JP4183744B1 - Dispensing device and dispensing method - Google Patents

Abstract

[PROBLEMS] To ensure traceability of a dispensing amount.
The amount of fluctuation in the state value of the microwave when a chip before and after dispensing is inserted into a cavity resonator when dispensing an arbitrary number of shots from the chip is obtained, and the correspondence relationship prepared in advance is obtained. By applying the fluctuation amount acquired by the volume acquisition means, the dispensing volume of the liquid dispensed by an arbitrary number of shots is obtained, the dispensing volume is recorded, and a predetermined number of shots are provisionally dispensed from the chip The amount of fluctuation of the state value of the microwave when the tip before and after dispensing is inserted into the cavity resonator is obtained as a provisional variation, and the mass of the liquid dispensed by provisional dispensing is measured with a mass meter, Based on the measured mass and the specific gravity of the liquid, the volume of the liquid dispensed by provisional dispensing is acquired as a provisional dispensing volume, and the correspondence is adjusted based on the provisional variation and the provisional dispensing volume.
[Selection] Figure 5

Description

  The present invention relates to a dispensing device and a dispensing method.

In a conventional dispensing apparatus, a necessary amount is dispensed by increasing or decreasing the number of shots. On the other hand, an object volume measuring method using a Q value (loss factor) of a microwave has been proposed. (See Patent Document 1).
US Patent Registration No. 5554935

In the former dispensing device, it is assumed that the discharge amount per shot is constant, but in reality the discharge amount per shot is unknown, and the final dispensed amount is also unknown. There was a problem that there was. For this reason, there is a problem in that a record for specifying the actual dispensing amount cannot be left, and the traceability of the dispensing amount cannot be ensured. In addition, when the latter liquid volume measurement method is applied to a dispensing apparatus, it is possible to measure the actual dispensing amount, but there is a problem that the accuracy of the measurement result by microwave cannot always be guaranteed. It was. That is, the measurement result by the microwave changes due to a change in the environment and the like, and it becomes impossible to secure the correlation with the actual dispensing amount (for example, the dispensing amount measured by a standard electronic balance or the like). There was a problem.
The present invention has been made in view of the above problems, and an object of the present invention is to provide a dispensing apparatus and a dispensing method that can ensure the traceability of a dispensing amount.

  The present invention provides a dispenser that dispenses a predetermined amount per shot from a chip that receives a liquid, a microwave cavity resonator into which the chip can be inserted, and an arbitrary number of shots dispensed from the chip. The fluctuation amount acquisition means acquires the fluctuation amount of the state value of the microwave when the chip before and after dispensing is inserted into the cavity resonator, and the fluctuation amount acquisition means acquires the correspondence relationship prepared in advance. By applying the fluctuation amount, a dispensing volume acquisition unit that acquires a dispensing volume of the liquid dispensed by the arbitrary number of shots, a recording unit that records the dispensing volume, and a predetermined amount from the chip Provisional fluctuation amount acquisition means for acquiring, as a temporary fluctuation amount, a fluctuation amount of the state value of the microwave when the chips before and after dispensing when the number of shots is temporarily dispensed are inserted into the cavity resonator; For dispensing The mass of the dispensed liquid is measured with a mass meter, and based on the measured mass and the specific gravity of the liquid, the volume of the liquid dispensed by the provisional dispensing is acquired as a temporary dispensing volume. It is configured to include an injection volume acquisition unit, and an adjustment unit that adjusts the correspondence relationship based on the temporary variation amount and the temporary dispensing volume.

  Furthermore, the technical idea of the present invention can be embodied not only by a specific dispensing apparatus but also by the method. That is, the present invention can be specified as a dispensing method having steps corresponding to each means performed by the above-described dispensing apparatus. Of course, when the above-described dispensing apparatus reads the program to implement each of the above-described means, the technical features of the present invention can be applied to a program for executing a function corresponding to each of the means and various recording media on which the program is recorded. It goes without saying that the idea can be embodied. In addition, it cannot be overemphasized that the dispensing apparatus of this invention can be disperse | distributed by not only a single apparatus but a several apparatus.

