JPH0972920A - Method and apparatus for spot-deposition of liquid to material to be spot-deposited - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enhance measuring accuracy by performing a predetermined amt. of spot-deposition by correcting the fluctuations of an emitting amt. caused by the fluctuations of vapor pressure in a spot-depostion tip when a liquid is spot-deposited on a material to be spot-deposited by using the spot-deposition tip sucking and emitting the liquid. SOLUTION: A liquid 220 is received in the disposal spot-deposition tip 88 fitted to the leading end of a suction nozzle 91 in predetermined quantity slightly larger than spot-deposition quantity and, subsequently, spot-deposition introducing emitting pressure into the spot-deposition tip 88 to emit the liquid to a material 1 to be spot-deposited is continuously performed several times. In this case, the signal related to vapor pressure of an atmosphere is obtained and emitting pressure is corrected according to the change of the vapor deposition in the spot-deposition tip 88 after the liquid is sucked into the spot-deposition tip 88 is corrected to equalize the spot-deposition quantities at respective times of spot-deposition in continuous spot-deposition.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a disposable point for spotting a sample such as blood or urine or a spotting liquid such as a diluting liquid or a reference liquid onto a spotting material such as a dry analysis element or a dilution cup. The present invention relates to a liquid spotting method and a liquid spotting device for continuously discharging a fixed amount of liquid contained in a spotting tip onto a spotted material.

[0002]

2. Description of the Related Art In recent years, a dry-type dry analytical element has been developed which can quantitatively analyze a specific chemical component or a formed component contained in a sample by simply supplying a small droplet of the sample. It has been put to practical use. By using this dry analysis element, it is possible to analyze a sample simply and quickly as compared with the conventional wet analysis method. Therefore, its use is particularly necessary for medical institutions, laboratories, etc. that need to analyze a large number of samples. Is preferable.

In order to quantitatively analyze chemical components in a sample using such a dry analysis element, the sample is spotted on the dry analysis element and then this is incubator (incubator).
Incubate at room temperature for a predetermined time to cause a color reaction (dye formation reaction), and then measure a wavelength selected in advance by combining a predetermined biochemical substance in the sample with a reagent contained in the dry analysis element. This dry analytical element is irradiated with the irradiation light for measurement to measure its optical density, and from this optical density, a calibration curve that represents the correspondence between the optical density and the substance concentration of the prescribed biochemical substance is obtained. A biochemical analysis device is used which is configured to obtain the substance concentration of a predetermined biochemical substance in the sample, and then take out the used dry analytical element from the incubator and dispose of it in a waste box.

As the dry analysis element, a slide type, a film piece only, or the like is used. For such a dry analysis element, a sample should be accurately spotted by a prescribed amount. Is important in improving measurement accuracy. Further, even when diluting the sample to a predetermined concentration, the diluting liquid and the sample are spotted in a predetermined amount in a diluting cup with a spotting tip. It is necessary to accurately discharge the sample. Further, when measuring the electrolyte of the sample, a dry analytical element (electrolyte slide) having an electrode
Is used to measure the potential difference by spotting the reference liquid together with the sample, and it is necessary to accurately spot a predetermined amount of the sample and the reference liquid also on this electrolyte slide.

For spotting a liquid such as a sample, a diluting liquid or a reference liquid onto the spotting material such as the dry analysis element or the dilution cup as described above, the liquid is sucked by a suction nozzle to be spotted. This is done by discharging it onto the landing material,
A method is known in which the suction nozzle is cleaned every time the type of liquid changes, but in this method, contamination due to the previous liquid, especially the sample remaining, may cause a decrease in measurement accuracy, or during cleaning processing. Since a measurement capacity shortage occurs due to a decrease in operating rate, for example, U.S. Patent No. 4,340,39
As seen in No. 0, when a disposable spotting tip is fitted to the suction nozzle, liquid is sucked into the spotting tip and discharged to the spotted material, and when the liquid changes It has been used to replace the spotting tip with a new one.

By the way, in the spotting of a liquid using the spotting tip, a method of sucking a liquid corresponding to a single spotting amount into the spotting tip and discharging the whole liquid to the spotted material. However, it is difficult to obtain good spotting accuracy. In other words, even if it is attempted to discharge the entire amount of the liquid sucked into the spotting tip, the liquid remains attached to the tip of the spotting tip due to the surface tension. Occurs.

