JP2012154917A - Abnormality determination method of solid phase extraction and solid phase extraction device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To highly accurately determine abnormality at solid phase extraction and to provide a highly reliable solid phase extraction device.SOLUTION: A sample is dispensed to a solid phase extraction cartridge 9 filled with a solid phase extraction material, and the dispensed sample is pressurized by a pump 25 to perform solid phase extraction. A pressure waveform at the solid phase extraction is obtained by a pressure sensor 26 and is compared with a pressure waveform by a standard sample (at a pressurizing stage of a section 1, a constant pressure stage of a section 2, and a decreasing pressure stage of a section 3). Thus, abnormality at the solid phase extraction is highly accurately determined and a highly reliable solid phase extraction device is achieved by loading the abnormality determination means.

Description

The present invention relates to solid-phase extraction, and more particularly, to an abnormality determination method and solid-phase extraction apparatus when solid-phase extraction is performed under pressure.

  The solid phase extraction process combines the selective adsorption of the solid phase extraction material such as hydrophobicity and hydrophilicity with the selective elution in the eluate used in the subsequent elution process, thereby removing the extracted components in the sample. This treatment is intended to be selectively taken out into the eluate or to selectively adsorb unnecessary components in the sample to the solid phase extraction material.

  By using such a solid-phase extraction process, it becomes possible to measure and detect the target component in the sample with higher accuracy.

  However, since solid-phase extraction processing is handled differently for each sample and the extraction state must be carefully performed, processing is performed semi-automatically using a hand kit or a tool that automates partial processing. There are many cases.

  Here, the extraction performance in the solid-phase extraction process is determined depending on the material of the extraction material, but the extraction process is also an important performance determining element. For example, regarding the speed at which the sample passes through the extraction material, the performance of extracting the target component in the sample tends to decrease if the speed at which the sample passes through the extraction material is fast.

  In general, the extraction process is performed by passing a sample through a member filled with a solid-phase extraction material. At this time, a pressure difference is often used to allow the passage. However, when the pressure difference is constant, the speed at which the sample passes through the extraction material varies depending on, for example, the component and viscosity of the sample, and the type and physical properties of the extraction material. Therefore, even if the same extraction material is used, if the sample properties are different, the liquid passing speed may change and affect the extraction performance.

  Furthermore, the speed at which the sample passes through the extraction material is also affected by the state of sealing of the extraction material. For example, if the extractant is not evenly sealed in the container and there is a bias in the flow resistance of the sample due to the extractant, the sample will pass through a portion having a low flow resistance. In that case, since extraction is performed only at the portion through which the sample is passed, the extraction performance is different from that when the sample is passed uniformly. For this reason, it is necessary to maintain the performance by monitoring and managing the sample extraction state so that the solid-phase extraction process is always performed in a stable state.

  For example, Patent Document 1 is known as such a solid-phase extraction apparatus that automatically performs solid-phase extraction processing. Here, the sample to be extracted is dispensed into a plurality of containers in which the solid phase extraction material is sealed, and by simultaneously reducing the pressure of the plurality of containers by blocking outflow of air from other than the outflow portion of the sample, An extraction processing mechanism is described in which the sample is passed through, the extraction target is adsorbed on the extraction material, and then the washing solution and the elution solution are dispensed, and then the washing and elution treatment is similarly performed by suction under reduced pressure. .

  Further, Patent Documents 2, 3 and 4 propose mechanisms for solid-phase extraction by applying pressure from the sample dispensing side in the process of passing a sample through a solid-phase extraction material. Patent Documents 2, 3 and 4 also describe that a pressure sensor for monitoring the pressure inside the extraction container is provided, and the extraction state is monitored using the pressure acquired by the pressure sensor.

Japanese Patent No. 2832586 JP 2005-95159 A JP 2005-110670 A JP 2005-278438 A

  The extraction mechanism described in Patent Document 1 has a structure that can process a plurality of objects at the same time. However, it is necessary to perform processing on a plurality of objects under exactly the same conditions. Furthermore, even if the conditions are the same, if any one of the extractions is preceded, the atmosphere is in an open state, and there is a problem in that other extractions are affected.

  Furthermore, the method of Patent Document 1 needs to be batch processing and is not suitable for continuous processing with a constant cycle time. Furthermore, there is a problem in that other samples that have previously completed the extraction process cannot proceed to the next step due to the process for the target requiring the maximum time.

