Liquid Dispensing Device
By employing a temperature control and monitoring system to detect temperature changes during reagent ejection in the liquid dispensing device, the device can accurately identify dispensing abnormalities, improving its reliability and analytical accuracy.
Patent Information
- Application Number
- JP2024028842
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-08-05
- Filing Date
- 2024-02-28
- Publication Date
- 2025-04-10
- Estimated Expiration
- 2040-02-21
AI Technical Summary
Existing liquid dispensing devices struggle to accurately detect dispensing abnormalities, especially when the viscosity and surface tension of the liquid are low, and they lack a reliable method to determine normal reagent dispensing and ejecting for chemical reactions.
The implementation of a temperature control and monitoring system within the liquid dispensing device, which controls and monitors the temperature at the reaction position during reagent ejection. If the temperature change falls outside a predetermined threshold range, the system determines that the dispensing is abnormal.
This approach enhances the reliability of the liquid dispensing device by enabling the detection of dispensing abnormalities, ensuring accurate analysis results, and maintaining analytical reliability in automated analyzers.
Smart Images

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Abstract
Description
[Technical field]
[0001] The present invention relates to a liquid dispensing device, and more particularly to a liquid dispensing device used to collect samples, reagents, or reaction liquids between samples and reagents in devices that utilize chemical reactions, such as automatic analyzers. [Background technology]
[0002] In specimen testing such as biochemical testing or immunological serum testing, serum or plasma is often used as a sample, and if the sample is left for a long time after collection until testing, solids such as fibrin (hereinafter referred to as clots) will form in the sample. If this sample is run directly through an automatic analyzer, the clots may clog the sample probe. If the sample probe becomes clogged in this way, it will not be possible to dispense a specified amount of sample into a reaction vessel, and accurate analysis results will not be obtained. This means that the analytical reliability of the automatic analyzer will be greatly impaired.
[0003] As a means for solving such problems, a technology has been proposed in which a pressure sensor is provided in a dispensing flow path including a sample probe, and a clogging of the sample probe is detected based on pressure fluctuations.Patent Document 1 (JP Patent Publication 2004-125780A) discloses a technology that uses a pressure sensor to detect clogging caused by solid matter such as fibrin in the sample or sample dispensing abnormalities caused by air bubbles on the sample surface.
[0004] As another method, Patent Document 2 (JP Patent Publication 2011-17608A) discloses a technique for determining whether detection of the liquid level during reagent aspira-tion is normal or not based on a change in physical quantity during reagent discharge. This technique discloses that capacitance, electrical resistance, and the amount of light transmitted through a reaction vessel are used as physical quantities. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] JP 2004-125780 A [Patent Document 2] JP 2011-17608 A Summary of the Invention [Problem to be solved by the invention]
[0006] The method of using a pressure sensor in the dispensing channel (see Patent Document 1) is unable to obtain sufficient pressure change when the viscosity and surface tension of the liquid to be aspirated is low, making it difficult to accurately detect sample dispensing abnormalities. Furthermore, the technology described in Patent Document 2 is a means for determining whether or not liquid level detection during reagent aspira-tion is normal, but does not disclose a configuration capable of determining whether or not reagent dispensing and ejection for chemical reactions have been performed normally.
[0007] Therefore, in a liquid dispensing device that dispenses liquid (e.g., a reagent) for a chemical reaction, it is important to realize a means for determining whether the liquid has been ejected normally, regardless of the viscosity and surface tension of the liquid being dispensed.
[0008] Other objects and novel features will become apparent from the description of this specification and the accompanying drawings. [Means for solving the problem]
[0009] A brief outline of a representative embodiment of the present invention will be described below.
[0010] A liquid dispensing device in a representative embodiment is equipped with a temperature control unit that controls the temperature of a reaction position in a reaction vessel, and a temperature monitoring unit that monitors the temperature of the reaction position.The temperature monitoring unit monitors the temperature change at the reaction position when a reagent is ejected into the reaction vessel, and if the amount of temperature change falls outside a predetermined threshold range, it determines that a dispensing abnormality has occurred. Effect of the Invention
[0011] According to the representative embodiment, the reliability of the liquid dispensing device can be improved, and in particular, dispensing abnormalities of the liquid dispensing device can be detected. [Brief description of the drawings]
[0012] [Figure 1] 1 is a schematic diagram showing a configuration of a liquid dispensing device according to a first embodiment of the present invention. [Diagram 2] FIG. 13 is a graph showing temperature changes in a reaction section over time. [Diagram 3] FIG. 13 is a graph showing temperature changes in a reaction section over time. [Figure 4] 11 is a table showing minimum temperature thresholds for device states according to the present embodiment. [Diagram 5] FIG. 13 is a graph showing the temperature change of the reaction section with respect to time, and the derivative value of the temperature change amount with respect to time. [Figure 6] 11 is a table showing ΔT / Δt threshold values for device states according to the present embodiment. [Figure 7] 11 is a table showing ON / OFF time ratio thresholds for device states according to the present embodiment. [Figure 8] FIG. 11 is a schematic diagram showing the configuration of a liquid dispensing device according to a second embodiment of the present invention. [Figure 9] FIG. 11 is a schematic diagram showing the configuration of a liquid dispensing device according to a third embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0013] Hereinafter, the embodiments of the present invention will be described in detail with reference to the drawings. In all the drawings for explaining the embodiments, the same reference numerals are used for the members having the same functions, and the repeated explanations are omitted. In addition, in the embodiments, the explanations of the same or similar parts are not repeated as a rule, except when it is particularly necessary. (Embodiment 1)
[0014] In the following, a liquid dispensing device used for the operation of aspirating liquid in a container and dispensing it into another container, i.e., dispensing, will be described, which enables detection of abnormalities occurring in the dispensing path (liquid path) and the like, thereby improving the reliability of the liquid dispensing device. Specifically, when the amount of liquid discharged into the container (dispensing position) by dispensing is more or less than the desired amount, the occurrence of a dispensing abnormality is detected by utilizing the fact that the amount of temperature change at the dispensing position falls outside a predetermined range. The object to be dispensed may be either a sample or a reagent, but in this embodiment, the case of dispensing a reagent will be mainly described.
[0015] <Structure of liquid dispensing device> 1 is a schematic diagram showing the configuration of a liquid dispensing device according to the present invention. It is assumed that the liquid dispensing device of this embodiment is used in an automatic analyzer such as an immunological analyzer. Here, an example will be described in which a reagent is dispensed as the liquid to be dispensed.