From the above point, by sucking a larger amount of liquid than the discharge amount (spotting amount) so that the liquid remains in the spotting tip even after discharging a predetermined amount of liquid. It is considered to secure the spotting accuracy. Further, when the same liquid is spotted on a plurality of materials to be spotted by one spotting tip, the liquid is sucked into the spotting tip in excess of the spotting amount, and the liquid is sucked at each spotting. Then, the liquid is continuously spotted, or a slightly larger amount of liquid than the spotted amount for a plurality of times is sucked in advance and successively spotted on the material to be spotted.

Further, in the above-mentioned US patent, the suction system is opened to the atmosphere every time the liquid is sucked to return the inside of the spotting tip to atmospheric pressure, and the contained liquid is balanced by the surface tension with the inner surface of the spotting tip. The discharge is performed after lowering to.

[0009]

However, when performing continuous spotting using the disposable spotting tip as described above, a liquid larger than the spotting amount is stored in the spotting tip. It has been found that when a plurality of materials to be spotted are continuously spotted, the spotting amount varies depending on the spotting times and an error occurs in the measurement accuracy.

Explaining the above phenomenon concretely, as shown in the experimental results in FIG. 11, the first spotted amount is larger than the second and subsequent spotted amounts. In this experiment, a new spotting tip was fitted to the suction nozzle, and a larger amount of liquid (water in the experiment) than the spotting amount was sucked into the spotting tip, and then at a predetermined time interval (for example, 9 seconds). In order to obtain a predetermined spotting amount (10 μL), the same discharge pressure is introduced into each spotting tip in order to sequentially spot the dry analytical element as a spotted material. Liquid is ejected. Three types of dry analysis elements with different measurement items are used, but the amount of spotting itself varies depending on the type of dry analysis element. It was found that the amount of the first spotting was about 0.7 to 0.9 μL and the amount of the tipping chips was larger than that in the subsequent spotting.

The type of dry analytical element is GP
TP is a dry analytical element for measuring glutamate / pyruvate transaminase, LDH-P is a dry analytical element for measuring lactate dehydrogenase, and CRE-P2 is a dry analytical element for measuring creatinine. Also, the atmospheric condition is a temperature of 3
The temperature is 2 ° C. and the relative humidity is 30%.

Considering the cause of the phenomenon in which the spotted amount increases in the first time as described above, it has been clarified that the cause is due to the fluctuation of the vapor pressure in the spotting tip. That is, as shown in FIG. 12, when the liquid is sucked into a new spotting tip in a dry state (a) (when the liquid is sucked and then the air is sucked to raise the liquid level), this spotting is performed. The space inside the chip has the vapor pressure at the ambient temperature and humidity at the beginning, but as time passes, the sucked liquid evaporates and the vapor pressure inside rises, and the internal pressure rises as shown in (b). Since the liquid level is lowered, when the discharge pressure is introduced into the spotting tip to increase the internal pressure and the liquid is discharged as shown in FIG. The discharge amount increases by the amount corresponding to the internal vapor pressure difference, and the spotting accuracy decreases. After the second time, the inside of the spotting tip has a saturated vapor pressure and does not fluctuate, so that the spotting amount is stable.

The difference in the spotted amount depending on the type of dry analytical element is considered to be due to the difference in the wettability of the surface due to the difference in the composition of the reagent layer.

In contrast to the above-mentioned difference in the spotting amount, when the inside of the spotting tip is opened to the atmosphere for each spotting as in the above-mentioned US patent, the occurrence of the difference in the spotting amount due to the influence of vapor pressure is eliminated. It is possible, but the wetting property (water repellency) of the inner surface of the spotting tip and the difference in the viscosity due to the change of the liquid change the spotting accuracy due to the variation in the discharge amount due to this, and There is a problem that the suction system needs an open valve and the device becomes complicated.

As described above, when it is desired to continuously perform the spotting with a high precision of the spotting by using the disposable tip, the vapor pressure is saturated after the liquid is sucked into the new tip. Even if the same discharge pressure is supplied between the spotting until the spotting and the spotting after the saturation, the actual discharge amount is different.

The present invention has been made in view of the above circumstances, and a liquid spotting method and a liquid spotting method for a spotted material with a simple mechanism for improving the spotting accuracy without using an open valve or the like. It is intended to provide a device.

[0017]

A method for spotting a liquid on a material to be spotted according to the present invention, which has solved the above-mentioned problems, is a method for spotting a liquid on a disposable spotting tip fitted to the tip of a suction nozzle for sucking the liquid. Is stored in a predetermined amount larger than the spotting amount, and then a predetermined discharge pressure is introduced into the spotting chip to discharge the liquid in the spotting chip to the spotting material continuously multiple times. For performing, the signal relating to the vapor pressure of the atmosphere is obtained, and the discharge pressure is changed in each continuous spotting according to the change of the vapor pressure in the spotting tip after sucking the liquid into the spotting tip. The feature is that correction is performed so that the spotted amounts at the time of spotting become equal.