Hereinafter, according to the following order, a preferred embodiment of a dispensing device according to the present invention will be described in detail with reference to the drawings. The present invention is not limited to the embodiments.
(1) Configuration of dispensing device:
(2) Calibration (provisional dispensing) processing:
(3) Dispensing process:
(4) Modification:

(1) Configuration of dispensing device:
FIG. 1 is a block diagram schematically showing a configuration example of a dispensing apparatus according to an embodiment of the present invention. As shown in FIG. 1, the dispensing device 1 includes a plurality of dispensers 2a to 2h for sucking and discharging a liquid sample such as a reagent, and a drive unit for raising or lowering the dispensers 2a to 2h, respectively. 4a to 4h, and a dispensing control unit 6 that controls driving of the dispensers 2a to 2h and the driving units 4a to 4h in order to dispense a liquid sample into each of the wells 40a to 40h. In addition, the dispensing device 1 includes an input unit 10, a storage unit 11, and a control unit 12 that performs drive control of each component of the dispensing device 1. Furthermore, the dispensing apparatus 1 includes a microwave volume measuring unit 20 and eight electronic balances 30a to 30h. The electronic balances 30a to 30h correspond to the mass meter of the present invention, and the storage unit 11 corresponds to the recording means of the present invention.

  The dispensers 2a to 2h are respectively held by the drive units 4a to 4h. In the dispensers 2a to 2h, pipes for sucking or discharging a liquid sample are formed inside, and carbon tips 3a to 3h are provided at the tips, respectively. The material of the chip applicable to the present invention is not limited to carbon, and a general dielectric material can be applied. The dispensers 2a to 2h are arranged, for example, in the vicinity of each other, and can suck and collect the liquid samples in the liquid sample containers 50a to 50h at the same time. The drive units 4a to 4h hold the dispensers 2a to 2h, respectively, and perform driving to raise or lower the dispensers 2a to 2h when dispensing a liquid sample. Specifically, when the drive units 4a to 4h aspirate each liquid sample in the liquid sample containers 50a to 50h, the dispensers 2a to 2h are driven to descend toward the liquid sample containers 50a to 50h, respectively. After collecting each liquid sample, the dispenser 2a to 2h that sucks the liquid sample is driven to rise. When the dispensers 2a to 2h suck the liquid sample, the sucked liquid sample is received in the carbon chips 3a to 3h.

  The dispensing control unit 6 performs drive control of the dispensers 2a to 2h and the drive units 4a to 4h in order to dispense the liquid sample into the wells 40a to 40h. Specifically, the dispensing control unit 6 controls the liquid sample suction operation and the discharge operation by the dispensers 2a to 2h, and the ascending drive and the descending drive of the dispensers 2a to 2h by the drive units 4a to 4h. The liquid sample is dispensed into the wells 40a to 40h. In this case, the dispensing controller 6 individually controls the ascending drive and the descending drive of the dispensers 2a to 2h with respect to the drive units 4a to 4h. Thereby, the dispensing control unit 6 can raise or lower each of the dispensers 2a to 2h individually or simultaneously.

  Moreover, the dispensing control part 6 has the pipe lines 5a-5h connected to the dispensers 2a-2h, respectively, and adjusts the pressure in the dispensers 2a-2h via these pipe lines 5a-5h, respectively. The liquid sample suction operation and the discharge operation by the dispensers 2a to 2h are controlled. The dispensing control unit 6 collects, for example, each liquid sample in the liquid sample containers 50a to 50h by performing suction / discharge control of the dispensing devices 2a to 2h and drive control of the driving units 4a to 4h. Each liquid sample is dispensed (discharged) into the wells 40a to 40h by one shot. Once the liquid sample received in the carbon chips 3a to 3h is discharged into the wells 40a to 40h by dispensing, the volume of the liquid sample received in the carbon chips 3a to 3h gradually decreases. It will be done.

  The input unit 10 is realized using a keyboard or a mouse, and acquires information instructing the control unit 12. Specifically, information for designating the type (solvent / solute / concentration) of the liquid sample and information for designating the dispensing amount are acquired, and the control unit 12 is instructed. The storage unit 11 stores program data for executing various control processes of the control unit 12 and information instructed to be written by the control unit 12. Specifically, a storage device such as a hard disk drive or a flash memory corresponds to the storage unit 11. The control unit 12 includes a CPU, a RAM, and the like, and reads various program data from the storage unit 11 and executes various control processes while developing the program data on the RAM. Thereby, each operation | movement of the component part of the dispensing apparatus 1, for example, the dispensing control part 6, the input part 10, and the memory | storage part 11, and the input / output of information are controlled. The control unit 12 receives input of temperature and humidity and a Q value, which will be described later, from the microwave volume measurement unit 20, and receives input of mass from the electronic balances 30a to 30h.

