JP3507875B2 - Micro sample storage device - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to cryopreservation of a sample containing cells, and more particularly to a trace sample preservation device suitable for rapid cooling and heating of the sample for long-term preservation.

[0002]

2. Description of the Related Art In a conventional small sample storage apparatus for cryopreserving blood cells and various cells, a cryoprotective agent such as glycerin is added to a solution containing cells and the cells are slowly cooled at a cooling rate of several to several hundred ° C / min. A means for quick-freezing and freezing storage at −80 ° C. or lower is often used. However, the operation of adding the anti-frost damage agent and the operation of removing the anti-frost damage agent after thawing are complicated, and the operation requires several hours. In addition to these means, there is an ultra-rapid freezing method for rapidly freezing cells without using a frost damage protecting agent.
If a cooling rate of 000 ° C./s or more is not achieved, ice crystals will form inside and outside the cells and the cells will be destroyed. The ultra-rapid freezing method is mainly used as a pretreatment when observing a biological sample with an electron microscope. There are three types of this method: a collision method, a charging method, and a spray method. The collision method is a method of hitting a sample on a low-temperature metal block to freeze it rapidly. In this case, the thickness of the sample must be 100 μm or less in order to prevent the formation of ice crystals. Very little sample can be frozen. Both the charging method and the spraying method are methods in which a sample is charged into a refrigerant such as liquid nitrogen or liquid ethane, and the charging method is a solid sample and the spraying method is a liquid sample. In both cases, the sample is charged into a refrigerant such as liquid nitrogen, but the charging speed is several m to several hundred m / s.
In particular, the spray method atomizes the liquid into a few tens of μm
It is necessary to rush into the refrigerant at a high speed of s, which may cause cell damage.

References related to the above include Frozen, Vol.
7, No.656, pp560-567, and Journal of Microscopy, Vol.140, Pt1, pp17
-40 and so on.

[0004]

The conventional trace amount sample storage device includes at least one sample pretreatment unit, trace amount reduction unit, cooling unit, etc. There is a problem in that there is no device that prevents damage and rapidly freezes continuously, and individually stores for a long time. When storing samples, many samples are mixed and stored in a liquid nitrogen container or freezer, which makes storage management cumbersome.In addition, when the samples are stored or carried out, the outside air flows in and the temperature inside the storage chamber rises, and storage conditions are high. Becomes worse. Further, there is a problem that there is a risk of contamination between samples and contamination due to manual handling.

An object of the present invention is to provide a micro sample storage device capable of preventing cells from being damaged when freezing a solution containing cells and freezing cells continuously and rapidly for long-term storage individually. Especially.

[0006]

A trace sample storage apparatus according to the present invention comprises a pretreatment unit for pretreating a liquid sample containing particles or chemicals, a trace amount reducing unit for reducing the amount of the sample, and a trace amount for reducing the amount. A cooling unit that cools the sample, a transport unit that transports a small amount of sample in the device, a storage unit that stores a small amount of sample, a recovery unit that regenerates and recovers the stored sample, and a post-treatment that performs post-treatment on the regenerated sample comprising a part, an output section for inputting and outputting information to the control unit and the control unit, each of the parts are at least the cooling of the sample, the row cormorants configure the storage and playback on planar storage media.

The miniaturization unit includes a pipettor having a rotating mechanism and an elevating mechanism, a nozzle for atomizing and ejecting the sample sucked by the pipettor, and a detecting unit for optically detecting particles in the ejected sample. It consists of an electrode that is placed in front of the nozzle and controls the traveling direction of the atomized sample to drop the storage medium at a predetermined position.The cooling unit contacts and cools the storage medium, and the storage unit stores the storage medium at low temperature. The stacker has a stacker, and the collection unit has a collection mechanism that heats and defrosts the sample on the storage medium and collects it.The post-processing unit collects the regenerated sample on the storage medium in an external container and controls it. parts controls the respective parts in the device, at least a command, exchange of data to the input-output unit control section, the object by the communications and man-machine interface with an external network and the row of the Hare configuration
To solve.

Further, the micronization unit releases the liquid sample.
Particles contained in the liquid sample in the channel with the channel having the nozzle
Installed near the outlet of the nozzle and the first detection means to detect the child.
The first electrode to be struck and the direction of travel of the liquid sample droplets.
A second detection for detecting the position, velocity and traveling direction of the paddle droplet.
Ejection means and second electrode, and position, velocity and way of droplet
Having a third detecting means for detecting the direction and a third electrode
The above problem is solved by adopting a configuration.

Further , the flow path of the miniaturization section is formed by a double pipe.
In addition, the outlet of the inner pipe of the double pipe is provided in the flow path of the outer pipe,
The liquid sample is circulated and the carrier liquid is circulated in the outer tube.
The light source that illuminates the liquid sample flowing through the center and the inside of the liquid sample
And a detector for detecting scattered light and fluorescence from the particles.
The configuration may be different.

The cooling unit is composed of a cooling block containing a refrigerant passage through which the refrigerant supplied from the refrigerator flows and a heat transfer member on the cooling block, and cools the storage medium in contact with the heat transfer member. The configuration may be

Further, the cooling section includes a cooling block containing a refrigerant passage through which a refrigerant supplied from the refrigerator flows, and an n-type semiconductor and a p-type semiconductor provided on the cooling block and having a Peltier effect. An electrode formed on each end face of the semiconductor and an insulating part that insulates between the cooling block and the electrode on one end face of each semiconductor, and a sample storage part formed of an electrical conductor of a storage medium, respectively. above problems by the semiconductor in contact with the electrode of the other end face, a configuration for applying a voltage between the respective electrodes
To solve.

Further, a plurality of pairs of n-type semiconductors and p-type semiconductors may be connected in series, and a plurality of electric conductor portions may be provided on the storage medium so as to face the respective pairs of semiconductors.

Further, the flow path of the micronization section is formed of a double tube, and the outlet of the inner tube of the double tube is provided in the flow path of the outer tube so that the liquid sample can be circulated in the inner tube and the outer tube. The carrier liquid is circulated, and a light source for irradiating the liquid sample flowing through the center with light and a detector for detecting scattered light and fluorescence from particles in the liquid sample are provided. The inner tube exposed by penetrating the outer tube approximately at the center is bent, and an opening is provided at a position facing the storage medium of the inner tube .
And solve the above problems.

Elastic members are provided around the openings formed by cutting the bent inner pipe, and support members having rigidity higher than that of the elastic members are provided on the respective sides of the elastic members. Alternatively, the inner pipes on the upstream side and the downstream side of the opening may be embedded and the expandable actuators may be provided between the respective support members.

Further, a supporting member is provided around the opening formed by cutting the bent inner pipe, and inner pipes on the upstream side and the downstream side of the opening are embedded in the supporting member,
The support member above the opening is provided with two chambers separated by a diaphragm, and the first chamber close to the opening is in contact with the opening and filled with a fluid that is not mixed with the liquid sample, and the second chamber It is also possible to have a structure in which an expandable / contractible actuator is built in and the end face in the expansion / contraction direction of the actuator is connected to the first chamber via a diaphragm.

A supporting member is provided around the opening formed by cutting the bent inner pipe, and the inner pipes on the upstream side and the downstream side of the opening are embedded in the supporting member.
A configuration may be adopted in which a chamber is provided in a support member above the opening, a retractable actuator is built in the chamber, one end of the actuator in the extension / contraction direction is connected to one surface of the chamber, and the other end is connected to a piston that traverses the opening. .