  Further, in the extraction processing apparatuses proposed in Patent Documents 2 and 3, there is a problem that when a plurality of processes are performed at the same time, the air supply time is different between a single case and a plurality of cases.

  In addition, when a plurality of air is supplied simultaneously, there is no guarantee that the air can be supplied to each flow path at the same speed or pressure.

  On the other hand, in the extraction device proposed in Patent Document 4, as an extraction state monitoring method, an abnormal state is determined based on a maximum value and a speed change indicated by the pressure waveform in the extraction state and its time, etc. It is not possible to determine with high accuracy whether the abnormality is due to defective consumables encapsulated with the extraction material or the sample to be extracted, and it is also considered to manage changes over time of the device over a long period of time. Not.

  The present invention has been made in view of such a current state of solid phase extraction, and its main object is to provide an abnormality determination method capable of determining an abnormality of solid phase extraction with high accuracy.

  Another object of the present invention is to provide a highly reliable solid-phase extraction apparatus using the abnormality determination method, and to achieve these objects with high accuracy.

  The feature of the present invention for achieving the main object described above is that a sample is dispensed into a solid-phase extraction cartridge filled with a solid-phase extraction material, and the dispensed sample is pressurized to pass through the extraction material. In the method for determining an abnormality in phase extraction, an abnormality in the solid phase extraction is obtained by obtaining a pressure waveform during the solid phase extraction and comparing the pressure waveform with a pressure waveform obtained by other solid phase extraction. Is determined by waveform comparison.

  A feature of the present invention for achieving the other object is that a sample is dispensed into an extraction cartridge filled with a solid-phase extraction material, and the dispensed sample is pressurized and passed through the extraction material. In a solid-phase extraction apparatus for phase extraction, a syringe pump that supplies air for pressurization, a pressure sensor that detects a pressure inside a flow path from the syringe pump to the extraction cartridge, and a pressure waveform of a specific sample are stored And a means for judging abnormality by comparing the output waveform of the pressure sensor at the time of solid-phase extraction with the pressure waveform stored in the storage means by operating the syringe pump. It is in the place where solid phase extraction supported by the abnormality judgment of has been made possible.

  Further features of the present invention will become apparent from the embodiments of the invention described below.

  According to the present invention, since the abnormality of the solid phase extraction is determined by comparing the pressure waveforms, the abnormal state of the solid phase extraction can be determined with high accuracy. Furthermore, for example, by performing a waveform comparison according to the sample property according to the sample type, an appropriate determination process can be performed for each sample. In addition, a highly reliable apparatus can be realized by incorporating such an abnormality determination method into the solid phase extraction apparatus.

The block diagram of the solid-phase extraction apparatus which concerns on one Example of this invention. The flow-path block diagram of the extraction process part which concerns on one Example of this invention. Outline explanatory drawing of a solid phase extraction process. The block diagram of the extraction cartridge which concerns on one Example of this invention. The block diagram of the modification of the extraction cartridge which concerns on one Example of this invention. The flowchart of the extraction process determination which concerns on one Example of this invention. The flowchart of the abnormality determination process of the solid phase extraction which concerns on one Example of this invention. The graph of the example of an extraction pressure waveform. The graph of the example of a change of the pressure waveform by sample viscosity. Explanatory drawing of the waveform comparison parameter in one Example of this invention.

  Embodiments of the present invention will be described below with reference to the drawings.

  First, a series of solid phase extraction processes will be described with reference to FIG. The sample in the sample container 7 is sucked by the sample dispensing mechanism 15 and discharged to the extraction cartridge 9. The extraction cartridge 9 used in the solid phase extraction apparatus has a solid phase extraction material 34 enclosed therein. The sample passes through the solid-phase extraction material 34 by supplying air from the extraction nozzle 31 of the solid-phase extraction processing unit, and the measurement target in the sample is extracted, and unnecessary substances are drained.

  The extraction cartridge 9 is subjected to a cleaning process as necessary with the measurement target held on the solid-phase extraction material 34, and finally the eluate is dispensed into the extraction cartridge 9, and is similar to the above-described sample passing process. In this process, the liquid to be measured is eluted, and the liquid that has become the extraction sample liquid is received in the lower extraction container 10.