  FIG. 2 shows the configuration of the microwave volume measuring unit 20. In the figure, the microwave volume measuring unit 20 is roughly composed of four pairs of cavity resonators 21, 21, 21, 21 and microwave circuits 22, 22, 22, 22. In the present embodiment, the cavity resonators 21, 21, 21, 21 are all configured in the same manner, and are arranged in a line in the depth direction. FIG. 3 shows a horizontal cross section and a vertical cross section of the cavity resonator 21. In the figure, a main space 21a having a rectangular cross section and a temperature / humidity measurement space 21b are independently formed inside the cavity resonator 21a, and these are communicated by a sufficiently narrow communication passage 21c. Yes.

  A measurement board 21d (environmental measurement means) on which a temperature / humidity sensor is mounted is inserted into the temperature / humidity measurement space 21b. The temperature / humidity in the temperature / humidity measurement space 21b is measured by the temperature / humidity sensor, and the measurement result is obtained. It is possible to output to the microwave circuit 22. Since the main space 21a and the temperature / humidity measurement space 21b communicate with each other, it can be considered that the temperature / humidity measurement space 21a2 and the main space 21a1 have the same temperature / humidity. In the main space 21a, a transmission / reception antenna 21e electrically connected to the microwave power feeding connector and a substantially cylindrical insertion guide 21f are provided so as to penetrate the main space 21a in the vertical direction. The insertion guide 21f is formed of a dielectric, and the internal shape is substantially the same as the outer shape of the carbon chips 3a to 3h. The insertion guides 21f of the cavity resonators 21, 21, 21, 21 are arranged in a line. In the processing described later, the carbon chips 3a to 3h are inserted inside the insertion guide 21f, and the insertion direction thereof coincides with the penetration direction of the insertion guide 21f.

  The microwave circuits 22, 22, 22, and 22 are all configured similarly. The microwave circuits 22, 22, 22, and 22 are connected to the transmission / reception antennas 21e of the cavity resonators 21, 21, 21, and 21 that form pairs, respectively, and supply of transmission power in the transmission / reception antennas 21e and transmission / reception antennas 21e The reception state is analyzed and the temperature and humidity are measured by the measurement board 21d. The microwave circuit 22 includes a voltage-controlled oscillator (VCO) 22a, a power amplifier (AMP) 22b, a counter (CNT) 22c, a circulator (CIR) 22d, a detector (DET) 22e, and a digital / analog converter. (DAC) 22f, analog-digital converters (ADC) 22g and 22h, and a microcomputer (COM) 22i. The COM 22i generates a digital signal for controlling the resonance frequency of the microwave, and the digital signal is input to the VCO 22a via the DAC 22f.

  The CNT 22c receives the frequency-divided output from the VCO 22a, and the CNT 22c counts the oscillation frequency of the VCO 22a and outputs it to the COM 22i. Thereby, the COM 22i can control the oscillation frequency of the VCO 22a. In the present embodiment, 5.8 GHz band microwaves (<10 mW) designated as the ISM band are used. The output of the VCO 22a is power amplified by the AMP 22b and output to the transmitting / receiving antenna 21e via the CIR 22d. As a result, the transmission / reception antenna 21 e transmits a microwave in the cavity resonator 21, and a microwave resonant standing wave is formed in the cavity resonator 21. In the present embodiment, microwaves are oscillated in the TE01 mode, and the penetration direction of the insertion guide 21f is the electric field direction as shown in FIG. Further, the COM 22i controls the oscillation frequency of the VCO 22a so that the insertion guide 21f is positioned at a node portion in the electric field distribution of the resonant standing wave.

  The transmitting / receiving antenna 21e receives a resonant standing wave, and the received component is extracted by the CIR 22d and detected by the DET 22e. The detection signal from the DET 22e is input to the ADC 22g and input to the COM 22i as a digital signal. The ADC 22h is connected to the measurement board 21d, and outputs digital signals of temperature and humidity measured by the measurement board 21d to the COM 22i. The COM 22i calculates the Q value by dividing the resonance frequency f measured by the CNT 22c by the frequency width Δf of the received wave detected by the DET 22e, and outputs the Q value to the control unit 12. The Q value corresponds to a value obtained by dividing the reception power at the transmission / reception antenna 21e by the transmission power, and is also called a loss factor. It can be said that the smaller the Q value is, the larger the loss power in the cavity resonators 21, 21, 21, 21 is. Further, the 1 / Q value that is the reciprocal of the Q value corresponds to the state value of the present invention. In the present embodiment, the microwave circuits 22, 22, 22, 22 are provided independently of the cavity resonators 21, 21, 21, 21, but the microwave circuits 22, 22, 22, 22 are provided. These functions may be shared by the plurality of microwave circuits 22, 22, 22, 22. Next, the flow of each process performed by the dispensing apparatus 1 configured as described above will be described.