Further, it is also possible to provide an annular actuator which is expandable and contractable in the radial direction on the outer circumference of the inner pipe upstream of the opening of the bent inner pipe.

Further, the flow path of the micronization section is formed by a double tube and the outlet of the inner tube of the double tube is provided in the flow path of the outer tube so that the liquid sample is circulated in the inner tube and is conveyed to the outer tube. A liquid source that circulates the liquid and is equipped with a light source that irradiates the liquid sample flowing through the center with light and a detector that detects scattered light and fluorescence from particles in the liquid sample, and is provided between the detection unit by the detector and the storage medium. A circular ring that can be expanded and contracted in the radial direction on the outer circumference of the inner pipe upstream of the opening by opening the inner pipe through the outer pipe at approximately the center to expose the inner pipe and facing the storage medium. The actuator may be provided and a second outer tube for wrapping the opening may be provided.

Then, in the pipe wall of the inner pipe on the upstream side of the opening,
A configuration in which an annular actuator that can expand and contract in the radial direction is incorporated may be used.

In the storage section, the transport section includes a tubular support section, at least one transport unit including a drive roller housed in the support section and rotated by a drive source, and a driven roller facing the drive roller. A configuration having an up-and-down mechanism for moving the transport unit up and down and a rotating mechanism for rotating the transport unit may be used.

Further, the storage medium may have a structure having a flat substrate and a sample storage section divided into at least one section for storing the sample on the substrate.

The storage medium may have a structure having an information recording section.

The storage medium may have a structure in which a bridge having a heating resistor and a temperature sensor is provided in each section of the sample storage unit.

Further, the recovery section is provided with a drive section for arranging an opening provided in the bent section of the bent recovery tube through which the recovery liquid flows so as to face the storage medium, and for driving the recovery tube in the XYZ axis directions. You may have a structure.

A support member for supporting the recovery pipe may be provided near the opening of the recovery pipe, and a temperature sensor and a heater may be built in the support member.

Further, the recovery pipe may be a double pipe.

Further, the cell bank is configured to include any one of the above-mentioned minute sample storage devices.

[0028]

According to the present invention, a chemical is added to the sample in the pretreatment section and separated in the micronization section to form a trace amount of the sample, which is contacted and cooled with a storage medium in the cooling section to be frozen and stored. . The storage medium is stored in the storage section, and is regenerated in the collection section.
It is collected in the post-processing section.

Then, the sample is sucked by the pipettor of the pretreatment section and supplied to the micronization section. The micronization unit recognizes and sorts out particles such as cells in the sample, drops the droplets ejected from the nozzle tip at a predetermined position on the storage medium by the electric field formed by the electrode, freezes it, and the storage unit stores it. Is moved into the storage unit, held in the storage mechanism, and then carried in and out by the transfer unit. At the time of collection, the sample on the storage medium is heated and thawed in the collection unit, and collected in the container via the post-treatment unit.

Further, the sample sucked by the pipettor of the pretreatment section flows out from the inner pipe of the atomization section and becomes a slender flow at a constant flow rate. The flow is irradiated with light from a light source, and scattered light and fluorescence from fine particles contained in the flow are detected by a light receiving element to identify the particles. Further, the droplets separated and fly from the tip of the nozzle are dropped at a predetermined position on the storage medium by an electric field and frozen and stored.

Further, the advancing direction, velocity and size of the droplet after flight are detected by the second detecting means. A predetermined electric field is generated by the second electrode, the advancing direction and speed of the droplet that has passed through the second electrode are detected by a third detector, and the charge amount of the droplet is determined based on the change in direction and speed. It is estimated and the voltage applied to the third electrode is determined so that the droplet drops at a predetermined position on the storage medium.

Then, the storage medium that has reached the cooling unit contacts the heat transfer member and is cooled.

Further, the electrode on the semiconductor comes into contact with the sample storage section on the transferred storage medium, and a voltage is applied to the semiconductor to absorb heat from the sample storage section by the Peltier effect and cool it.

Further, a voltage is applied to the semiconductor circuits in series to individually cool the plurality of electric conductors on the storage medium.

The sample liquid flowing out of the inner tube of the double tube and flowing near the center of the double tube flows into the inner tube provided near the center of the downstream side and is positioned at a position facing the storage medium on the downstream side. The existing opening contacts the storage medium, freezes, and fixes on the storage medium.

Further, the actuator expands and contracts, the cut portion of the tube wrapped with the elastic member opens and closes, and a part of the sample is extruded and brought into contact with the facing storage medium and freeze-fixed.

Further, due to the expansion and contraction of the actuator, the diaphragm is displaced and the fluid is projected to the open portion of the tube, and the sample flowing in the tube is pushed out to the storage medium side and comes into contact with the surface of the storage medium and is frozen and fixed.

Then, the piston is projected to the open portion by the actuator and the sample is pushed out toward the storage medium to freeze-fix it.

Further, the actuator is expanded and contracted in the radial direction to push the sample toward the storage medium to bring it into contact with the storage medium, thereby freezing and fixing.

Furthermore, the actuator inside the double tube is expanded and contracted in the radial direction to push the sample toward the storage medium and bring it into contact with the storage medium, thereby freezing and fixing.

Then, the actuator built in the tube inside the double tube is expanded and contracted in the radial direction to push the sample toward the storage medium to bring it into contact with the storage medium, thereby freezing and fixing.

Further, the storage medium is sandwiched by the rollers in the transport unit and introduced into the micronization section by the rotation of the rollers. When the processing in the miniaturization unit is completed, it is guided to the storage unit and stored in the stacker stack from the transport unit by the vertical movement mechanism and the rotation mechanism.

Furthermore, the dropletized sample is stored in each small section on the storage medium.

Now, the information recording medium section holds information about the sample stored on the storage medium.

Further, the temperature history of the sample is controlled by adjusting the current flowing through the heating resistor based on the signal from the temperature sensor.

Further, the heat generated by the heating resistor causes the bridge to bend and the contact thermal resistance between the central portion of the bridge and the storage medium substrate increases, so that the temperature rise by the heating resistor becomes steeper.

Then, the recovered liquid and the frozen sample are brought into contact with each other at the opening of the recovery tube, the sample is melted and recovered in the recovery tube.
The temperature of the tip of the recovery mechanism is kept constant by adjusting the current flowing through the heater by the output of the temperature sensor.

Further, the drive unit moves the opening of the recovery tube onto the sample on the storage medium, lowers the recovery mechanism to bring the opening into contact with the sample, and the sample is melted and recovered by the recovery liquid in the opening. .

Then, the recovered liquid flowing out from the tube inside the double tube comes into contact with the frozen sample on the storage medium to melt the sample.
The thawed sample is sucked from the outer tube and collected together with the collected liquid.