[0016] The liquid dispensing device of this embodiment includes a liquid suction and discharge unit (liquid suction and discharge section) 1, a reaction unit 2, a reaction container 3, and a reagent container 4. The liquid suction and discharge unit 1 and the reaction unit 2 that constitute the liquid dispensing device are connected to a computer 11. A sample container containing a liquid sample is disposed in a location not shown.
[0017] The liquid suction / discharge unit 1 is composed of a support 17, a reagent flow path 18, a probe 101, an arm 102, a syringe pump 103, an electromagnetic valve 104, and a water supply pump 105. In a suction operation using the syringe pump 103, a piston constituting the syringe pump 103 is pulled outward from the syringe pump 103 to suction the reagent (chemical liquid) in the reagent container 4 into the reagent flow path 18. In a discharge operation using the syringe pump 103, the piston is pushed inward from the syringe pump 103 to discharge the reagent (chemical liquid) through the reagent flow path 18 into a reaction container 3 (dispensing position) constituting the reaction unit 2. In the present application, the operation of suctioning the liquid in the reagent container 4 and discharging the liquid into another container, the reaction container 3, is called dispensing.
[0018] One end of the reagent flow path 18 is connected to a syringe pump 103, and a probe (sample probe) 101 that functions as both a discharge port and a suction port is formed at the other end. In FIG. 1, the arm 102 and the support unit 17 are separated from each other, but the upper surface of the support unit 17 is connected to the bottom surface of the arm 102. A part of the reagent flow path 18 is fixed to the arm 102, and the probe 101 is located directly below the end of the arm 102 opposite to the support unit 17 side. For example, the columnar support unit (pillar) 17 rotates around an axis, so that the arm 102 and the probe 101 rotate around the axis. Also, the support unit 17 moves up and down, so that the arm 102 and the probe 101 also move up and down. By such rotation and lifting motion, the lower end of the probe 101 can be immersed in the reagent in the reagent container 4, and suction can be performed using the probe 101, and further, the probe 101 moved directly above the reaction container 3 can eject the reagent to the reaction position.
[0019] The syringe pump 103 is connected via an electromagnetic valve 104 to a water supply pump 105 for supplying washing water for washing the inside of the reagent flow path 18 , the inside of the syringe pump 103 and the inside of the probe 101 .
[0020] The reaction unit 2 is composed of a constant temperature block 106, a temperature sensor 107, a heater 108, a temperature monitoring unit 109, and a temperature control unit 110. The reaction vessel 3 is placed inside the recess on the top surface of the constant temperature block 106. The constant temperature block 106 is made of a metal with high thermal conductivity such as aluminum (Al), and the temperature of the constant temperature block 106 is controlled to a constant temperature of around 37°C. The heater 108 is arranged along the side of the reaction vessel 3. Here, by using the temperature-controlled constant temperature block 106 and the heater 108, the temperature of the reaction vessel 3 and the inside of the reaction vessel 3 (dispensing position) are controlled to a temperature suitable for a chemical reaction between the sample and the reagent. The heat generation of the heater 108 is controlled, for example, by a pulse wave with a constant current value. The reaction vessel 3 is a disposable vessel, and is used to mix and react the sample and the reagent in the vessel. Here, the interior of the reaction vessel 3 into which the liquid (sample or reagent) discharged from the probe 101 is poured is referred to as a dispensing position.
[0021] The temperature sensor 107 is disposed immediately below the position where the reaction vessel 3 is placed in the thermostatic block 106. The temperature sensor 107 is disposed, for example, so as to be in contact with the bottom surface of the reaction vessel 3 when the reaction vessel 3 is placed in the thermostatic block 106. The temperature sensor 107 is provided to monitor the temperature of the liquid (sample or reagent, or a mixture thereof) in the reaction vessel 3, that is, the temperature at the dispensing position. Therefore, the temperature sensor 107 is disposed immediately below the dispensing position. In other words, the temperature sensor 107 is disposed immediately below the position where the liquid (e.g., reagent) is dropped in the reaction vessel 3.
[0022] The temperature monitoring unit 109 is connected to both the temperature sensor 107 and the temperature control unit 110, and is a mechanism that calculates, stores, or displays the temperature at the dispensing position detected, for example, by using the temperature sensor 107. The temperature control unit 110 is connected to both the temperature monitoring unit 109 and the heater 108, and is a mechanism that adjusts the temperature of the heater 108 and the temperature of the constant temperature block 106 in accordance with the temperature information at the dispensing position transmitted from the temperature monitoring unit 109, thereby maintaining the temperature of the reaction vessel 3 at a predetermined temperature.
[0023] The reagent container 4 is kept in a refrigerator (not shown) for the period during which the reagent in the container is to be used (for example, several days to several weeks). The temperature in the refrigerator is kept below 10°C, for example, at about 4 to 10°C. In other words, the reagent container 4 is kept below 10°C during dispensing. In this way, the temperature of the liquid in the reagent container 4 is lower than the temperature of the dispensing position controlled by the temperature control unit 110.
[0024] The computer 11 is composed of a control unit 12, a storage unit 13, a display unit 14, and an input unit 15. The control unit 12 is connected to the reaction unit 2, and specifically, for example, is connected to each of the temperature monitoring unit 109 and the temperature control unit 110. The control unit 12, for example, controls the temperature adjustment function by the temperature control unit 110. Specifically, the control unit 12, for example, switches the temperature adjustment function on and off. In addition, the control unit 12 sends temperature information sent from the temperature monitoring unit 109 to the storage unit 13, and sends to the storage unit 13 the lengths of the on time and off time of the pulse wave applied to the heater 108 by the temperature control unit 110 to adjust the heat generation of the heater 108. These temperature information and time information are stored in the storage unit 13 connected to the control unit 12, and are displayed on the display unit 14 connected to the storage unit 13.
[0025] The control unit 12 is also connected to the liquid aspirating and dispensing unit 1, and controls, for example, the rotation and lifting of the arm 102, the up and down movement of the syringe pump 103 for pumping or aspirating, the opening and closing of the solenoid valve 104, and the operation of the water supply pump 105. That is, the control unit 12 controls the amount of dispensing. This amount of dispensing is set via the control unit 12 based on information inputted by the input unit 15. The control unit 12 sends information such as the operation speed pattern and operation amount of the liquid aspirating and dispensing unit 1 to the storage unit 13. The control unit 12 also controls the cooling temperature of the liquid in the reagent container 4. This cooling temperature is set via the control unit 12 based on information inputted by the input unit 15.
[0026] The storage unit 13 is connected to the control unit 12, the display unit 14, and the input unit 15. The storage unit 13 stores the operation speed pattern and operation amount of the liquid suction and discharge unit 1, as well as the temperature control target value of the dispensing position by the temperature control unit 110. The storage unit 13 also stores parameters necessary for device control, such as anomaly determination thresholds described below, as a table.