The above-mentioned correction of the discharge pressure is performed by a signal related to the vapor pressure. However, the variation amount of the vapor pressure after sucking the liquid into the spotting tip is such that the saturated vapor pressure becomes higher as the temperature of the atmosphere becomes higher. The higher the humidity, and the lower the humidity in the atmosphere, the larger the difference from the saturated vapor pressure.Therefore, the correction amount is determined based on this characteristic.However, the correction is simplified depending on the spotting environment. Alternatively, the correction may be performed based on the measurement of either the temperature or the humidity.

Further, specifically, the discharge pressure at the first spotting is corrected to be lower than the discharge pressure at the second spotting, or the liquid is sucked into the spotting tip, It is preferable to correct the discharge pressure during the period until the vapor pressure in the spotting tip becomes saturated.

On the other hand, the liquid spotting device of the present invention sucks a predetermined amount of liquid into the spotting tip fitted to the tip of the suction nozzle for sucking the liquid, and then discharges the liquid into the predetermined spotting tip. The liquid suction and discharge means for introducing pressure to discharge the liquid to the spotted material is provided, and the detection means for detecting a signal related to the vapor pressure of the atmosphere, and preset based on the signal of the detection means Correction means for obtaining a correction amount of the discharge pressure from the correction characteristic and outputting a correction signal to the liquid suction / discharge means.

[0021]

According to the present invention as described above, the discharge pressure is corrected in accordance with the vapor pressure change in the spotting tip after the liquid is sucked, by the signal relating to the vapor pressure of the atmosphere, Good spotting accuracy can be ensured by accurately correcting the amount by which the vapor pressure rises to the saturated vapor pressure and the liquid level lowers as the liquid evaporates by reducing the discharge pressure. This allows
The amount of spotting can be corrected without being affected by the wettability of the inner surface of the spotting tip, and a mechanism such as an open valve is not required, so the cause of failure does not increase and the original discharge amount It can be realized by adding a correction means to the control mechanism, which is advantageous in terms of cost.

[0022]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 2 is a perspective view showing a schematic mechanism of a biochemical analysis device equipped with an example liquid spotting device. In this example, a case where a dry analysis element using a film piece is used as a material to be spotted and a sample is spotted as a spotting liquid is shown.

The biochemical analysis device 10 includes an element storage means 11 (supplier) which stores an unused rectangular dry analysis element 1 and a dry analysis element 1 disposed on the side of the element storage means 11. An incubator 12 for maintaining a constant temperature for a predetermined time, an element transfer means 13 for transferring the dry analytical element 1 from the element storage means 11 to the incubator 12, and a sample storage means 14 for storing a plurality of samples such as serum and urine, Sample storage means
The device 14 is provided with a spotting device 15 for spotting the sample 14 onto the dry analysis element 1 during the transportation by the element transporting means 13, and a measuring means 16 arranged below the incubator 12.

As shown in FIG. 3, the dry analytical element 1 comprises a light transmissive support 1a (base film) made of a plastic film such as PET (polyethylene terephthalate) and a reagent layer 1b including a developing layer laminated on the light transmissive support 1a (base film). ing. If necessary, an abrasion-resistant protective layer (not shown) made of a fibrous material such as cloth is laminated on the reagent layer 1b, or the protective layer is configured to also serve as a spreading layer. But it's okay.

In the dry state before use, the dry analytical element 1 tends to have a curved shape with the reagent layer 1b facing inward, and the degree of the curvature depends on the type of the reagent layer 1b and the degree of drying. When the reagent layer 1b of the dry analysis element 1 is mixed with a predetermined component of the sample dropped from the spotting tip 88 of the spotting device 15, a color reaction (dye formation reaction) is performed after a constant temperature incubation (incubation). Containing a reagent (including a chemical analysis reagent or an immunological analysis reagent) that causes the above, and has a reagent layer 1b set for each chemical component or formed component to be measured in the sample corresponding to the measurement item. A plurality of types of dry analytical element 1 are prepared.

