JP2009041961A - Washing method of probe for handling liquid and analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method which keeps a proper analyzing result in an analyzer equipped with a probe for handling a liquid, has an advantage for minimizing a washing cost, is friendly to the global environment and satisfies economical efficiency and reliability, and the analyzer. <P>SOLUTION: In this washing method of the probe for handling the liquid, the probe for handling the liquid is allowed to fall to a liquid container, which houses an analyzing liquid and has the information related to the amount of the analyzing liquid beforehand, from a position above the container, it is detected whether the tip part of the probe arrives at the liquid surface of the analyzing liquid in the container, in relation to the falling operation of the probe, the probe is allowed to fall up to the distance of the diving quantity necessary for the handling of the liquid by the probe on the basis of the detected liquid surface position to execute the handling of the liquid, the washing range in the probe is determined on the basis of the information compared with the advance information related to the falling quantity of the probe and the amount of the analyzing liquid, so that the intensity of the washing of the probe is altered according to the washing range. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention is applied to biological analysis for medical purposes such as various research such as drug discovery and diagnosis, and is provided in an analysis apparatus that performs, for example, biochemical analysis, immunological analysis, genetic analysis, and the like. The present invention relates to a cleaning method for cleaning a probe that performs various liquid handling on a liquid sample and / or a liquid reagent. The present invention also relates to an analyzer for performing the cleaning method.

  An analysis apparatus that automates analysis of biochemistry or the like in a biological application, for example, a clinical test, includes a probe for handling various analysis liquids (samples, reagents, and the like). In such a liquid handling probe, for example, a dispensing means for sucking a desired amount of analysis liquid and supplying the desired amount of liquid to another container or the like, or stirring the liquid to be mixed in the liquid container Stirring means for doing this is mentioned. For example, the dispensing unit having at least a suction mechanism is usually provided with a cleaning unit for effectively cleaning a nozzle portion for sucking and holding the analysis liquid. This cleaning means normally detects the liquid level so that the dispensing nozzle of the suction mechanism does not penetrate too deeply into the liquid level, and it enters under the liquid level based on this liquid level detection data. The amount is calculated, and the suction mechanism is lowered by the calculated movement amount.

  However, there may be a case where liquid level detection data in which the liquid level detection mechanism is erroneous is sent out due to a characteristic noise component such as a container dirt or bubbles. In this case, a suction mechanism such as a reagent probe may be inserted deeply into the container in which the liquid remains sufficiently in the liquid container. Therefore, conventionally, the suction state is monitored by a pump pressure or the like. Therefore, it was necessary to stop the entire operation of the analyzer that performed erroneous suction and to allow the user to manually replace or clean the dispensing nozzle.

  In addition, dispensing means including a liquid level detection mechanism capable of detecting the presence or absence of bubbles or the like has been proposed (for example, Patent Documents 1, 2, and 3).

JP-A-11-271328 JP-A-11-218539 JP-A-2005-17144

However, depending on the composition of biological material, various additives used to maintain its biological activity, and temperature conditions for maintaining activity, the frequency and amount of noise components such as bubbles generated Some (size and / or quantity) vary, and some have characteristics that are very prone to foaming. If you try to detect the liquid level for this type of analytical liquid, you can set a threshold for foam detection. There is a possibility that it cannot be detected outside and the detection accuracy varies. In addition, before the suction mechanism reaches the liquid level, the liquid level may be detected to cause idle suction or empty discharge (or liquid feeding), or may be scattered by air or result data may be defective. In this way, for various types of noise that cannot be handled by the bubble detection function, not only is it unknown how far the dispensing nozzle has entered the liquid level, but to what extent the dispensing nozzle Since it was difficult to grasp whether the container was dirty, it was difficult to prevent carryover between containers as dispensing destinations.

  In addition, when suction is repeatedly performed from a container in which bubbles or the like are arbitrarily generated, the liquid level can fluctuate depending on the generation amount of bubbles or the like, so the accurate remaining amount of liquid cannot be grasped, and the next time The dispensing volume can be inaccurate.

  On the other hand, in the analysis apparatus, a stirring probe having a rotating blade or a vibrator for stirring at the tip is attached to the reaction liquid in the reaction container to the required depth for the reaction container in which the sample and the reagent are dispensed. Stirring is performed in the invading state. Such a stirring probe also generates and / or generates noise components such as bubbles according to the composition of the sample and / or reagent contained in the reaction liquid in the reaction vessel and the set temperature for adjusting the reaction in the reaction liquid. Due to the difference in volume, it was difficult to prevent carryover between reaction vessels.

  An object of the present invention is to provide a cleaning method for a liquid handling probe that can perform proper cleaning even when the liquid level detection by the liquid handling probe is incorrect or uneven.

  Another object of the present invention is to provide a method capable of accurately updating the remaining amount of liquid in a container after liquid suction even when the liquid level is detected depending on whether bubbles or the like are generated. .

  Furthermore, still another object of the present invention is to enable analysis by suppressing contamination without stopping the apparatus by appropriately changing the cleaning power when contamination of the dispensing nozzle is predicted. It is to provide a method for cleaning a dispensing nozzle.

  In order to achieve the above-described object, the present invention provides a liquid handling probe from a position above the liquid container with respect to a liquid container that contains an analysis liquid and has information on the liquid amount in advance. By lowering, it is detected whether or not the tip portion of the probe has reached the liquid level of the analysis liquid in the liquid container in association with the downward movement of the probe, and the liquid level position detected by the detection is detected. Therefore, liquid handling is performed by lowering the probe to a distance corresponding to the amount of subtraction required for liquid handling by the probe, and based on comparison information comparing the amount of descent of the probe with prior information on the liquid amount. And a cleaning range for the probe is determined, and the cleaning strength for the probe is changed in accordance with the determined cleaning range. A method of cleaning Ndoringu probe. Here, the liquid handling may be dispensing and / or agitation of the analysis liquid, so that dispensing or agitation operation may be performed. Further, the liquid handling is an analysis liquid dispensing operation, and by changing the cleaning range to be determined based on the type of the analysis liquid and the amount of liquid to be sucked, noise components can be easily generated. It is possible to provide a cleaning method according to the size. In addition, the liquid handling is an analysis liquid stirring operation, and by changing the cleaning range to be determined based on the type of the analysis liquid and the temperature information of the analysis liquid in the liquid container, a variety of Appropriate probe washing can always be performed when performing biological reactions.

