on the rotating plate 62 shown in FIG. At this time, the container mounting portion 61 is slid on the rotating plate 62 and pushed in so that the guide block 63 shown in FIG. 8 is inserted into the groove 70 shown in FIG. 11, and the positioning pin 65 is inserted as shown in FIG. It is fitted into the positioning hole 69 by the urging force of the compression spring 64. Accordingly, the container mounting portion 61 is locked to the projecting portion 66 and positioned so as to be coaxial with the rotating plate 62.
[0077]
(C) Automatic preparation operation Next, the following steps (1) to (18) are automatically performed by the control system shown in FIG.
(1) When the user installs the container mounting unit 61 on the rotating plate 62 as described above and inputs a start command to the input unit 135 (FIG. 17), the stepping motor 45 rotates clockwise, and accordingly. When the turntable 42 rotates and the sensor is turned on, it stops at the initial position shown in FIG. At this time, the first sample container Ts and the two empty mixing containers Tm on both sides thereof are aligned on a straight line L as shown in FIG. At the same time, the first holder 68 containing the first sample container Ts faces the magnet coupling 91 as shown in FIG.
[0078]
(2) Next, the stepping motors 4 and 17 shown in FIG. 1 are driven, and the catcher 27 grips the right mixing container Tm of the two empty mixing containers Tm on the straight line L in FIG. The mixing container rotating mechanism 44 is inserted into the second holder 86. At this time, power is already supplied to the film heater 87 (FIG. 4) of the mixing container rotating mechanism 44, and the temperature of the second holder 86 is maintained at 42 ° C.
[0079]
(3) Next, the stepping motors 4 and 17 are driven to separate the catcher 27 from the second holder 86 while leaving the empty mixing container Tm in the second holder 86.
(4) Next, the stepping motors 4 and 16 are driven to insert the first pipette 28 into the diluent container 34, aspirate 340 μL of the diluent into the reagent container 169 (FIG. 24), and Heat to ° C.
(5) Next, the stepping motor 16 is driven to pull out the first pipette 28 from the diluent container 34, and sucks 20 μL of air into the sample container 168. This forms an air gap with a volume of 20 μL.
[0080]
(6) Next, the stepping motors 4 and 16 are driven to insert the first pipette 28 into the sample container Ts existing on the straight line L in FIG. At this time, the first pipette 28 is held at a position eccentric from the axis of the sample container Ts.
[0081]
(7) Next, the stepping motor 45 rotates counterclockwise for a predetermined time. Accordingly, the pulley 58 rotates counterclockwise, and the sample container Ts on the straight line L also rotates counterclockwise. While the sample container Ts is rotating, the first pipette 28 aspirates the sample (40 μL) in the sample container Ts into the sample container 168 (FIG. 24) and discharges the sample. Then, the suction / discharge operation is repeated. The sample is sufficiently stirred by the rotation operation of the sample container Ts with respect to the eccentric first pipette 28 and the suction / discharge operation of the first pipette 28.
[0082]
(8) Next, after the first pipette 28 discharges all the samples in the sample container 168, the first pipette 28 aspirates the sample from the sample container Ts by 50 μL. In the sample container 168, an air gap having a volume of 20 μL is formed between the aspirated sample and the diluent in the step (5), and the two do not mix.
[0083]
(9) Next, the stepping motors 4 and 16 are driven to pull out the first pipette 28 from the sample container Ts and insert it into the empty mixing container Tm inserted in the second holder 86 in the step (2). At this time, the first pipette 28 is held at a position eccentric from the axis of the inserted mixing container Tm.
[0084]
(10) Next, the first pipette 28 discharges 340 μL of the diluted solution heated to 42 ° C. and the sucked 50 μL of the sample into the mixing container Tm. At the same time, the stepping motor 45 rotates counterclockwise for a predetermined time. Therefore, the mixing container Tm containing the diluent and the sample also rotates about the axis.
[0085]
During the rotation of the mixing container Tm, the first pipette 28 repeats the suction / discharge operation with a maximum volume of about 70 μL so that the liquid does not enter the reagent storage section 169.
By the rotation operation of the mixing container Tm with respect to the eccentric first pipette 28 and the suction / discharge operation of the first pipette 28, a diluted specimen uniformly diluted 8-fold is prepared.
[0086]
(11) Next, the stepping motors 4 and 16 are driven to pull out the first pipette 28 from the mixing container Tm.
(12) Next, the stepping motors 4 and 17 are driven to insert the second pipette 29 into the mixing container Tm. At this time, the second pipette 29 is held at a position eccentric from the axis of the mixing container Tm.