(2) Calibration (Temporary Dispensing) Process FIG. 4 shows the overall flow of the process executed by the dispensing apparatus 1. In the same figure, the dispensing apparatus 1 of this embodiment performs a calibration process (step S100-) first, and then performs a dispensing process (step S300-). Here, the calibration process will be described first. FIG. 5 shows the flow of the calibration process. In step S100, the input unit 10 accepts designation of the type (solvent / solute / concentration) of the liquid sample to be dispensed and designation of the dispensing amount via the keyboard or mouse. The specified information is stored in the storage unit 11.

  When starting the calibration process, it is assumed that the carbon chips 3a to 3h are mounted on the dispensers 2a to 2h in advance, and liquid samples to be dispensed are prepared in the liquid sample containers 50a to 50h. . In step S110, the empty carbon chips 3a to 3h attached to the dispensers 2a to 2h are controlled by the driving units 4a to 4h by controlling the driving of the dispensers 2a to 2h. 21 and 21 are inserted into the respective insertion guides 21f. Here, since the four cavity resonators 21, 21, 21, and 21 are provided, four of the eight carbon chips 3a to 3h can be simultaneously inserted into the insertion guides 21f.

  In step S115, the COM 22i calculates the respective Q values in a state where four of the carbon chips 3a to 3h are inserted into the respective insertion guides 21f at the same time, and the controller 12 calculates the respective microwave circuits 22, 22, 22 , 22 to obtain the Q value. As described above, the Q value is a value corresponding to the power loss in the cavity resonators 21, 21, 21, 21, and the Q value corresponding to the initial power loss caused by the carbon chips 3a to 3h in a state where no liquid is received. Can be obtained. When the Q values for four of the carbon chips 3a to 3h can be obtained, in step S120, the drive units 4a to 4h are controlled to drive the dispensers 2a to 2h, thereby remaining four pieces. The carbon chips 3 a to 3 h are inserted into the insertion guides 21 f of the cavity resonators 21, 21, 21, 21. In step S125, the initial Q value is acquired in the same manner. The Q values acquired in steps S115 and S125 are stored in the storage unit 11 in association with the dispensers 2a to 2h.

  In step S150, the drive units 4a to 4h are controlled to drive the dispensers 2a to 2h, and the drive control unit 6 is further adjusted to adjust the pressure in the dispensers 2a to 2h, thereby dispensing the dispensers 2a to 2h. The liquid sample is aspirated by. Thereby, the liquid samples prepared in the liquid sample containers 50a to 50h are received in the carbon chips 3a to 3h. In steps S160 to S175, the Q value in a state where the liquid sample is received in the carbon chips 3a to 3h is obtained for each of the dispensers 2a to 2h by performing the same procedure as in steps S110 to S125. To do. Also in this case, the acquired Q value is stored in the storage unit 11 in association with the dispensers 2a to 2h. In step S180, by causing the drive units 4a to 4h to control the driving of the dispensers 2a to 2h, the dispensers 2a to 2h are moved directly above the electronic balances 30a to 30h, and further distributed to the drive control unit 6. By adjusting the pressure in the dispensers 2a to 2h, the liquid sample is dispensed one shot at a time from the dispensers 2a to 2h onto the upper plates of the electronic balances 30a to 30h. The dispensing here corresponds to the temporary dispensing of the present invention.

  In step S190, the control unit 12 acquires the mass of the liquid sample measured by the electronic balances 30a to 30h. In step S200, the controller 12 calculates the volume (temporary dispensing volume v) of the liquid sample temporarily dispensed by the dispensers 2a to 2h to the electronic balances 30a to 30h (temporary dispensing volume acquisition means). . Specifically, the provisional dispensing volume v of the liquid sample can be calculated by acquiring the specific gravity of the liquid sample based on the type of the liquid sample input in step S100 and dividing the mass by the specific gravity. it can. In addition, the specific gravity corresponding to the designated liquid sample can be obtained by storing a database storing the specific gravity of each liquid sample in the storage unit 11. Of course, the specific gravity itself may be input at the time of step S100.

  Also here, the provisional dispensing volume v acquired is stored in the storage unit 11 in association with each of the dispensers 2a to 2h. In steps S210 to S225, the Q value in a state where the liquid sample is received in the carbon chips 3a to 3h is acquired for each of the dispensers 2a to 2h by performing the same procedure as in steps S110 to S125. Also in this case, the acquired Q value is stored in the storage unit 11 in association with each dispenser 2a to 2h. In step S230, the control unit 12 acquires the temperature and humidity for each of the cavity resonators 21, 21, 21, and 21, and stores them in the storage unit 11 as the reference temperature ts [K] and the reference humidity hs [%], respectively.