  Further, the present invention provides each dispensing when a predetermined amount is dispensed by aspirating the analyzing liquid a plurality of times from a liquid container that contains the analyzing liquid and has information about the liquid amount in advance. The information on the liquid level or the liquid level in the liquid container before suction is prepared, the liquid level in the liquid container is detected by a liquid level detection mechanism, and the liquid level detection mechanism is applied. The liquid level detected by the above and the information are compared, and based on the comparison result, the strength of cleaning the dispensing nozzle in each dispensing is changed, and the liquid remaining after suction in the liquid container is changed. It is also a dispensing nozzle cleaning method characterized in that information on the liquid amount or the liquid surface height corresponding to the amount is determined and the determined information is used as preparation information in the next dispensing. According to the present invention, the remaining amount data can be appropriately updated even if a malfunction occurs in the liquid level detection, so that appropriate cleaning can always be performed. Here, when the liquid level detection mechanism has a function capable of detecting noise information such as bubbles, and the liquid level detection mechanism detects the noise information, the liquid level position detected by the liquid level detection mechanism Is determined as a true liquid level and suction is performed with a submerged amount corresponding to the amount to be sucked, and the remaining amount of liquid after suction is determined based on the previous liquid amount information instead of the liquid level position. In this way, the remaining amount data can be updated appropriately while performing suction based on the true liquid level. Further, in the case where the liquid level detection mechanism does not have a function of detecting noise information such as bubbles, the liquid level detected by the liquid level detection mechanism is significantly different from the previous liquid amount information. In this case, suction is performed with a subtraction amount corresponding to the sum of the amount to be sucked and the amount set for the presence of noise, and the remaining amount of liquid after suction is not the liquid level position but the advance amount. If the determination is made based on the liquid amount information, the probe suction and the remaining amount data can be updated without being affected by the presence or absence of noise components. In addition, when the comparison result reflects an erroneous liquid level due to erroneous detection of the liquid level detection mechanism, a change that increases the cleaning strength for the dispensing nozzle may be performed. preferable.

Further, according to the analyzer of the present invention, a probe for entering a liquid for analysis in the liquid container and performing a predetermined liquid handling operation, a liquid container to be handled among the plurality of liquid containers, and the probe And a liquid level detecting means for acquiring information on the amount of liquid or the liquid level in the liquid container, and a transfer means for positioning the same at the same position, and a height of the tip of the probe. Cleaning means for cleaning the probe by switching to two or more different cleaning forces, and depending on the amount of penetration of the probe after the liquid level detection obtained by the liquid level detection means by the cleaning means And a control means for switching the cleaning power. Here, the switching of the cleaning force by the control means is performed by selectively positioning the probe with respect to a plurality of cleaning liquids having different cleaning powers stored in independent cleaning tanks in the cleaning means. Cleaning with an appropriate cleaning force can be selected only by moving the probe.
Further, the switching of the cleaning power by the control means may be executed by changing the cleaning power of the cleaning liquid supplied to the common cleaning tank in the cleaning means, and in this case, a reduction in space can be obtained. In addition, it is possible to change the cleaning power in the cleaning process. Further, the control means stores a type for each of a plurality of liquid containers, and a subtraction amount obtained by adding a subtraction amount to be added for each type of analysis liquid to a predetermined subtraction amount of the probe. If the cleaning means is switched based on the amount of subsidence after the data generation, handling and cleaning according to generation of noise components in a predictable range can be performed. Can be executed. In addition, the data generation unit is configured to be able to set a plurality of submerged amounts according to the occurrence frequency and / or amount of noise components expected for each type of analysis liquid, so that any liquid type can be set. On the other hand, appropriate cleaning is always performed. Similarly, the data generation unit can set a plurality of submerged amounts in accordance with the frequency and / or amount of noise components expected based on the temperature management information for each type of analysis liquid. preferable.

  In the analyzer, the tip of the probe has a dispensing nozzle for sucking and dispensing the analysis liquid in the liquid container, and the cleaning means is moved by the dispensing nozzle. It is convenient to place it in the middle. Further, the suction means has a dispensing cycle comprising a plurality of suction operations executed at different timings from the same liquid container and a cleaning operation by the cleaning means executed between each suction operation. Practical efficiency is good. In addition, the suction means includes a chip replacement section for mounting a replaceable chip on the dispensing nozzle portion and dispensing the same analysis liquid a plurality of times. Proper liquid handling and probe cleaning. Further, the tip of the probe has a stirring means for immersing the analysis liquid in the liquid container to a desired depth to perform stirring, and the moving destination where the stirring means moves to a position away from the liquid container. However, it is practically preferable to arrange the cleaning means. Further, the agitation means is configured to be able to switch the cleaning power by executing the agitation operation according to the sinking amount in a state where it has entered the cleaning tank in the cleaning means, so that a special configuration for cleaning is provided. Is preferable because the cleaning cost is further reduced.

  ADVANTAGE OF THE INVENTION According to this invention, the method and analyzer which can be wash | cleaned appropriately with respect to the submergence (for example, excessive descent | fall amount etc. by a bubble etc.) with respect to the analysis liquid of the probe for liquid handling which cannot be controlled can be provided. Furthermore, it is possible to provide a method and an apparatus capable of performing appropriate probe cleaning even when the liquid level detection malfunctions by maintaining accurate analysis liquid remaining amount data.

The best mode for carrying out the invention will be described in detail with reference to the drawings.
First, an automatic analyzer according to this embodiment will be described with reference to FIG. FIG. 1 is a plan view showing a schematic configuration of the automatic biochemical analyzer according to the first embodiment.
Referring to FIG. 1, in the automatic analyzer according to the present embodiment, a reaction disk 2, a sample turntable 3, and a reagent turntable 4 are arranged in the apparatus main body 1. A plurality of reaction containers 5 are arranged in a ring on the concentric circle on the reaction disk 2, and a plurality of sample containers (sample containers) 6 are arranged in a ring on the concentric circle on the sample turntable 3. ing. In addition, a plurality of reagent bottles 7 are annularly arranged on the concentric circumference on the reagent turntable 4. Here, as described in JP-A-2007-147658, the reagent bottle 7 is installed so as to be able to rotate on a turntable, and a sedimentary component (a solution containing a fine particulate reagent or a liquid high-viscosity reagent in the reagent bottle). Etc.) may always be kept in a uniform suspension.

Here, the sample container 6 contains a sample to be analyzed, that is, blood, urine, fecal lysate, cultured cell solution, and the like. In the reagent bottle 7, a plurality of types of biochemical analysis reagents necessary for analysis items are individually stored. The reaction disk 2, the sample turntable 3, and the reagent turntable 4 are intermittently rotated by a rotation mechanism (not shown), respectively, so that predetermined positioning is possible. In the reaction disk 2, a liquid dispensing position P1, a reagent dispensing position P3, a stirring position P5, a measurement position P6, and a reaction container cleaning position P7 are stored and set in an apparatus controller (not shown). Similarly, a sample aspiration position P2 and a reagent aspiration position P4 are set in the sample turntable 3 and the reagent turntable 4, respectively.

  Further, the apparatus main body 1 is provided with a sample dispensing unit 8 and a reagent dispensing unit 9. Each of the sample dispensing unit 8 and the reagent dispensing unit 9 has a dispensing probe (not shown) at the tip, and can be moved up and down and rotated. The dispensing probes are each connected to a syringe pump (not shown) so that a specimen or sample can be aspirated and discharged. In addition, a cleaning liquid feed pump (not shown) that supplies cleaning liquid into the dispensing probe is connected, and the inside of the dispensing probe can be cleaned by discharging the cleaning liquid from the tip of the dispensing probe after the dispensing operation. Yes. All operations by these dispensing probes are controlled by probe driving units 21 and 22 corresponding to the dispensing units 8 and 9.

  The sample dispensing unit 8 is disposed at a position where it can go back and forth between the sample dispensing position P1 and the sample aspirating position P2 by a rotating operation. Dispensing provided in the sample dispensing unit 8 is located between the sample dispensing position P1 and the sample aspirating position P2 on the path through which the sample dispensing unit 8 passes by rotation. A specimen cleaning tank 10 for cleaning the probe is provided.

