Evaporation concentration mechanism and automated analyzer equipped therewith

Abstract

Provided are an evaporation concentration mechanism that is capable of adjusting the amount of evaporation of a liquid while being inexpensive and simple, and an automatic analysis device including the same. An intake part 310 includes: an exhaust flow passage 314 having one end connected to an exhaust part 320 and the other end connected to an opening of a reaction container through contact between the intake part and the reaction container; and a through hole 312 that allows outside air to flow into the reaction container. The exhaust part includes: a negative pressure generation source 321 for generating negative pressure; an exhaust pipe 324 connecting the negative pressure generation source and the exhaust flow passage of the intake part; and an atmospheric air introduction part 322 for introducing atmospheric air into the exhaust pipe. An atmospheric air introduction pipe 323 is attachable to and detachable from the atmospheric air introduction part.

Description

TECHNICAL FIELD

[0001] The present invention relates to an evaporation and concentration mechanism and an automatic analyzer equipped with the same.

BACKGROUND ART

[0002] As a method for analyzing specific components contained in a sample, for example, there is a method using LC-MS in which liquid chromatography (LC) and a mass spectrometer (MS) are connected online.

[0003] The use of LC-MS is also expanding into the field of clinical testing, where biological samples such as blood and urine are analyzed by automatic analyzers. When biological samples such as blood and urine (hereinafter simply referred to as samples) are analyzed by LC-MS, it is necessary to perform pretreatment to improve the purification degree of the samples. For example, the component to be analyzed contained in the sample is extracted by a method such as solid phase extraction (SPE) or liquid-liquid extraction (LLE). Furthermore, in order to achieve high-sensitivity detection by LC-MS, evaporation and concentration may be performed to evaporate the extract from which the component to be analyzed has been extracted, so as to increase the concentration of the component to be analyzed.

[0004] As techniques for performing such evaporation and concentration of samples, for example, the techniques described in Patent Documents 1 to 2 are known. In the evaporation treatment described in Patent Document 1, the reaction vessel holding the sample liquid is connected to a pressure reduction source via a pressure reduction flow path, and the concentration treatment is performed by reducing the pressure inside the reaction vessel. Further, Patent Document 2 discloses a stopper for distilling off volatile substances, which is suitable for vaporizing and removing volatile substances from a solution containing volatile substances contained in a container. The stopper for distilling off volatile substances is provided with a through-hole through which vaporized volatile substances are discharged, and a groove is formed on its side surface, which connects a gas inlet located at the upper edge of the stopper and a gas outlet located at the lower edge of the stopper. It is stated that when the container is depressurized, the volatile substances are agitated by the gas blown at high speed into the container through the groove, and the vaporization of the volatile substances is promoted. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International Publication No. 2022 / 185707 [Patent Document 2] International Publication No. 2008 / 078765 [Overview of the project] [Problems that the invention aims to solve]

[0006] Automated analyzers are used in a variety of environments. For example, when used in areas at high altitudes, the atmospheric pressure is lower than at sea level, which can lead to a lower boiling point and easier evaporation, potentially causing the evaporation rate to exceed the design value. Patent Document 1 discloses controlling the depressurization rate in the concentration process, but the final depressurization amount is the same regardless of whether the depressurization rate is controlled or not, and adjustment of the evaporation rate is not considered. Patent Document 2 also does not consider adjusting the amount of vaporized volatile substances.

[0007] The object of the present invention is to provide an evaporation and concentration mechanism that can adjust the amount of liquid evaporated with an inexpensive and simple mechanism, and an automated analyzer equipped therewith. [Means for solving the problem]

[0008] An evaporation concentration mechanism according to one embodiment of the present invention is an evaporation concentration mechanism for evaporating and concentrating a liquid contained in a reaction vessel, comprising: a vessel mounting section for installing the reaction vessel; an intake section that can contact the reaction vessel so as to cover the opening of the reaction vessel; and an exhaust section for exhausting gas from the reaction vessel through the intake section, wherein the intake section has an exhaust passage at one end connected to the exhaust section and the other end connected to the opening of the reaction vessel by contact between the intake section and the reaction vessel, and a through hole that allows outside air to flow into the reaction vessel, wherein the exhaust section comprises a negative pressure source for generating negative pressure, an exhaust pipe connecting the negative pressure source and the exhaust passage of the intake section, and an atmosphere introduction section for introducing atmospheric air into the exhaust pipe, wherein the atmosphere introduction section has a detachable atmosphere introduction pipe. [Effects of the Invention]