  Through the above processing, the information shown in FIG. 6 is stored in the storage unit 11. In FIG. 6, the state of the carbon chips 3a to 3h is schematically shown. First, the Q value when the carbon chips 3a to 3h are empty (state A) is acquired for each of the dispensers 2a to 2h (steps S115 and S125), and the liquid immediately before the provisional dispensing (step S180) is performed. The Q values for the carbon chips 3a to 3h in the state in which the amount is received (state B) are acquired for the dispensers 2a to 2h (steps S165 and S175). Furthermore, the Q values for the carbon chips 3a to 3h in the state (state C) in which the liquid amount immediately after the provisional dispensing (step S180) is received are acquired for the respective dispensing devices 2a to 2h (step S215). , S225). On the other hand, the provisional dispensing volume v of the liquid sample discharged by provisional dispensing (step S180) is also acquired.

上記の（１）式において、Ｅは電界強度を示し、ｆは周波数を示し、εは液体試料の誘電率を示す、ｔａｎδは誘電正接を示している。このように、吸収電力Ｗはカーボンチップ３ａ〜３ｈにおける液体試料の体積ｑに対応した値であり、同様にＱ値もカーボンチップ３ａ〜３ｈにおける液体試料の体積ｑに対応した値であることが分かる。 In step S240, based on each information acquired by step S225, the control part 12 produces the correspondence of Q value and the volume q of the liquid sample in carbon chip 3a-3h. In the state B and the state C, it can be said that the volume of the liquid sample received by the carbon chips 3a to 3h is reduced by the provisional dispensing volume v measured by the electronic balances 30a to 30h. it can. Here, the Q value is a value obtained by dividing the received power by the transmitted power, and the reciprocal (1 / Q) is considered to be a value corresponding to the loss (absorption) power in the cavity resonators 21, 21, 21, 21. be able to. Further, the relationship of the following equation (1) is established between the volume q of the liquid sample and the absorbed power W in the carbon chips 3a to 3h.

In the above equation (1), E represents the electric field strength, f represents the frequency, ε represents the dielectric constant of the liquid sample, and tan δ represents the dielectric loss tangent. Thus, the absorbed power W is a value corresponding to the volume q of the liquid sample in the carbon chips 3a to 3h, and similarly, the Q value is also a value corresponding to the volume q of the liquid sample in the carbon chips 3a to 3h. I understand.

  FIG. 7 shows an example of an experimental result of investigating the correspondence between the volume q of the liquid sample in the carbon chips 3a to 3h and the reciprocal of the Q value (1 / Q value). The horizontal axis represents the 1 / Q value, and the vertical axis represents the volume q of the liquid sample in the carbon chips 3a to 3h. As shown in the figure, the volume q can be uniquely specified based on the 1 / Q value. Note that the correspondence illustrated in FIG. 6 is generally represented by a linear function. Further, according to the above equation (1), the intercept of the linear function corresponds to the initial loss (loss in a state where no liquid sample is received in the carbon chips 3a to 3h), and the slope corresponds to ε × tan δ. Can be considered. The value of this intercept can be obtained from the Q value in state A, and the slope value is the difference between 1 / Q values in state C and state B (corresponding to the temporary fluctuation amount of the present invention) between states B and C. Can be obtained by dividing by the provisional dispensing volume v corresponding to the difference in volume. In addition, the control part 12 which calculates the value of inclination is equivalent to the temporary fluctuation amount acquisition means of this invention.

  In step S240, the control unit 12 creates a linear function as shown in FIG. 7 based on the above-described intercept and inclination. According to the linear function, a volume q corresponding to an arbitrary 1 / Q value can be obtained. Then, a volume q corresponding to each 1 / Q value over the entire range is calculated based on a linear function, and table data describing a correspondence relationship between the 1 / Q value and the volume q is stored in the storage unit 11. Of course, a linear function (intercept, slope) may be stored in the storage unit 11 as a correspondence relationship. The slope described above is a physical property value specific to the liquid sample corresponding to the dielectric constant ε and the dielectric loss tangent tan δ, and is inherently a property that can be uniquely specified from the liquid sample, but it is an actual measured value as in this embodiment. By creating a correspondence relationship based on the above, it is possible to ignore the influence of various variable elements typified by temperature and humidity. In step S240, it can be considered that the above correspondence is newly created based on the intercept and inclination based on the actual measurement, or that the linear function is adjusted based on the intercept and inclination based on the actual measurement. In addition, since different liquid samples may be received in each of the dispensers 2a to 2h, and individual variations of the cavity resonators 21, 21, 21, and 21 exist, the above-mentioned each of the dispensers 2a to 2h. The corresponding correspondence is created.

