JP4113426B2 - Sample processing equipment - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a sample processing apparatus that irradiates a mixed liquid (mixed fluid) of a sample and a sample processing liquid (sample processing agent) with electromagnetic waves.
[0002]
[Prior art and its problems]
In fields such as biochemistry, when a sample such as a biological tissue piece is chemically analyzed, a process of reacting the sample with a sample treatment agent such as a reagent is performed prior to the analysis. In this reaction treatment, for example, a sample treatment agent is dropped on a sample attached to a slide glass, and the sample treatment agent is infiltrated into the sample. It is known that the reaction is promoted by irradiating the sample infiltrated with the sample treatment agent with microwaves. Generally, the microwave is applied to the slide glass using a microwave oven for reaction treatment. Irradiating. This reaction processing microwave oven has the same configuration as the food microwave oven. Therefore, the electromagnetic field distribution in the space portion is non-uniform, causing a problem that uneven reaction occurs in the sample. In addition, since the microwave propagates in the air inside the cavity and is irradiated to the specimen, for example, the energy efficiency in the microwave irradiation to the specimen is low, and the microwave having a higher output than that originally required for the reaction process. I needed an oscillator.
[0003]
On the other hand, in the field of biochemistry and the like, a sample processing apparatus adopting a flow injection analysis method (FIA method) is used as a means for performing chemical analysis of a fluid specimen (sample) such as blood and urine easily and quickly. ing. This apparatus automatically performs a series of sample processing flows such as a mixing process of a sample and a sample processing liquid, a reaction promoting process between the mixed sample and the sample processing liquid, and an analysis process of the sample after the reaction. . This sample processing apparatus includes a piping tube having a very small diameter, in which a carrier liquid is continuously flowed. The sample processing apparatus injects a sample and a sample processing agent into a piping tube, and performs the above-described series of sample processing in the piping tube while transporting this with a carrier liquid. In general, in such a sample processing apparatus, a reaction is promoted by heating a fluid mixture of a sample and a sample processing agent with a heater.
[0004]
Here, in the reaction between the sample and the sample processing solution, it is desirable that the sample and the sample processing solution are uniformly mixed in order to prevent uneven reaction. However, since the sample and the sample processing solution are blended in a small-diameter piping tube, it is difficult to mix them evenly. In reaction systems such as chemical synthesis and hybridization, it is known that the reaction is promoted by irradiation with microwaves, but there is no effective irradiation method in the FIA method.
[0005]
Patent Document 1 below discloses a sample processing apparatus that introduces a reagent into a planar reagent development surface to bring the sample into a reagent infiltrated state and irradiates the sample with microwaves.
[0006]
[Patent Document 1]
Japanese Patent Laid-Open No. 2002-206997
The present invention has been made in view of the above problems, and an object thereof is to provide a sample processing apparatus having a new structure.
[0008]
Another object of the present invention is to provide a sample processing apparatus that prevents uneven reaction between a sample and a sample processing agent and realizes highly accurate sample processing.
[0009]
Another object of the present invention is to provide a sample processing apparatus for effectively and uniformly irradiating a sample and a sample processing agent accommodated in an elongated tube and a small piping tube with a microwave.
[0010]
[Means for Solving the Problems]
The present invention provides a waveguide body in which an irradiation space in which a mixed fluid in which a sample processing agent is mixed with a sample stays or passes is formed in a waveguide, and the mixed fluid in the irradiation space is irradiated with the electromagnetic wave. And a tube body that is inserted into the irradiation space and in which the compounded fluid is disposed, and is provided at a temperature detection position outside the irradiation space in the tube body, and detects the temperature of the compounded fluid at the temperature detection position. A temperature sensor, a pump connected to the tube body, and a means for controlling the pump to adjust the position of the compounded fluid in the tube body, and arranging the compounded fluid in the irradiation space during electromagnetic wave irradiation And a control unit that arranges the blended fluid at the temperature detection position during temperature detection .