  The reagent dispensing unit 9 is disposed at a position where the reagent dispensing unit 9 can be moved back and forth between the reagent dispensing position P3 and the reagent suction position P4 by a rotating operation. Then, between the reagent dispensing position P3 and the reagent aspirating position P4, on the path through which the reagent dispensing unit 9 passes by rotation, the dispensing probe provided in the reagent dispensing unit 9 A reagent cleaning tank 11 for cleaning is disposed.

  In addition, a stirring unit 12 is provided at the outer peripheral position of the stirring position P5 so that the liquid mixture in the reaction vessel 5 sequentially stopped at the stirring position P5 of the reaction disk 2 is sequentially stirred while moving up and down. It has become. In addition, the agitation unit 12 rotates so as to reciprocate between the agitation position P5 and the agitation washing tank 27, and moves to the agitation washing tank 27 after agitation with respect to the reaction vessel 5 every time. By moving, the stirring probe is immersed in the cleaning liquid in the cleaning tank. Here, a stirring probe (not shown) is provided at the tip of the stirring unit 12, and the mixed solution in the reaction vessel 5 is uniformly mixed by an appropriate stirring mechanism (for example, a rotatable rotating blade), and a washing tank. In 27, it is rinsed in sufficient contact with each cleaning solution. All the operations in the stirring unit 12 are controlled by the probe driving unit 23.

  As one component characterizing this embodiment, the sample dispensing unit 8, the reagent dispensing unit 9 and the stirring unit 12 are the liquids in the sample container 6, the reagent container 7 and the reaction container 5, respectively (ie, , Specimen, reagent, reaction mixture) are connected to the submerged amount determining units 24, 25, and 26 for determining how much each probe has submerged. In order to determine the amount of immersion in the liquid, a liquid level detection mechanism (not shown) is provided for each probe. Here, the liquid level detection mechanism provided in the dispensing probe of the sample dispensing unit 8 has a configuration for detecting the liquid level of the sample stored in the sample container 6 positioned at the sample suction position P2. ing. The liquid level detection mechanism provided in the dispensing probe of the reagent dispensing unit 9 has a configuration for detecting the liquid level of the sample stored in the reagent container 7 positioned at the reagent suction position P4. Yes. Further, the liquid level detection mechanism provided in the stirring probe of the stirring unit 12 has a configuration for detecting the liquid level of the mixed liquid stored in the reaction vessel 5 on the reaction disk 2 positioned at the stirring position P5. Yes.

  As another component that characterizes this embodiment, each of the cleaning tanks 10, 11, and 27 includes two storage portions for storing two types of cleaning liquids having different cleaning powers. That is, as shown in FIG. 1, each of the cleaning tanks 10, 11, and 27 contains two types of cleaning liquids independently by a partition and the like, and is a series of cleanings such as cleaning with a detergent necessary for cleaning and rinsing with a buffer solution. It has a mechanism for executing the cleaning process. Here, in order to make the cleaning power different, it is assumed that cleaning liquids having different types and / or concentrations of detergents are used in each of the two accommodating portions. Moreover, it is preferable that the types and concentrations of the detergents in the cleaning liquids for the sample probe, the reagent probe, and the stirring probe are different.

  A measurement unit 13 is disposed at the outer peripheral position of the measurement position P6, and measurement signals such as absorbance and fluorescence (or luminescence) intensity of the mixed solution in the reaction vessel 5 that has come to the position of the measurement position P6 are measured. It is configured to do. A reaction container cleaning unit 14 is disposed at the outer peripheral position of the reaction container cleaning position P7, and the liquid mixture that has been measured and analyzed is discarded and the reaction container is cleaned.

  All the operation elements provided in FIG. 1 are controlled so that required analysis is performed by a control unit for the entire apparatus (not shown).

  In this embodiment, it is uniquely determined whether normal cleaning or relatively strong cleaning is performed based on the determination results by the respective submerged amount determination units 24, 25, and 26, and the control is performed accordingly. Of the two storage units of each of the cleaning tanks 10, 11, 27 by giving an instruction to the probe driving units 21, 22, 23 to perform normal cleaning or relatively strong cleaning Then, the probe is caused to descend and enter the housing portion having the cleaning liquid having an appropriate cleaning power. In the cleaning tanks 10, 11, and 27, when the probe is submerged to the required depth in the cleaning liquid in the selected storage unit, the cleaning is always completed within the same time by a constant cleaning operation. The probe water immersion operation with respect to the cleaning liquid may be configured to always have a constant water immersion amount, or may be configured to be adjusted to a depth corresponding to the determined submerged amount. In addition, by monitoring whether the probe is immersed in the cleaning liquid using the liquid level detection mechanism unique to each probe, it is possible to monitor the cleaning state and synchronize the ON / OFF state of the cleaning operation to eliminate waste of the cleaning operation. It is.

  According to this embodiment, a dispensing probe that is dispensed with a different sample or reagent each time and washed and reused, or agitated that is washed and reused each time the liquid mixture in each reaction vessel is stirred. In the case of using a probe, the appropriate amount of cleaning is always performed by determining the amount of probe penetration with respect to each analysis liquid (ie, sample, reagent, reaction mixture) required for analysis. In particular, according to this determination method, even if a malfunction occurs due to the liquid level detection mechanism unique to each probe, the amount of penetration is determined so that proper cleaning can be performed, and cleaning with an appropriate cleaning power can be performed. In addition, it is possible to always perform analysis with excellent reproducibility without stopping the analyzer, and to minimize the cleaning cost.

  FIG. 2 is a diagram schematically showing the configuration of the main part of the automatic analyzer according to the second embodiment of the present invention. The automatic analyzer 100 shown in FIG. 1 dispenses a sample and a reagent into a reaction vessel, performs optical measurement on the liquid in the reaction vessel, and controls the drive of the measurement mechanism 101. The central control unit 201 that analyzes the measurement result in the measurement mechanism 101 is an apparatus that automatically and continuously performs immunological analysis of a plurality of samples by cooperation of these two mechanisms. In the following description, it is assumed that the automatic analyzer 100 performs immunological measurement using a heterogeneous reaction. Note that the apparatus described in this embodiment may be a bioimmune complex type analyzer that performs biochemical analysis as in the first embodiment in any combination.

  First, the measurement mechanism 101 of the automatic analyzer 100 will be described. The measurement mechanism 101 includes a sample transfer unit 102 that stores and sequentially transfers a plurality of racks 121 on which sample containers 122 that store a sample Sp are mounted, and a carrier that stores a carrier reagent applied to an antigen-antibody reaction with the sample Sp. A carrier reagent container holding unit 103 for holding a reagent container 123, a liquid reagent container holding unit 104 for holding a liquid reagent container 124 for storing various liquid reagents, and a reaction container for holding a reaction vessel 125 for reacting a sample and a reagent. A holding unit 105.

  The carrier reagent container holding unit 103 includes a wheel that holds the carrier reagent container 123, and a driving unit that is attached to the center of the bottom surface of the wheel and rotates the wheel about a vertical line passing through the center. Similarly to the carrier reagent container holding unit 103, the liquid reagent container holding unit 104 and the reaction container holding unit 105 each have a wheel and driving means for rotating the wheel.

  Each container holding part is maintained at a constant temperature. For example, the liquid reagent container holding unit 104 is set to a temperature lower than room temperature in order to suppress the deterioration and denaturation of the reagent, and is set to a temperature approximately equal to the human body temperature in the reaction container holding unit 105.