(3) Dispensing process When the correspondence can be prepared as described above, the process proceeds to the dispensing process. FIG. 8 shows the flow of the dispensing process. This dispensing process is executed mainly by the control unit 12 executing a control program. In steps S300 to S315, the Q value in a state where the liquid sample is received in the carbon chips 3a to 3h is acquired for each of the dispensers 2a to 2h by performing the same procedure as in steps S110 to S125. That is, the Q values corresponding to the carbon chips 3a to 3h in a state (immediately before the dispensing) before the volume of the liquid sample received by dispensing is reduced are acquired for each of the driving units 4a to 4h. In step S320, the dispenser 2a to 2h is moved directly above the wells 40a to 40h by causing the dispensing controller 6 to control the driving of the dispensers 2a to 2h, and further dispensed to the drive controller 6. By adjusting the pressure in the containers 2a to 2h, the liquid sample is discharged by the dispensers 2a to 2h.

  In the present embodiment, a desired volume of the liquid sample to be dispensed into the wells 40a to 40h is designated in advance, and the ejection operation for the number of shots corresponding to the volume is repeated. The dispensers 2a to 2h are formed so that the discharge amount of one shot becomes a constant rated amount, and the required number of shots can be obtained by dividing the desired volume by the rated amount of one shot. it can. When the necessary number of shots is ejected, the ejection is terminated. In steps S330 to S345, the Q value in a state where the liquid sample is received in the carbon chips 3a to 3h is acquired for each of the dispensers 2a to 2h by performing the same procedure as in steps S110 to S125. That is, the Q values corresponding to the carbon chips 3a to 3h in a state where the volume of the liquid sample received by dispensing is reduced (immediately after dispensing) are acquired for each of the dispensers 2a to 2h. In step S350, the control unit 12 acquires the temperature and humidity for each of the cavity resonators 21, 21, 21, and 21 and stores them in the storage unit 11 as the dispensing temperature tm [K] and the dispensing humidity hm [%], respectively. To do.

  As described above, when the control unit 12 acquires the Q value (1 / Q value), the dispensing temperature tm, and the dispensing humidity hm corresponding to the carbon chips 3a to 3h before and after dispensing, the control is performed in step S360. The part 12 calculates the dispensing volume V. Here, the correspondence created (adjusted) in step S240 in the calibration process is read from the storage unit 11 and used. First, the volume q1 of the liquid received in the carbon chips 3a to 3h immediately before dispensing is obtained by applying the 1 / Q value obtained immediately before dispensing in steps S300 to S315 to the correspondence described above. . Similarly, by applying the 1 / Q value immediately after dispensing obtained in steps S330 to S345 to the above-described correspondence, the volume q2 of the liquid received in the carbon chips 3a to 3h immediately after dispensing is obtained. . The 1 / Q value before and after dispensing corresponds to the fluctuation amount of the present invention, and the control unit 12 in step S360 corresponds to the fluctuation amount acquisition means of the present invention.

  Then, the difference between the volumes q1 and q2 immediately before and after the dispensing is calculated as the dispensing volume V (dispensing volume acquisition means). Furthermore, the reference temperature ts, the reference humidity hs, the dispensing temperature tm, and the dispensing humidity hm measured in advance from the storage unit 11 are acquired, and the dispensing volume V is corrected based on these. That is, the dispensing volume V is corrected based on the difference between the temperature / humidity condition when the correspondence is created in step S240 and the temperature / humidity condition when the dispensing is actually performed (correcting means). For example, a ratio of the dispensing temperature tm and the dispensing humidity hm to the reference temperature ts and the reference humidity hs may be calculated, and the dispensing volume V may be multiplied by a correction coefficient based on the ratio. Optimum correction coefficients can be prepared by conducting preliminary experiments in which the temperature and humidity are converted.

  Thus, by performing correction based on temperature and humidity, it is possible to suppress the influence of temperature and humidity dependency such as dielectric constant ε and dielectric loss tangent tan δ. When the corrected dispense volume V is obtained as described above, the dispense volume V is stored in the storage unit 11. When storing the dispensing volume V, information for specifying the dispensing date and time and the dispensers 2a to 2h is stored in association with each other. Next, when another dispensing is performed (when the same carbon chips 3a to 3h are used and the same liquid sample is dispensed), only the dispensing process may be repeated. In the dispensing process executed again, the dispensing volume V can be corrected by the temperature and humidity immediately after the dispensing, and the accurate dispensing volume V can be recorded.