  By such a series of extraction processes, an extracted sample liquid containing the measurement object can be obtained. In general, the content of an object to be measured is measured by measuring an extracted sample solution from which unnecessary substances in the sample are removed by a solid-phase extraction process using a measuring instrument such as a photometer.

  Next, a solid phase extraction apparatus according to an embodiment of the present invention will be described with reference to FIG. FIG. 1 particularly shows the configuration of the extraction processing unit, and the components not related to the present invention are omitted. In FIG. 1, a solid phase extraction apparatus 101 receives a display unit 1, an input unit 2, a calculation processing unit 3, a storage unit 4, an external communication interface unit 5 that performs communication processing with the outside, a print output unit 6, and an extraction process. Sample placement unit 8 in which a sample container 7 into which a sample has been dispensed is placed, a placement unit 11 for consumables such as an extraction cartridge 9 and an extraction container 10, a processing unit 12 for performing processing sequentially using the extraction cartridge, and used for extraction processing Reagent placement section 14 for placing various reagent containers 13 such as washing liquid and eluate to be run, sample dispensing mechanism 15 for dispensing these samples and chemicals to a solid phase extraction cartridge, reagent dispensing mechanism 16, and solid phase for performing extraction processing An extraction processing unit 17, an extraction container installation unit 18 in which an extraction container is disposed, an extraction sample liquid dispensing mechanism 19 that dispenses the extracted sample liquid, and a control unit 20 that controls these mechanism elements are included.

  Furthermore, the sample information reading unit 21 for reading the sample information attached to the sample container 7, the extraction cartridge information reading unit 22 for reading the manufacturing information of the extraction cartridge 9 attached to the extraction cartridge 9, and the reagent container are attached. A reagent information reading unit 23 for reading reagent information is provided.

  Further, in the present embodiment, the detection unit 24 that measures the measurement object using the extraction processing sample subjected to the solid phase extraction is combined. Here, the detection unit 24 is a detector that can be applied to measure an object, and may be a photometer or other detectors.

  Next, the solid phase extraction processing operation of the apparatus in FIG. 1 will be described. The solid phase extraction process described below is a processing operation common to a standard sample for controlling the extraction state of the apparatus or a control sample in addition to a sample as an actual measurement target.

  As will be described in detail later, the sample is stored in a bar code label on which information for identifying the sample is described, or a sample container 7 to which an RFID or IC chip is attached. This sample information is read by the sample information reading unit 20 arranged in the sample setting unit 8. Further, a bar code label, RFID or IC chip is also attached to the extraction cartridge 9, and this information is read by the extraction cartridge information reading unit 21.

  Here, the sample information and the like can be imported into the apparatus in addition to the method of automatically reading the information provided with the reading unit as described above, even if the operator inputs the information manually by the input unit 2 of the apparatus. good. In this case, it is not necessary to provide an information reading unit for the sample and the extraction cartridge.

  The extraction cartridge 9 is sequentially moved by the movement of the processing unit 12 in which the extraction cartridge 9 is installed, and a sample is dispensed by the sample dispensing mechanism 15 at a dispensing amount in accordance with the extraction conditions input, set, and stored in the apparatus. Dispense into the extraction cartridge 9. The extraction cartridge 9 that has received the dispensing of the sample moves to the extraction unit processing 17. In this embodiment, since the processing unit 12 has a circular table shape, the movement is performed by a rotational motion.

  In the extraction unit process 17, the extraction nozzle 31 (FIG. 3) is joined to the extraction cartridge 9 to perform the extraction process. After extracting the sample, the reagent dispensing mechanism 16 adds the cleaning liquid and discharges the cleaning liquid. Thereafter, the eluate is dispensed in the same manner, and the extracted sample liquid from which the measurement target is eluted is extracted into the extraction container 10.

  The extraction container 10 moves the extraction container 10 to the position of the extraction sample liquid dispensing mechanism 19 by the movement of the extraction container installation unit 18, and the extraction sample liquid in the extraction container 10 is sent to the detection unit 24, and the detection unit At 24, the measurement object is detected. The output of the detector 24 is subjected to concentration calculation, unit conversion processing and the like in the calculation processing unit 3 and is displayed on the display unit 1 as a desired measurement result, and is also stored in the storage unit 4 together with information on the sample. The operator outputs the measurement result from the print output unit 6 or transmits it to the host computer via the external communication interface unit 5 as necessary.