[0027] The display unit 14 is connected to the storage unit 13, and the screen of the display unit 14 displays the status of the liquid dispensing device, an alarm, or input information from the input unit 15. FIG. 1 shows an image 16 as an example displayed on the display unit 14. The status of the liquid dispensing device, as shown in the image 16, is, for example, reagent information (name of the reagent), the amount of reagent dispensed, the liquid cooling temperature, and the reaction temperature. The amount of reagent dispensed is a set value of the amount of liquid (e.g., reagent) dispensed into the reaction container 3 using the liquid suction and discharge unit 1. The liquid cooling temperature is the temperature of the reagent container 4 that is kept cold. The reaction temperature is the temperature at the reaction position measured by the temperature sensor 107 and the temperature monitoring unit 109. The alarm is a display for notifying the occurrence of an abnormality that has occurred in the liquid dispensing device.
[0028] The input information from the input unit 15 is, for example, reagent information (reagent name), reagent dispensed amount, liquid cooling temperature, and reaction temperature. That is, the input unit 15 is connected to the display unit 14 via, for example, the memory unit 13, and is a mechanism for inputting information required for the operation of the liquid dispensing device to the memory unit 13. This information is, for example, reagent information (reagent name), reagent dispensed amount, liquid cooling temperature, and reaction temperature. That is, the reagent information (reagent name) displayed on the display unit 14 is input by the input unit 15. Also, each of the reagent dispensed amount, liquid cooling temperature, and reaction temperature displayed on the display unit 14 can be set to a value input by the input unit 15. The display unit may display the reagent dispensed amount, liquid cooling temperature, and reaction temperature, which are target values set by inputting from the input unit 15, together with the actual measured liquid cooling temperature and reaction temperature.
[0029] <Operation of liquid dispensing device> Next, the operation of the liquid dispensing device of this embodiment will be described with reference to Fig. 1. The liquid dispensing device aims to mix a sample (e.g., serum) and a reagent, both of which are liquid, by dispensing them from separate containers into one reaction container, and to cause the sample and the reagent to react with each other.
[0030] At the start of operation, a reaction vessel 3 is transported from a reaction vessel storage position (not shown) to a reaction position on the thermostatic block 106 by a reaction vessel transport mechanism (not shown). The thermostatic block 106 is kept at 37° C. Next, although not shown, a sample liquid suction and discharge unit for the sample is used to suction the sample from the sample vessel and discharge the sample into the reaction vessel 3. Thereafter, the inside of the syringe pump 103 and the inside of the reagent flow path 18 are washed with wash water supplied from the water supply pump 105.
[0031] Next, the arm 102, which moves between a reagent aspirating position and a discharge position on the reaction container, is moved horizontally. After the arm 102 is moved to the reagent aspirating position, the support part 17, the arm 102 and the probe 101 are lowered to insert the probe 101 into the reagent container 4, and then the reagent in the reagent container 4 is aspirated by the operation of the syringe pump 103. At this time, the reagent container 4 is held in a refrigerator kept at a temperature of 10° C. or less.
[0032] Next, the arm 102 moves up to pull the probe 101 up above the reagent container 4, and then the arm 102 moves horizontally to a discharge position above the reaction container with the reagent held within the probe 101. Next, the arm 102 moves down at the discharge position above the reaction container to stop the tip of the probe 101 at the top surface of the reaction container 3, and then the syringe pump 103 operates to discharge the reagent into the reaction container 3.
[0033] The temperature monitoring unit 109 obtains temperature data from the temperature sensor 107 for a certain period of time before the reagent is dispensed into the reaction vessel 3, and calculates the average temperature. Just before the reagent starts to be dispensed into the reaction vessel 3, the temperature control unit 110 temporarily stops the temperature control of the constant temperature block 106 and the heater 108, and the temperature monitoring unit 109 monitors the temperature while the reagent is being dispensed into the reaction vessel 3 using the temperature sensor 107. Then, just after the reagent is dispensed, the temperature control unit 110 starts temperature control of the constant temperature block 106 and the heater 108 again. In other words, the temperature control function of the temperature control unit 110 is stopped while dispensing (dispensing) is being performed.
[0034] The temperature monitoring unit 109 extracts the minimum value (lowest temperature) from the temperature data during the reagent dispensing time output from the temperature sensor 107. If the minimum value of the temperature data, i.e., the minimum temperature at the dispensing position, is outside a predetermined threshold range, it is determined that there has been an abnormality in the dispensing of the liquid. In other words, if the amount of temperature change at the dispensing position is outside a predetermined threshold range after the liquid suction and dispensing unit 1 starts dispensing the liquid into the reaction vessel 3, it is determined that there has been an abnormality in dispensing. For example, if the threshold range is 34°C or less, if the minimum temperature at the dispensing position during reagent dispensing is 34.5°C, it is determined to be abnormal, and if it is 33.5°C, it is determined to be normal.
[0035] Here, the presence or absence of a dispensing abnormality is determined based on whether or not the minimum temperature at the dispensing position is within a predetermined threshold range. However, the presence or absence of a dispensing abnormality may also be determined based on whether or not the difference between the average temperature before the reagent is discharged and the minimum temperature falls outside a predetermined threshold range. In this case, the threshold range is set to, for example, 3°C or less, and an abnormality is determined when the difference between the average temperature (for example, 37°C) and the minimum temperature at the dispensing position is, for example, 2.5°C.
[0036] In addition, before calculating the average value of the temperature data at the dispensing position before the reagent is discharged, and before extracting the minimum value of the temperature data during the discharge time, a smoothing process such as taking a moving average with respect to time may be performed on each temperature data. In addition, although the sample is dispensed and then the reagent is dispensed in this example, this order may be reversed.
[0037] 1 also shows air bubbles that exist between the reagent in the probe 101 and the liquid (e.g., water) in the reagent flow path 18 that extends from the inside of the syringe pump 103 to the side of the probe 101. The presence of such air bubbles in the reagent flow path 18 separates the reagent from the liquid (e.g., water) and prevents the reagent from being discharged excessively.
[0038] <Effects of this embodiment> In specimen tests such as biochemical tests or immunological serum tests performed using a liquid dispensing device, serum or plasma is often used as a sample, and if these are left for a long time after collection until testing, clots such as fibrin will form in the sample. If this sample is run directly through the liquid dispensing device, the clots may clog the probe. If the probe is clogged in this way, a specified amount of sample cannot be dispensed into a reaction vessel, and accurate analysis results cannot be obtained. This means that the analytical reliability of an automatic analyzer using a liquid dispensing device is greatly impaired. Moreover, such problems can occur not only in dispensing samples, but also in dispensing reagents.