[0087]
(13) Next, the second pipette 29 discharges 10 μL of the staining solution supplied from the staining solution container 112 shown in FIG. 16 to the mixing container Tm. At the same time, the stepping motor 45 rotates counterclockwise for a predetermined time. Therefore, the mixing container Tm also rotates around the axis. During the rotation of the mixing container Tm, the second pipette 29 repeats the suction / discharge operation. By the rotation operation of the mixing container Tm with respect to the eccentric second pipette 29 and the suction / discharge operation of the second pipette 29, the stain is uniformly mixed with the diluted sample, and the analysis sample is prepared. The prepared analysis sample is kept at 42 ° C. by the film heater 87 of the mixing container rotating mechanism 44.
[0088]
(14) Next, the stepping motors 4 and 17 are driven to pull out the second pipette 29 from the mixing container Tm.
(15) Next, the stepping motors 4 and 17 are driven, the mixing container Tm is pulled out of the second holder 86 by the catcher 27, transported to the third pipette 48, and the third pipette 48 is inserted into the mixing container Tm. Then, the third pipette 48 sucks the sample for analysis from the mixing container Tm.
(16) Next, the stepping motors 4 and 17 are driven, and the empty mixing container Tm with the catcher 27 is inserted into the disposal hole 35 of the container disposal part 46 and disposed.
[0089]
(17) Next, the stepping motors 4 and 17 are driven, the catcher 27 grasps and lifts the upper part of the cleaning device 52, and inserts the third pipette 48 into the cleaning device 52. Thereby, the third pipette is washed.
(18) Next, the stepping motors 4, 16, 17 are driven to return the cleaning device 52 to the position shown in FIG. 1, and the first pipette 28, the second pipette 29, the catcher 27 and the horizontal moving plate 8 are moved to the position shown in FIG. Return to the position shown in.
[0090]
Next, when Nb drive pulses are applied to the stepping motor 45 and the turntable 42 rotates clockwise, the next sample container Ts and the empty mixing container Tm are arranged on the straight line L in FIG. Prepare for preparation of sample for analysis.
[0091]
Sample analysis operation In the configuration shown in FIGS. 16 and 17, first, when the valves 101 and 102 are opened for a predetermined time, the analysis sample prepared by the sample preparation device shown in FIG. The pressure fills the flow path 139 between the valves 101 and 102 via the third pipette 48. Then, the valves 101 and 102 are closed.
[0092]
Next, the sample is discharged from the nozzle 113 to the sheath flow cell 107 by the syringe pump 133 pushing the sample in the flow path 139 to the nozzle 113 at a constant flow rate.
At the same time, the sheath liquid heated to 42 ° C. by the temperature control unit 115 is supplied to the sheath flow cell 107 by opening the valve 105.
[0093]
As a result, the sample is wrapped in the sheath liquid and further narrowed down by the orifice 111 to form a sheath flow. The orifice 111 has a square hole with a side of 100 to 300 μm, and is made of optical glass.
[0094]
By forming the sheath flow in this manner, the particles or formed components contained in the sample can be flowed in a line through the orifice 111 one by one. The sample and the sheath liquid that have passed through the orifice 111 are discharged from a drain port 114.
[0095]
Then, a laser beam emitted from the laser light source 117 is applied to the sample stream 126 flowing through the orifice 111 by being narrowed down to an elliptical shape by the condenser lens 118. The size of the ellipse is approximately the same as the test particle diameter in the sample flow direction, for example, about 10 μm, and is sufficiently larger than the test particle diameter in the direction perpendicular to the sample flow direction, for example, about 100 to 400 μm. is there.
[0096]
Laser light that has passed through the flow cell 107 as it is without hitting particles in the sample is shielded by the beam stopper 119. Forward scattered light and forward fluorescent light emitted from the particles that have received the laser light are collected by the collector lens 120 and pass through the pinhole 121 of the light shielding plate 130. Then, the light reaches the dichroic mirror 122.
[0097]
Fluorescence having a longer wavelength than the scattered light passes through the dichroic mirror 122 as it is, and after the scattered light is further removed by the filter 123, detected by the photomultiplier tube 124 and output as a fluorescence signal 127 (pulse analog signal). . The scattered light is reflected by the dichroic mirror 122, received by the photodiode 125, and output as a scattered light signal 128 (pulse analog signal). Then, the fluorescence signal 127 and the scattered light signal 128 are input to the control unit 134 shown in FIG.