The dry analytical element 1 is housed in a cartridge 20 as shown in FIG. 4 for each measurement item. The cartridge 20 accommodates a large number of dry analytical elements 1 in a stacked state with the light-transmissive support 1a facing downward, and as shown in FIG. 2, the disk-shaped frame 22 of the element accommodating means 11 is accommodated therein. A plurality of cartridges are mounted in parallel in the inner or outer cartridge storage portions 22a arranged in the. The frame 22 is rotatably supported by the base portion 24, and is rotationally driven by a supplier motor (not shown) installed in the base portion 24 so that the predetermined cartridge storage portion 22a is stopped at the take-out position corresponding to the element transfer means 13. Controlled.

The outer peripheral portion of the frame 22 is covered with a cover.
The cartridge 20 is provided so that the inside is hermetically sealed, and the cartridge 20 is inserted and taken out from an insertion opening 25a having an opening / closing lid provided on the upper surface. Further, a dehumidifying agent storage portion 27 is provided in the central portion of the frame 22, and the dehumidifying agent storage portion 27 is loaded with the dehumidifying agent from an input port 25b having an opening / closing lid formed in the central portion of the upper surface of the cover 25. Then, the inside of the element housing means 11 is kept in a dry state with low humidity. On the other hand, each cartridge 20
An opening / closing shutter (not shown) that is opened when a predetermined dry analytical element 1 is taken out of the cartridge is provided by a suction cup 70 for taking out the element carrying means 13 inserted through the shutter so that the dry analytical element 1 at the lowermost stage of the cartridge 20 is It is taken out.

Next, the incubator 12 is a disc-shaped main body 40.
Is rotatably supported by a rotary drive mechanism 41 in the lower center, and a plurality of cells 42 accommodating the dry analytical elements 1 are arranged at predetermined intervals on the circumference of the main body 40. Element 1 is incubated.

From the element housing means 11 to the incubator 12
The transporting means 13 for transporting the dry analytical element 1 is a suction cup 70 for taking out the dry analytical element 1 from the cartridge 20.
And the dry analytical element 1 held by the suction cup 70 for extraction
The above, in the cell 42 of the incubator 12, and a horseshoe-shaped transfer member 73 that is inserted from the side opening into the cell 42 of the incubator 12 while being held and received from below with the reagent layer 1b being the upper surface. An insertion suction cup 76 for advancing and retracting the dry analytical element 1 held by the transfer member 73 from the lower side of the cell 42 and holding the dry analytical element 1 is provided.

As shown in FIG. 4, the take-out suction cup 70 is provided with an upward suction cup 70a for adsorbing and holding the lower surface of the support 1a of the dry analytical element 1, and the suction cup 70a is provided at the transfer base 70b. While being supported, a decompression pipe from a suction pump (not shown) is connected, and the transfer base 70b is provided to be movable back and forth and up and down by a moving mechanism (not shown).

Then, the suction cup 70 for taking out rises and is inserted from the opening formed in the bottom surface of the cartridge 20 to adsorb and hold the side of the support 1a of the dry analytical element 1 at the lowermost stage, and slightly descends. In the curved state, it moves horizontally to take out laterally from the opening 20a formed in the side surface of the cartridge 20, and then moves downward to come out of the shutter opening of the cover 25 of the element housing means 11 and further forward. It is driven so as to convey it to the spotting position side.

Further, as shown in FIG. 5, the transfer member 73 is formed in a flat plate shape in a substantially horseshoe shape for sucking and holding the dry analytical element 1 on the upper surface thereof, and a notched recessed portion 73a is formed at the center of the front end thereof. Are formed on the fork portion 73b extending forward, and suction holes 74 are formed on the fork portion 73b on both sides of this fork portion and the back portion of the recess 73a.
Is provided. A decompression pipe 75 from a suction pump is connected to the suction hole 74. In addition, the transfer member
The base of 73 is linked to a drive mechanism (not shown) so that it can be inserted and moved from the spotting position into the cell 42 of the incubator 12 through the side opening.

When receiving the dry analytical element 1 from the eject suction cup 70, the transfer member 73 holds the dry analytical element 1 as shown in FIG. 6 (A). It moves toward the suction cup 70 and its recess 73 as shown in (B).
The suction cup 70 for extraction is located in a, and the dry analytical element 1 is located above it.
Is stopped, and then the extraction suction cup 70 is moved downward to hold the dry analytical element 1 held on the extraction suction cup 70 as shown in (C) by the fork portion 73b of the transfer member 73. And recess
It is suction-held around 73a. Further, since the suction position accuracy of the dry analysis element 1 by the extraction suction cup 70 is secured, the holding position accuracy of the dry analysis element 1 by the transfer member 73 is good, and the dry analysis element 1 is held by this transfer member 73. A predetermined amount of the sample is spotted by the spotting device 15 on the central portion of the reagent layer 1b of the dry analysis element 1 in the above state.