  Next, details of the extraction process will be described with reference to FIG. Note that FIG. 2 shows only one flow path configuration, but when performing a plurality of parallel processes, a plurality of these flow paths can be prepared.

  A quantifiable syringe pump 25 is used as an actuator for supplying air to the extraction cartridge 9. The syringe pump 25 is driven using a pulse motor capable of speed control. Further, the pressure sensor 26 is disposed in the middle of the flow path piping on the discharge side of the syringe pump 25. The flow path is provided with a three-way electromagnetic valve 27 for switching between the flow path of the extraction cartridge 9 and the atmosphere open flow path, and a filter 28 is provided in the flow path on the air open side.

  Further, an air pump 29 is disposed downstream of the syringe pump 25, and a two-way electromagnetic valve 30 is provided in the flow path between the air pump 29 and the syringe pump 25. A filter 28 is provided on the air suction side of the air pump 29. The operations of these flow path components are performed by the control unit 20. An electrical control signal and a circuit signal for this purpose are indicated by a dotted line 33, and the air piping flow path is indicated by a solid line 32.

  The three-way solenoid valve 27 is in a state of being connected to a flow path on the air release side where the filter 28 is provided, and blocks the flow path on the extraction nozzle 31 side. In this state, the syringe pump 25 performs air suction / discharge in accordance with preset sample extraction conditions. Since the internal pressure generated by the syringe pump 25 can be changed by the volume to be sucked and discharged, a pressure according to each extraction condition can be generated. After suctioning air with the syringe pump 25, the three-way solenoid valve 27 is switched, the atmosphere open side is shut off, and the air is discharged by connecting to the flow path on the extraction nozzle 31 side, thereby extracting at the pressure used for the extraction process. The sample in the cartridge 9 is pressurized and extracted.

  After the completion of extraction, the air pump 29 in the subsequent stage of the syringe pump 24 is operated and the two-way electromagnetic valve 30 is opened for the purpose of washing the inside of the extraction nozzle 31 with air. The air can be replaced.

  Furthermore, during extraction, for example, when the extraction is completed, the air pump 29 is operated, whereby the internal pressure can be increased again from the state where the internal pressure initially generated by the syringe pump 25 has decreased. Such an operation can forcibly discharge samples and the like that are water droplets at the end of extraction, and can prevent dripping at unnecessary locations.

  Here, as an example, the internal pressure when the internal pressure is increased by compressing the internal volume of the flow path with the volume sucked and discharged by the syringe pump 25 will be described.

The initial volume of the pipe flow path 32 to the extraction cartridge 9 in a state where the syringe pump 25 is stopped is unique to the apparatus. This is the flow channel initial volume V0. The initial pressure in the flow path is the atmospheric pressure P0. At this time, when the volume sucked by the syringe pump 25 is V1, and the space inside the flow path is closed, the ideal flow path internal pressure P2 after the syringe discharge operation is
P2 × V0 = P1 × (V0 + V1) (1)
Can be obtained. Therefore, the ideal flow path internal pressure P2 is
P2 = P1 × (V0 / V1) / V0 (2)
It becomes.

In addition, in the actual flow path on the apparatus, a loss occurs due to deformation of the piping and the like. Therefore, the pressure P2 ′ generated in the actual apparatus is obtained using the coefficient α.
P2 ′ = α × P1 × (V0 / V1) / V0 (3)

  The coefficient α is obtained by measuring with an actual apparatus.

  The pressure obtained by the above calculation is generated by the above-described discharge of the syringe pump 25, and the time taken to generate this pressure depends on the discharge operation time of the syringe pump 25.

An example of the pressure waveform is shown in FIG. If the discharge operation time of the syringe pump 25 is sufficiently earlier than the passage time of the sample solid-phase extraction material, the internal pressure maintains the maximum pressure value P2 ′ for a certain time. This pressure maintenance time is continued until the passage of the sample through the solid-phase extraction material is completed and the compressed air is released to the atmosphere side.

  If the same extraction cartridge 9 is used and the operation of the syringe pump 25 for supplying air is the same, the pressure waveform is basically the same waveform as normal waveforms A and B.

  When the operation of the syringe pump 25 is the same, the increase value (maximum value) of the internal pressure becomes the same value regardless of the sample in the result of the expression (3).