[0050]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will be described with reference to FIG. As shown in FIG. 1, a pretreatment unit 2 for pretreating a liquid sample 11 containing particles or chemicals, a miniaturization unit 3 for miniaturizing the sample 11, and a cooling unit 5 for cooling the microvolume sample. A transport unit 6 for transporting a small amount of sample in the apparatus, a storage unit 7 for storing a small amount of sample, a recovery unit 8 for regenerating and recovering the stored sample, a post-processing unit 9 for post-processing a regenerated sample,
The control unit 10 and the input / output unit 101 for inputting / outputting information to / from the control unit 10 are provided, and the respective units 2, 3, 5, 6, 7,
8, 9, 10, and 101 are configured to perform at least cooling, storage, and reproduction of the sample on the planar storage medium 4. That is, a pretreatment part 2 adds a classification reagent such as a fluorescent dye or an antifreezing agent such as glycerin or DMSO to a sample 11 of cells, proteins, genes, drugs, etc. to be preserved / processed, and the micropartization part 3 Separate and form a small amount of sample 11. In the cooling unit 5, the storage medium 4 is set in a cooled state, and a small amount of the sample 11 emitted from the miniaturization unit 3 is brought into contact with it, cooled, frozen, and fixed. Storage medium 4
Is stored in a specific position in the storage unit 7 and is sent to the collection unit 8 as appropriate. A small amount of the sample 11 on the storage medium 4 is subjected to a regenerating operation such as thawing, and is subjected to a treatment such as removal of the chemical added in the post-treatment section 9 or addition of a new chemical, and then a regenerated sample 12 is obtained. Provided. The transport unit 6 handles the storage medium 4 in the device. Further, the control unit 10 cooperatively controls each unit in the apparatus, receives information about a sample and an operation command through the input / output unit 101, and outputs a processing state of the sample, a storage location, and a state of the apparatus. It should be noted that the sample 11 that has been reduced in amount by the reduction unit 3 may be directly sent to the post-processing unit 9. In addition, the regenerated sample 12 may be put into the pretreatment unit 2 again as the sample 11. According to this embodiment, various kinds of minute samples such as cells can be automatically preserved, so that the samples can be easily managed and the labor can be saved.

FIG. 2 shows another embodiment of the present invention. In this embodiment, a pretreatment unit 2 for suctioning and supplying the sample 11 into the apparatus, a miniaturization unit 3 for atomizing the sample 11 to sort particles such as cells in the sample, and a microparticle 11 for holding and storing the sample 11. Storage medium 4, a cooling unit 5 for cooling the storage medium 4, a transport unit 6 for transporting the storage medium 4 from the entrances / outlets 13, 14 in the loading / unloading device, a storage unit 7 for storing the storage medium 4, and a storage unit A collection unit 8 that collects the sample 11 on the medium 4, a post-processing unit 9 that collects the regenerated sample 12 on the storage medium 4 of the collection unit 8 into an external container 93, and a refrigerator 51 that cools the cooling unit 5.
And a control unit 10 for cooperatively controlling each unit in the apparatus 1, and an input / output unit 101 for performing a command to the control unit 10, data exchange, communication with an external network, a man-machine interface, and the like.

Next, the operation of this embodiment will be described. The tip of the pipettor 22 is inserted into the container 23 containing the sample 11 by the elevating mechanism 211 and the rotating mechanism 212 of the pretreatment unit 2, and the sample 11 is sucked and supplied to the micronization unit 3. Miniaturization part 3
The sorting mechanism 31 of is a mechanism adopted in a cell sorter for separating and collecting cells, and electrically and optically recognizes and sorts particles such as cells in the sample 11 flowing through the flow path in the miniaturization unit 3. Then, the droplet 33 discharged from the channel tip 32
After being charged by the electrode 34, the advancing direction of the droplet 33 is controlled by the electrode 35 to which a predetermined voltage is applied, and the droplet 33 is dropped at a predetermined position on the facing storage medium 4. The storage medium 4 is cooled to a predetermined temperature suitable for the sample 11 by the cooling unit 5, and the droplets 33 dropped on the storage medium 4 are frozen and fixed on the storage medium 4. After the sample 11 is dropped onto the storage medium, the transport unit 6 moves the storage medium 4 into the storage unit 7. A temperature / humidity sensor 71 is installed in the storage unit 7,
The refrigerator 51 is operated by the signal of the temperature / humidity sensor 71 to keep the inside of the storage unit 7 at a predetermined temperature and humidity. Further, the storage unit 7 has a storage mechanism 72 such as a stacker, and holds a plurality of storage media 4 and carries them in and out by the transport unit 6. When carrying out the storage medium 4 from the storage unit 7, it is transported to the collection unit 8 by the transport unit 6,
The collection mechanism 82 heats and thaws the sample 11 on the storage medium 4, and the regenerated sample is collected in the container 93 via the post-processing unit 9 or taken out together with the storage medium 4 from the inlets / outlets 13 and 14. The chemical / sample 11 dropped on the storage medium 4 without cooling the storage medium 4 may be directly transported to the recovery unit 8 by the transport unit 6 and recovered from the post-processing unit 9 into the container 93. Also, a plurality of droplets 33 may be dropped at the same position on the storage medium 4. According to this embodiment, since a small amount of chemicals / samples are collision-cooled onto the storage medium, rapid cooling is possible, and the samples can be stored with high quality. In addition, since it can be stored at a specific position on the storage medium, management of chemicals and samples becomes easy.

3 and 4 show another embodiment of the present invention. The present embodiment relates to the configuration and operation of the miniaturization unit 3. The flow path 1131 exiting from the sheath liquid container 113 shown in FIG. 3 is connected to the three-way valves 115, 116, 117. The three-way valves 115, 116 and 117 are respectively the syringe pumps 118, 119 and 120 and the sample driving flow path 1
151, cleaning flow channel 1161, and sheath liquid flow channel 117
1 to switch connection between the flow channel 1131 and each syringe pump or each flow channel. The flow path and the interior of the syringe pump are filled with the sheath liquid.

The operation sequence of this embodiment will be described with reference to FIG. First, the elevating mechanism 211 and the rotating mechanism 212 of the pretreatment unit 2 raises / rotates the pipettor 22.
Then, the flow path connecting the syringe pump 118 and the pipettor 22 is connected by the three-way valve 115, and the syringe pump 11
The sample 11 in the container 23 is aspirated by 8. After sucking a predetermined amount of the sample 11, the syringe pump 118 is stopped, the tip of the pipetter is inserted into the injection port 213 by the elevating mechanism 211 and the rotating mechanism 212, and the syringe pump 120 and the sheath liquid channel 1171 are connected by the three-way valve 117. To do. Next, the syringe pumps 118 and 120 are driven to supply the sample 11 and the sheath liquid to the flow cell 301, respectively.
Discharge at a constant flow rate. As a result, the sample 11 sucked in from the pretreatment unit 2 becomes the tapered hollow cylindrical flow cell 30.
1 is enclosed by a sheath flow 112 discharged from a nozzle 302 located at the center of the flow cell 1 and flowing from a flow path on the side surface of the flow cell, and flows down in the center of the flow cell as a slender flow (sample flow 111) at a constant flow velocity. Fine particles such as cells contained in the sample flow 111 scatter light emitted from the light source 303 or are dyed with a fluorescent substance and are excited by the emitted light to emit fluorescence. These lights are detected by the light receiving element (first detecting means) 304, and the kind of particles is discriminated by the amount of received light. From the tip of the flow cell, droplets containing a sample separate and fly at a constant cycle due to the vibration of the ultrasonic transducer 305 at a constant frequency, but since the flow velocity is constant, the droplets 33 containing particles can be identified. An electrode 34 exists near the tip of the flow cell, and a predetermined voltage is applied according to the type of particle to charge the droplet 33. The charged droplet 33 is a counter electrode 35 including a plurality of electrodes having a potential difference.
As a result, the generated electric field causes the path to change in accordance with the amount of charge and drops to a predetermined position on the storage medium 4 cooled by the cooling unit 5 (storage droplet 331). Further, unnecessary liquid droplets (discarded liquid droplets 332) are discarded into the waste liquid container 124 via the waste liquid recovery pipe 1241. When the above operation is completed, the pipette 22 is inserted into the cleaning port 125 by the elevating mechanism 211 and the rotating mechanism 212, the three-way valve 116 is switched to connect the syringe pump 119 and the flow path 1161, and the syringe pump 119 is driven. The pipette 22 is washed. The waste liquid generated by the cleaning is recovered in the waste liquid container 124 via the cleaning liquid recovery pipe 1251. According to the present embodiment, a very small amount of chemicals / samples can be fixed in a specific position on the storage medium, so that a large number of chemicals / samples can be stored in a small space. In addition, analytical data can be obtained from a small amount of chemicals and samples.