[0098]
The calculation unit 134a calculates the scattered light pulse width Fscw and the scattered light intensity Fsc from the pulse width and the maximum value of the scattered light signal 128, respectively.
Further, the calculation unit 134a similarly calculates the fluorescence pulse Flw and the fluorescence intensity Fl from the pulse-like fluorescence signal 127.
[0099]
Therefore, the control unit 134 creates a distribution map (histogram or scattergram) based on the obtained Fscw, Fsc, Flw, and Fl, and classifies red blood cells, cylinders, glass cylinders, bacteria, and the like. Then, the classified particles are counted (counted) and converted into the number per 1 μL of the sample. The result is output to the output unit 138 together with various distribution maps. Thus, the analysis operation of one analysis sample is completed. Then, the turntable 42 is sequentially rotated for the remaining four samples in the sample container Ts, and the preparation of the sample for analysis and the analysis operation are performed.
[0100]
The syringe pump 131 shown in FIG. 16 operates in the above-described preparation steps (4), (7), (8), and (10) of the sample for analysis, and aspirates the sample and diluent into the first pipette 28.・ Discharge is performed.
[0101]
The syringe pump 132 and the valves 103 and 104 shown in FIG. 16 operate in the above-described analysis sample preparation step (13). That is, the valve 104 is opened, the staining liquid is once sucked from the staining liquid container 112 by the syringe pump 132, then the valve 104 is closed and the valve 103 is opened, and a predetermined amount of the sucked staining liquid is supplied to the second pipette by the syringe pump 132. Discharge from 29. Further, by opening and closing the valve 103 and reciprocally driving the syringe pump 132, the second pipette 29 is caused to perform a suction / discharge operation.
[0102]
In the embodiment described above, the sample sucked from the sample container stored in the first holder 68 is configured to be discharged to the mixing container stored in the second holder 86, but the present invention is not limited to this. Instead, various configurations can be adopted, such as discharging a sample aspirated from a sample container placed in another place to a mixing container accommodated in the first holder 68.
[0103]
【The invention's effect】
According to the present invention, the reagent to be heated is heated by the heater via the metal block when passing through the liquid supply tube, and is heated and the bubbles are removed when passing through the bubble removing channel. In addition, it is possible to provide a reagent temperature control unit capable of simultaneously performing heating and removing bubbles with a simple configuration.
[Brief description of the drawings]
FIG. 1 is a front view showing a sample preparation device according to the present invention.
FIG. 2 is a top view of a main part of the apparatus shown in FIG.
FIG. 3 is a longitudinal sectional view of a main part of the apparatus shown in FIG.
FIG. 4 is a longitudinal sectional view of a main part of the apparatus shown in FIG. 1;
FIG. 5 is a longitudinal sectional view of a main part of the device shown in FIG. 1;
FIG. 6 is a longitudinal sectional view of a main part of the apparatus shown in FIG. 1;
FIG. 7 is a side view showing a state where a container mounting portion is removed from the apparatus shown in FIG. 1;
FIG. 8 is a top view showing a state where a container mounting portion is removed from the apparatus shown in FIG.
9 is a top view of a container mounting portion of the device shown in FIG.
FIG. 10 is a sectional view taken along the line AA of FIG. 9;
11 is a sectional view taken along the line BB of FIG. 9;
12 is a bottom view of the container mounting portion of the device shown in FIG.
FIG. 13 is a side view of a catcher of the device shown in FIG. 1;
14 is a top view of the catcher of the device shown in FIG.
FIG. 15 is a side view of a disposable container used in the apparatus shown in FIG.
FIG. 16 is an explanatory diagram showing an optical system and a fluid system of the sample analyzer according to the present invention.
FIG. 17 is a block diagram showing a control system of the sample analyzer according to the present invention.
FIG. 18 is an explanatory diagram showing the installation state of the photo interrupter according to the present invention.
FIG. 19 is a flowchart showing an operation of initializing the turntable according to the present invention.
FIG. 20 is a top view of the temperature control unit according to the present invention.