[0009] The present invention provides an evaporation and concentration mechanism that allows for adjustment of the evaporation rate with an inexpensive and simple mechanism, and an automated analyzer equipped therewith. Other issues, configurations, and effects will be clarified by the following description of the embodiments. [Brief explanation of the drawing]

[0010] [Figure 1] A schematic diagram showing the overall configuration of the automated analyzer. [Figure 2] A diagram showing an example of a pre-processing step for analytical analysis using an automated analyzer. [Figure 3A] A schematic diagram illustrating an example of an evaporation and concentration mechanism. [Figure 3B] A schematic diagram illustrating an example of an evaporation and concentration mechanism. [Figure 4] A diagram showing the difference in evaporation rate depending on whether or not the atmospheric inlet pipe is connected. [Figure 5] A diagram showing the difference in evaporation rate depending on the length of the atmospheric inlet pipe. [Figure 6] A diagram showing the relationship between the atmospheric inlet pipe and the amount of outside air flowing in. [Figure 7] A schematic diagram showing how vapor is drawn in by the intake section. [Modes for carrying out the invention]

[0011] Embodiments of the present invention will be described below with reference to the drawings. In the embodiments of the present invention, an automated analyzer combining an LC-MS as an analytical mechanism with a sample pretreatment mechanism will be described as an example. However, the present invention can also be applied to an automated analyzer that combines a separation mechanism such as capillary electrophoresis with a detector such as a spectrophotometer as an analytical mechanism.

[0012] Figure 1 is a schematic diagram showing the overall configuration of the automated analyzer. The automated analyzer 100 mainly consists of a pre-processing unit 101 for pre-treating the sample, a separation unit 102 for separating components in the sample, an analysis unit 103 for analyzing the separated components, and a control unit 104 that controls each mechanism of the device and analyzes and outputs the detection results from the analysis unit 103.

[0013] The pre-processing unit 101 includes a transport mechanism 112 for transporting a sample container 111 containing the sample to be analyzed to a sample dispensing position, an incubator (reaction vessel disk) 120 capable of maintaining the solution in the reaction vessel 116 at a constant temperature by mounting the reaction vessel 116 in multiple openings 119, a reagent disk 122 for holding multiple reagent containers 121 containing reagents, and a sample dispensing mechanism 113 for dispensing the sample from the sample container 111 transported to the sample dispensing position into the reaction vessel 116 housed in the openings 119 of the incubator 120. To avoid contamination, the sample dispensing mechanism 113 attaches a dispensing tip when dispensing the sample. The attachment and detachment of the dispensing tip is performed in the dispensing tip attachment / detachment unit 114. Unused dispensing tips 115a stored in the dispensing tip rack 115 are transported to the dispensing tip attachment / detachment unit 114 by the transport mechanism 118.

[0014] Furthermore, the pre-processing unit 101 includes a magnetic separation mechanism 124 that separates magnetic beads in the solution contained in the reaction vessel 116 using the magnetic force of a magnet, a transport mechanism 125 that transports the reaction vessel 116 between the incubator 120 and the magnetic separation mechanism 124, and an evaporation concentration mechanism 131 that evaporates and concentrates the analyte components in the solution in the reaction vessel 116.

[0015] Further, the pretreatment unit 101 includes a transport mechanism 132 that transports the reaction container 116 between the incubator 120 and the evaporative concentration mechanism 131, and a separation unit dispensing mechanism 133 that dispenses the solution in the reaction container 116 after evaporative concentration to the separation unit 102 that separates components in the sample.

[0016] The magnetic separation mechanism 124 is provided on the rotation track 126 of the reagent dispensing mechanism 123. The reagent dispensing mechanism 123 can discharge a reagent to the reaction container 116 supported by the magnetic separation mechanism 124, or aspirate the solution in the reaction container 116.

[0017] The incubator 120 has a function of keeping the temperature of the reaction container 116 placed in the opening 119 constant, and incubates the reaction container 116 placed in the opening 119 for a predetermined time.