  The measurement mechanism 101 also includes a sample dispensing unit 106 for dispensing the sample Sp accommodated in the sample container 122 on the sample transfer unit 102 into the reaction container 5 held by the reaction container holding unit 105, and a carrier reagent container holding A carrier reagent dispensing unit 107 for dispensing the carrier reagent contained in the carrier reagent container 123 on the unit 103 into the reaction container 125, and a liquid reagent contained in the liquid reagent container 4 on the liquid reagent container holding unit 104. A liquid reagent dispensing unit 108 for dispensing the reaction vessel 125 to the reaction vessel 125, and a reaction vessel transfer unit for transferring the reaction vessel 125 to install or remove the reaction vessel 125 from the reaction vessel holding unit 105 109.

  The sample container 122 is affixed with an information code recording medium (not shown) in which identification information for identifying a sample contained therein is encoded and recorded in an information code such as a barcode or a two-dimensional code. Similarly, an information code recording medium in which identification information for identifying a reagent contained therein is encoded and recorded is also attached to the carrier reagent container 123 and the liquid reagent container 124 (not shown). Therefore, the measurement mechanism 101 is attached to the information code reading unit CR1 that reads the information code attached to the sample container 122, the information code reading unit CR2 that reads the information code attached to the carrier reagent container 123, and the liquid reagent container 124. The information code reading unit CR3 for reading the information code is provided. Furthermore, in the present invention, information recorded by coding identification information into an information code for identifying a reaction liquid (which may be any combination of a sample, a liquid reagent, and a carrier reagent) to be later dispensed also into the reaction container 125 Each code recording medium is affixed (not shown). Therefore, the measurement mechanism 101 further includes an information code reading unit CR4 that reads the information code attached to the reaction container 125.

  The sample dispensing unit 106 is realized by the dispensing apparatus 100 according to the present embodiment. On the operation line of the sample dispensing unit 106, a tip storage unit 116 for holding an unused tip (not shown) at the tip of the probe 121 and a used disposable tip (not shown) from the probe 121. A chip discarding unit 126 for removing and discarding is provided. When the tip is attached to the probe 11 of the sample dispensing unit 106, the tip is attached by lowering the probe 11 at a predetermined tip attachment position in the tip storage unit 116. On the other hand, when the tip discarding unit 126 removes the tip from the probe, for example, a jig having a slit-shaped notch is provided in the tip discarding unit 126, and after inserting the probe 121 into the slit portion, the probe 121 The used chip may be removed by raising it and automatically dropped into the disposal box.

  The carrier reagent dispensing unit 107 and the liquid reagent dispensing unit 108 have substantially the same configuration as the sample dispensing unit 106. In the present embodiment, it is not assumed that the tip of the probe is attached to the tip of the probe by the carrier reagent dispensing unit 107 and the liquid reagent dispensing unit 108, but each time the sample is dispensed, similar to the sample dispensing unit 106. It is also possible to adopt a configuration in which a new tip is attached to the tip of the probe.

  On the operation line of the reaction vessel transfer unit 109, a reaction vessel storage unit 119 that holds an unused reaction vessel 125 and a reaction vessel disposal unit 129 that discards a used reaction vessel 125 are provided. The reaction container transfer unit 109 may have any configuration as long as the liquid can be transferred without spilling even when there is a liquid inside the reaction container 125.

  Next, the configuration of the measurement mechanism 101 will be described. The measurement mechanism 101 includes a B / F washing unit 110 that performs B / F washing of the carrier reagent, a stirring unit 111 that has a stirring rod that stirs the liquid contained in the reaction vessel 125, and a reaction in the reaction vessel 125. A photometric unit 112 that detects light emitted from the liquid. The B / F cleaning unit 110 discharges the B / F cleaning liquid such as physiological saline to the reaction container 125 and the B / F cleaning liquid after the B / F cleaning is sucked from the reaction container 125 and discarded. A suction nozzle.

As a feature of the present invention, the dispensing probes provided in each of the sample dispensing unit 106, the carrier reagent dispensing unit 107, and the liquid reagent dispensing unit 108 are the same as those described in the first embodiment. It is assumed that the liquid level detection mechanism is integrated. As shown in FIG. 2, each of the sample dispensing unit 106, the carrier reagent dispensing unit 107, and the liquid reagent dispensing unit 108 includes cleaning devices 133 and 132 for cleaning each dispensing probe. 131 is arranged in the middle of the probe trajectory. In each of the cleaning devices 131 to 133, a cleaning solution supply / discharge structure is formed on the side and bottom of the cylindrical cleaning tank. The cleaning flow rate and the detergent concentration in each of the cleaning devices 131 to 133 are controlled by the cleaning control units 134 to 136. Here, the control of the cleaning control units 134 to 136 is performed by relatively increasing the cleaning flow rate and / or the detergent concentration with respect to the probe that requires a strong cleaning power according to the above-described criteria for the cleaning method of the present invention. Adjust the value to clean the probe. Conversely, for probes that can be cleaned with normal cleaning power, the standard cleaning flow rate and / or detergent concentration, which is the normal cleaning mode, is set. For the configuration for adjusting the strength of the cleaning power, reference may be made to, for example, JP-A-4-169551, JP-A-57-39353, and the like. Japanese Patent Laid-Open No. 5-307043 may be referred to for the configuration of the cleaning means for using the replaceable disposable tip for multiple dispensing.

  The photometry unit 112 has a photomultiplier tube that can detect weak light. Note that when measuring fluorescence generated from the reaction solution, a light source for irradiating excitation light may be provided as the photometric unit 112.

  In the measurement mechanism 101 having the above-described configuration, the angle at which the reaction container holding unit 105 rotates by one rotation operation is determined in advance, and the sample Sp and various reagents are dispensed simultaneously and frequently by the rotation. All the components are arranged so as to be configured. In this sense, FIG. 2 is merely a schematic illustration of the components of the measurement mechanism 101. That is, the mutual positional relationship between the components of the measurement mechanism 101 is a design matter that should be determined according to conditions such as the rotation mode of the wheel of the reaction container holding unit 105.

  Next, the configuration of the central control unit 201 of the automatic analyzer 100 will be described. The central control unit 201 receives a data generation unit 202 that generates analysis data of the sample Sp based on the measurement result in the measurement mechanism 101, and information necessary for analyzing the sample Sp and an operation instruction signal of the automatic analyzer 100. An input unit 203, an output unit 204 that outputs information including analysis results, a storage unit 205 that stores information including analysis results, and a control unit 206 that controls the automatic analyzer 100 are provided.

  The control unit 206 controls various operations of the automatic analyzer 100 by reading a program stored in the storage unit 205 from the memory. For this reason, the control part 206 has the function of the control part 15 of the dispensing apparatus 100 applied as the sample dispensing part 106. The output unit 204 also has the function of the output unit 29 of the dispensing device 1.

  When the central control unit 201 having the above configuration receives the measurement result from the photometry unit 112, the data generation unit 202 calculates the light emission amount of the reaction liquid in the reaction vessel 125 based on the measurement result sent from the photometry unit 112. To do. Further, the data generation unit 202 quantitatively obtains the components of the reaction solution by referring to information such as a calibration curve and analysis parameters obtained from the standard sample in addition to the calculation result of the light emission amount of the reaction solution described above, Analytical data of the sample Sp is generated. The analysis data obtained in this way is output from the output unit 204 while being stored and stored in the storage unit 205.