[0039] As described above, in the liquid dispensing device, dispensing abnormalities may occur due to clogging in the liquid flow path, i.e., a shortage of liquid dispensed into the reaction vessel by dispensing. Another example of such dispensing abnormalities may be an excessive amount of reagent dispensed into the reaction vessel due to an operational abnormality of the syringe pump.
[0040] In this embodiment, the occurrence of such abnormalities can be detected by detecting the fluctuation in the amount of temperature change at the dispensing position due to an abnormality in the amount of dispensed. That is, when the amount of dispensed is reduced below a specified amount due to clogging in the probe 101 shown in FIG. 1, the amount of reagent supplied to the reaction vessel 3, which has been kept at 10°C or less, becomes insufficient. Therefore, the amount of temperature drop at the reaction vessel due to dispensing becomes small, so that the abnormality in dispensing can be detected. Also, when an abnormality in the syringe pump 103 causes an excessive amount of reagent to be supplied to the reaction vessel 3, the amount of temperature drop at the reaction vessel becomes large, so that the abnormality in dispensing can be detected.
[0041] For this reason, in this embodiment, the upper limit or lower limit or both of the temperature change amount at the reaction position that decreases due to dispensing are set in advance as an abnormality judgment threshold (minimum temperature threshold). Here, the temperature at the dispensing position including before and after the dispensing operation varies, for example, as shown in the graph in FIG. 2. The horizontal axis of the graph in FIG. 2 is time, and the vertical axis is the temperature of the reaction section (dispensing position). As shown in FIG. 2, the temperature at the dispensing position before the dispensing start time t1 is constant, but the temperature at the dispensing position drops rapidly immediately after the dispensing start time t1, and then rises again to a constant value. At this time, if dispensing is performed normally, the minimum value of the temperature falls within the range T1 (for example, 33 to 35°C) between the two dashed lines shown in FIG. 2. This temperature range T1 is the temperature range in which dispensing is determined to have been performed normally, and the upper and lower limits of the range T1 are the abnormality judgment thresholds. Therefore, when the temperature at the dispensing position is larger or smaller than the range T1, it is determined that a dispensing abnormality has occurred, and an alarm is displayed on the display unit 14 shown in FIG. 1.
[0042] Furthermore, when the dispensed amount is smaller, the temperature change at the dispensing position due to dispensing is smaller than that shown in the graph in Figure 2. Figure 3 shows a graph of the temperature change at the dispensing position over time when the dispensed amount is small. In this case, since the amount of temperature change at the dispensing position is relatively small, range T2 (e.g., 35.5 to 36.5°C), which is the temperature range within which dispensing is determined to have been performed normally, is smaller than range T1 (see Figure 2) when the dispensed amount is relatively large.
[0043] Here, the specific values of the judgment time and the minimum temperature threshold, which are determined in advance according to the type of reagent, the reagent cooling set temperature, the reaction unit set temperature, and the dispensing amount, are shown in the table of FIG. 4. The judgment time shown in FIG. 4 is the time from the start of dispensing to the end of detection of the minimum temperature at the dispensing position. If the minimum temperature at the dispensing position is outside the minimum temperature threshold, it is determined that a dispensing abnormality has occurred. As shown in FIG. 4, the smaller the dispensing amount, the shorter the judgment time and the smaller the range of the minimum temperature threshold. Therefore, if the dispensing amount becomes excessively small, the range of the minimum temperature threshold becomes extremely small, making it difficult to accurately detect the occurrence of a dispensing abnormality. Therefore, in a device that detects a dispensing abnormality by monitoring the amount of temperature change as in this embodiment, it is desirable for the dispensing amount to be 50 μl or more from the viewpoint of ensuring the reliability of the judgment of the occurrence of an abnormality.
[0044] The memory unit 13 shown in Fig. 1 stores a plurality of types of judgment times and minimum temperature thresholds that are predefined according to the type of reagent, reagent cooling set temperature, reaction unit set temperature, and dispensing amount, respectively, shown in Fig. 4. The memory unit 13 determines (selects) the judgment time and minimum temperature threshold according to, for example, the type of reagent, the temperature of the reagent, and the temperature of the reaction position. That is, in this embodiment, the control unit 12 sets the cooling temperature of the liquid in the reagent container 4 and the dispensing amount. The memory unit 13 automatically selects an optimal minimum temperature threshold from the plurality of types of minimum temperature thresholds prestored in the memory unit 13 according to information input by the input unit 15, and monitors the dispensing state.
[0045] Also, the information in the table shown in FIG. 4 can be displayed on the screen of the display unit 14. That is, the type of reagent, the set reagent cooling temperature, the set reaction unit temperature, and the dispensing amount can be input using the input unit 15. As a result, the corresponding judgment time and minimum temperature threshold value are read out from the storage unit 13 and displayed on the screen of the display unit 14. Also, the judgment time and minimum temperature threshold value can be input from the input unit 15 in accordance with the status of the device. As a result, the respective values of the judgment time and minimum temperature threshold value can be changed from the values previously stored in the storage unit 13.
[0046] In addition, in the table of FIG. 4, the reagent cooling set temperature and the reaction unit set temperature are both constant, but when the difference between these temperatures is large, that is, when the temperature difference between the reagent and the dispensing position is large, the amount of temperature change at the dispensing position during dispensing becomes larger. Specifically, when the difference between the temperature of the reagent (reagent cooling set temperature) and the temperature of the reaction position (reaction unit set temperature) is 25°C or more, the reliability of determining the occurrence of an abnormality can be improved. In this embodiment, the reagent cooling set temperature is set to 10°C or less, and the reaction unit set temperature by the temperature control unit 110 (see FIG. 1) is 35°C or more. In other words, the temperature control unit 110 controls the temperature of the dispensing position to be heated to 35°C or more.
[0047] In addition, if temperature measurement is performed by the temperature monitoring unit 109 while the temperature control unit 110 (see FIG. 1), which has a high temperature control capability, is in operation, even if the temperature at the dispensing position drops due to dispensing, the temperature immediately returns to a predetermined value, making it difficult to detect the drop in temperature. Therefore, in this embodiment, the temperature control unit 110 temporarily stops the temperature control of the constant temperature block 106 and the heater 108 immediately before the reagent starts to be discharged into the reaction vessel 3. Then, the temperature monitoring unit 109 monitors the temperature while the reagent is being discharged into the reaction vessel 3, and immediately after the discharge of the reagent is completed, the temperature control unit 110 resumes the temperature control of the constant temperature block 106 and the heater 108. In this way, by temporarily stopping the temperature control during the dispensing operation, the minimum value of the temperature drop at the dispensing position can be easily detected. Therefore, the reliability of the judgment of the occurrence of a dispensing abnormality can be improved.