FIG. 5 shows another embodiment of the present invention. This embodiment relates to the sorting mechanism of the miniaturization unit 3. The droplet 33 separated from the tip of the flow cell 301 passes through the electrode (first electrode) 34, and the light source 307 and the lens 30.
A detector group (second detecting means) 3141, 31 of a detector 314 composed of 8, 309, 311 and position sensors 310, 312 having a linear (one-dimensional) detector.
42 and detector group (third detecting means) 3143, 31
Pass 44. The detector 314 converts the light emitted from the light source 307 into sheet light 3081 that forms a plane perpendicular to the traveling direction of the droplet 33 (direction toward the paper surface) by the lens 308. The optical axes of the position sensors 310 and 311 are on the same plane as the sheet light and are substantially perpendicular to each other.
The scattered light or fluorescence from the liquid droplet 33 passing through 81 is detected, and the position of the liquid droplet 33 at the moment when the liquid droplet 33 passes through the sheet light 3081 is detected. Droplets 3 after the outputs of the detectors 3141 and 3142 are processed by the control unit 10 and passed through the electrode 34
3. Find the speed and direction of travel. Further, information on the size and shape of the droplet can be obtained from the intensity of scattered light or fluorescence from the droplet 33. A predetermined voltage is applied between the electrode plates of the electrode (second electrode) 341 facing each other, and a predetermined electric field is applied. The droplet 33 that has passed through the electrode 341 receives a force corresponding to the amount of charge and changes its speed and traveling direction. This is detector 3
143 and 3144 detect like detectors 3141 and 3142. With this, the charge amount of the droplet is estimated. Based on this information and the data of the velocity and traveling direction of the droplet after passing through the detectors 3143 and 3144, the electrode (third electrode) is arranged so that the droplet may drop to a predetermined position on the storage medium 4 located below. The voltage applied to the x and y direction deflection electrodes 351 and 352 of the electrode 35 is determined. In this embodiment, two sets of detectors detect the traveling direction and velocity of the liquid droplets, but the light from the light source of the detectors is made into parallel light having a rectangular or circular cross section by a lens, and two-dimensional detectors are used. It is also possible to use the position sensor having the detection unit of 1) to detect scattered light or fluorescence from a droplet moving in parallel light, obtain the trajectory of the droplet, and detect the traveling direction and velocity of the droplet.
According to this embodiment, since the position, the moving direction, the speed, and the charge amount of the droplet can be measured, the guide of the droplet by the electrode is accurate, and the droplet can be accurately dropped at a predetermined position on the storage medium.

FIG. 6 shows another embodiment of the present invention. FIG. 6 shows a cooling means for the storage medium 4 of the cooling unit 5. The storage medium 4 that has reached the cooling unit 5 is cooled by contacting the sample storage unit 42 with the heat transfer member 514 on the cooling block 512 that contains the refrigerant channel 511 in which the refrigerant supplied from the refrigerator 51 flows. The heat transfer member 514 is made of metal or ceramic (beryllia; BeO) having high heat conductivity, and has a heat capacity several times or more larger than that of the sample storage unit 42. According to this embodiment, the heat conductivity of the heat transfer member is high, the heat capacity is large, and the sample storage section can be cooled rapidly, so that the operation time for cooling the sample can be shortened.

FIG. 7 shows a cooling means for the storage medium in the cooling section. The sample storage unit 42 on the storage medium 4 is made of a conductor such as metal. Further, the cooling unit has an n-type semiconductor 52 having a Peltier effect, a p-type semiconductor 53, electrodes 541 to 544 formed at both ends of each semiconductor, and a refrigerant channel 511 through which a refrigerant supplied from the refrigerator 51 flows. The cooling block 512 and the electrode 54
1, 544 are in contact with each other via an insulating portion 513 having an electrical insulating effect. Electrodes on semiconductor 542,543
Forms a thermocouple circuit from the electrode 541 to the electrode 544 in contact with the transferred sample storage unit 42 on the storage medium 4. The sample storage unit 42 uses the current 551 flowing in this circuit.
Depending on the amount of heat absorbed by the Peltier effect, the electrode 54
It is cooled to a temperature lower than the 1,544 side. Also, the temperature of the sample storage unit 42 can be raised by reversing the direction of the current. According to the present embodiment, the temperature of the sample storage unit can be lowered beyond the capacity of the refrigerator, so that the cooling rate of the sample in contact with the sample storage unit can be increased. Further, since the temperature of the sample storage section can be controlled by adjusting the current flowing through the circuit, the sample storage section can be maintained at a temperature suitable for the sample. Further, the sample can be heated by reversing the current flowing through the circuit.

FIG. 8 shows another embodiment of the present invention. In this embodiment, n-type semiconductors 521 to 523 having a Peltier effect are used.
And a plurality of pairs (each pair) of p-type semiconductors 531 to 533 are arranged in series, and the sample storage unit 42 on the storage medium 4 is provided with the insulator 420 and each semiconductor assembly on the surface of the insulator 420 facing the semiconductor. And the electrodes 421 to 423 formed correspondingly to form a thermocouple circuit electrically connected in series. Although three semiconductor sets are shown in FIG. 8, the number of sets can be changed arbitrarily. Further, different circuits may be provided to partially cool or heat the sample storage unit 42. Alternatively, a flat plate may be placed on the semiconductor set and further the semiconductor set may be formed thereon to increase the temperature difference between the cooling block 512 and the sample storage unit 42. According to this embodiment, since a plurality of semiconductor groups are formed, the number of thermocouples increases, and the heat absorption amount and the heat generation amount increase. Also,
It is possible to partially control the temperature of the sample storage unit or increase the temperature difference in the sample storage unit.