[0018] The separation unit 102 is, for example, an LC, and includes a column or the like for separating components in the reaction solution dispensed by the separation unit dispensing mechanism 133. The separation unit 102 separates components in the reaction solution dispensed from the reaction container 116 by the separation unit dispensing mechanism 133, and sequentially introduces the separated components to the analysis unit 103. The analysis unit 103 is, for example, an MS, ionizes the components introduced from the separation unit 102, detects the ion amount (that is, the component amount), and outputs the detection result to the control unit 104.

[0019] First, the basic steps of the analysis process will be described. Figure 2 is a diagram showing an example of the pretreatment step of the analysis process by the automatic analyzer 100. Prior to starting the pretreatment, an unused reaction container 116 is installed from the reaction container mounting rack 117 to the opening 119 on the incubator 120 by the transport mechanism 118.

[0020] First, the sample containing the component to be analyzed is aspirated from the sample container 111 by the sample dispensing mechanism 113, and discharged into the reaction container 116 of the incubator 120 (Step S200).

[0021] Next, the reagent dispensing mechanism 123 aspirates an internal standard substance as a reagent corresponding to the analyte from the reagent container 121 of the reagent disk 122 and discharges it into the reaction vessel 116 (step S201). Next, the reagent dispensing mechanism 123 aspirates a reagent, for example, a deproteinizer, from the reagent container 121 of the reagent disk 122 and discharges it into the reaction vessel 116 (step S202). Next, the reagent dispensing mechanism 123 aspirates a suspension of magnetic beads as a reagent from the reagent container 121 of the reagent disk 122 and discharges it into the reaction vessel 116 (step S203).

[0022] Subsequently, the reaction vessel 116 containing the sample, internal standard substance, reagents, and magnetic beads is transported by the transport mechanism 125 to the magnetic separation mechanism 124 for washing the magnetic beads (step S204).

[0023] The cleaning process for the magnetic beads is described below. In the magnetic separation mechanism 124, the magnetic force of the magnet 201, positioned along the outer surface of the reaction vessel 116, collects the magnetic beads holding the analyte and internal standard material on the inner wall surface of the reaction vessel 116 (shown as magnetic bead group 202 in Figure 2). In this state, the reagent dispensing mechanism 123 aspirates and discards the solution from the reaction vessel 116. At this time, the reaction vessel 116 remains with the magnetic beads and the analyte and internal standard material held by the magnetic beads. Subsequently, the reagent dispensing mechanism 123 aspirates a cleaning solution from the reagent container 121 of the reagent disk 122 to wash away impurities other than the substances held by the magnetic beads (analyte and internal standard material), and discharges it into the reaction vessel 116. At this time, the constraint on the magnetic beads by the magnetic force of the magnet 201 may be temporarily released. Subsequently, with the magnetic beads gathered on the inner wall surface of the reaction vessel 116 by the magnet 201, the reagent dispensing mechanism 123 aspirates and discards the solution (washing solution) from the reaction vessel 116, thereby washing the magnetic beads.

[0024] Next, the reagent dispensing mechanism 123 aspirates the eluate, which elutes the analyte and internal standard substance from the magnetic bead group 202, from the reagent container 121 of the reagent disk 122 and discharges it into the reaction vessel 116 (step S205).

[0025] Next, with the magnetic beads 203, from which the analyte and internal standard substances have been eluted, gathered on the inner wall surface of the reaction vessel 116 by the magnetic force of the magnet 201, the reagent dispensing mechanism 123 draws up the solution (purified solution) from the reaction vessel 116 (step S206) and discharges it into an unused reaction vessel 116v in an incubator 120, which is different from the reaction vessel 116, located in the magnetic separation mechanism 124 (step S207). Incubation is performed on the purified solution contained in the reaction vessel 116v as needed.

[0026] Next, the transport mechanism 132 transports the reaction vessel 116v containing the purified liquid to the evaporation and concentration mechanism 131, where the components in the purified liquid are evaporated and concentrated (step S208). The detailed configuration of the evaporation and concentration mechanism 131 will be described later.

[0027] Furthermore, if the composition of the purification solution is to be changed so that the analyte binds to the separation column (not shown) provided in the separation unit 102, the reagent dispensing mechanism 123 draws the diluent from the reagent container 121 of the reagent disk 122 and discharges it into the reaction vessel 116v.