[0048] As described above, in this embodiment, the occurrence of a dispensing abnormality can be determined by monitoring the amount of temperature change at the dispensing position, thereby improving the reliability of the liquid dispensing device. Here, the case where the object to be dispensed is a reagent has been described, but since a dispensing abnormality can occur when dispensing a sample, the liquid dispensing device of this embodiment may also be used for dispensing a sample.
[0049] <Variation 1> In order to determine whether a dispensing error has occurred, the differential value of the temperature change during the reagent dispensing time may be used in addition to the temperature difference before and during the dispensing time of the reagent. In other words, a normal dispensing determination range may be set to the minimum value of the slope of the graph showing the temperature change at the dispensing position.
[0050] FIG. 5 shows a graph of the temperature at the dispensing position including before and after the dispensing operation with a solid line. The horizontal axis of the graph shown in FIG. 5 is time, and the vertical axis is the temperature of the reaction section (dispensing position). FIG. 5 also shows a graph of the differential value ΔT / Δt with respect to time Δt of the temperature change amount ΔT at the dispensing position (ΔT / Δt curve) with a dashed line. Here, if dispensing is performed normally, the minimum value of the differential of the temperature change amount falls within the range T3 between the two dashed lines shown in FIG. 5. This range T3 of the differential value is the temperature range in which dispensing is determined to have been performed normally, and the upper and lower limits of the range T3 are the abnormality determination thresholds. Thus, in this modified example, the time differential of the temperature at the dispensing position at a certain time after the start of dispensing the liquid into the reaction vessel 3 (see FIG. 1) is used as the temperature change amount.
[0051] The table in FIG. 6 shows specific values of the judgment time and ΔT / Δt threshold value, which are determined in advance according to the type of reagent, the reagent cooling set temperature, the reaction unit set temperature, and the dispensing amount. The ΔT / Δt threshold value is the temperature range (range T3) within which it is determined that dispensing has been performed normally. Unlike FIG. 4, the reaction unit set temperature is shown to be 65° C., for example. As shown in FIG. 6, the ΔT / Δt threshold value is always constant regardless of the dispensing amount. However, if the dispensing amount is small, the time for judgment is shortened, and there is a risk that the reliability of the judgment of the presence or absence of an abnormality will decrease. Therefore, from the viewpoint of ensuring the reliability of the judgment of the occurrence of an abnormality, it is desirable for the dispensing amount to be 50 μl or more.
[0052] The memory unit 13 shown in Fig. 1 stores a plurality of types of judgment times and ΔT / Δt thresholds that are determined in advance according to the type of reagent, the reagent cooling set temperature, the reaction unit set temperature, and the dispensing amount, respectively, shown in Fig. 6. The memory unit 13 determines (selects) the judgment time and the ΔT / Δt threshold according to, for example, the type of reagent, the temperature of the reagent, and the temperature of the reaction position.
[0053] Also, the information in the table shown in FIG. 6 can be displayed on the screen of the display unit 14. That is, the type of reagent, the set reagent cooling temperature, the set reaction unit temperature, and the dispensing amount can be input using the input unit 15. As a result, the corresponding judgment time and ΔT / Δt threshold value are read out from the storage unit 13 and displayed on the screen of the display unit 14. Also, the judgment time and ΔT / Δt threshold value can be input from the input unit 15 in accordance with the status of the device. As a result, the respective values of the judgment time and ΔT / Δt threshold value can be changed from the values previously stored in the storage unit 13.
[0054] <Variation 2> The occurrence of a dispensing abnormality may be judged using a drive current applied by the temperature control unit to return the temperature of the dispensing position, which has dropped due to the discharge of the reagent, to the original reaction unit set temperature.
[0055] That is, a dispensing abnormality may be determined using the drive current that the temperature control unit 110 shown in Fig. 1 applies to control the heater 108. For example, when the heater 108 is controlled by a pulse wave with a constant current value, a temperature change can be detected based on the ratio of the on time to the off time of the pulse current.
[0056] When the temperature of the thermostatic block 106 is kept constant at 37° C., the ratio of the on time to the off time of the pulse current is also controlled to be a constant ratio. In contrast, when the temperature of the dispensing position and the thermostatic block 106 drops, the ratio of the on time to the off time increases in order to raise the temperature of the dispensing position and the thermostatic block 106 to 37° C.
[0057] As another example, the heater may be controlled by changing the drive current value. In this case, the temperature change can be detected by integrating the current value over time. When the temperature of the thermostatic block is kept constant at 37°C, it is possible to control the temperature to a constant temperature (37°C) with a low drive current value, whereas when the temperature of the dispensing position and the thermostatic block 106 drops, the drive current value is increased to raise the temperature of the dispensing position and the thermostatic block 106 to 37°C.
[0058] The temperature monitoring unit 109 records the on / off time or the integral value of the pulse current for maintaining a constant temperature of the thermostatic block 106. The temperature monitoring unit 109 calculates the amount of change in energy consumption of the temperature control unit 110 using the ratio of the on / off time or the integral value after the start of dispensing the liquid into the reaction vessel 3.
[0059] The table in FIG. 7 shows specific values of the judgment temperature and the ON / OFF time ratio threshold, which are predefined according to the type of reagent, the reagent cooling set temperature, the reaction unit set temperature, and the dispensing amount. The judgment temperature is the temperature at the dispensing position, and is the temperature at which the measurement (calculation) of the ON / OFF time ratio, which started after the start of dispensing, is terminated. The ON / OFF time ratio threshold is the range of values within which dispensing is determined to have been performed normally, among the ratios of the ON time to the OFF time of the pulse current that the temperature control unit 110 applies to control the heater 108. In this modification, after the liquid suction and dispensing unit 1 shown in FIG. 1 starts dispensing the liquid into the reaction vessel 3, if the amount of change in energy consumption of the temperature control unit 110 falls outside the range of a predefined threshold (ON / OFF time ratio threshold), it is determined that dispensing is abnormal.
[0060] Here, unlike FIG. 4, for example, the case where the reagent cooling set temperature is 5°C is shown. As shown in FIG. 7, the judgment temperature is constant regardless of the dispensed amount. The judgment temperature is basically the same as the reaction unit set temperature. If the dispensed amount is small, the range of the ON / OFF time ratio threshold becomes small, and there is a risk that the reliability of the judgment of the presence or absence of an abnormality will decrease. Therefore, from the viewpoint of ensuring the reliability of the judgment of the occurrence of an abnormality, it is desirable that the dispensed amount is 50 μl or more.