[0011]
According to the above configuration, an irradiation space is formed in the waveguide path in the waveguide, and the compounded fluid is directly exposed to electromagnetic waves in the irradiation space. Therefore, it is possible to irradiate the blended fluid with electromagnetic energy with high energy efficiency, and for example, it is possible to perform sample processing with a lower output oscillator. Here, it is desirable that the traveling wave travels through the waveguide. In the case of this configuration, the mixed fluid hits the traveling electromagnetic wave regardless of the position in the irradiation space or the position of the irradiation space in the waveguide. Therefore, electromagnetic waves are uniformly irradiated without being affected by the position where the blended fluid is subjected to electromagnetic wave irradiation, and reaction unevenness between the sample and the sample processing agent can be prevented.
[0012]
Further, by irradiating the blended fluid with electromagnetic waves, for example, particles contained in the sample and the sample processing agent can be directly vibrated. Thereby, for example, the sample and the sample processing agent are further mixed to form a uniform mixture. Therefore, for example, in the case where the sample and the sample processing agent are configured to react with each other, it is possible to prevent or reduce reaction unevenness due to insufficient mixing of the sample and the sample processing agent.
[0013]
In a preferred aspect of the present invention, a fluid processing unit that is fitted in the irradiation space and into which the blended fluid is placed, a temperature sensor that detects a temperature of the blended fluid in the fluid processing unit, and the detected blending And a control unit that controls the amount of the electromagnetic wave applied to the blended fluid based on the temperature of the fluid.
[0014]
Here, for the blended fluid, electromagnetic waves in a frequency band that gives a temperature change to the fluid are used, and preferably microwaves are used. The blended fluid is put into a fluid processing unit fitted in the irradiation space, and the control unit controls the electromagnetic wave irradiation amount to the blended fluid based on the temperature of the blended fluid. Therefore, for example, the compounded fluid can be maintained at an appropriate temperature, such as a temperature at which the reaction between the sample and the sample processing agent is further promoted. In addition, as control of electromagnetic wave irradiation amount, the aspect which ON / OFF-controls the electromagnetic wave signal supplied to a waveguide body, and generates an electromagnetic wave in a pulse form, for example may be sufficient. Further, for example, the fluid processing unit may be configured to have a portion protruding outside the irradiation space, and the electromagnetic wave irradiation amount may be controlled by physically moving the mixed fluid into the protruding portion and the irradiation space. . In addition, for example, a mode in which the fluid processing unit is physically taken in and out of the irradiation space may be employed. Incidentally, the fluid processing unit is preferably a tubular member in which the compounded fluid is flowed or placed therein, but may be a container or the like that stores the compounded fluid therein. In addition, the sample and sample processing agent which comprise this compounding fluid are the aggregate | assembly of these solid particles, such as a liquid and a bead, or these mixtures, for example.
[0015]
Further, in a preferred aspect of the present invention, a tube body that is inserted into the irradiation space and in which the compounded fluid is disposed, a pump connected to the tube body, and the pump is controlled to control the pump body. And a control unit that adjusts the position of the blended fluid and places the blended fluid in the irradiation space.
[0016]
According to the said structure, a control part controls a pump, adjusts the position of the mixing fluid in a tube body, and arrange | positions it in irradiation space. Thereby, for example, the arrangement process of the blended fluid in the irradiation space can be easily automated. Furthermore, if the control unit is, for example, an aspect that takes out the blended fluid after completion of irradiation from the irradiation space by controlling the pump, the arrangement process of the blending process and the series of steps of the fetching process can be automated.
[0017]
In a preferred aspect of the present invention, the control unit combines the suction operation and the discharge operation of the pump, and performs intermittent control in which the blended fluid is intermittently arranged in the irradiation space. Thereby, it is possible to irradiate the mixed fluid with electromagnetic waves at a desired timing, and it is possible to easily realize timing control of electromagnetic wave irradiation to the mixed fluid.
[0018]
In a preferred aspect of the present invention, the apparatus includes a temperature sensor that detects a temperature of the blended fluid, and the control unit performs the intermittent control based on the detected temperature of the blended fluid. In addition, as an electromagnetic wave irradiated to the blended fluid, a frequency band that causes a temperature change in the blended fluid is used, and preferably a microwave is used.