  Therefore, normal extraction is performed when there is an abnormality in the solidification extraction material in the extraction cartridge 9, there is a material defect, or there is a sample abnormality such as high or low viscosity of the sample to be extracted or poor sample dispensing. Compared to the pressure waveform obtained by normal processing with the cartridge 9 and a standard sample, the abnormal waveforms A and B have different shapes.

FIG. 8 shows a comparison chart of extraction waveforms when the sample viscosity is changed. The pressure waveform when the concentration of water or a glycerin aqueous solution is changed to change the sample viscosity is shown. When the viscosity increases due to the increase in the glycerin concentration, as shown in FIG. 8, since the operation of the syringe pump 25 is the same, the rise of the pressure is the same, but the maximum pressure maintenance time tends to be extended. .

  Therefore, the pressure waveform of the process using one or more standard samples is obtained and stored in advance according to the conditions such as sample type, sample amount, and extraction material type, and the same as the pressure waveform in the actual sample performed under each measurement condition. By comparing with the pressure waveform of the standard sample of the condition, or by comparing with a plurality of pressure waveforms such as the upper limit and lower limit of the measurement condition, the defect of the extraction cartridge 9 or the abnormality of the sample can be determined with high accuracy. Is possible.

  Here, an example of an abnormality determination method by waveform comparison, which is one of the features of the present invention, and an example of a comparison parameter for the method will be described with reference to FIG.

  In FIG. 9, section 1 is a pressurization stage in which the internal pressure of the extraction cartridge rises due to pressurization of the pump. Section 2 is a process until sample extraction is completed, and shows a slight pressure drop, but is a substantially constant pressure stage. Further, the section 3 is in a pressure-lowering stage where the extraction is completed and the air used for pressurization passes through the extraction material.

  Here, since the pressure increase rate shown in the section 1 is a pressure generated by the operation of the syringe pump, it indicates a constant pressure increase rate, and if the extraction is not completed at the end of the operation, the standard It becomes the same waveform as the waveform.

  Therefore, when the amount of pressure increase per unit time in section 1 and the maximum pressure value are different from the standard waveform, it can be determined that the abnormal operation of the syringe pump and the sample dispensing amount are not normal. By comparing this state with the standard waveform, it is possible to determine an abnormality in the pressurization stage.

  The section indicated by section 2 corresponds to the time for the sample to be extracted to pass through the solid-phase extraction material. The waveform in this section shows a slight pressure drop, but basically the maximum pressure value must be maintained. Furthermore, the time shown in the section 2 varies depending on the amount of sample and the viscosity of the sample. When the sample amount is small or the viscosity of the sample is low, the time indicated by the section 2 is shortened. On the contrary, when the amount of sample is large or the viscosity is high, the time of section 2 is extended.

  Therefore, in the constant pressure stage of section 2, it is possible to determine whether the sample dispensing amount is poor or the viscosity of the sample is within the appropriate range of the extraction process by comparing the constant pressure duration with the standard waveform. Furthermore, it can be determined that the extraction has not been performed completely if the pressure does not drop after a certain period of time.

  In the step-down stage in section 3, the pressure drop per unit time is used for comparison with the standard waveform. If the pressure drop rate is not within the allowable range in the difference from the standard waveform, it may be determined that extraction is insufficient because the sample may not be completely passed.

  In this way, by dividing the comparison of pressure waveforms into a plurality of stages and determining and comparing characteristic parameters for each stage, it is possible to determine an abnormality in solid phase extraction with very high accuracy. As a comparison method when divided into a plurality of stages, there is a method of comparing areas indicated by waveforms. The area of the section 1 must match the area obtained from the standard waveform as long as there is no abnormality. If they do not match, it can be determined as abnormal. Further, when the difference from the area obtained from the standard waveforms in the sections 2 and 3 is not within the allowable range, it is determined that there is an abnormality.

  An example of the extraction cartridge 9 is shown in FIGS. 4A and 4B. The extraction cartridge 9 includes a cartridge container 38, a solid phase extraction material 34, and a filter 39 having a flow path diameter smaller than the solid phase extraction material particle diameter above and below the solid phase extraction material. In such an extraction cartridge 9, in this embodiment, in order to identify the extraction cartridge 9, FIG. 4A shows an example in which a barcode label 35 indicating manufacturing information of the extraction cartridge 9 is attached, and FIG. 4B shows an IC chip 36 (or , RFID 37) is shown. In the present embodiment, the information on the bar code label 35 or the IC chip 36 attached to the extraction cartridge 9 is read and used for parameter setting of individual solid phase extraction and data management of the extraction waveform.