9 and 10 show another embodiment of the present invention. In this embodiment, the sample solution is stored by spotting the sample solution on the storage medium. The flow path from the sheath liquid container 113 to the pretreatment unit 2 and the flow cell 301 is the same as that of the embodiment shown in FIG. 3, and the detection of particles in the sample flow 111 is also the same as in FIG. A sample separation section including a sample flow introduction pipe (inner pipe) 1111 for collecting the sample flow 111 and a sheath flow collection pipe (outer pipe) 1121 for collecting the sheath flow 112 is provided downstream of the flow cell 301 (see FIG. 11). Sample flow introduction tube 111
The end of 1 has an opening facing the storage medium 4 at the tip of the spotting mechanism 52, and a part of the sample 11 contained in the sample flow 111 emerging from the opening comes into contact with the storage medium 4 and is frozen. And is fixed on the storage medium 4. The spotting mechanism 52 is installed on the XYZ stage 53 which is movable in the horizontal and vertical directions, moves the opening with respect to the storage medium 4, and spots the sample at an arbitrary position. The remaining sample flow 111 is sucked by the syringe pump 126 from the adjacent sample recovery pipe 1221 via the three-way valve 123. Also, the sheath flow 112
Is sucked by the syringe pump 121 from the sheath flow recovery pipe 1121 via the three-way valve 122. The waste liquid sucked by the syringe pumps 121, 126 is the three-way valves 122, 12
3 is discharged from the syringe pumps 121 and 126, and is discharged from the pipe 1241 to the waste liquid container 124. According to this embodiment, it is not necessary to atomize the sample and the liquid droplets do not fly in the air, so that the storage position of the sample can be determined more accurately. In addition, since droplets do not scatter, it is effective in preventing contamination in the device.

FIG. 12 shows another embodiment of the present invention. This embodiment shows the structure and operation of the tip of the spotting mechanism. The sample flow 111 flows into the spotting mechanism 52 from the sample introduction pipe 1111, passes through the spotting pipe 521 connected to the sample introduction pipe 1111 to reach the tip 522 of the spotting mechanism, and is turned to the sample recovery pipe 1221. . The spotting tube 521 at the tip of the spotting mechanism is wrapped in an elastic member 523 having elasticity such as rubber or resin, and further, both sides are wrapped in a supporting member 524 having rigidity higher than that of the elastic member 523. Also,
An actuator 525 such as a piezoelectric element or a solenoid is sandwiched between support members 524. The spotting tube 521 has a cutting portion 526 at the tip of the spotting mechanism, but is normally connected by the elasticity of an elastic member 523 to connect the sample flow 111 to the sample introducing tube 1.
The sample recovery pipe 1221 is guided from the 111 side. When a storage object such as a cell detected in the flow cell 301 upstream of the sample introduction tube reaches the tip of the spotting mechanism from the sample introduction tube 1111 via the spotting tube 521, a signal from a control unit (not shown) Actuator 525
Expand and contract, and the elastic member 523 also expands and contracts accordingly, and the cutting portion 526 of the spotting tube 521 wrapped in the elastic member 523.
Sample flow 111 containing samples such as cells during opening and closing
1112 is extruded from the cutting portion 526 to the tip of the spotting mechanism. Part of the sample flow extruded at this time 11
12 contacts the storage medium 4 facing each other, is rapidly cooled, and is freeze-fixed on the storage medium 4. A part 1 of the sample flow adhered to the tip of the spotting mechanism by descending the tip of the spotting mechanism by an XYZ stage (not shown) that supports the spotting mechanism 52.
After spotting 112 on the storage medium, the spotting mechanism may be raised to perform spotting. According to the present embodiment, the cutting portion is opened only when spotting is performed, so that an unnecessary sample flow does not adhere to the storage medium.

FIG. 13 shows another embodiment of the present invention. The spotting tube 521 of this embodiment is open at the tip of the spotting mechanism. A chamber (second chamber) 528 separated by a diaphragm 527 exists inside the support member 524 near the tip of the spotting mechanism, and the diaphragm 527 is vibrated by the actuator 525. A chamber (first chamber) 529 connected to the chamber 528 on the side of the opening of the spotting tube with the diaphragm 527 interposed therebetween is filled with a fluid such as a gas or a liquid that does not mix with the sample flow 111. Flow cell 3 upstream of sample introduction tube
When the storage object such as cells detected in 01 reaches the tip of the spotting mechanism from the sample introduction tube 1111 via the spotting tube 521, the actuator 525 expands and contracts due to a signal from the control unit (not shown), The diaphragm 527 is displaced so that the fluid in the chamber 529 is projected to the opening of the spotting tube. As a result, the sample flow 111 containing the object to be stored, which has flowed through the spotting tube 521, is pushed out to the side of the storage medium 4. As a result, a part of the sample flow 111 including the storage object comes into contact with the surface of the cooled storage medium and is rapidly cooled and freeze-fixed. According to this embodiment, since the actuator drives a small amount of fluid having a small mass, the size of the actuator is reduced.

Another embodiment of the present invention is shown in FIG. In this embodiment, instead of the diaphragm 527 of the previous embodiment, the piston 5271 projects to the open part of the spotting tube by the actuator 525 and pushes part of the sample flow 111 to the storage medium side. According to the present embodiment, the driving force of the actuator is directly transmitted to the piston without passing through the fluid, so that the sample flow can be pushed out at high speed.

FIG. 15 shows another embodiment of the present invention. In this embodiment, an opening is provided in the spotting tube 521 at the tip of the spotting mechanism,
The sample flow 111 is connected to the spotting pipe 5212 on the sample recovery pipe side.
Aspirate from. An annular actuator 525 is installed outside the spotting tube 5211 on the side of the sample introducing tube, and storage targets such as cells detected in the flow cell 301 upstream of the sample introducing tube are transferred from the sample introducing tube 1111 to the spotting tube 5211.
When reaching the tip of the spotting mechanism via 1, the actuator 525 is expanded and contracted in the radial direction by a signal from a control unit (not shown) to push a part of the sample flow 111 to the storage medium side and contact the storage medium 4. Then, it is rapidly cooled and freeze-fixed. According to this embodiment, since the number of movable parts is small, the structure is simple and the number of failures is reduced.

FIG. 16 shows another embodiment of the present invention. In this embodiment, the spotting pipe 521 is formed of a double pipe. The sample introducing pipe side is an inner spotting pipe 5211, and the sample collecting pipe side is an outer spotting pipe (second outer pipe) 5212. The sample flow emerging from the spotting tube 5211 side is the spotting tube 5
212 is sucked. An annular actuator 525 is installed outside the spotting tube 5211, and storage targets such as cells detected in the flow cell 301 upstream of the sample introducing tube are spotted from the sample introducing tube 1111 via the spotting tube 521. When reaching the tip of the mechanism, the actuator 525 expands and contracts in the radial direction by a signal from a control unit (not shown), a part of the sample flow 111 is pushed out to the storage medium side, contacts the storage medium 4, and is rapidly cooled. It is frozen and fixed.
According to this embodiment, since the spotting tube is concentric, the tip of the spotting mechanism can be downsized. Further, since the spotting pipe is small, a plurality of spotting pipes can be arranged in parallel at the tip of the spotting mechanism.

FIG. 17 shows another embodiment of the present invention. In this embodiment, the actuator 5 is attached to the spotting tube 5211 of the above embodiment.
This is a configuration including 25. According to this embodiment, since the actuator does not come into contact with the sample flow, contamination of the sample flow by the actuator and corrosion of the actuator due to the sample flow can be prevented.