As shown in FIG. 2, the sample storage means 14 has a rotary table 85 which is rotated by a rotary drive mechanism 86.
A plurality of sample containers 87 containing samples are held on the outer peripheral portion of the rotary table 85, and the sample containers 87 are sequentially moved to the supply position. A spotting tip 88 mounted on the tip of a suction nozzle 91, which will be described later, is housed on the inner peripheral side.

The spotting device 15 for spotting each sample in the sample container 87 onto the dry analysis element 1 conveyed to the incubator 12 has a suction nozzle 91 for sucking and discharging the sample, and the suction nozzle 91. The tip of the above is a pipette-shaped spotting tip 88
Is detachably mounted, and is vertically and rotatably moved by a drive mechanism 92 to suck and move the sample from the sample storage means 14 to the dry analysis element 1 held on the transfer member 73. Put on the spots. Further, the suction nozzle of the spotting device 15
The spotting tip 88 at the tip of 91 is replaced when the sample is changed.

By the way, the spotting device 15 will be described in detail with reference to FIG.
The configuration is as shown in. That is, this spotting device
Reference numeral 15 denotes a sampling arm 201 that supports a suction nozzle 91 at one end thereof so as to be vertically movable, and a sampling arm 201.
At the other end of 201, a vertically extending spline shaft 202 holding the sampling arm 201 in a horizontal direction, and a claw portion that engages with a groove portion 202a formed in the side wall of the spline shaft 202 in the axial direction are provided.
A belt wheel 203 having a small-diameter portion and a large-diameter portion, which is relatively fixed in the rotational direction and relatively movable in the axial direction with respect to the spline shaft 202, the belt 205, and the belt 205 in a predetermined direction. First (moving in the direction of arrow A) to rotate the belt wheel 203 in a predetermined direction by a predetermined amount.
Motor 204, a collar 206 fixed to the bottom of the spline shaft 202, a belt 207 screwed to the side wall of the collar 206, and the belt 207 moved in a predetermined direction (arrow B direction). A second motor 208 for moving the spline shaft 202 up and down by a predetermined amount is provided.

Further, the spotting device 15 adjusts the pressure in the air passage inside the suction nozzle 91 and the pressure inside the spotting tip 88 to suck the sample, and then introduces a predetermined discharge pressure to discharge the sample. It is provided with a hose 209, a syringe 210 and a third motor 211 which constitute the sample suction / discharge means, and a nozzle vertical movement sensor 212 for detecting the vertical movement of the suction nozzle 91.

The syringe 210 is for moving the internal piston member to generate a negative pressure and a positive pressure in accordance with the normal rotation or the reverse rotation of the third motor 211, and the pressure is generated by the suction nozzle 91 by the hose 209. It is introduced into the internal space of the spotting tip 88 via the internal air passage.

Further, each of the above-mentioned motors 204, 208, 21
It is provided with a control circuit 213 for controlling the rotation of No. 1 and a computer 214 which receives a detection signal from the nozzle vertical movement sensor 212 and outputs a predetermined motor control signal to the control circuit 213 according to a predetermined sequence program.

Further, the spotting device 15 includes a temperature sensor.
215 and a humidity sensor 216 are installed, and the detection signals from both sensors are similarly input to the computer 214, and the computer 214 responds to the fluctuation of the vapor pressure according to the preset correction characteristic based on this signal. It includes a correction unit that corrects the discharge pressure, that is, the drive control of the third motor 211.

Next, a spotting method using the above apparatus will be described with reference to FIG. First, as shown in FIG.
A predetermined amount larger than the spotted amount (one spotted amount × number of spotted spots) is sucked into the sample 220, and this spotting tip 88 is set above the dry analytical element 1 from the initial position. After this, the sampling arm 201 is lowered, and when the tip of the spotting tip 88 comes into contact with the dry analytical element 1, the lowering of the spotting tip 88 is stopped, but the sampling arm 201 is lowered, as shown in FIG. 7B. The flag 212a is inserted into the slit of the sensor 212, and it is detected that the tip of the spotting tip 88 is in contact with the dry analytical element 1. After this, the sampling arm 201 rises, but conversely to the above, the flag is detected from the slit of the sensor 212.
It is detected that 212a has come off and the tip of the spotting tip 88 has separated from the dry analytical element 1. Also, the timing when the flag 212a is completely removed from the slit of the sensor 212 is the suction nozzle.
The collar portion 91a of 91 is adjusted so as to substantially coincide with the timing of contact with the upper surface of the sampling arm 201. Thereafter, as shown in FIG. 7C, the spotting tip 88 responds to the rising of the sampling arm 91. As it rises, the vapor pressure-corrected discharge pressure is introduced into the spotting tip 88, and the same predetermined amount of sample 220 is discharged onto the dry analysis element 1 at each spotting. Ascending speed of spotting tip 88 at this time and specimen
The discharge speed of 220 depends on the sample development speed of the dry analysis element 1, the viscosity of the sample 220, etc. so that the sample 220 is not interrupted on the way and the discharged sample 220 rises and the spotting tip is applied.
The value is controlled so that it does not adhere to the side wall of the tip of 88.