  According to the dispensing process described above, the dispensed volume V actually dispensed can be stored in the storage unit 11 each time dispensing is performed by the dispensers 2a to 2h. Therefore, the actually dispensed volume can be managed not only by the number of shots but also by the dispensed volume V measured using microwaves. The value of the dispensing volume V is obtained based on the correspondence created (adjusted) in the calibration process described above, and the correlation with the electronic balances 30a to 30h is ensured in the calibration process. Yes. Therefore, according to the dispensed volume V stored in the storage unit 11, the traceability of the volume of the liquid sample actually dispensed into the wells 40a to 40h can be ensured.

  Furthermore, even when the temperature and humidity change during the dispensing process, the dispensing volume V can be corrected by the temperature and humidity immediately after dispensing, and the dispensing volume V can be recorded with higher accuracy. The dispensing volume V is obtained based on the volume q of the liquid sample remaining on the carbon chips 3a to 3h, and a measurement result with little influence of volatilization during or after the dropping can be obtained. Therefore, even when the liquid sample has high volatility, high measurement accuracy can be realized. However, in the calibration process, the electronic balances 30a to 30h are affected by volatilization when measuring the provisional dispensing volume v. Therefore, when the calibration process is performed on a liquid sample having high volatility, It is necessary to measure the mass while preventing volatilization by, for example, sinking droplets in a low specific gravity liquid on the balances 30a to 30h.

(4) Modification:
In the above, the calibration process is performed in advance before the dispensing process, but the timing for executing the calibration process is not limited to the one before the dispensing process. For example, the calibration process may be performed before and after the dispensing process. In the calibration process performed after the dispensing process, the initial loss (loss in a state where no liquid sample is received in the carbon chips 3a to 3h: the value corresponding to the intercept) cannot be measured. It can be measured in the calibration process. On the other hand, the slope in FIG. 7 can be obtained for both before and after the dispensing process, and for example, the correspondence can be created by adopting the average of both slopes.

  By doing in this way, the influence of the temporal change before and after dispensing can be reduced. Furthermore, since the volume q of the liquid sample received in the carbon chips 3a to 3h is different before and after dispensing, the influence of the fluctuation of the Q value caused by the volume q of the liquid sample can be reduced. Of course, it is also possible to perform an intermediate calibration process during the dispensing process. Note that the temperature and humidity can be measured independently of the calibration process. Therefore, it is possible to measure the temperature and humidity during the dispensing process and perform correction based on the temperature and humidity. What is necessary is just to select the optimal execution frequency of a calibration process between the required dispensing speed and measurement accuracy. In the calibration process of the above-described embodiment, provisional dispensing is performed for one shot, but provisional dispensing may be performed over a plurality of shots as a matter of course. The dispensing volume V stored in the storage unit 11 may be displayed on a printer, a display, or the like as well as simply stored.

  In the above-described embodiment, the eight dispensers 2 a to 2 h are provided with four cavity resonators 21, 21, 21, 21. However, the number of these is limited to the illustrated example. Is not to be done. For example, eight cavity resonators may be provided for the eight dispensers 2a to 2h. Furthermore, the configuration of the cavity resonator 21 is not limited to that illustrated in FIG. FIG. 9 shows a horizontal cross section of two cavity resonators 121 and 121 according to the modification. In the figure, cavity resonators 121 and 121 are integrally formed, and mutual main spaces 121a and 121a are partitioned by a common wall surface. As described above, the plurality of cavity resonators 121 and 121 may be integrally formed. Also, one temperature / humidity measurement space 121b communicating with both the main spaces 121a and 121a is formed. When the plurality of cavity resonators 121 and 121 are integrally formed, the difference in temperature and humidity between the individual main spaces 121a and 121a can be ignored. Therefore, the cavity resonators 121 and 121 can be formed compactly by providing the common temperature and humidity measurement space 121b.

  The penetration direction of the insertion guides 121f and 121f of the cavity resonators 121 and 121 of this modification is the magnetic field direction of the resonance standing wave in the main spaces 121a and 121a. Further, the insertion guides 121f and 121f are located at the antinodes in the electric field distribution of the resonant standing wave. With such an arrangement, the Q value corresponding to the volume q of the liquid sample received in each of the carbon chips 3a to 3h can be obtained as in the above-described embodiment. Here, the two cavity resonators 121 and 121 are illustrated, but four or eight resonators may be used. Although the axial directions of the transmission / reception antennas 121e and 121e and the insertion guides 121f and 121f are orthogonal to each other, the positions of the transmission / reception antennas 121e and 121e are shifted by changing the sizes of the main spaces 121a and 121a. It is possible to ensure compactness.