  When the dispensing apparatus 100 is applied as the sample dispensing unit 106 of the automatic analyzer 100, remark information is added as error information to a list of analysis results displayed on the output unit 204, for example. You may make it display clearly at which stage abnormality was detected.

An outline of analysis processing in the automatic analyzer 100 having the above configuration will be described. Here, as an example, among the enzyme immunoassay (EIA), which is an example of a heterogeneous reaction, the concentration of a predetermined antigen in the sample Sp is measured by using a two-step sandwich method (non-competitive method). The case where it does is demonstrated. First, a carrier reagent containing a solid phase carrier sensitized by an antibody that specifically binds to a predetermined antigen in the sample Sp is dispensed into the reaction vessel 5 by the carrier reagent dispensing unit 107, and then the reaction vessel 125 is added to the reaction vessel 125. The sample Sp is dispensed by the sample dispensing unit 106, the carrier reagent and the sample are mixed by the stirring unit 111, and the first immune reaction (antigen-antibody reaction) is performed. The configuration of the agitation unit 111 is not necessarily a type of agitation mechanism that penetrates into the liquid as in the first embodiment. However,
When the stirring unit 111 is a type of stirring mechanism that penetrates into the liquid, the cleaning unit need not necessarily have two types of cleaning tanks as shown in FIG. The detergency can also be changed by performing agitation with different agitation forces according to the measurement items in a state where they have sufficiently entered the tank.

  After the first immune reaction described above, B / F washing of the B / F reaction solution is performed in the B / F washing unit 110, and the sample Sp (containing the antigen is released without specifically binding to the antibody). ) And antibodies are separated and removed from the solid support. Subsequently, an enzyme (first reagent) as a labeling substance is excessively added to the reaction solution after the B / F washing by the liquid reagent dispensing unit 108 to cause the second immune reaction. Even after the second immune reaction, B / F washing of the reaction solution is performed in the B / F washing unit 110 to separate and remove excess labeling substance and the like from the solid phase carrier. Note that, also in the second immune reaction, the stirring by the stirring means as described above or the cleaning power change using the stirring function may be executed.

  Thereafter, a chromogenic substrate (second reagent) in which the enzyme, which is a labeling substance, exhibits an activity is dispensed by the liquid reagent dispensing unit 108 into the reaction solution after the second B / F washing. A color development reaction is performed with the labeling substance, and the amount of light developed by the color development reaction is optically measured by the photometry unit 112. The data generation unit 202 performs a comparison operation between the data obtained by the measurement in the photometric unit 112 and the data (calibration curve) obtained from a standard sample whose concentration of the antigen is known, thereby performing a sample Sp of the antigen to be analyzed. Analytical data is generated by quantitatively determining the concentration in the medium.

  As an immunoassay method, a one-step sandwich method (competitive method) can be applied instead of the two-step sandwich method described above. In addition, as immunoassays using heterogeneous reactions other than enzyme immunoassays, for example, fluorescent immunoassay (FIA) using a fluorescent substance as a labeling substance, radioimmunoassay (RIA) using a radioisotope as a labeling substance ), Chemiluminescent enzyme immunoassay (CLEIA) using a chemiluminescent substrate as a labeling substance, and spin reagent immunoassay (SIA) using a spin reagent as a labeling substance can also be applied. It is also possible to perform an immunological analysis of a sample using a homogeneous reaction using the automatic analyzer 100. In this case, it is not necessary to perform B / F washing of the reaction solution as in the case of the heterogeneous reaction described above.

  According to the automatic analyzer 100 according to the present embodiment described above, by applying the dispensing device 1 according to the present embodiment as the sample dispensing unit 106, the mounting failure of the tip to the probe 121 or the sample Abnormalities such as adhesion of Sp to the probe 121 can be detected in real time, so that carryover and contamination can be prevented. As a result, it is possible to reduce the work load when the operator performs maintenance on the automatic analyzer 100.

  According to the dispensing device and the automatic analyzer according to the embodiment of the present invention described above, a thin tubular probe having conductivity and a detachable attachment to one end portion in the longitudinal direction of the probe, An insulating tip, probe transporting means for transporting the probe, contact detection means for electrically detecting contact between the probe and the liquid to be sucked or discharged at the tip of the tip, and the probe transporting means Disposable type chip comprising: a control unit that controls to stop driving of the probe transfer unit when the contact detection unit detects contact between the probe and the liquid during transfer of the probe. Detects abnormalities that occur when dispensing a sample with the use of this in real time to prevent carryover and contamination. It is possible to prevent a decrease in Rutotomoni dispensing accuracy.

  Further, according to the present embodiment, since the detection means that is expensive and requires a space for arrangement, such as a camera and an optical sensor, is unnecessary, the cost required for mounting the device is suppressed, and the device It becomes possible to easily realize downsizing and space saving.

  The best mode for carrying out the present invention has been described in detail so far, but the present invention should not be limited only by the above-described embodiment. For example, when dispensing a sample in the dispensing apparatus according to the present invention (and the sample dispensing part of the automatic analyzer), the syringe and the tube are filled with a cleaning liquid composed of an incompressible fluid such as ion exchange water. It is also possible to adopt a configuration in which the discharge pressure and the suction pressure are transmitted from the syringe to the tip of the tip via this cleaning liquid. The present invention can also be applied to the case where a highly viscous liquid containing gel or saccharide is handled as the analysis liquid. In high-viscosity liquids, noise components such as bubbles may remain for a long time. Therefore, when handling multiple times, setting of the cleaning method that always considers the presence of bubbles and remaining amount data Is preferably updated.

  The dispensing apparatus according to the present invention can also be applied to an automatic analyzer that performs biochemical analysis, immunological analysis, genetic analysis, etc. alone or in any combination. When performing biochemical analysis, a light source that generates white light, a spectroscopic optical system that splits light transmitted through the reaction vessel out of the white light generated from the light source into a predetermined frequency component, and the spectroscopic optical system What is necessary is just to comprise a photometry part by using the light receiving element which receives the light for every component disperse | distributed by (1). Further, the central control unit of the automatic analyzer calculates the absorbance of the reaction solution of the sample and the reagent based on the measurement result in the photometry unit, and generates the analysis data of the sample using the calculated absorbance. That's fine.

  As described above, the present invention can include various embodiments and the like not described herein, and various design changes and the like can be made without departing from the technical idea specified by the claims. It is possible to apply.

  FIG. 3 is a block diagram showing an analyzer for carrying out the method for cleaning a dispensing probe of the present invention. A probe lifting / lowering drive unit 401 for moving the probe 408 up and down is attached to the distal end of the rotation arm 407 whose rotation is controlled by the probe driving unit 406. On the rotation trajectory of the probe 408, a plurality of liquid containers 412 are held at equal intervals along the circumference of the rotating disk 413 whose rotation is controlled by the table driving means 402. One of the liquid containers 412 held on the rotating disk 413 is stopped at a predetermined suction position and coincides with the rotation locus of the probe 408. In addition, a microplate 409 as a reaction vessel is disposed on the rotation locus of the probe 408 in a state where it is immobilized by a fixing means (not shown). The microplate 409 has a structure in which a large number of wells are formed in a grid pattern, and is transported in a two-dimensional manner in the X and Y directions by a transport device (not shown). A specific well is positioned with respect to a predetermined discharge position provided. Between the liquid container 412 at the suction position and the well at the discharge position, the first cleaning tank 410 and the second cleaning tank 411 are arranged at different positions on the rotation locus while the probe 408 is moving. . It is assumed that the cleaning solution stored in the first cleaning tank 411 contains a detergent having a stronger cleaning power than the second cleaning tank 410.