[0028] The purified liquid obtained through the above pretreatment process is drawn from the reaction vessel 116v by the separation unit dispensing mechanism 133 and discharged to the separation unit 102. The components separated in the separation unit 102 are ionized in the analysis unit 103 and the amount of ions (i.e., the amount of components) is detected. The detection result from the analysis unit 103 is output to the control unit 104, and the control unit 104 calculates the concentration value of the components in the sample using a calibration curve.

[0029] The evaporation and concentration process in this embodiment will now be described. The automated analyzer 100 can adjust the evaporation rate to meet the evaporation performance required for the device.

[0030] Figures 3A and 3B schematically show an example of an evaporation concentration mechanism 131. The evaporation concentration mechanism 131 includes a container mounting section 302 for installing a reaction vessel 116v containing the purified liquid obtained in the pretreatment step, and an intake section 310 and an exhaust section 320 for drawing in vapor (gas) from the reaction vessel 116v. Figure 3A shows a bird's-eye view of the container mounting section 302 and the intake section 310. The container mounting section 302 includes one or more container receiving sections 301 for receiving the reaction vessel 116v and a heating section 303 for heating the reaction vessel 116v. A Peltier element or heater with controllable temperature can be used in the heating section 303. The intake section 310 includes an arm 311 and a support column 313. An exhaust passage 314 (see Figure 7) for drawing in steam from the reaction vessel 116v is formed within the arm 311 and the support column 313. One end of the exhaust passage 314 is connected to the exhaust section 320, and the other end is formed to connect to the opening of the reaction vessel 116v when the arm 311 contacts the reaction vessel 116v so as to cover it. Furthermore, the arm 311 is provided with a through hole 312 for allowing outside air to flow into the reaction vessel 116v when steam is drawn in.

[0031] Figure 3B shows the configuration of the exhaust section 320. The exhaust section 320 includes an exhaust mechanism 321 and an air intake section 322 for introducing outside air, located in the middle of the exhaust piping 324 that connects the exhaust passage 314 in the intake section 310 to the exhaust mechanism 321. An air intake pipe 323 is detachably attached to the air intake section 322. It is possible to choose whether or not to connect the air intake pipe 323 to the air intake section 322, and it is also possible to prevent the introduction of outside air by not connecting the air intake pipe 323 and sealing the air intake pipe connection part of the air intake section 322. Furthermore, while the example in Figure 3B includes one atmospheric inlet and the end of the atmospheric inlet pipe 323 is open to the atmosphere, this is not the only option. For example, multiple atmospheric inlets 322 may be provided, or an opening may be provided in the middle of the atmospheric inlet pipe 323 to open to the atmosphere, or multiple openings may be provided in the atmospheric inlet pipe 323. The atmospheric inlet 322 may be configured as a pipe with branching sections such as a Y-shaped pipe or a T-shaped pipe, or as a block with holes through which gas flows. The holes in the block do not need to be tubular as long as gas flows through them, and any shape that is easy to mold, such as a triangular or square cross-section, can be appropriately selected. Two blocks with grooves may be joined together. An example of an exhaust mechanism 321 is a negative pressure source that exhausts by generating negative pressure, such as a vacuum pump such as a rotary pump. High vacuum is not required, so any so-called roughing pump can be applied.

[0032] Furthermore, when vapor is drawn in through the intake section 310, condensed vapor may liquefy at the intake section 310 and drip. If this dripping enters the reaction vessel, the evaporation and concentration rate will decrease, so it is advisable to take measures to prevent dripping. For example, heating the intake section 310 to prevent vapor from condensing on its surface is effective. In addition, continuing to perform dry suction even after exhaust has finished and the intake section 310 has been moved away from the reaction vessel 116v is also an effective countermeasure.

[0033] The method for adjusting the evaporation rate will be explained with an example. Figure 4 shows the results of evaporation concentration performed using the evaporation concentration mechanism 131 shown in Figures 3A and 3B, both with and without the atmospheric inlet pipe connected. The experiment was conducted under the same conditions except for the connection of the atmospheric inlet pipe. The evaporation rate on the vertical axis represents the ratio of the volume of the evaporated sample to the volume of the sample before evaporation concentration. In this example, the evaporation rate is approximately 60% without the atmospheric inlet pipe, while it is slightly less than 80% with the atmospheric inlet pipe, indicating an increase in the evaporation rate.