[0019]
DETAILED DESCRIPTION OF THE INVENTION
A preferred embodiment (hereinafter referred to as an embodiment) of the present invention will be described with reference to the drawings. In the present embodiment, a case where the sample processing apparatus according to the present invention functions as an analysis apparatus of the FIA method will be described as an example. This sample processing apparatus has a piping tube, a mixing process for generating a mixing fluid by mixing a liquid sample and a reagent, and a reaction for promoting the reaction between the sample and the sample processing agent (reagent) in the mixing fluid. A series of sample processing flows consisting of an acceleration process, a pre-analysis process that is performed prior to the analysis of the sample after the reaction acceleration process, and an analysis process that performs the sample analysis, etc. Run in the tube.
[0020]
FIG. 1 is a diagram schematically showing components that function mainly in the reaction promotion process in the sample processing apparatus. Therefore, in the following description, it is assumed that the blending process is finished and the mixed fluid 12 has already been injected into the piping tube 10.
[0021]
The oscillator 16 generates an electromagnetic wave signal (high frequency) that is an AC signal under the control of the control unit 18. In the present embodiment, the oscillator 16 is a semiconductor oscillator and generates a high frequency of 2450 MHz, for example. This electromagnetic wave signal is supplied to the waveguide 14 via the microwave cable 20.
[0022]
The waveguide 14 is a tubular member formed of a conductor, and a space portion as a waveguide path is formed along the extending direction of the waveguide 14. When a high frequency is supplied to the waveguide 14, an electromagnetic wave is generated in this space portion. In the present embodiment, the frequency of the electromagnetic wave signal is adjusted so that a microwave is generated in the space. Here, a dummy load 24 is connected to the waveguide 14 via a microwave cable 22, and impedance matching is performed between them. Therefore, a good traveling wave state in which a traveling wave travels from the microwave cable 20 side toward the microwave cable 22 side is formed in the waveguide 14. Further, the description will be continued with reference to FIG.
[0023]
The waveguide 14 of the present embodiment is a rectangular waveguide having a rectangular cross section, and one end 14a and the other end 14b thereof are closed. In this embodiment, for example, rectangular waveguides having a horizontal width and a vertical width (thickness) of 100 mm and 60 mm, respectively, are employed, and the length is set to a length at which, for example, a 2450 MHz microwave resonates. ing. A plug 28 as an input terminal and a plug 30 as an output terminal are provided on one end 14a side and the other end 14b side of the upper surface 26 of the waveguide 14, respectively. The microwave cables 20 and 22 are connected via 28 and 30. Circular openings 34 and 36 are formed in the upper surface 26 and the lower surface 32 in the vicinity of the center of the waveguide 14, and communicate with the internal space.
[0024]
FIG. 3 shows an enlarged view of a part of the cross section of the waveguide 14 in the present embodiment. Here, regarding the relative positions of the openings 34 and 36, when a normal to the upper surface 26 passing through the center of the opening 34 is virtually assumed, the openings 34 and 36 are so positioned that the center of the opening 36 is positioned on the normal. Are arranged respectively. In the present embodiment, the diameters of the openings 34 and 36 are both 3 mm. Here, the diameters of these openings 34 and 36 are extremely small compared to the wavelength of the microwave. Therefore, micro leakage from the openings 34 and 36 does not occur or is negligible. Therefore, even if a micro is generated in the waveguide 14, it is possible to prevent the surrounding members and the like from being affected by electromagnetic waves, and to prevent inadvertent loss of electromagnetic wave energy.
[0025]
In the space 38, an irradiation space 40 indicated by a two-dot chain line in the drawing is provided. The irradiation space 40 is a cylindrical space connected to the opening 34 and the opening 36 in the space portion 38. In an actual apparatus, the piping tube 10 (see FIG. 2) is inserted into the irradiation space 40 through the openings 34 and 36. Therefore, the part of the piping tube 10 arranged in the irradiation space 40 is irradiated with the electromagnetic wave 42 that travels in the direction of the arrow in the space 38, and the electromagnetic wave 42 travels through the part. In addition, the broken line in a figure represents roughly the electromagnetic wave 42 which generate | occur | produces in the waveguide 14 (space part 38).