[0061] The memory unit 13 shown in Fig. 1 stores a plurality of types of judgment temperatures and ON / OFF time ratio thresholds that are determined in advance according to the type of reagent, the reagent cooling set temperature, the reaction unit set temperature, and the dispensing amount, respectively, shown in Fig. 7. The memory unit 13 determines (selects) the judgment temperature and the ON / OFF time ratio threshold according to, for example, the type of reagent, the temperature of the reagent, and the temperature of the reaction position.
[0062] 7 can be displayed on the screen of the display unit 14. That is, the type of reagent, the set reagent cooling temperature, the set reaction unit temperature, and the dispensing amount can be input using the input unit 15. As a result, the corresponding judgment time and ON / OFF time ratio threshold value are read out from the storage unit 13 and displayed on the screen of the display unit 14. Also, the judgment time and ON / OFF time ratio threshold value can be input from the input unit 15 in accordance with the status of the device. As a result, the respective values of the judgment time and the ON / OFF time ratio threshold value can be changed from the values previously stored in the storage unit 13. (Embodiment 2)
[0063] 8 is a schematic diagram showing the configuration of a liquid dispensing device in embodiment 2. It is assumed that the liquid dispensing device of this embodiment will be used in, for example, an immunological analyzer. Here, an example will be described in which a reagent is dispensed as the liquid to be dispensed. This liquid dispensing device is composed of a liquid discharge nozzle unit 5, a reaction unit 2, a reaction container 3, and a reagent container 4.
[0064] The liquid ejection nozzle unit 5 is composed of a nozzle 201, a reagent flow path 202, a syringe pump 103, an electromagnetic valve 104, a water supply pump 105 and a switching valve 206, and the nozzle 201 and the reagent container 4 are connected via the reagent flow path 202 in which the switching valve 206 is formed midway.
[0065] The configurations of the syringe pump 103, the solenoid valve 104, and the water supply pump 105 are the same as those in the first embodiment. Of the reagent flow paths 202 extending in three directions from the switching valve 206, the first reagent flow path 202 has a nozzle 201 at its end, the end of the second reagent flow path 202 is immersed in the liquid (reagent) in the reagent container 4, and the end of the third reagent flow path 202 is connected to the syringe pump 103. In other words, the reagent flow paths 202 extending from the nozzle 201, the syringe pump 103, and the reagent container 4 are all connected to the switching valve 206. The reaction container 3 constituting the reaction unit 2 is disposed directly below the nozzle 201.
[0066] The configuration of the reagent container 4 and the configuration of the reaction unit 2 are the same as those in the first embodiment. A computer 11 is connected to the liquid dispensing device. The configuration of the computer 11 is the same as that in the first embodiment. That is, a control unit 12 constituting the computer 11 is connected to the reaction unit 2, and specifically, for example, is connected to each of the temperature monitoring unit 109 and the temperature control unit 110. The control unit 12 is also connected to the liquid discharge nozzle unit 5, and for example, operates the switching valve 206, and controls the vertical movement of the syringe pump 103 for pressure delivery or suction, the opening and closing of the solenoid valve 104, and the operation of the water supply pump 105.
[0067] Next, the operation of the liquid dispensing device of this embodiment will be described with reference to Fig. 2. Before the liquid dispensing device starts operating, the inside of the reagent flow path 202 between the syringe pump 103 and the switching valve 206 is filled with water, and the insides of the reagent flow paths 202 between the reagent container 4 and the switching valve 206 and between the nozzle 201 and the switching valve 206 are each filled with a reagent.
[0068] When the liquid dispensing device starts operating, the reaction vessel 3 is transported from a reaction vessel storage position (not shown) to a reaction position on the thermostatic block 106 by a reaction vessel transport unit (not shown). The thermostatic block 106 is kept at 37°C. Next, a sample (not shown) is dispensed into the reaction vessel 3 using the liquid dispensing device. The operation performed to dispense the sample is similar to the operation to dispense a reagent, which will be described next.
[0069] Next, the switching valve 206 is switched to the suction position. That is, the switching valve 206 is operated so that the reagent flow path 202 on the syringe pump 103 side and the reagent flow path 202 on the reagent container 4 side are electrically connected. Then, the reagent in the reagent container 4 is sucked into the reagent flow path 202 by the suction operation of the syringe pump 103. Next, the switching valve 206 is switched to the reagent discharge position. That is, the switching valve 206 is operated so that the reagent flow path 202 on the syringe pump 103 side and the reagent flow path 202 on the nozzle 201 side are electrically connected. Then, the reagent is discharged from the nozzle 201 into the reaction container 3 by the discharge operation of the syringe pump 103.
[0070] The temperature monitoring unit 109 obtains temperature data from the temperature sensor 107 for a certain period of time before the reagent is dispensed into the reaction vessel 3, and calculates the average temperature. Immediately before the reagent starts to be dispensed into the reaction vessel 3, the temperature control unit 110 temporarily stops the temperature control of the constant temperature block 106 and the heater 108, and the temperature monitoring unit 109 monitors the temperature while the reagent is being dispensed into the reaction vessel 3 using the temperature sensor 107. Then, immediately after the reagent is dispensed, the temperature control unit 110 starts temperature control of the constant temperature block 106 and the heater 108 again.
[0071] The temperature monitoring unit 109 extracts the minimum value (lowest temperature) from the temperature data during the reagent discharge time output from the temperature sensor 107. If the minimum value of the temperature data, i.e., the minimum temperature at the dispensing position, is outside a predetermined threshold range, it is determined that there has been an abnormality in the discharge of the liquid. In other words, if the amount of temperature change at the dispensing position is outside a predetermined threshold range after the liquid discharge nozzle unit 5 starts dispensing the liquid into the reaction vessel 3, it is determined that there has been a dispensing abnormality. For example, if the threshold range is 34°C or less, if the minimum temperature at the dispensing position during reagent discharge is 34.5°C, it is determined to be abnormal, and if it is 33.5°C, it is determined to be normal.
[0072] Here, the presence or absence of a dispensing abnormality is determined based on whether or not the minimum temperature at the dispensing position is within a predetermined threshold range. However, the presence or absence of a dispensing abnormality may also be determined based on whether or not the difference between the average temperature before the reagent is discharged and the minimum temperature falls outside a predetermined threshold range. In this case, the threshold range is set to, for example, 3°C or less, and an abnormality is determined when the difference between the average temperature (for example, 37°C) and the minimum temperature at the dispensing position is, for example, 2.5°C.