[0034] Figure 5 shows the results of evaporation concentration performed by varying the length of the connected atmospheric inlet pipe. The vertical axis shows the average evaporation rate obtained from multiple experiments. In this experiment, atmospheric inlet pipes of four different lengths—100 mm, 400 mm, 800 mm, and 1030 mm—were connected. It can be seen that the average evaporation rate was highest with the shortest length of 100 mm, and decreased as the atmospheric inlet pipe length increased. Therefore, it can be seen that the evaporation rate can be adjusted by adjusting the length of the atmospheric inlet pipe. The change in evaporation rate due to the length of the atmospheric inlet pipe is thought to depend on the amount of air flowing into the atmospheric inlet pipe per unit time. Therefore, it is possible to adjust the evaporation rate not only by changing the length of the atmospheric inlet pipe, but also by changing the diameter of the atmospheric inlet pipe, the position and number of atmospheric inlet sections, etc. Furthermore, it is also possible to adjust the evaporation rate by combining multiple methods of adjusting the amount of air flow.

[0035] Figure 6 shows the theoretical calculation results of the relationship between the length of the atmospheric inlet pipe and the flow rate in the experiment shown in Figure 5. In the exhaust section 320 shown in Figure 3B, a pressure gauge was placed in the exhaust piping between the atmospheric inlet section 322 and the exhaust mechanism (vacuum pump) 321, and the pressure at the inlet of the exhaust mechanism 321 was measured. The total flow rate was calculated as the air flow rate discharged by the exhaust mechanism from the pressure gauge value, using a vacuum pump (exhaust mechanism, negative pressure source) characteristic curve that shows the relationship between the degree of vacuum and the air flow rate. The atmospheric inlet pipe side flow rate, i.e., the air flow rate flowing in from the atmospheric inlet pipe 323, and the intake section side flow rate, i.e., the amount of air flowing in from the intake section 310, were calculated as follows. The pressure loss in the atmospheric inlet pipe 323 can be determined by theoretical calculation. On the other hand, the pressure loss in the intake section 310 was calculated from the results of exhausting by directly connecting the intake section 310 and the exhaust mechanism 321. Based on the pressure losses in the atmospheric inlet pipe 323 and the intake section 310 calculated in this manner, the flow rate balance was calculated and determined as the flow rate on the atmospheric inlet pipe side and the flow rate on the intake section side.

[0036] Figure 5 shows that the evaporation rate is higher when 100 mm and 400 mm atmospheric inlet pipes are connected compared to when no inlet pipe is used. Furthermore, the evaporation rate tends to decrease as the length of the atmospheric inlet pipe increases. Figure 6 shows that the total flow rate decreases as the length of the atmospheric inlet pipe increases, showing a similar trend to the evaporation rate. However, looking at the breakdown of the total flow rate, the flow rate on the atmospheric inlet pipe side decreases as the total flow rate decreases, while the flow rate on the intake side is lower when a 100 mm atmospheric inlet pipe is connected than when a 400 mm atmospheric inlet pipe is connected, showing a trend in the opposite direction to the total flow rate or the flow rate on the atmospheric inlet pipe side.

[0037] Figure 7 is a schematic diagram of steam suction by the intake section 310. When exhaust by the exhaust mechanism 321 begins, outside air flows in through the through hole 312 provided in the arm 311. The influx of outside air through the through hole 312 generates an airflow inside the reaction vessel 116v, agitating the surface of the purified liquid 330 and increasing the surface area of ​​the purified liquid 330 in contact with the outside air. This change in surface area is thought to affect the evaporation rate of the purified liquid 330. In this embodiment, by connecting a relatively short atmospheric inlet pipe, much of the total flow rate exhausted by the exhaust mechanism 321 is supplied by outside air from the atmospheric inlet pipe, thereby reducing the flow rate on the intake side. This is thought to enable efficient intake of the outside air flowing in through the through hole 312 as airflow inside the vessel.