  Next, an extraction process determination flow according to an embodiment of the present invention will be described with reference to the flowchart of FIG. Before entering the extraction process, the operator first stores extraction parameters such as a sample to be measured, an extraction cartridge type, and an extraction pressure in the extraction parameter DB in advance (steps 500 and 501).

  When the processing is started (step 503), the sample number is read (step 504) to recognize the type of the sample and refer to the extraction parameters such as the sample amount, the extraction cartridge, and the extraction pressure stored in the extraction parameter DB ( In step 505), the identification information of the extraction cartridge 9 is read (step 506), the pump suction / discharge volume is calculated (step 507), and then the extraction process is executed (step 508).

  Here, the sample information is obtained from the sample number in step 504, and it is recognized whether or not the sample is a standard sample or an apparatus state or a sample for performance evaluation such as an extraction cartridge. This is because, for a standard sample or the like, the pressure waveform obtained by the extraction process is stored in the pressure waveform storage DB as a waveform for comparison and reference. As another method, a method of recognizing a standard sample by providing a plurality of sample setting units in the sample setting unit 8 and setting a specific position of the sample setting unit as a dedicated arrangement position 40 of the standard sample may be used. In addition, in the case of a standard sample, there are cases where a plurality of standard samples are used or the same sample is extracted under a plurality of extraction conditions. In this case, extraction processing is performed for each condition and each pressure waveform is stored. .

  In the extraction process (step 508), based on the equations (1) to (3), the compression volume due to the operation of the pump is calculated, and the waveform determination process is performed by comparison with the extracted pressure waveform (step 509). If it is a value within the calculated value, it is determined as normal, and the pressure waveform is stored in the pressure waveform storage DB 502 together with information that can specify the sample, the extraction cartridge manufacturing information, and the extraction conditions (step 512).

  When it is determined that the pressure waveform is abnormal compared with the calculated value, an alarm process is performed to notify the operator (step 510), and if necessary, the apparatus is stopped (step 511). The waveform at that time is also related information. And stored in the pressure waveform storage DB 502 (step 512).

  The processing end (A) in FIG. 5 is connected to the front end (A) of the processing in the flowchart shown in FIG. 6, and the processing of the abnormality determination flow by the waveform comparison in FIG. 6 is continued. Therefore, as described above, in the case of creating a comparative waveform such as a standard sample or an abnormal waveform, the processing is completed up to FIG. 5, and FIG.

  In FIG. 6, after the actual sample extraction process shown in FIG. 5 is executed, a pressure waveform to be compared with the sample is selected and referenced from the pressure waveform of the standard sample stored in the pressure waveform storage DB 502 (step 601), an abnormality is determined by comparison with the pressure waveform of the actual sample (step 602).

  This abnormality determination (step 602) is performed by comparing the waveform with the standard sample for each of the sections 1 to 3, using the comparison parameters described in FIG. In other words, the pressure increase in section 1 is the amount of pressure increase per unit time and the maximum pressure value, the constant pressure stage in section 2 is the duration of constant pressure, and the pressure decrease in section 3 is compared with the amount of pressure decrease per unit time. Make a decision.

  The abnormality determination at this time is performed with an allowable range that can ensure the performance of the extraction process. For example, as for the waveform of the rising pressure, the shape up to the maximum pressure and the final maximum pressure value are almost constant unless any mechanism malfunctions or air leakage from the flow path occurs. Therefore, the tolerance of detection error by the pressure sensor is set for the pressure waveform of the standard sample.

  The duration of the maximum pressure value varies depending on the sample amount and sample viscosity. For example, when the sample amount is the same as that of the standard sample, the duration is extended as the sample viscosity increases. Therefore, when the extraction performance in the extraction process converges within a certain range, the allowable time fluctuation range, or when the processing time is limited, the processing allowable time is set. Further, the waveform shape of the pressure drop is set to this allowable range by comparing with the shape leading to the atmospheric pressure drop of the standard sample or the final pressure value.