FIG. 18 shows another embodiment of the present invention. This embodiment relates to the transport section 6 and the storage section 7, and shows a part of the storage section 7. The transport unit 6 includes a driving roller 62 that is driven to rotate by a driving source 61 such as a motor, and a driving roller 62.
The driven roller 63 facing the
2 and nip it, and contacts the storage medium 4 which is driven by the rotation of the driving roller 62 to rotate) (see FIG. 2). The storage medium 4 inserted from the doorway 13 is stored in the sensor 64 of the transport unit 601.
The sensor 64 sends a detection signal to the control unit 10. Based on this detection signal, the control unit 10 instructs the transport unit 601 to start the operation, and introduces the storage medium into the miniaturization unit 3. When the tip of the storage medium 4 crosses the miniaturization unit 3 and reaches the sensor 65, a detection signal is sent from the sensor 65 to the control unit 10.
Is emitted to. The control unit 10 stops the transport unit 601 based on this detection signal and sorts the storage medium 4 into the sorting mechanism 3
It is stopped at a position facing the first flow path tip 32. When the processing in the miniaturization unit 3 is completed, the control unit 10 drives the transport unit 602 and guides the storage medium 4 to the storage unit 7. Storage section 7
The entered storage medium 4 is detected by the sensor 66, and a detection signal is sent to the control unit 10. The control unit 10 drives the transport unit 602 based on this detection signal. When the sensor 67 detects the front end of the storage medium 4, a detection signal is sent to the control unit 10, and the control unit 10 stops the transport unit 602 based on this and stops the storage medium 4 in front of the stacker 72. .

The transport unit in the storage unit 4 is composed of a cylindrical support portion 6051 for holding the transport unit, an up-and-down mechanism for raising and lowering these, and a rotating mechanism for rotating them. The vertical mechanism penetrates the base 681 inside the storage unit 7, the plate 682 outside the storage unit 7, and the outer wall 73 of the storage unit 7 and connects the base 681 and the plate 682 with the shaft 683.
And a motor 684 installed on the outer wall 73 and the motor 6
The linear movement mechanism 685 is configured to move the plate 682 up and down by a ball screw attached to the rotating shaft of 84. The rotation mechanism has a structure in which the rotation shaft of the motor 691 on the base 681 (or via a power transmission system such as a gear) is coupled to the upper surface of the support portion 6051, and the direction of the transport unit is changed by the rotation of the motor 691. The transport unit is positioned by an up-and-down mechanism and a rotating mechanism, and the controller 10 counts pulses from an encoder (not shown) installed on the motor rotation shaft of each mechanism to obtain the number of rotations and the rotation angle of the motor, and the linear movement is performed. The position of the transport unit can be determined by determining the amount of movement of the mechanism and the rotation angle of the transport unit. Further, it goes without saying that the position of the transport unit can be obtained by signals from a distance sensor, an optical switch, etc. installed on the outer wall 73, the stacker 72, etc.

The control section 10 moves the storage medium 4 in the transport unit in front of a predetermined stacker section by rotating the transport unit 90 ° and vertically moving the transport unit by means of an up-and-down mechanism and a rotating mechanism. The drive mechanism is operated to feed the storage medium 4 into the compartment. When the installation of the storage medium 4 is completed, the transport unit returns to the initial position (the position where the storage medium 4 is received from the drive unit of the microminiaturization unit 3) by the vertical movement mechanism 68 and the rotation mechanism 69.

When taking out the storage medium 4 stored in a predetermined section of the stacker 72, the control unit 10 confirms that there is no other storage medium in the transport unit by a signal from a sensor (not shown) in the transport unit. Then, the transport unit is rotated 90 ° and moved up and down to move the transport unit to the front of a predetermined section in which the storage medium 4 is present. Stacker 7
There is an auxiliary mechanism 65 on the opposite side with respect to the two, but the auxiliary mechanism 65 includes a plate 652 that supports an actuator 651 such as a solenoid that has a shaft that moves in and out, and a guide rod 653 (a plate 652 that penetrates the plate 652. (Movable in the axial direction of the guide rod 653) and a linear movement mechanism 654 that drives the plate 652 up and down along the guide rod 652 by a motor and a ball screw. The auxiliary mechanism 65 rotates the ball screw by a predetermined number of rotations and an angle based on a command from the control unit 10, moves the plate 652 to the section where the storage medium 4 exists, and the storage medium 4 is moved by the axis of the actuator 651 on the plate 652. Stick out to the transport unit side. The protruding storage medium 4 is captured by the transport unit in the transport unit and taken into the transport unit. Next, the transport unit is returned to the initial position (the position where the storage medium 4 is received from the drive unit of the micronization unit 3) by the vertical mechanism and the rotation mechanism, and the storage medium 4 is transferred to the transport unit one after another and transferred to the reaction processing unit 8. To do. According to this embodiment, a plurality of transport units, stackers, and auxiliary mechanisms can be connected in series as a unit, so that the storage amount can be easily increased or decreased by adding or reducing units.

19 to 21 show another embodiment of the present invention. This embodiment relates to the structure of a storage medium. The storage medium is basically composed of a flat substrate 41 and a sample storage unit 42 which is a region on the substrate 41 for storing samples and chemicals. The sample storage unit 42 is attached to the substrate 41 by adhesion or welding as a separate component from the substrate 41 (see FIG. 19), or is formed by directly processing the surface of the substrate 41 (see FIG. 20).
The surface of the sample storage unit 42 may be formed into a concavo-convex pattern by a processing technique such as etching or sputtering to form a region composed of a plurality of small sections 43 (see FIG. 20). The dropletized sample is stored in each of the small compartments. According to this embodiment, the samples and the chemicals can be stored in the planar storage unit divided into the sections, and the positions of the stored samples and the chemicals are digitized, so that the information management becomes easy.

FIG. 22 shows another embodiment of the present invention. In the storage medium of this embodiment, a plurality of bridges 44 are formed in a small section 43 in the sample storage unit 42, and heating resistors 451 and 452 and temperature sensors 461 and 462 are provided at the legs and the central portion of the bridge 44. In the central portion of the bridge 44, the sample 11 whose amount has been reduced by the reducing unit is frozen and stored.
The storage medium is formed by bonding two substrates 47 and 48 together. On the upper substrate 47, a bridge 44, an amplifier for amplifying the output from the temperature sensor of each bridge on the substrate, and a heating resistor are provided. There is a circuit portion 471 equipped with a driver that supplies current. The circuit unit 471 is connected to the control unit 10 shown in FIG. 1 via a connector 472, receives a current, and sends and receives a signal from the temperature sensor and a command signal from the control unit 10. The recording medium 473 is an information recording medium such as a magnetic stripe, a bar code, a RAM and a ROM, and holds information about the sample stored on the storage medium. When the recording medium 473 is a magnetic stripe, information is exchanged with the control unit 10 by a recording / reproducing head (not shown) provided in the transport unit or the storage unit. In the case of RAM, ROM, etc., the circuit unit 471
Information is exchanged with the control unit 10 via a dedicated electrode (not shown). The lower substrate 48 has recesses 48 facing the legs of each bridge 44 on the upper substrate 47.
1 and a convex portion 482 (protruding a few tens of micrometers or less with respect to the substrate surface) which is sandwiched between the concave portions 481 and faces the central portion of the bridge 44. Pasted together. With this structure, the central portion of the bridge comes into contact with the convex portion 482 to be cooled, and the sample 11 is also cooled.