FIG. 21 is a sectional view taken along the line EE in FIG. 20;
FIG. 22 is a sectional view taken on line FF of FIG. 20;
FIG. 23 is a sectional view taken along line GG of FIG. 22;
FIG. 24 is a longitudinal sectional view of a pipette according to the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Main frame 2 Sliding rail 3 Slider 4 Stepping motor 5 Driving pulley 6 Follower pulley 7 Timing belt 8 Horizontal moving plate 9 Connector 10 Sliding rail 11 Sliding rail 12 Sliding rail 13 Slider 14 Slider 15 Slider 16 Stepping motor 17 Stepping motor 18 Drive pulley 19 Drive pulley 20 Drive pulley 21 Drive pulley 22 Timing belt 23 Timing belt 24 Support member 25 Support member 26 Support member 27 Catcher 28 First pipette 29 Second pipette 30 Connector 31 connecting device 32 connecting device 33 mounting table 34 diluent container 35 disposal hole 40 output shaft 41 support frame 42 turntable 43 turntable rotation mechanism 44 mixing container rotation mechanism 45 stepping motor 46 container disposal unit 47 support frame 48 third Pipette G 49 Slide rail 50 Slider 51 Support member 52 Cleaning device 53 Pulley 54 Drive shaft 55 One-way clutch 56 Pulley 57 Sample container rotating mechanism 58 Pulley 59 Shaft 60 Timing belt 61 Container mounting unit 62 Rotating plate 63 Guide block 64 Compression spring 65 Positioning pin 66 Projection 67 Empty container receiving hole 68 First holder 69 Positioning hole 70 Groove 71 Handle 72 Penetrating recess 73 Bottom plate 74 Hole 75 Bar magnet 76 Bearing holder 77 Bearing 78 Boss 79 One-way clutch 80 Spur gear 81 Damper 82 Spur gear 83 Coupling 84 Mounting plate 85 Holding member 86 Second holder 87 Film heater 88 Hole 89 Oilless bush 90 Pin 91 Magnet coupling 92 Bar magnet 93 Bar magnet 94 Finger 95 Finger 96 Pin 97 Pin 98 Body 99 Tension spring 100 Tension spring 101 Valve 102 Valve 103 Valve 104 Valve 105 Valve 106 Valve 107 Sheath flow cell 108 Sheath flow cell 109 Sheath liquid container 110 Sheath liquid supply port 111 Orifice 112 Staining liquid container 113 Nozzle 114 Drain outlet 115 Temperature control Unit 117 Laser light source 118 Condenser lens 119 Beam stopper 120 Collector lens 121 Pinhole 122 Dichroic mirror 123 Filter 124 Photomultiplier tube 125 Photodiode 126 Sample flow 127 Fluorescence signal 128 Scattered L light signal 129 Scattered L light signal 130 Light shield plate 131 Syringe pump 132 Syringe pump 133 Syringe pump 134 Control unit 135 Input unit 137 Drive circuit unit 38 Output unit 139 Flow path F Flange T tube 141 Position sensor 142 Position sensor 143 Position sensor 144 Temperature sensor 145 Temperature sensor 146 Temperature sensor 147 Thermal protector 148 Sheath liquid heater 149 Metal block 150 Heat insulation block 151 Heat insulation block 152 Bubble removal flow path 153 First drain passage 154 Second drain passage 155 Nipple 156 Nipple 157 Nipple 158 O-ring 159 Pipe 160 Through hole 161 Liquid supply tube 162 Depression 163 Insulation material 164 Insulation material 165 Top end 166 Base end 167 Suction unit 168 Sample storage unit 169 Reagent storage section 170 Connection section 171 Connection section 172 Heat storage pipe 173 Protective cover

Claims (8)

A metal block for heat storage, a heater for heating the metal block, a bubble removing channel formed in vertical contact with the metal block, and a second portion connected to an upper end and a lower end of the bubble removing channel, respectively. A first and a second drainage path, a liquid supply path connected between the upper end and the lower end to a bubble removing flow path, and one end connected to the liquid supply path and provided so as to be in thermal contact with the metal block. A liquid supply tube provided, a reagent to be heated is supplied from the other end of the liquid supply tube, bubbles contained in the reagent are discharged from the first drainage path, and the reagent from which the bubbles have been removed is supplied to the second drainage liquid. Reagent temperature control unit discharged from the channel. The reagent temperature control unit according to claim 1, wherein the metal block has a plurality of holes penetrating in a horizontal direction, and the liquid supply tube spirally penetrates the plurality of holes. The reagent temperature control unit according to claim 1, wherein the bubble removing flow path is provided through the metal block, and has an inner diameter larger than that of the liquid supply tube. 2. The reagent temperature control unit according to claim 1, wherein the heater has a plate shape and is attached to an outer surface of the metal block. The reagent temperature control unit according to claim 1, further comprising a temperature control thermistor. 2. The reagent temperature control unit according to claim 1, further comprising a heat insulating material for preventing heat radiation of the metal block. The reagent temperature control unit according to claim 1, wherein the reagent is a sheath liquid supplied to the sheath flow cell. A sample analyzer using the reagent temperature control unit according to claim 1.

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