In the state after the spotting, the specimen 220 remains in the spotting tip 88, and when the next spotting is continuously performed,
From the beginning, when a sufficient amount of sample is aspirated from the beginning, the spotting tip 220 contains more samples than necessary for the next spotting, and the next dry type The analysis element 1 is spotted by the same process as above. Also,
Even when the sample 220 is aspirated after each spotting, the sample 220 is further aspirated from the sample container 87 into the spotting tip 88 on the sample 220 remaining by a predetermined amount, and then the same steps as described above are performed. A predetermined amount of the sample 220 is ejected onto the dry analytical element 1 for spotting.

The correction of the discharge pressure introduced into the spotting tip 88 is performed so that the discharge pressure of the first time becomes lower than the discharge pressure of the second time and thereafter.

That is, when the sample 220 is replaced, that is, when the sample 220 is sucked from a different sample container 87, the spotting tip 88 is also replaced with a new one, and the spotting tip 88 is replaced.
Although the sample 220 is sucked into the inside, the inside of the new spotting tip 88 has an atmospheric atmosphere (water vapor pressure) corresponding to the ambient temperature and humidity as described above. This spotting tip
When the sample 220 is sucked into the 88, the vapor pressure in the spotting tip 88 changes with the evaporation of the sample 220 and rises to the saturated vapor pressure. The sample in the spotting tip 88 is increased by this increase in vapor pressure.
The liquid level of 0 drops, and if the first spotting is performed in that state, a larger amount of the sample 220 than the set discharge amount will be spotted,
The discharge pressure corrected low corresponding to the fluctuation of the vapor pressure generated corresponding to the temperature and the humidity at that time is introduced to perform spotting. Two
During the second and subsequent spots, the sample 220 remains in the spotting tip 88, so that the internal vapor pressure becomes constant and the discharge amount does not fluctuate. And spot them.

The fluctuation of the vapor pressure changes depending on the time elapsed after the sample 220 is sucked into the new spotting tip 88. For example, the fluctuation is 2-3 seconds after the suction. It starts to reach a saturated state in about 10 seconds, and the degree of correction is changed according to the time from suction to spotting. That is, in the case where the first spotting is performed 10 seconds after the suction, the first discharge pressure is corrected to be reduced as described above, and the second and subsequent discharges are performed with the uncorrected discharge pressure. To control. In addition, when spotting is performed a plurality of times before the elapse of 10 seconds, it is necessary to make a correction according to the vapor pressure fluctuation at that time.

Next, the spot application program of the computer 214 will be described with reference to the flowchart shown in FIG. First, a predetermined motor drive signal is output from the control circuit 213 to the first motor 204, and the sampling arm 201 is rotated by the rotation of the first motor 204 (direction of arrow C) to be positioned on the sample container 87 ( S1). After that, the control circuit 213 outputs a predetermined motor drive signal to the second motor 208, the sampling arm 201 is lowered by the rotation of the second motor 208 (direction of arrow D), and the tip of the spotting tip 88 is sampled. Insert into the specimen 220 in container 87 (S
2).

In this state, the control circuit 213 outputs a predetermined motor drive signal to the third motor 211, and the syringe 210 is operated by the rotation of the third motor 211. The operation of this syringe 210 causes the suction nozzle inside the hose 209.
The inside of the ventilation passage of 91 and the inside of the spotting tip 88 are in a negative pressure state, and the specimen 220 is sucked into the spotting tip 88 from the tip of the spotting tip 88 (S3).

Next, from the control circuit 213 to the second motor 208
Output a predetermined motor drive signal to the second motor 208
Rotation causes the sampling arm 201 to rise and the spotting tip 88 to rise (S4), after which the control circuit 213 outputs a predetermined motor drive signal to the first motor 204,
The rotation of the first motor 204 causes the sampling arm 201 to rotate.
Is rotated to move the spotting tip 88 onto the dry analytical element 1 (S5). Then, from the control circuit 213 to the second motor
The second motor is made to output the predetermined motor drive signal to 208.
The rotation of 208 lowers the sampling arm 201 to lower the spotting tip 88 (S6).