The control unit 10 controls the temperature history of the sample 11 by adjusting the current flowing through the heating resistors 451 and 452 based on the signals from the temperature sensors 461 and 462 on the bridge 44 during cooling and heating. When the temperature of the legs rises due to the heat generated by the heating resistor 451 on the legs of the bridge 44,
The legs are thermally expanded and the bridge 44 is bent, and the contact pressure between the central portion of the bridge and the convex portion is reduced. The contact thermal resistance changes depending on the contact pressure (generally, the larger the contact pressure is, the smaller the contact thermal resistance is), but the decrease in contact pressure increases the contact thermal resistance between the central portion and the convex portion of the bridge. As a result, the temperature rise due to the heating resistor 452 becomes steeper. In addition, the heat is prevented from flowing out to a portion other than the bridge 44 during heating, and the temperature rise of other small sections can be prevented. Further, when the heating is stopped, as the temperature of the bridge decreases, the contact pressure between the central portion of the bridge and the convex portion increases and the contact thermal resistance decreases, so that a sharp temperature decrease can be realized.

According to this embodiment, since the sample storage portion is formed by the bridge having a small heat capacity, the temperature change of the sample on the bridge can be made sharp. Further, since the temperature sensor and the heating resistor are present on the bridge, the temperature of the bridge can be precisely controlled. Further, since the recording medium exists on the storage medium, the storage medium itself can be easily managed and distributed.

23 and 24 show another embodiment of the present invention. FIG. 23 shows an apparatus for collecting the sample on the storage medium. The device mainly comprises a post-processing section 9 and a recovery mechanism 82. At the time of collection, the pipettor 92 of the post-processing unit 9 is inserted into the suction port 917 by the elevating mechanism 911 and the rotating mechanism 912. At the same time, the syringe pump 918 is operated by the three-way valve 915.
Is connected to the flow path in the pipetter 92. In addition, the recovery mechanism 5
The syringe pump 923 and the recovery liquid introducing pipe 9221 are connected by the four-way three-way valve 922. As a result, a flow path from the syringe pump 923 to the pipettor 92 is formed. The syringe pump 918 and the syringe pump 923 each simultaneously start a suction operation and a discharge operation. The recovery liquid sucked from the recovery liquid container 914 is discharged from the syringe pump 923 and is supplied from the recovery liquid introducing pipe 9221 to the tip of the recovery mechanism 82. The recovered liquid comes into contact with the sample on the storage medium at the tip of the recovery mechanism, takes in the melted sample, and sucks it from the recovered liquid suction pipe 9222 on the pipetter 92 side into the flow path inside the pipettor 92. Next, each syringe pump is stopped, the elevating mechanism 911 and the rotating mechanism 912 are operated, and the pipettor 92 is inserted into the container 93. Next, the syringe pump 918 is driven to discharge the recovery liquid containing the sample in the pipettor 92 into the container 93, thereby completing the recovery operation.

According to this embodiment, since a part of the sample on the storage medium can be recovered while being kept in the apparatus in a state where the storage medium is cooled, contamination of the storage medium and deterioration of the sample due to temperature rise can be prevented. .

FIG. 25 shows another embodiment of the present invention. This embodiment relates to the structure of the tip of the recovery mechanism. The inside of the recovery pipe 821, whose both ends are connected to the recovery liquid introduction pipe 9221 and the recovery liquid suction pipe 9222, is filled with the recovery liquid injected from the recovery liquid introduction pipe 9221. An opening 822 exists in the recovery pipe 821 at the tip of the recovery mechanism, and the periphery is surrounded by the support member 82.
Supported by 3. A temperature sensor 824 and a heater 825 exist inside the support member 823. The controller 10 shown in FIG. 1 controls the heater 825 based on the output of the temperature sensor 824.
The temperature of the tip of the recovery mechanism is kept constant by adjusting the current flowing through. At the time of sample recovery, the opening 822 of the recovery tube 821 is moved onto the traced sample 11 on the storage medium 4 by the XYZ stage 83 shown in FIG. Next, the recovery mechanism 82 is lowered by the XYZ stage 83 to bring the opening 822 into contact with the sample 11, the syringe pump 823 is driven, and the recovery liquid is injected from the recovery liquid introduction pipe 9221. The sample 11 is melted by the recovery liquid at the opening 922, and the recovery liquid suction pipe 92
It is inhaled by 22 and collected by the pipetter 92 and processed by the post-processing section. When the collection is completed, the collection mechanism 82 is raised by the XYZ stage 83 to be separated from the storage medium 4 to prepare for the next collection.

According to this embodiment, since the recovery mechanism accesses only the sample to be recovered, it is possible to prevent the temperature rise and deterioration of other samples on the storage medium.

FIG. 26 shows another embodiment of the present invention. In this embodiment, the recovery pipe 821 has a double-tube structure, and the recovery liquid from the recovery liquid inlet pipe side recovery pipe 8211 is sucked to the recovery liquid suction pipe side to recover the sample. Note that, in FIG. 26, the recovered liquid suction pipe is the inner pipe and the recovered liquid introduction pipe is the outer pipe, but the recovered liquid suction pipe may be the outer pipe and the recovered liquid introduction pipe may be the inner pipe.

According to this embodiment, since the collecting tube is concentric, the tip of the collecting mechanism can be downsized. Moreover, since the recovery pipe is small, a plurality of recovery pipes can be arranged in parallel at the tip of the recovery mechanism.

As another embodiment of the present invention, the cell bank is
It is configured to include any one of the micro sample storage devices.

[0081]

EFFECTS OF THE INVENTION According to the present invention, a minute and minute amount of a sample of cells or drugs can be rapidly frozen and stored at a high density, and each sample can be accessed individually. It becomes possible to save and it becomes easy to operate and manage.

[Brief description of drawings]

FIG. 1 is a configuration diagram showing an embodiment of the present invention.

FIG. 2 is a configuration diagram of the device shown in FIG.

FIG. 3 is a configuration diagram of a miniaturization unit shown in FIG. 1.

FIG. 4 is a diagram showing an operation sequence of FIG. 3;

5 is an enlarged view of a main part of FIG.

6 is a configuration diagram of a cooling unit shown in FIG.

FIG. 7 is a configuration diagram showing another embodiment of the cooling unit.

FIG. 8 is a configuration diagram showing another embodiment of the cooling unit.

FIG. 9 is a configuration diagram showing another embodiment of the miniaturization unit.

FIG. 10 is a diagram showing an operation sequence of FIG. 9;

FIG. 11 is an enlarged configuration diagram of a main part of the sample separation unit shown in FIG. 9.

FIG. 12 is a configuration diagram of a tip of a spotting mechanism.

FIG. 13 is a configuration diagram showing another embodiment of the tip of the spotting mechanism.

FIG. 14 is a configuration diagram showing another embodiment of the tip of the spotting mechanism.

FIG. 15 is a configuration diagram showing another embodiment of the tip of the spotting mechanism.

FIG. 16 is a configuration diagram showing another embodiment of the tip of the spotting mechanism.

FIG. 17 is a configuration diagram showing another embodiment of the tip of the spotting mechanism.

FIG. 18 is a configuration diagram of a transport unit and a storage unit.

FIG. 19 is a configuration diagram of a storage medium.

FIG. 20 is a configuration diagram of a storage medium.

FIG. 21 is a configuration diagram of a storage medium.

FIG. 22 is a perspective view showing a configuration of a storage medium.

FIG. 23 is a configuration diagram of a recovery unit.

FIG. 24 is a diagram showing an operation sequence in FIG. 23.

FIG. 25 is a configuration diagram of a tip of a recovery mechanism.

FIG. 26 is a configuration diagram showing another embodiment of the tip of the recovery mechanism.