  If no abnormality is found in the above abnormality determination processing (step 602), the subsequent extraction processing such as washing and elution is continued (step 603), and if there is a next sample (step 613), FIG. Returning to the tip 5 (B), extraction and abnormality determination are performed for all samples.

  If an abnormality is recognized, an alarm process (step 604) is performed, and then the sample extraction process is stopped (step 605). In FIG. 6, it is further determined whether or not a similar abnormality has occurred multiple times (N = 2 or more) in the same sample (step 606), and if it occurs N or more times, an alarm is generated. The process of stopping the extraction is performed (steps 607 and 608). At this time, the N determination processes may be performed twice or more consecutively.

  For example, if the extraction cartridge used for sample extraction has an extraction error even when another sample is extracted with the same lot number, an alarm is displayed on the device as a warning to use the extraction cartridge with that lot number. (Step 609), and processing for stopping the use of the extraction cartridge is performed (Step 611). In this case, if another lot of extraction cartridge cannot be prepared, the process ends (steps 612 and 614).

  As a result, it is possible to judge the problem of the sample and the defect in the manufacturing unit of the extraction cartridge, and to prevent frequent occurrence of the defect of the extraction process, and waste the consumables such as the reagent and the extraction cartridge and the sample. This can be prevented beforehand.

  In addition, as a diagnosis of the apparatus state using the standard sample, it is also possible to check the apparatus state using a standard sample having a viscosity within a range that the apparatus can normally handle. For example, it is determined whether the maximum pressure value and the extraction time during the extraction process are within the allowable range using samples of the apparatus allowable lower limit viscosity and the upper limit viscosity, and if there is an abnormality, the problem of the extraction cartridge, or It can be determined that there is an abnormality in the detection of the pressure sensor.

  Furthermore, if the equipment has a function to display the pressure waveform during the extraction of the standard sample in chronological order for each extraction condition, the operator can monitor the time-dependent change of the pressure waveform during the extraction and manage the equipment status. can do.

  Furthermore, in this embodiment, since the abnormality is determined by comparing the pressure waveform with the standard sample, the abnormal state extraction and determination process according to the sample and the extraction conditions is compared to the process of determining only by the fixed value inside the apparatus. It can be performed. However, the waveform for comparison is not limited to the standard sample, and it can be implemented even with a specific comparative sample or an extraction waveform preceding in the case of continuous extraction.

DESCRIPTION OF SYMBOLS 1 ... Display part 2 ... Input part 3 ... Calculation processing part 4 ... Memory | storage part 5 ... External communication interface 6 ... Print output part 7 ... Sample container 8 ... Sample container installation part 9 ... Extraction cartridge 10 ... Extraction container 11 ... Consumable installation Unit 12 ... Processing unit 13 ... Reagent container 14 ... Reagent container installation unit 15 ... Sample dispensing mechanism 16 ... Reagent dispensing mechanism 17 ... Extraction processing unit 18 ... Extraction container installation unit 19 ... Extracted sample liquid dispensing mechanism 20 ... Control unit DESCRIPTION OF SYMBOLS 21 ... Sample information reading part 22 ... Extraction cartridge information reading part 23 ... Reagent information reading part 24 ... Detection part 25 ... Syringe pump 26 ... Pressure sensor 27 ... Three-way solenoid valve 28 ... Filter 29 ... Air pump 30 ... Two-way solenoid valve 31 ... Extraction nozzle 32 ... Extraction flow path pipe 33 ... Control circuit 34 ... Solid phase extraction material 35 ... Bar code 36 ... IC chip 37 ... RFID
38 ... Cartridge container 39 ... Filter 101 ... Solid phase extraction device

Claims (13)