[0073] In addition, before calculating the average value of the temperature data at the dispensing position before dispensing the reagent and before extracting the minimum value from the temperature data during the dispensing time, a smoothing process such as taking a moving average with respect to time may be performed on each temperature data. Also, although the sample is dispensed and then the reagent is dispensed in this example, this order may be reversed.
[0074] The control unit 12, the storage unit 13 and the display unit 14 operate in the same manner as in the first embodiment, and the input unit 15 is used in the same manner as in the first embodiment.
[0075] In this embodiment, the configuration and operation are the same as those of the first embodiment, except that the reagent flow path 202 is fixed and the reagent flow path 202 is switched by the switching valve 206 when the reagent is aspirated and discharged. Therefore, in this embodiment, the same effects as those of the first embodiment can be obtained. (Embodiment 3)
[0076] 9 is a schematic diagram showing the configuration of a liquid dispensing device according to a third embodiment of the present invention. It is assumed that the liquid dispensing device of this embodiment is used in, for example, a hybridization device for DNA chips. Here, an example will be described in which a reagent and a sample are dispensed as the liquid to be dispensed.
[0077] The liquid dispensing device of this embodiment is composed of a liquid dispensing unit 6, a reaction unit 7, a reagent container 4, a sample container 8, a DNA chip cartridge 9, and a waste liquid unit 10. The liquid dispensing unit 6 is composed of a liquid suction nozzle 301, a switching valve 302, a liquid delivery pump 303, and a flow path 304. The DNA chip cartridge 9 is composed of a DNA chip 305, a cartridge (reaction container) 306, and a septa (a pipe insertion part having a sealing function) 307. The reaction unit 7 is composed of a constant temperature block 308, a temperature sensor 309, a heater 310, a temperature monitoring part 311, and a temperature control part 312. The liquid inlet 313 is connected to the liquid dispensing unit 6, and the liquid outlet 314 is connected to the waste liquid unit 10. The DNA chip cartridge 9 is installed in the reaction unit 7. The DNA chip cartridge 9 can be removed to the outside of the reaction unit 7.
[0078] In the liquid dispensing unit 6, each of the three liquid aspirating nozzles 301 is connected to a switching valve 302, which is connected to a flow path 304 having a liquid feed pump 303 formed therein. The end of the flow path 304 opposite the switching valve 302 is connected to a liquid inlet 313 of a cartridge 306 constituting the DNA chip cartridge 9. Some of the three liquid aspirating nozzles 301 are inserted into reagent containers 4, and the other liquid aspirating nozzles 301 are inserted into sample containers 8.
[0079] The thermostatic block 308 is made of a metal having high thermal conductivity such as aluminum, and the thermostatic block 308 is controlled to a constant temperature appropriately selected from a range of 20 to 95°C by the temperature control unit 312. The temperature sensor 309 is arranged so as to contact the side of the DNA chip cartridge 9 placed at the reaction position in the thermostatic block 308. The dispensing position here is a place surrounded by the thermostatic block 308, and is the place where the DNA chip cartridge 9 is placed in FIG. 9. The temperature of the dispensing position here means the temperature of the liquid in the DNA chip cartridge 9. The heater 310 connected to the temperature control unit 312 is arranged along the side of the DNA chip cartridge 9. The reagent container 4 and the sample container 8 are placed at room temperature during the period when the reagent and sample in each container are used. The room temperature here is, for example, 15 to 32°C. The DNA chip 305 is placed in the cartridge 306.
[0080] The waste liquid unit 10 is composed of a waste liquid container 19. Into the container 19, a flow path extending from a liquid outlet of a cartridge 306 is inserted.
[0081] A computer 11 is connected to the liquid dispensing device. The configuration of the computer 11 is the same as that of the first embodiment. That is, a control unit 12 constituting the computer 11 is connected to the reaction unit 7, and more specifically, is connected to, for example, a temperature monitoring unit 311 and a temperature control unit 312. The control unit 12 is also connected to the liquid dispensing unit 6, and, for example, operates the switching valve 302 and controls the operation of the liquid delivery pump 303.
[0082] Next, the operation of the liquid dispensing device of this embodiment will be described with reference to Fig. 9. At the start of operation, the DNA chip cartridge 9 is transported from a cartridge storage position (not shown) to a reaction position in the thermostatic block 308 by a cartridge transport unit (not shown) and placed therein. The DNA chip cartridge 9 is fixed to the reaction position by a retainer (not shown). The thermostatic block 308 is kept at 65°C. Next, the switching valve 302 is switched so as to connect the liquid suction nozzle 301 immersed in the reagent to the flow path 304. Next, the reagent is delivered using the liquid delivery pump 303, and the reagent is discharged into the DNA chip cartridge 9 via the septum 307.
[0083] The temperature monitoring unit 311 obtains temperature data of the dispensing position for a certain period of time before the reagent is discharged into the DNA chip cartridge 9 from the temperature sensor 309, and calculates the average temperature. The temperature control unit 312 temporarily stops the temperature control of the constant temperature block 308 immediately before the reagent starts to be discharged into the DNA chip cartridge 9, and the temperature monitoring unit 311 monitors the temperature of the dispensing position during the time the reagent is being discharged into the DNA chip cartridge 9 with the temperature sensor 309. The temperature control unit 312 starts temperature control again immediately after the reagent discharge is completed. The temperature monitoring unit 311 extracts the minimum value (lowest temperature) from the temperature data of the dispensing position during the reagent discharge time output from the temperature sensor 309, and if the difference from the above average temperature before the reagent discharge falls outside a predetermined threshold range, it determines that there has been an abnormality in the discharge of the liquid. For example, when the threshold range is 63°C or more and 64°C or less, if the minimum temperature of the dispensing position during the reagent discharge is 64.5°C, it is determined to be abnormal, if it is 63.5°C, it is determined to be normal, and if it is 62.5°C, it is determined to be abnormal.
[0084] The control unit 12, the storage unit 13 and the display unit 14 operate in the same manner as in the first embodiment, and the input unit 15 is used in the same manner as in the first embodiment.
[0085] In this embodiment, the reagent flow path 304 is fixed, and the reagent and sample are switched during aspiration by a switching valve 302. Except for the presence of a waste liquid unit 10 and the structure of the reaction unit 7, the other configurations and operations are the same as those of the first embodiment.