[0038] As described above, according to this embodiment, the amount of outside air flowing in from the intake can be adjusted by changing the length of the atmospheric intake pipe, thereby making it possible to adjust the amount of evaporation from the reaction vessel. Furthermore, in the case of an automatic analyzer equipped with such an evaporation and concentration mechanism, the amount of evaporation may exceed the design value depending on the installation environment. In such cases as well, an automatic analyzer that can obtain a predetermined evaporation rate can be realized by switching the length and / or diameter of the atmospheric intake pipe.

[0039] It should be noted that the present invention is not limited to the embodiments and modifications described above, but includes various other modifications. For example, the embodiments described above are described in detail to make the present invention easier to understand, and are not necessarily limited to those having all the configurations described. For example, in the example described above, an example in which the concentration process is performed by heat treatment and exhaust treatment was shown, but an example in which it is performed by exhaust treatment alone is also possible. It is possible to perform the concentration process of the sample even with exhaust treatment alone. Also, the analysis unit 103 may be an optical analyzer other than a mass spectrometer. [Explanation of symbols]

[0040] 100...Automatic analyzer, 101...Pre-processing unit, 102...Separation unit, 103...Analysis unit, 104...Control unit, 111...Sample container, 112...Transportation mechanism, 113...Sample dispensing mechanism, 114...Dispensing tip loading / unloading unit, 115...Dispensing tip mounting rack, 115a...Dispensing tip, 116,116v...Reaction vessel, 117...Reaction vessel mounting rack, 118...Transportation mechanism, 119...Opening, 120...Incubator, 121...Reagent container, 122...Reagent disc, 123...Reagent dispensing mechanism, 124... 125...Transportation mechanism, 126...Rotating orbit, 131...Evaporation and concentration mechanism, 132...Transportation mechanism, 133...Dispensing mechanism for separation section, 201...Magnet, 202...Magnetic bead group, 203...Magnetic bead group, 301...Container receiving section, 302...Container installation section, 303...Heating section, 310...Intake section, 311...Arm, 312...Through hole, 313...Support column, 314...Exhaust passage, 320...Exhaust section, 321...Exhaust mechanism, 322...Atmospheric introduction section, 323...Atmospheric introduction pipe, 324...Exhaust piping.

Claims

1. An evaporation and concentration mechanism for evaporating and concentrating a liquid contained in a reaction vessel, A container installation section for installing the reaction vessel, An intake portion that can come into contact with the reaction vessel so as to cover the opening of the reaction vessel, It has an exhaust section that exhausts the gas in the reaction vessel via the intake section, The intake section includes an exhaust passage, one end of which is connected to the exhaust section and the other end of which is connected to the opening of the reaction vessel by contact between the intake section and the reaction vessel, and a through hole that allows outside air to flow into the reaction vessel. The exhaust section comprises a negative pressure source that generates negative pressure, an exhaust pipe connecting the negative pressure source and the exhaust passage of the intake section, and an air intake section that introduces air into the exhaust pipe, wherein the air intake section is an evaporation and concentration mechanism in which the air intake pipe is detachable.

2. In claim 1, The aforementioned atmospheric inlet pipe is an evaporation and concentration mechanism that allows for the selection of an atmospheric inlet pipe to be installed in the atmospheric inlet section from a plurality of atmospheric inlet pipes with different lengths and / or inner diameters.

3. In claim 1, The aforementioned atmospheric intake section is a branching section of the exhaust piping, or a block provided with holes through which gas flows, in an evaporation and concentration mechanism.

4. In claim 1, The exhaust section is an evaporation and concentration mechanism comprising a plurality of the aforementioned air intake sections.

5. In claim 1, The container installation section is provided and has a heating section for heating the reaction vessel, An evaporation and concentration mechanism that evaporates and concentrates the liquid contained in the reaction vessel by heating the reaction vessel with the heating unit and exhausting the gas in the reaction vessel through the intake unit.

6. An automatic analyzer comprising an evaporation concentration mechanism according to any one of claims 1 to 5, An automated analyzer comprising an analysis unit for analyzing the liquid contained in the reaction vessel, which has been concentrated by the evaporation concentration mechanism.

7. In claim 6, The evaporation and concentration mechanism is an automated analyzer to which the atmospheric inlet pipe, selected according to the specified evaporation rate, is connected.

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