After this, the system waits until a signal for detecting that the tip of the spotting tip 88 has come into contact with the dry analysis element 1 is input from the sensor 212 to the computer 214 (S7), and when this signal is input. , The control circuit 213 to the second motor 20
8 to output a predetermined motor drive signal, and the second motor 20
The rotation of 8 is once stopped to stop the descending of the sampling arm 201 (S8), and then the second motor 208 is rotated in the reverse direction to raise the sampling arm 201 (S9).

It waits until a signal for detecting that the tip of the spotting tip 88 has separated from the dry analytical element 1 is inputted from the sensor 212 to the computer 214 (S10), and when this signal is inputted, the first time. It is determined whether or not it is spotted (S11).
Temperature sensor 215 and humidity sensor for the first spot application
A signal 216 is input (S12), and a discharge pressure correction amount is calculated based on the correction characteristic as shown in FIG. 9 to be described later based on this signal, and a motor from the control circuit 213 for the third motor 211 is calculated based on this correction amount. Correct the drive signal (S1
3). In addition, in the second and subsequent spots, the above step S1
2 and step S13 without performing the correction in step S13
Go to 4.

In step S14, the control circuit 213 starts the third
The motor 210 outputs a motor drive signal, and the third motor 211 rotates to operate the syringe 210. Due to the operation of the syringe 210, a predetermined discharge pressure is introduced into the hose 209, the air passage of the suction nozzle 91 and the spotting tip 88 to bring the positive pressure state, and the specimen 220 in the spotting tip 88 is kept at a predetermined speed. It is ejected onto the quantitative dry analysis element 1.

Thereafter, the control circuit 213 outputs a predetermined motor drive signal to the first motor 204 and the second motor 208 so that the spotting tip 88 is returned to the initial position in preparation for the next spotting processing. Allow (S15).

As shown in FIG. 9, the correction characteristic of the discharge pressure, that is, the reduction correction amount of the discharge pressure, that is, the drive amount of the third motor 211, becomes larger as the detected temperature becomes higher, and becomes larger as the detected humidity becomes lower. The correction map is stored in advance in the memory of the computer 214 based on such correction characteristics.

In this example, the sensor 212 detects that the spotting tip 88 is in contact with the dry analytical element 1 and controls the rising speed and the discharge speed (timing) of the sampling arm 201. It is also possible not to use the sensor 212. That is, in FIG. 7, the stop position of the sampling arm 201 is set to be in the state of (b), and then the discharge pressure is applied to the inside of the spotting tip 88 while raising the sampling arm 201. The sample 220 is discharged from the tip of the spotting tip 88 at the timing when the tip of the spotting tip 88 starts to separate from the dry analysis element 1.

Further, as shown in FIG. 10, after the sample 220 is sucked into the spotting tip 88, a small amount of air may be further sucked to form an air reservoir at the tip of the spotting tip 88. First, the spotting tip 88 that has sucked the sample 220 is moved to directly above the dry analysis element 1 (FIG. 10a), and then the syringe 210 is operated by the rotation of the third motor 211 to move the inside of the air passage of the suction nozzle 91 to the negative side. A small amount of air as pressure is applied to the tip 88
Aspirate to the tip of the (Fig. 10b).

Next, the spotting tip 88 is lowered, the tip thereof is brought into contact with the dry analytical element 1 (FIG. 10c), and the spotting tip 88 is raised according to the detection of the contact state (FIG. 10c).
d) At the same time, the discharge pressure is introduced into the ventilation passage of the suction nozzle 91 to start the discharge of the sample 220. Spotting tip 88
At the position where the tip of the spotting tip 88 and the surface of the dry analysis element 1 are separated by a predetermined distance by the air at the tip of
0 is discharged onto the dry analytical element 1 (FIG. 10).
e).

The spotted dry analytical element 1 is incubated in the incubator 12, and the measuring means 16 arranged below the incubator 12 (see FIG. 2).
Measured by This measuring means 16 is a dry analytical element 1
And a photometric head 95 for measuring the optical density due to the color reaction between the sample and the sample. The photometric head 95 transmits the irradiation light for measurement containing light of a predetermined wavelength through the light-transmissive support 1a and the reagent layer.
The light from the light source 96 (lamp) is incident on the photometric head 95 through the filter 97, and the reflected light is detected by the reagent in the photometric head 95. Irradiate layer 1b. As the filter 97, a plurality of types corresponding to inspection items are installed on a disc 98, and the disc 98 is rotated by a motor 99 to select a filter 97 having a predetermined characteristic corresponding to a measurement item. Has been done.