[0086] As described above, in this embodiment, the occurrence of a dispensing abnormality can be determined by monitoring the amount of temperature change at the dispensing position. The dispensing abnormality referred to here is, for example, a decrease in the amount of dispensing caused by a blockage in the flow channel 304, or an excessive amount of reagent discharged into the DNA chip cartridge 9 caused by, for example, an operational abnormality of the liquid delivery pump 303. Therefore, in this embodiment, the reliability of the liquid dispensing device can be improved.
[0087] Here, the reagent container 4 and the sample container 8 are stored at room temperature, but the DNA chip cartridge 9 is kept warm at a higher temperature (for example, 65°C) than room temperature. Therefore, when the amount of reagent supplied is less than a predetermined amount, the amount of temperature drop at the dispensing position is small, so that the occurrence of a dispensing abnormality can be detected. Specifically, since the difference between the temperature of each of the reagent container 4 and the sample container 8 and the temperature at the dispensing position is 25°C or more, the occurrence of a dispensing abnormality can be detected with high accuracy. Here, the case of dispensing a reagent has been described, but since a dispensing abnormality can occur when dispensing a sample, the liquid dispensing device of this embodiment may also be used for dispensing a sample.
[0088] The invention made by the present inventors has been specifically described above based on the embodiments thereof. However, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the spirit of the invention. [Explanation of symbols]
[0089] 1 Liquid suction and discharge unit 2, 7 reaction units 3 Reaction vessel 4 Reagent containers 5 Liquid discharge nozzle unit 6 Liquid dispensing unit 8. Sample Container 9 DNA chip cartridge 10 Waste liquid unit 11. Computers 12 Control section 13 Storage section 14 Display section 15 Input section 16 images 17 Support part 18, 202 Reagent flow path 19 Container 101 Probe 102 Arm 103 Syringe Pump 104 Solenoid valve 105 Water Pump 106, 308 Thermostatic block 107, 309 Temperature sensor 108, 310 Heater 109, 311 Temperature monitoring section 110, 312 Temperature control unit 201 Nozzle 206, 302 Switching valve 301 Liquid suction nozzle 303 Liquid delivery pump 304 Flow Path 305 DNA Chip 306 Cartridge 307 Septa 313 Liquid inlet 314 Liquid outlet
Claims
1. A container for containing a liquid; a liquid aspirating and dispensing unit that aspirates the liquid in the container and dispenses it into a reaction unit that is a dispensing position; A thermostatic block that keeps the reaction unit warm; a heater for heating the reaction unit and the thermostatic block; A temperature sensor that outputs temperature data of the reaction unit; a temperature monitoring unit that monitors the temperature of the reaction unit based on data from the temperature sensor; a temperature control unit that controls the temperature of the reaction unit by adjusting the temperatures of the heater and the constant temperature block based on temperature information of the reaction unit from the temperature monitoring unit; a control unit connected to each of the liquid suction and discharge unit and a reaction unit including the temperature control unit and the temperature monitoring unit; A storage unit connected to the control unit; a display unit and an input unit respectively connected to the storage unit; Equipped with the temperature monitoring unit determines that a dispensing abnormality has occurred when an amount of temperature change of the reaction unit monitored by the temperature monitoring unit falls outside a predetermined threshold range after the liquid suction and discharge unit starts dispensing the liquid into the reaction unit, The control unit sets a cooling temperature of the liquid in the container and an amount of the dispensing; A liquid dispensing device that automatically selects an optimal threshold value from one or more types of threshold values pre-stored in the memory unit, in accordance with information inputted by the input unit.
2. 2. The liquid dispensing device according to claim 1, A liquid dispensing device, wherein the temperature of the liquid in the container is lower than the temperature of the reaction section controlled by the temperature control section.
3. 3. The liquid dispensing device according to claim 2, A liquid dispensing device, wherein the temperature of the liquid in the container is 10°C or less.
4. 3. The liquid dispensing device according to claim 2, The temperature control unit controls the temperature of the reaction unit to be 35° C. or higher.
5. 3. The liquid dispensing device according to claim 2, A liquid dispensing device, wherein the difference between the temperature of the liquid in the container and the temperature of the reaction section controlled by the temperature control section is 25° C. or more.
6. 2. The liquid dispensing device according to claim 1, A liquid dispensing device, wherein the amount of the liquid dispensed to the reaction section is 50 μl or more.
7. 2. The liquid dispensing device according to claim 1, The temperature control is stopped before the liquid is discharged to the reaction section; the liquid dispensing device restarts the temperature control after discharging the liquid to the reaction section.
8. 2. The liquid dispensing device according to claim 1, A liquid dispensing device, wherein the temperature sensor constituting the temperature monitoring unit is disposed immediately below a position where the liquid is dropped.
9. 2. The liquid dispensing device according to claim 1, A liquid dispensing device that uses, as the amount of temperature change, a difference between an average temperature of the reaction section within a certain time period before the liquid is discharged and a minimum temperature of the reaction section after the liquid is started to be discharged.
10. 2. The liquid dispensing device according to claim 1, A liquid dispensing device, wherein the amount of temperature change is a time derivative of the temperature of the reaction section at a certain time after the start of dispensing of the liquid.
11. A container for containing a liquid; a liquid suction and discharge unit that discharges the liquid in the container into a reaction unit that is a dispensing position; A temperature control unit that controls the temperature of the reaction unit using a heater; a monitoring unit that monitors energy consumption due to a current that is passed by the temperature control unit to control the heater; Equipped with The monitoring unit determines that a dispensing abnormality has occurred when the change in energy consumption of the temperature control unit falls outside a predetermined threshold range after the liquid suction and discharge unit starts dispensing the liquid into the reaction unit.
12. 12. The liquid dispensing device according to claim 11, A liquid dispensing device wherein the monitoring unit records the on / off time of a control current pulse for the temperature control, and calculates the amount of change in the energy consumption of the temperature control unit using the ratio of the on / off time after the start of dispensing the liquid into the reaction unit.
13. 12. The liquid dispensing device according to claim 11, A liquid dispensing device wherein the monitoring unit records the current value for the temperature control over time, and calculates the amount of change in the energy consumption of the temperature control unit using the integral value of the current value after the start of dispensing the liquid into the reaction unit.
14. 12. The liquid dispensing device according to claim 11, a control unit connected to each of the liquid suction and discharge unit and a reaction unit including the temperature control unit and the monitoring unit; A storage unit connected to the control unit; a display unit and an input unit respectively connected to the storage unit; and The control unit sets a cooling temperature of the liquid in the container and an amount of the liquid to be dispensed; A liquid dispensing device that automatically selects an optimal threshold value from a plurality of types of threshold values pre-stored in the storage unit, in accordance with information inputted via the input unit.
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