It is a block diagram of a dispensing apparatus. It is a block diagram of a microwave volume measurement unit. It is sectional drawing of a cavity resonator. It is a flowchart of the process which a dispensing apparatus performs. It is a flowchart of a calibration process. It is a figure which illustrates typically the data acquired by a calibration process. It is a graph which shows the correspondence of the volume in a carbon chip, and 1 / Q value. It is a flowchart of a dispensing process. It is sectional drawing of the cavity resonator concerning a modification.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Dispensing apparatus, 2a-2h ... Dispenser, 4a-4h ... Drive part, 5a-5h ... Pipe line, 6 ... Dispensing control part, 10 ... Input part, 11 ... Memory | storage part, 12 ... Control part, DESCRIPTION OF SYMBOLS 20 ... Microwave volume measurement unit, 21 ... Cavity resonator, 21a ... Main space, 21b ... Temperature / humidity measurement space, 21c ... Communication path, 21d ... Measurement board, 21e ... Transmission / reception antenna, 21f ... Insertion guide, 22 ... Microwave Circuit, 22a ... VCO, 22b ... AMP, 22c ... CNT, 22d ... CIR, 22e ... DET, 22f ... DAC, 22g, 22h ... ADC, 22i ... COM, 40a-40h ... well, 50a-50h ... liquid sample container.

Claims (8)

A dispenser for dispensing a predetermined amount per shot from a tip receiving liquid;
A microwave cavity resonator into which the chip can be inserted;
Fluctuation amount acquisition means for acquiring a fluctuation amount of the state value of the microwave when the chip before and after dispensing when dispensing an arbitrary number of shots from the chip is inserted into the cavity resonator;
Dispensing volume acquisition means for acquiring a dispensing volume of the liquid dispensed by the arbitrary number of shots by applying the fluctuation amount acquired by the fluctuation amount acquisition means to a predetermined correspondence relationship;
Recording means for recording the dispensing volume;
Temporary fluctuation amount acquisition for acquiring the fluctuation amount of the state value of the microwave as the temporary fluctuation amount when the chip before and after dispensing when the predetermined number of shots are temporarily dispensed from the chip is inserted into the cavity resonator Means,
The mass of the liquid dispensed by the temporary dispensing is measured by a mass meter, and the volume of the liquid dispensed by the temporary dispensing is acquired as the temporary dispensing volume based on the measured mass and the specific gravity of the liquid. A provisional dispensing volume acquisition means,
A dispensing apparatus comprising: adjusting means for adjusting the correspondence relationship based on the temporary variation amount and the temporary dispensing volume.   The dispensing apparatus according to claim 1, wherein the state value is based on a loss factor of the microwave. Environmental measurement means for measuring temperature and / or humidity in the cavity resonator;
The dispensing apparatus according to claim 1, further comprising a correcting unit that corrects the dispensing volume based on the measured temperature and / or humidity.   4. The component according to claim 3, wherein the environment measuring unit is provided in a space independent of the main space while communicating with the main space in which the state value of the microwave is acquired in the cavity resonator. Note device.   The said cavity resonator and the said dispenser are provided with two or more pairs, and acquisition and recording of the said dispensing volume are performed about each pair, The Claim 1 characterized by the above-mentioned. Dispensing device.   6. The component according to claim 1, wherein the insertion direction of the chip is a direction of the electric field of the microwave, and the insertion position of the chip is a node position of the electric field intensity distribution. Note device.   6. The component according to claim 1, wherein the insertion direction of the chip is a magnetic field direction of the microwave, and the insertion position of the chip is an antinode position of an electric field intensity distribution. Note device. A dispensing method using a dispenser that dispenses a predetermined amount from a chip that receives a liquid per shot, and a microwave cavity resonator into which the chip can be inserted,
Obtaining the amount of fluctuation of the state value of the microwave when the chip before and after dispensing when dispensing an arbitrary number of shots from the chip is inserted into the cavity resonator,
By applying the fluctuation amount acquired by the fluctuation amount acquisition means to the correspondence prepared in advance, the dispensing volume of the liquid dispensed by the arbitrary number of shots is acquired,
Record the dispensing volume above,
The amount of fluctuation in the state value of the microwave when the tip is inserted into the cavity resonator before and after the provisional dispensing of a predetermined number of shots from the tip is obtained as a provisional variation amount,
The mass of the liquid dispensed by the temporary dispensing is measured by a mass meter, and the volume of the liquid dispensed by the temporary dispensing is acquired as the temporary dispensing volume based on the measured mass and the specific gravity of the liquid. And
A dispensing method, wherein the correspondence is adjusted based on the temporary variation amount and the temporary dispensing volume.

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