  In the analyzer having such a configuration, after the probe 408 moves above the liquid container 412 which stops on the rotation trajectory of the probe, the probe starts to descend. The probe 408 has a known liquid level detection mechanism based on electrostatic capacity, enters the liquid container 412, acquires a detection signal that seems to be the liquid level of the analysis liquid, and sends it to the control unit 405. The probe lowering amount thus far is sent to the control unit 405 in real time by the lowering amount measuring unit 403. In addition, since the type of the analysis liquid to be sucked is registered and managed by the table driving means 402, the amount of subtraction that can be surely obtained even if the liquid level detection malfunctions due to noise components is set. As a result, the control unit 405 performs a determination to be described later in an arithmetic circuit in the control unit, and calculates the amount of the probe 408 to be submerged. Next, the probe 405 moves above the microplate 409 and discharges a required amount of analysis liquid in a state where the well to be discharged is stopped by XY driving. Next, the probe 408 that has finished the desired amount of suction and discharge is selectively placed above any one of the first and second cleaning tanks 410 and 411 based on the amount of subtraction calculated by the control unit 405. It is moved and stopped for a certain period of time with a sufficient amount of water immersed in the cleaning liquid. In this way, the probe 408 having been cleaned with an appropriate cleaning force moves to the next liquid container 412 to be aspirated and the well to be discharged (reaction container), and repeats the same operation. The controller 405 updates the remaining amount data in the liquid container based on a procedure described later for each of the suction, discharge, and cleaning cycles. Therefore, when the probe 408 needs to suck the same kind of analysis liquid again, appropriate dispensing and cleaning are always performed based on the latest remaining amount data.

  The probe 408 is a conductive member, and by connecting to the capacitance measuring unit 404, a liquid suction / discharge function as a dispensing probe and a liquid level detection function are integrated, and the probe 408 is located below the probe 408. The capacitance is measured. The height of the probe 408 that moves up and down by the probe lifting / lowering control unit 401 is mainly measured by the lowering amount measuring unit 403. The control unit 405 not only controls the operation of all the means shown in FIG. 3 according to a desired analysis sequence, but also controls the inside of the liquid container 412 based on the descending amount of the probe 408 and the output signal from the capacitance measurement unit 404. The liquid level detection and the descending amount of the probe 408 are associated with each other, and an instruction is given to perform cleaning according to the amount of probe 408 submerged.

When the control unit 405 determines / instructs the probe cleaning with the normal cleaning power, the probe 408 having sucked the analysis liquid is transferred into a specific well of the microplate 409 at the discharge position, and the required discharge is performed. After performing the above, the probe 408 is transferred to the first cleaning tank 410 having normal cleaning power to perform normal level cleaning, and the probe 408 is moved with respect to the next suction liquid container 412. Move to next dispensing.

When the control unit 405 determines / instructs the probe cleaning with a strong cleaning power, the probe 408 having sucked the analysis liquid is transferred into a specific well of the microplate 409 at the discharge position, and the required discharge is performed. Then, the probe 408 is transferred to the second cleaning tank 411 having a strong cleaning power to perform normal level cleaning, and the probe 408 is moved relative to the next suction liquid container 412.

FIG. 4 is a schematic diagram showing a state in which the dispensing probe 408 that has entered the liquid container 412 with respect to various analysis liquids in the present invention and a range to be cleaned. That is, FIG. 4A shows the amount of penetration (arrow in the figure) when the liquid level detection mechanism integrated with the probe 408 malfunctions and enters the liquid excessively. FIG. 4B shows a state in which the probe has entered and is aspirated with the minimum necessary amount of subtraction (arrow in the figure) after appropriate liquid level detection has been performed. FIG. 4C shows a contamination range when the probe 408 enters when bubbles 501 having a relatively small diameter are uniformly generated on the entire liquid surface (arrow in the figure), and the amount of penetration into the liquid itself is as follows. Although there are few, since many small diameter bubbles 501 exist in the vicinity of the liquid surface, the range to be cleaned is relatively large. FIG. 4D shows a contamination range when the probe 408 enters a liquid surface in which bubbles having a relatively large diameter 502 are mixed with bubbles having a small diameter (arrow in the figure), and the amount of penetration similar to that in FIG. 4C. In spite of this, the contact with the large-diameter bubbles 502 results in a state where the most dirty range to be cleaned is present. As described above, it can be seen that there are various cleaning ranges (indicated by arrows in the drawing) of the probe 408 depending on whether the liquid level detection is appropriate or the state of generation of bubbles. In this example, bubbles are shown as noise components for detecting the liquid level.However, even if some of the components of the liquid for analysis are dried due to adhesion or evaporation on the container wall surface, A noise component may be generated. Note that the malfunction of liquid level detection due to noise components such as bubbles can occur in various detection methods such as capacitance, conductivity, air pressure change amount, and ultrasonic sensor. Further, when the analysis liquid to be handled is a very small amount and is a liquid container containing a relatively large volume of analysis liquid, a more serious dive error tends to occur. In addition, even when the volume of the analysis liquid stored in the liquid container is relatively small (for example, 50 microliters or less), the amount of liquid to be handled by the probe is very small (for example, 20 microliters or less). Similarly, the cleaning range is likely to vary due to a dive error.

  Next, a method for cleaning the liquid handling probe of the present invention will be described. In the following example, a case where a dispensing probe is used as the liquid handling means will be described. However, the present invention is not limited to this and can be applied to a stirring probe or the like. The determination procedure will be described with reference to FIGS.

First determination procedure In this procedure, the sample and / or reagent is separated by a dispensing probe applied to the analyzer as described in the first embodiment or the second embodiment. You can refer to the order method. FIG. 5 shows a flow chart for determining the amount of penetration of the dispensing probe into the liquid container containing the type of analysis liquid that does not frequently bubble.
(1) The dispensing probe having the liquid level detection mechanism is moved above the liquid container containing the analysis liquid to be sucked and stopped, and then the liquid level is continuously detected while the probe is slowly lowered.
Then, when a liquid level detection signal generated when the probe reaches the liquid level is detected, the descent of the probe is temporarily stopped. At this time, the α value and the β value are acquired by setting the descending amount of the dispensing probe required until the liquid level is detected as α, and the post-detection descending amount set according to the desired suction amount as β.
(2) After obtaining the β value in the above (1), the latest predicted liquid level height γ is obtained based on the initial value stored in the liquid container and the remaining amount update information based on the dispensing history. To do. Here, in the first dispensing operation, the initial value that is the amount of the analysis liquid that has just been set in the analyzer can be set to the latest predicted liquid level height γ. In addition, in the second and subsequent dispensing operations, the latest predicted liquid level is calculated by calculating the sum of the dispensing amounts corresponding to the number of dispensings from the first dispensing operation and subtracting from the initial value. The height γ can be set.
(3) (α + β) −γ is calculated using the values of α, β, and γ acquired in (1) and (2) above. Then, it is determined whether the value of (α + β) −γ is larger than an appropriate threshold value δ.
Here, the value of δ is a numerical value determined by the dispensing volume to be aspirated and the cross-sectional area of the analytical container to be aspirated, and is specifically classified when the dispensing probe detects an incorrect liquid level. It is set to be able to.
(4) In this way, if the above-mentioned determination in (3) is No (No), the control unit functions to execute normal cleaning power, while the determination in (3) is YES. If (yes), the control unit functions to execute cleaning with strong cleaning power.