The reflected light from the reagent layer 1b is optical information (specifically, the amount of light) according to the amount of dye produced in the reagent layer 1b.
The reflected light carrying the optical information is incident on the photo-detecting element of the photometric head 95, photoelectrically converted, and sent to the determination unit via an amplifier (not shown). The determination unit determines the optical concentration of the dye generated in the reagent layer 1b based on the level of the input electric signal, and identifies the substance concentration of a predetermined biochemical substance in the sample.

Element injecting means 17 (see FIG. 2) is arranged at the element injecting position of the incubator 12, and the element injecting means 17 adsorbs and lifts the measured dry analytical element 1 in the cell 42. Suction cup 81, a substantially horseshoe-shaped transfer member 82 for taking out the dry analytical element 1 picked up by the discharge suction cup 81 and carrying it out of the incubator 12, and taken out by the transfer member 82. It is composed of a suction cup 83 for discarding the dry analytical element 1 and discarding it in the waste box 84.

In addition, in the spotting, the tip of the spotting tip may be stopped at a position of a predetermined distance and then discharged before contacting the surface of the dry analysis element as in the above example. Further, as the dry analysis element, not only the dry film element as described above but also the slide type element having a frame may be used.

[Brief description of drawings]

FIG. 1 is a schematic diagram showing a liquid spotting device for a dry analytical element as a spotted material according to an embodiment of the present invention.

FIG. 2 is a perspective view showing a schematic configuration of a biochemical analysis device equipped with the device shown in FIG.

FIG. 3 is a perspective view showing a state where the dry analytical element is spotted.

FIG. 4 is a perspective view showing a taken-out state of the dry analytical element.

FIG. 5 is a perspective view of a main part of a transfer member.

FIG. 6 is a schematic diagram showing in sequence the delivery of the dry analytical element from the ejection suction cup to the transfer member.

FIG. 7 is a schematic view showing an example of a method of spotting on a dry analytical element in order.

FIG. 8 is a flowchart for explaining a spot application program of the computer shown in FIG.

FIG. 9 is a characteristic diagram showing correction characteristics of discharge pressure.

FIG. 10 is a schematic diagram sequentially showing another example of a method for spotting on a dry analytical element.

FIG. 11 is a graph showing the relationship between the number of spots and the amount of spots in conventional continuous spotting.

FIG. 12 is a schematic diagram for explaining the cause of the difference in the spotted amount.

[Explanation of reference symbols] 1 dry analysis element (point-to-be-attached material) 10 biochemical analysis apparatus 15 point-attaching apparatus 88 point-attaching tip 91 suction nozzle 201 sampling arm 204 first motor 208 second motor 209 hose 210 syringe 211 number Motor 213 Control circuit 214 Computer 215 Temperature sensor 216 Humidity sensor 220 Sample

Claims (4)

[Claims] 1. A disposable spotting tip fitted to the tip of a suction nozzle for sucking a liquid contains a predetermined amount of liquid larger than the spotting amount, and then a predetermined discharge pressure is applied in the spotting tip. In the method of spotting a liquid onto a spotting material by continuously introducing and discharging the liquid in the spotting tip to the spotting material, a signal relating to the vapor pressure of the atmosphere is obtained. , The discharge pressure is corrected according to the change of the vapor pressure in the spotting tip after sucking the liquid into the spotting tip so that the spotting amount at each spotting in the continuous spotting becomes equal. A method for spotting a liquid on a spotted material, comprising: 2. The liquid onto the spotted material according to claim 1, wherein the discharge pressure at the first spotting is corrected to be lower than the discharge pressure at the second spotting. How to spot. 3. The method for depositing liquid on a spotting material according to claim 1, wherein the discharge pressure is corrected by detecting at least one of the temperature and the humidity of the atmosphere. 4. A spotting material is sucked into a spotting tip fitted to the tip of a suction nozzle for sucking a liquid, and then a predetermined discharge pressure is introduced into the spotting tip to deposit a material to be spotted. In a liquid spotting device comprising a liquid suction / ejection means for ejecting the liquid, a detection means for detecting a signal related to the vapor pressure of the atmosphere, and a correction characteristic preset based on the signal of the detection means. A liquid spotting device, comprising: a correction unit that obtains a correction amount of the discharge pressure by means of and outputs a correction signal to the liquid suction / discharge unit.