[0026]
Returning to FIG. The piping tube (capillary) 10 is a catheter-like member having a small diameter, and in this embodiment, the inner diameter and the outer diameter are 2 mm and 3 mm, respectively. The piping tube 10 is disposed through the waveguide 14 and is inserted into the irradiation space 40. The piping tube 10 functions as an introduction path for introducing the blended fluid 12 into the irradiation space 40 and functions as a discharge path for discharging the blended fluid 12 from the irradiation space 40. Moreover, in the site | part currently inserted in the irradiation space 40 in the piping tube 10, electromagnetic waves are permeate | transmitted and the mixed fluid 12 is irradiated with the electromagnetic waves. In addition, although the piping tube 10 in this embodiment is a silicon tube, it should just be a tube formed with the material which permeate | transmits electromagnetic waves not only in this.
[0027]
In the small-diameter piping tube 10, the blended fluid 12 forms a fluid layer. Both sides of the fluid layer of the blended fluid 12 are filled with a carrier liquid such as buffer liquid or water adjacent to the fluid layer.
[0028]
A carrier liquid is stored in the carrier liquid tank 44. The pump 46 is connected to the carrier liquid tank 44 and to the piping tube 10. The pump 46 discharges (supplies) the carrier liquid in the carrier liquid tank 44 into the piping tube 10 based on the control of the pump control unit 18 a in the control unit 18. Further, the carrier liquid in the piping tube 10 is sucked (pulled out) and discharged to the carrier liquid tank 44. By the suction operation and the discharge operation of these pumps 46, the blended fluid 12 is transported by the carrier liquid that functions as a pressure transmission medium, and moves in the piping tube 10 along its extending direction.
[0029]
The moving liquid amount detecting unit 48 supplies the liquid amount of the carrier liquid that is supplied to or extracted from the pipe tube 10 in accordance with the suction operation and the discharge operation, that is, the carrier between the pipe tube 10 and the carrier liquid tank 44. The amount of liquid movement is detected, and the detection result is output to the control unit 18a. The control unit 18 a adjusts the arrangement position of the blended fluid 12 in the piping tube 10 based on the movement amount, for example, positions the blended fluid 12 in the irradiation space 40, and is disposed in the irradiation space 40. The blending fluid 12 is positioned outside the waveguide 14.
[0030]
The temperature sensor 44 detects the temperature of the blended fluid 12 in the piping tube 10 and outputs the detection result to the irradiation control unit 18 b in the control unit 18. Here, the blended fluid 12 is exposed to microwaves by being disposed in the irradiation space 40, and the temperature rises. In general, in the reaction between the sample and the reagent constituting the blended fluid 12, there is an optimum temperature or optimum temperature zone suitable for the reaction, such as the most accelerated reaction. The controller 18b intermittently arranges the blended fluid 12 in the irradiation space 40 based on the detected temperature of the blended fluid 12 so that the blended fluid 12 is maintained at the optimum temperature or the optimum temperature band. Take control.
[0031]
Incidentally, as shown in FIG. 2, the temperature sensor 44 in the present embodiment is disposed on the outer surface of the piping tube 10 at a position upstream from the waveguide 14 and spaced from the waveguide 14. A temperature detection region 50 adjacent to the temperature sensor 44 is provided in the piping tube 10, and the blended fluid 12 is disposed in this temperature detection region 50, whereby temperature detection is performed. The temperature sensor 44 may be provided on the surface of the piping tube 10 disposed in the irradiation space 40 (see FIG. 1) and directly detect the mixed fluid 12 in a state where it is exposed to electromagnetic waves. In the case of this configuration, the temperature sensor 44 is preferably provided with a configuration that protects against the influence of electromagnetic waves.
[0032]
Next, the operation of this sample processing apparatus in the reaction promotion process will be described with reference to FIG. Prior to the reaction promotion process, on the upstream side of the piping tube 10, a desired blending processing unit separately injects the sample and the reagent into the piping tube 10 to generate a fluid layer of the blended fluid 12.
[0033]
The pump 46 (see FIG. 1) performs a discharge operation to supply the carrier liquid to the upstream side of the blended fluid 12. In the present embodiment, the upstream carrier liquid is supplied so as to be directly adjacent to the blended fluid 12, but an air layer may be arranged between the blended fluid 12 and the carrier liquid. In addition, the carrier liquid is also filled on the downstream side of the blended fluid 12, and in the present embodiment, it is directly adjacent to the blended fluid 12.