  According to this first determination procedure, in the liquid type in which the generation frequency and generation amount of noise components such as bubbles are almost zero or negligible, the probe is excessively contained in the liquid due to erroneous liquid level detection. Since control can be performed so as to switch to cleaning with a strong cleaning power when submerged, stable analysis results can be obtained without unnecessary cleaning.

Second determination procedure Fig. 6 is a flowchart for determining the amount of the dispensing probe that has entered the liquid container containing the type of analysis liquid that frequently bubbles. In the following description, parts similar to those of the first determination criterion (and FIG. 5) described above are omitted.
(1) Acquire the type of liquid (= based on ease of foaming) contained in the container to be aspirated.
(2) An additional submerged amount (量) after detection is acquired from the liquid type.
(3) Acquire each α value and β value, where α is the descent amount of the dispensing probe required until the liquid level is detected, and β is the descent amount after detection set according to the desired suction amount. .
(4) The latest predicted liquid level height γ is acquired based on the initial value stored in the liquid container and the remaining amount update information based on the dispensing history.
(5) A threshold value δ is set, and it is determined whether (α + β + K) −γ> δ.
Here, δ is preferably a value considering K.
(6) If the determination in (5) is No (no), normal cleaning power is executed. If the determination in (5) is YES, cleaning with strong cleaning power is executed.
In the second determination procedure, if the liquid type has a high foaming frequency and / or a large amount of foam, an additional submerged amount K after the liquid level detection is set to a large value in order to prevent empty suction. Therefore, the subsequent contamination is prevented by performing cleaning with increased detergency.

  According to this first determination procedure, in the liquid type in which the generation frequency and generation amount of noise components such as bubbles are almost zero or negligible, the probe is excessively contained in the liquid due to erroneous liquid level detection. Since control can be performed so as to switch to cleaning with a strong cleaning power when submerged, stable analysis results can be obtained without unnecessary cleaning.

  As described above, the present invention has been described with reference to the drawings. However, as another aspect, the present invention has a bubble detection function in a prediction mode when a liquid (sample, reagent, reaction mixture) is expected to generate bubbles. In addition, a dispensing nozzle cleaning method (Example 1) for application to a dispensing means having a liquid level detecting means can also be provided. Further, the present invention provides a dispensing method using a dispensing nozzle and a dispensing nozzle for application to a dispensing means having a liquid level detecting means that does not have a foam detection function in a prediction mode where foam generation is expected. A cleaning method (Example 2) can also be provided. According to these other aspects (Examples 1 and 2), the present invention provides a method for updating the remaining amount of liquid for analysis that can accurately update the remaining amount of liquid in the container depending on whether or not bubbles are detected. It can also be understood as an invention.

In addition, in each description of the following different modes, it is assumed that there are one or more assumptions as described below. Therefore, it is preferable to adopt a determination procedure in which one or more of the following assumptions are appropriately applied depending on the analysis liquid, the purpose of dispensing, and the like.
Assumption 1: The first detection is not performed at a position deeper than the true liquid level.
(In other words, the first detection is a true liquid level or a false liquid level such as bubbles above the liquid level.)
Assumption 2: The amount of liquid in the container at the initial stage (when the first suction is performed) is known.
Assumption 3: Depending on the type of liquid, one or more of the generation frequency of bubbles, the amount of bubbles, and the water level of bubbles can be predicted.
Assumption 4: The bubble generation frequency, the bubble amount, and the bubble water level may vary depending on the liquid amount, the suction amount, and the conveying operation.

The following shows another embodiment of the method of the present invention having a prediction mode in which bubble generation is expected.
Procedure Procedure Applied to Predictive Mode Where Foam Generation is Expected Example 1. When it has a liquid level detection means provided with a bubble detection function (a) Both a bubble and a true liquid level are detected specifically.
(B) A determination based on the detection information is executed.
(C) The nozzle is lowered by the subtraction amount β corresponding to the suction amount with respect to the true liquid level detection decrease amount α.
In (b), the detected true liquid level is determined as the starting point of the amount of subsidence necessary for sucking the liquid, and the amount of subsidence is strictly defined.
(D) A desired amount of liquid is sucked and discharged into a container to be discharged.
(E) The nozzle is washed with the strength according to the determination result of (b).
If “no bubbles”, perform a mild wash.
If “bubbles”, perform heavy washing.
In (e), the water level of the foam may be calculated based on the nozzle lowering amount when the foam is detected and the nozzle lowering amount when the true liquid level is detected. Since the contamination range of the nozzle can be determined by adding to the amount of subtraction, it is preferable in that the cleaning amount can be adjusted according to the nozzle range to be cleaned.
(F) Data is updated to a remaining amount obtained by subtracting the suction amount from the predicted remaining amount γ.
In this (f), the detected true liquid level is the remaining amount excluding the liquid amount of the entire bubble, but it does not reflect the amount of the entire bubble generated in the container, so the true remaining amount cannot be calculated. . Therefore, in calculating the true liquid remaining amount, the remaining amount is updated using the predicted remaining amount data without using the detection data. In this example 1, a value obtained by subtracting the liquid amount corresponding to the dive amount β from the predicted remaining amount γ is updated as the latest remaining amount data.

Example 2. In the case of a liquid level detecting means having no bubble detecting function (an additional descending amount K corresponding to the degree of bubbles is set in advance).
(A) The difference between the detected decrease amount α and the predicted remaining amount γ is calculated.
(B) The determination according to the difference value obtained in (a) is executed.
If the difference is almost zero (no significant difference), it is judged as “no bubble” and “true liquid level”.
If there is a significant difference or more, it is determined that “bubbles exist”.
(C) The nozzle is lowered according to the determination result of (b).
If there is no bubble, the nozzle is lowered by the subtraction amount β corresponding to the suction amount with respect to the detected decrease amount α without performing additional lowering.
If there is “bubble”, the nozzle is lowered to a depth obtained by adding an additional lowering amount (additional subsidence amount after detection) K and a subsidence amount corresponding to the suction amount.
(D) Aspirate the liquid and execute dispensing.
(E) The nozzle is washed with the strength according to the determination result of (b).
If “no bubbles”, mild cleaning (cleaning with normal cleaning power) is performed.
If “bubbles” are present, heavy cleaning (cleaning with stronger cleaning power than usual) is performed.
(F) The remaining amount data is updated according to the determination result of (b).
If there is no bubble, the data is updated to the remaining amount obtained by subtracting the addition amount of α and the suction amount from the γ value.
If there is “bubble”, the data is updated to the remaining amount obtained by subtracting the suction amount from the γ value.
Here, information indicating that it is determined to be a bubble is preferably added to the updated remaining amount data.

  The present invention can be variously modified in accordance with the gist of the method and apparatus described above. For example, since the generation of noise components such as bubbles may easily occur depending on the relationship between the volume of the liquid container and the handling amount such as suction as described above, the probe cleaning range is limited in handling in such a relationship. There may be a response such as adding. Further, by providing the probe with a means for measuring the generation amount (size and / or quantity) of noise components such as bubbles, the determination performance of the cleaning range and remaining amount data may be improved. .