[Explanation of symbols]

2 Pretreatment section 3 Trace reduction unit 4 Storage medium 5 Cooling unit 6 Transport section 7 Storage 8 Collection Department 9 Post-processing section 10 Control unit 11 samples 101 Input / output unit

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI G05D 22/00 G05D 22/00 A 23/00 23/00 Z 23/19 23/19 A (72) Inventor Isao Yamazaki Ibaraki Prefecture 502 Jinrachicho, Tsuchiura City, Ltd., Mechanical Engineering Laboratory, Hitachi, Ltd. (56) Reference Japanese Patent Laid-Open No. 5-18874 (JP, A) Special Table 3-504076 (JP, A) Special Table 4-502580 (JP, A) ) (58) Fields surveyed (Int.Cl. ⁷ , DB name) B01L 11/00 G01N 1/00 G01N 33/48-33/98 G01N 35/00-37/00 A01N 1/00-65/02

Claims (9)

(57) [Claims] 1. A liquid sample containing particles or chemicals is pretreated.
A pretreatment unit for processing, and a trace amount reducing unit for reducing the amount of the sample,
In the cooling unit that cools the trace amount of trace amount sample,
A transport unit for transporting a small amount of sample and a storage unit for storing the small amount of sample.
Tube section, collection section for reclaiming stored sample, and regeneration
To the post-processing unit that performs post-processing of the sample, the control unit, and the control unit
Each unit has an input / output unit that inputs and outputs information.
At least for cooling, storage and regeneration of the sample in a planar
On the storage medium of, The miniaturization unit is a pipettor having a rotation mechanism and a lifting mechanism.
And a nozzle that atomizes and ejects the sample sucked by the pipettor
And the emitted particles in the sample are optically detected.
The detection part, and the atomized particle that is arranged in front of the nozzle
Control the direction of travel of the sample and drop the storage medium at a predetermined position.
The cooling unit is in contact with the storage medium.
Cooling, the storage unit is a shelf-shaped space for cryopreserving the storage medium.
It has a tacker, and the recovery unit heats the sample on the storage medium.
It has a collection mechanism that defrosts and collects, and the post-processing unit stores it as above.
The regenerated sample on the medium is collected in an external container, and the control unit
Control each part of the
Directives, data exchange, communication with external networks
Communication and man-machine interface Very small amount
Sample storage device. 2.Pretreatment of liquid samples containing particles or chemicals
A pretreatment unit for processing, and a trace amount reducing unit for reducing the amount of the sample,
In the cooling unit that cools the trace amount of trace amount sample,
A transport unit for transporting a small amount of sample and a storage unit for storing the small amount of sample.
Tube section, collection section for reclaiming stored sample, and regeneration
To the post-processing unit that performs post-processing of the sample, the control unit, and the control unit
Each unit has an input / output unit that inputs and outputs information.
At least for cooling, storage and regeneration of the sample in a planar
On the storage medium of The micronization unit is a flow path that has a nozzle for discharging a liquid sample.
And first detecting particles contained in the liquid sample in the flow channel
Detection means and the first provided near the outlet of the nozzle
Of the liquid sample and the droplet of the liquid sample
Second detection means for detecting the position, speed and traveling direction of
The second electrode and the position, velocity and direction of travel of the droplet.
Having a third detecting means for detecting and a third electrode Very small amount
Sample storage device. 3. The micro sample storage device according to claim 1, wherein the flow path of the micro-quantification part is formed by a double tube and the outlet of the inner tube of the double tube is in the flow path of the outer tube. A light source for irradiating the liquid sample flowing through the center with the liquid sample flowing through the inner tube and the carrier liquid flowing through the outer tube and detecting scattered light and fluorescence from particles in the liquid sample are provided. A trace sample storage device comprising a detector. 4. The trace amount sampler according to claim 1, wherein the cooling unit includes a cooling block containing a refrigerant passage through which a refrigerant supplied from a refrigerator flows, and a heat transfer member on the cooling block. The micro sample storage device is characterized in that a storage medium is contact-cooled onto the heat transfer member. 5.Pretreatment of liquid samples containing particles or chemicals
A pretreatment unit for processing, and a trace amount reducing unit for reducing the amount of the sample,
In the cooling unit that cools the trace amount of trace amount sample,
A transport unit for transporting a small amount of sample and a storage unit for storing the small amount of sample.
Tube section, collection section for reclaiming stored sample, and regeneration
To the post-processing unit that performs post-processing of the sample, the control unit, and the control unit
Each unit has an input / output unit that inputs and outputs information.
At least for cooling, storage and regeneration of the sample in a planar
On the storage medium of The cooling unit is a refrigerant flow through which the refrigerant supplied from the refrigerator flows.
A cooling block with a built-in passage and provided on the cooling block
N-type semiconductor and p-type semiconductor having the Peltier effect
And the electrical charges formed on each end face of each semiconductor.
A pole, one end of the cooling block and each semiconductor
The storage medium consists of an insulating part that insulates between the surface electrodes.
The sample storage part formed by the electric conductor of
Contact the electrode on the other end of the
ApplyWill doMicro sample storage device. 6. The micro sample storage device according to claim 5, wherein a plurality of pairs of n-type semiconductors and p-type semiconductors are connected in series, and a plurality of electrical conductors are provided on the storage medium so as to face the respective semiconductor pairs. A micro sample storage device characterized by being provided with. 7.Pretreatment of liquid samples containing particles or chemicals
A pretreatment unit for processing, and a trace amount reducing unit for reducing the amount of the sample,
In the cooling unit that cools the trace amount of trace amount sample,
A transport unit for transporting a small amount of sample and a storage unit for storing the small amount of sample.
Tube section, collection section for reclaiming stored sample, and regeneration
To the post-processing unit that performs post-processing of the sample, the control unit, and the control unit
Each unit has an input / output unit that inputs and outputs information.
Is the above At least cooling, storage, and regeneration of the sample are flat
On the storage medium of The flow path of the miniaturization part is formed by a double tube and the inner tube of the double tube is formed.
The outlet of the liquid sample is installed in the flow path of the outer tube, and the liquid sample flows
Through the outer pipe and the carrier liquid flowing through the center.
A light source for irradiating the liquid sample with light and particles in the liquid sample
A detector for detecting scattered light and fluorescence from the child,
In front of approximately the center between the detector and the storage medium by the detector
The inner tube exposed by penetrating the outer tube is bent to
An opening is provided in the tube at a position facing the storage medium.
Trace sample storage device characterized by. 8. The micro sample storage device according to claim 7 , wherein an elastic member is provided around an opening formed by cutting a bent inner tube, and the elastic member is provided on each side of the elastic member. Providing a support member with great rigidity,
A micro sample storage device, characterized in that inner pipes on the upstream side and the downstream side of the opening are embedded in the respective support members, and expandable and contractible actuators are provided between the respective support members. 9. The micro sample storage device according to claim 7 , wherein a supporting member is provided around an opening formed by cutting a bent inner tube, and the inside of the supporting member is provided with an upstream side of the opening. Each inner pipe on the downstream side is buried, two chambers separated by a diaphragm are provided in the support member above the opening, and the first chamber close to the opening is in contact with the opening and It is filled with a fluid that is not mixed with the liquid sample, and has an expandable actuator inside the second chamber.
A micro sample storage device, characterized in that the end face of the actuator in the expansion / contraction direction is connected to the first chamber via the diaphragm.