[0034]
By supplying the carrier liquid to the upstream side of the blended fluid 12, the blended fluid 12 moves to the downstream side and is disposed in the waveguide 14 (irradiation space 40). Prior to the placement in the waveguide 14, the temperature of the blended fluid 12 is detected in the temperature detection region 50, and the temperature detected before the microwave irradiation is detected by the micro-tube to the blended fluid 12 described later. It may be used for intermittent control in wave irradiation.
[0035]
When the carrier liquid is supplied to the upstream side of the blended fluid 12, the blended fluid 12 moves downstream toward the waveguide 14. In this movement, the temperature of the blended fluid 12 may be detected in the temperature detection region 50, and the temperature of the blended fluid 12 immediately before the microwave irradiation may be used for controlling the microwave irradiation amount described later.
[0036]
The blending fluid 12 is positioned and stopped in the irradiation space 40 as shown in FIG. In the present embodiment, the width of the fluid layer of the blended fluid 12 in the extending direction of the piping tube 10 is set to be equal to or less than the width (thickness) of the irradiation space 40 in the vertical direction.
[0037]
Next, a high frequency is supplied to the waveguide 14, and a 2450 MHz microwave 42 is generated in the waveguide 14 and travels in the direction of the arrow in the figure as a traveling wave. Thereby, the microparticles constituting the sample and the reagent resonate, and the sample and the reagent are more positively mixed and uniformly mixed. Therefore, uneven reaction of the sample is prevented, and the temperature of the blended fluid 12 rises and the reaction is promoted by microwave irradiation. In addition, the broken line in a figure represents roughly the electromagnetic wave 42 which generate | occur | produces in the waveguide 14 (space part 38).
[0038]
Based on a desired program, the control unit 18 (see FIG. 1) retains the blended fluid 12 for a predetermined period (irradiation period), and then causes the pump 46 to perform a suction operation to extract a predetermined amount of the carrier liquid in the pipe tube 10. Make it. Thereby, the blended fluid 12 moves to the upstream side and is saved outside the irradiation space 40. The control unit 18 places the blended fluid 12 outside the irradiation space 40 for a predetermined period (a retreat period), and then causes the pump 46 to discharge and inject a predetermined amount of carrier liquid into the piping tube 10. Thereby, the blended fluid 12 is positioned in the irradiation space 40 and is irradiated with microwaves as described above. The controller 18 combines the suction operation and the discharge operation of the pump 46 as described above, and performs intermittent control in which the blended fluid 12 is intermittently disposed in the irradiation space 40. In the present embodiment, the blended fluid 12 is retracted to the upstream side of the waveguide 14, but may be retracted to the downstream side. Further, the upstream side and the downstream side may be combined.
[0039]
Here, in this intermittent control, the control unit 18 arranges the blended fluid 12 in the temperature detection region 50 as necessary, and adjusts the irradiation period and the withdrawal period based on the temperature of the blended fluid 12 detected thereby. The amount of electromagnetic wave irradiation to the blended fluid 12 is controlled so that the blended fluid 12 is maintained at the optimum temperature or the optimum temperature range.
[0040]
After the intermittent control is completed, the carrier fluid is supplied into the piping tube 10, and the blended fluid 12 moves to the unit that performs the pre-analysis process and the analysis process arranged on the downstream side of the waveguide 14. Receive processing. The sample and the reagent are successively supplied via the carrier liquid layer to the upstream side of the blended fluid 12, and a plurality of blended fluids separated from each other by the carrier liquid layer are generated. The intermittent control is also performed for the plurality of blended fluids, and after the same reaction promotion process as described above is performed, a pre-analysis process and an analysis process are performed.
[0041]
In the present embodiment, a semiconductor oscillator is used as the low-power oscillator 14 (see FIG. 1) because of the configuration in which the compounded fluid 12 is directly irradiated with electromagnetic waves in the waveguide 14 (irradiation space 40). Here, the semiconductor oscillator can generate an electromagnetic wave signal having various frequencies. For example, the semiconductor oscillator can generate an electromagnetic wave having a frequency (resonance frequency) that is an integral multiple of the natural frequency in the waveguide 14 in the space portion 38. Therefore, the control unit 18a may control the oscillator 14 to switch the traveling wave frequency to a different resonance frequency based on the temperature of the blended fluid 12, for example, and irradiate the blended fluid 12. Further, this frequency switching control may be combined with the intermittent control.