  As described above, according to the present invention, it has a remarkable advantage that the cleaning cost can be minimized while maintaining an appropriate analysis result for any analyzer equipped with a probe for liquid handling. It is an object of the present invention to provide a method and apparatus that are friendly to the global environment and satisfy economic efficiency and reliability.

It is a top view which shows schematic structure of the automatic analyzer which concerns on the 1st Embodiment of this invention. It is a top view which shows schematic structure of the automatic analyzer which concerns on the 2nd Embodiment of this invention. It is a conceptual diagram for demonstrating the structure for performing the washing | cleaning method according to the submerged amount of the dispensing probe of this invention. It is a schematic diagram for showing the relationship between the type of liquid and the amount of penetration of the probe for liquid handling. It is a flowchart which shows an example of the determination method in the probe cleaning method of this invention. It is a flowchart which shows the example of another determination method of the probe washing | cleaning method of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Analyzer main body 2 Reaction disk 3 Sample turntable 4 Reagent turntable 5 Reaction container 6 Sample (sample) container 7 Reagent bottle 8 Sample dispensing unit 9 Reagent dispensing unit 10 Sample washing tank 11 Reagent washing Tank 12 Stirring unit 102 Sample transfer part 103 Carrier reagent container holding part 104 Liquid reagent container holding part 122 Sample container 123 Carrier reagent container 124 Liquid reagent container 125 Reaction container CR1, CR2, CR3, CR4 Information code reading parts 131, 132, 133 Cleaning device

Claims (19)

By lowering a liquid handling probe from a position above the liquid container with respect to a liquid container that contains analysis liquid and has information on the liquid amount in advance, the tip of the probe is moved to the liquid Detecting whether or not the liquid level of the analysis liquid in the container has been reached in association with the downward movement of the probe;
Based on the liquid level position detected by the detection, the probe is lowered to a distance corresponding to the amount of subtraction required for the liquid handling by the probe, and the liquid handling is executed.
Based on the comparison information comparing the amount of descent of the probe and the prior information on the liquid amount, determine the cleaning range in the probe,
A cleaning method for a probe for liquid handling, wherein the cleaning strength of the probe is changed according to the determined cleaning range. The cleaning method according to claim 1, wherein the liquid handling is dispensing and / or stirring of a liquid for analysis. The cleaning according to claim 1, wherein the liquid handling is a dispensing operation of an analysis liquid, and the cleaning range to be determined is changed based on a type of the analysis liquid and a liquid amount to be sucked. Method. The liquid handling is an analysis liquid stirring operation, and the cleaning range to be determined is changed based on a type of the analysis liquid and temperature information of the analysis liquid in the liquid container. 2. The cleaning method according to 1. Applied between each dispensing when a required amount of liquid is aspirated a plurality of times from a liquid container that contains analytical liquid and has information about the liquid volume in advance.
Prepare information on the liquid volume or liquid level in the liquid container before suction,
The liquid level in the liquid container is detected by a liquid level detection mechanism,
Compare the liquid level height detected by the liquid level detection mechanism and the information,
Based on the comparison result, the strength of washing of the dispensing nozzle in each dispensing is changed, and information on the liquid amount or the liquid level corresponding to the remaining amount of liquid after suction in the liquid container is determined. And
A method for cleaning a dispensing nozzle, wherein the determined information is used as preparation information for the next dispensing. When the liquid level detection mechanism has a function capable of detecting noise information such as bubbles, and the liquid level detection mechanism detects the noise information, the liquid level position detected by the liquid level detection mechanism is true. The suction is performed with the amount of subsidence corresponding to the amount to be sucked as judged as the liquid level, and the remaining liquid amount after the suction is determined based on the previous liquid amount information instead of the liquid level position. The method for cleaning a dispensing nozzle according to claim 5. When the liquid level detection mechanism does not have a function of detecting noise information such as bubbles, and the liquid level detected by the liquid level detection mechanism is significantly different from the previous liquid amount information. Performs suction with a subtraction amount corresponding to the sum of the amount to be sucked and the amount set for the presence of noise, and the remaining liquid amount after suction is not the liquid level but the prior liquid amount 6. The method of cleaning a dispensing nozzle according to claim 5, wherein the determination is performed based on information. When the comparison result reflects an erroneous liquid level height due to erroneous detection of the liquid level detection mechanism, a change is made to increase the strength of cleaning with respect to the dispensing nozzle. The method for cleaning a dispensing nozzle according to any one of 5 to 7. A probe for entering a liquid for analysis in a liquid container and performing a predetermined liquid handling operation;
Transfer means for positioning the liquid container to be handled and the probe at the same position among the plurality of liquid containers;
A liquid level detecting means provided in association with the height of the tip of the probe, for obtaining information relating to the amount of liquid or the liquid level in the liquid container;
Cleaning means for cleaning the probe by switching to two or more different cleaning powers,
An analysis apparatus comprising: control means for switching a cleaning force by the cleaning means in accordance with an amount of penetration of the probe after the liquid level detection obtained by the liquid level detection means.   The switching of the cleaning force by the control unit is performed by the transfer unit selectively positioning the probe with respect to a plurality of cleaning liquids having different cleaning powers stored in independent cleaning tanks in the cleaning unit. The analyzer according to claim 9, wherein the analyzer is characterized in that   The analyzer according to claim 9, wherein the switching of the cleaning power by the control unit is executed by changing the cleaning power of the cleaning liquid supplied to a common cleaning tank in the cleaning unit. The control unit generates a subtraction amount obtained by adding a subtraction amount to be added for each type of analysis liquid to a predetermined subtraction amount of the probe and a storage unit that stores the type for each of a plurality of liquid containers. The analyzer according to claim 9, further comprising: a data generation unit, wherein the cleaning unit is switched based on a sinking amount after the data generation. The analysis according to claim 12, wherein the data generation unit can set a plurality of submerged amounts in accordance with a frequency and / or amount of noise components expected for each type of analysis liquid. apparatus. The data generation unit is capable of setting a plurality of submerged amounts in accordance with the frequency and / or amount of noise components expected based on temperature management information for each type of analysis liquid. The analyzer according to claim 13. The tip of the probe has a dispensing nozzle for sucking and dispensing the analysis liquid in the liquid container, and the cleaning means is disposed in the middle of the movement of the dispensing nozzle. The analyzer according to any one of claims 9 to 14.   The suction means has a dispensing cycle comprising a plurality of suction operations executed at different timings from the same liquid container and a cleaning operation by the cleaning means executed between each suction operation. The analyzer according to claim 15.   17. The analysis according to claim 16, wherein the suction means includes a chip replacement unit for mounting a replaceable chip on the dispensing nozzle portion and dispensing the same analysis liquid a plurality of times. apparatus. The tip of the probe has a stirring means for immersing the analysis liquid in the liquid container to a desired depth for stirring, and the stirring means moves to a position away from the liquid container. 14. The analyzer according to claim 9, further comprising a cleaning unit. The said stirring means is comprised so that a washing | cleaning force can be switched by performing the stirring operation according to the said submerged amount in the state penetrate | invaded with respect to the washing tank in the said washing | cleaning means. Analysis equipment.

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