In a method of dispensing a sample to a solid-phase extraction cartridge filled with a solid-phase extraction material, pressurizing the dispensed sample and allowing the extraction material to pass through, and determining an abnormality in solid-phase extraction,
Obtain the pressure waveform during the solid phase extraction,
An abnormality determination method for solid phase extraction, wherein the abnormality of solid phase extraction is determined by comparing the pressure waveform with another solid phase extraction pressure waveform. In the solid phase extraction abnormality determination method according to claim 1,
The pressure waveform of a specific sample or a plurality of specific samples as the other pressure waveform is stored in advance as the pressure waveform of the other solid phase extraction,
An abnormality determination method for solid phase extraction, wherein abnormality determination is performed by comparing a single or a plurality of pressure waveforms of the specific sample with the waveform of the acquired pressure waveform. In the solid phase extraction abnormality determination method according to claim 2,
The specific sample is a standard sample,
A pressure waveform obtained by solid phase extraction of the standard sample is stored in advance as a pressure waveform for comparison,
When different standard samples exist depending on the types of samples to be handled, sample concentration, solid-phase extraction material, or solid-phase extraction equipment, a pressure waveform is stored for each of these standard samples. Abnormal judgment method of phase extraction. In the solid phase extraction abnormality determination method according to claim 1,
The pressure waveform is divided into a pressurization stage, a constant pressure stage, and a pressure reduction stage,
The method of determining abnormality in solid phase extraction, wherein the comparison between the acquired pressure waveform and another pressure waveform is divided into the pressurization stage, the constant pressure stage, and the pressure reduction stage. In the solid phase extraction abnormality determination method according to claim 4,
The obtained pressure waveform is compared with other pressure waveforms by comparing the pressure increase amount and maximum pressure value per unit time in the pressurization stage, the duration of constant pressure in the constant pressure stage, and the pressure decrease amount per unit time in the pressure reduction stage. An abnormality determination method for solid-phase extraction, comprising comparing any or all of the above and determining abnormality. In the solid phase extraction abnormality determination method according to claim 1,
A syringe pump and a flow path for supplying pressurized air from the syringe pump to the extraction cartridge;
From the internal volume of the syringe pump, the total flow path volume until the extraction material passes through the extraction cartridge, and the compression ratio due to the air volume supplied by the syringe pump, the rising pressure inside the flow path is obtained by calculation,
An abnormality determination method for solid phase extraction, wherein the abnormality of the pressure waveform is determined by comparing the calculated value and the acquired pressure waveform. In the solid phase extraction abnormality determination method according to claim 6,
It has a pressure waveform storage DB,
The pressure waveform acquired by the extraction process is stored in the pressure waveform storage DB,
Comparing the pressure waveform stored in the pressure waveform storage DB with the pressure waveform obtained by the other solid-phase extraction, and determining the abnormality of the solid-phase extraction, the abnormality determination method of the solid-phase extraction . In the solid phase extraction abnormality determination method according to claim 1 or 6,
An abnormality determination method for solid phase extraction, characterized in that when it is determined as abnormal by the abnormality determination, the next solid phase extraction is stopped and the occurrence of the abnormality is displayed. In a solid-phase extraction apparatus for solid-phase extraction by dispensing a sample into an extraction cartridge filled with a solid-phase extraction material, pressurizing the dispensed sample and passing the extraction material through,
A syringe pump that supplies air for pressurization, a pressure sensor that detects a pressure in a flow path from the syringe pump to the extraction cartridge, a storage unit that stores a pressure waveform of a specific sample, and the syringe pump. A solid phase extraction apparatus comprising: means for determining abnormality by comparing the output waveform of the pressure sensor during solid phase extraction with the pressure waveform stored in the storage means.   The solid-phase extraction apparatus according to claim 9, further comprising a three-way electromagnetic valve in a flow path between the syringe pump and the extraction cartridge, wherein the three-way electromagnetic valve opens one flow path to the atmosphere, and the other A solid phase extraction apparatus characterized in that the flow path is a flow path for supplying pressurized air from the syringe pump to the extraction cartridge.   The solid-phase extraction apparatus according to claim 9 or 10, further comprising an air pump for forcibly supplying air to a flow path from the syringe pump to the extraction cartridge, and supplying the air supplied from the air pump to the extraction cartridge side A solid-phase extraction apparatus characterized in that air can be supplied from the air pump to the extraction flow path by controlling the flow path so that the air is supplied to the air.   The solid phase extraction apparatus according to claim 9, further comprising means for stopping the solid phase extraction by the sample determined to be abnormal or the extraction cartridge used for the abnormality determination in response to the abnormality determination of the abnormality determining means. A solid phase extraction apparatus characterized by the above.   10. The solid-phase extraction apparatus according to claim 9, further comprising means for reading the identification information of the sample and the identification information of the extraction cartridge, and storing the identification information of the sample and the extraction cartridge in association with the pressure waveform determined to be abnormal. A solid-phase extraction apparatus comprising storage means for performing

Images