[0042]
Although the sample processing apparatus of this embodiment is a structure which irradiates a traveling wave to the mixing | blending fluid 12, you may utilize a standing wave. In this case, similarly to the above-described embodiment, for example, it is desirable that the piping tube 10 is configured to penetrate so as to be orthogonal to the waveguide 14. In this case, since the diameter of the piping tube 10 is small, there is no substantial difference in the progress of the reaction due to the difference in position in the radial direction within the tube 10. Therefore, the reaction unevenness accompanying electromagnetic wave irradiation can be prevented or reduced.
[0043]
In the sample processing apparatus in the above embodiment, the case where the width of the blended fluid layer in the extending direction of the piping tube 10 is set to be equal to or smaller than the width of the irradiation space 40 in the vertical direction has been described. On the other hand, the case where the width | variety of a combination fluid layer is wider than the width | variety of this irradiation space 40 is demonstrated. In this case, for example, the control unit 18 supplies the carrier liquid into the piping tube 10 at a constant speed, causes the one end to the other end of the blended fluid 12 to be hidden in the irradiation space 40, and scans the blended fluid 12 with the electromagnetic wave 42. You can do it. In addition, the mixed fluid 12 may be irradiated with the electromagnetic wave 42 by reciprocating the scan irradiation a plurality of times, for example.
[0044]
In the above embodiment, for example, since the plurality of blended fluids 12 are exposed to traveling waves or arranged in the irradiation space 40 having the same electromagnetic wave distribution, for example, a stable reaction result can always be obtained. In the same type of blended fluid 12, a highly reproducible reaction process can be realized.
[0045]
Incidentally, a plurality of piping tubes 10 may be provided for a single waveguide 14. In this configuration, when a standing wave is used for electromagnetic wave irradiation, it is desirable to arrange each piping tube 10 at a position where the phase of the standing wave is the same. Thereby, it is possible to prevent the piping tube 10 from causing a difference in the degree of reaction promotion. In the above-described embodiment, the case where the waveguide 14 is used has been described as an example. However, for example, a stripline, a microstripline, or the like may be used as the waveguide.
[0046]
【The invention's effect】
According to the present invention, a sample processing apparatus having a new structure is provided.
[0047]
Another object of the present invention is to provide a sample processing apparatus that prevents uneven reaction between a sample and a sample processing agent and realizes highly accurate sample processing.
[Brief description of the drawings]
FIG. 1 is a diagram schematically showing components that function mainly in a reaction promoting process in a sample processing apparatus according to the present invention.
FIG. 2 is a diagram showing a waveguide in the present embodiment and peripheral members such as a piping tube provided in the waveguide.
FIG. 3 is a schematic diagram illustrating the structure of a waveguide in the present embodiment.
4 is a diagram schematically showing a state in which a compounded fluid is arranged in the irradiation space in the waveguide shown in FIG. 2;
[Explanation of symbols]
10 piping tube, 12 compounding fluid, 14 waveguide.

Claims (3)

An irradiation space in which a mixed fluid in which a sample treatment agent is mixed in a sample stays or passes is formed in a waveguide path, and the waveguide irradiates the electromagnetic wave to the mixed fluid in the irradiation space ;
A tube body that is inserted into the irradiation space and in which the blended fluid is disposed;
A temperature sensor provided at a temperature detection position outside the irradiation space in the tube body, and detecting the temperature of the blended fluid at the temperature detection position;
A pump connected to the tube body;
A means for controlling the pump to adjust the position of the compounded fluid in the tube body, wherein the compounded fluid is disposed in the irradiation space during electromagnetic wave irradiation, and the compounded fluid is brought to the temperature detection position during temperature detection. A control unit to be arranged;
Sample processing apparatus which comprises a. The sample processing apparatus according to claim 1 ,
The said control part combines the suction operation and discharge operation of the said pump, and performs the intermittent control which arrange | positions the said mixing fluid intermittently in the said irradiation space, The sample processing apparatus characterized by the above-mentioned. The sample processing apparatus according to claim 2 , wherein
The sample processing apparatus, wherein the control unit performs the intermittent control based on the detected temperature of the blended fluid.

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