JPS6332324A - Liquid dispensing device - Google Patents

Abstract

PURPOSE:To contrive to powder the necessary amount of sample and to widen a range, and to improve the performance and reliability of a device in the use of a multi-item automatic analyzing device, etc., by controlling the rotating speed of a pulse motor through a driving circuit according to the suction of the sample, etc. CONSTITUTION:This dispensing device consists of a probe 8 which pipettes the liquid sample, etc., a syringe pump 1 which drives a piston 3 for the suction and discharging of the sample here by a pulse motor 6, a driving circuit 17 for the pulse motor 6, and a control circuit 16 which controls the circuit 17. The circuit 16 consists of a basic clock generating circuit 18 composed of a crystal oscillator, etc., and an arithmetic part 19 which determines the rotating speed (f) and movement quantity of the motor 6 according to the suction amount of the sample, and the rotating speed (f) is determined by a specific formula. Consequently, the moving speed of the liquid in the probe 8 is controlled with a speed almost proportional to the suction amount V of the sample, the moving speed is extremely; small almost at the minimum dispensation amount, and the liquid never becomes thin. Further, the dispensing speed increases almost at the maximum dispensation amount and fast operation is enabled.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a liquid dispensing device, and in particular, to high precision and high reliability sampling of minute amounts in which liquid samples, reagents, etc. are quantitatively dispensed by pipetting. The present invention relates to a liquid dispensing device such as a multi-item automatic analyzer suitable for various applications.

[Conventional technology]

Dispensing devices used for quantitative dispensing of liquid samples and reagents in multi-item automatic analyzers include, for example.

There is an apparatus discussed on pages 43 to 44 of "Clinical Automated Analysis" edited by Kyo Ozawa, published by Kodansha in 1985, and the case of sample dispensing will be explained below. Two syringe pumps, a microsyringe and a millisyringe, and a purified water storage bottle are connected to the probe for pipetting the sample in sequence, and a third syringe pump is connected between the two syringe pumps and between the millisyringe pump and the storage bottle, respectively. 1. A second solenoid valve is provided, and the flow path system is filled with purified water. Of the two syringe pumps, the microsyringe pump is used for pipetting the sample, and suction and ejection of the sample with the probe is achieved by the operation of the piston within the microsyringe pump. In a multi-item automatic analyzer, the required sample is different for each analysis item, so it is necessary to change the amount of piston movement for each analysis item.This change is achieved by moving the piston with a computer-controlled pulse motor. By controlling the amount of movement, it is possible to form a lotus. The milli-syringe pump is used to clean the inner periphery of the probe after pipetting is completed, and discharges a certain amount of purified water sucked into the syringe from the probe via the first electromagnetic valve to clean the inner periphery of the probe.

Next, a sample sampling operation using a sampling device having one or more configurations will be explained. Before sample suction, the probe sucks a small amount of air into its tip, then moves to the sample position, immerses its tip into the sample, and sucks in the required amount of sample by the suction operation of the microsyringe. At this time, the first
and the second solenoid valve is in a closed state. The intake amount is set to be slightly larger than the amount to be exhaled. When the sample suction is completed, the probe rises and moves to the discharge position, the reaction vessel moves to the cleaning position, discharges the excess sample that has been sucked in, and then opens the first solenoid valve to discharge the sample into the millisyringe. The discharge operation of the pump discharges a certain amount of water to wash the inside of the probe, and the outside is also washed with washing water from the outside. After that, close the first solenoid valve, open the second solenoid valve, and suck the purified water in the syringe with the suction operation of the millisyringe pump.
Close the second solenoid valve. Additionally, a microsyringe pump sucks a small amount of air into the tip of the probe and waits for the next job. This small amount of air was added to prevent the sample from diluting with water.

The above-mentioned conventional sampling device has sufficient accuracy compared to the conventional multi-item automatic analyzer.

Although it has satisfied the reliability and fulfilled its role, it has become necessary to improve it in line with the progress and development of automatic analyzers in recent years. In other words, with the diversification and increase in the number of clinical biochemical tests, there is a growing need for an increase in the number of analysis items and an increase in analysis processing capacity.
Although this problem has been solved by increasing the speed of device operation, there is a need for even higher speeds in order to realize smaller, more efficient devices. In addition, there is a high demand for improvement in device performance, and especially in sample sampling devices that directly affect device performance, there is a need to further miniaturize the dispensing amount, widen the range, and ensure accuracy.

For example, the minimum sample amount required for analysis is moving from 5 μQ to 3 μQ, and even less, while some analysis items require a sample amount of 20 μA to ensure sensitivity. In addition, the cycle time for a series of device operations has almost doubled from 20 seconds to 12 seconds and then to 6 seconds, and the operation speed of sampling devices has also increased. It's proportionally faster.

Previously, samples were dispensed in the range of 5μ0 to 2oμ, but now we can maintain and improve the accuracy by dispensing samples from 3μ2 or less to 20μQ at about twice or four times the speed compared to conventional methods. There is a need to.

Factors that affect sample dispensing accuracy by pipetting, that is, sampling accuracy.

6. Accuracy of dispensing amount can be improved by ensuring its shape and dimensions even when speeding up, as there are not only accuracy differences in dispensing amount but also changes in concentration of the sample due to contact between the sample and purified water in the probe, etc. However, the dilution of the sample due to water is greatly affected by increasing the suction and discharge speeds.

As is well known, the flow of fluid in a pipe has a velocity distribution in which the velocity is zero at the pipe wall in a cross section with respect to the flow direction and is twice the average flow velocity in the center due to the viscosity of the fluid. ,
This is the first cause of thinning of the sample. For this reason, when pipetting a sample, the sample is diluted near the interface between the sample and water due to contact between the sample and water.

In other words, when a sample is sucked into the probe, the sample enters the flow of water at the center of the flow, and when it is expelled, the washing end of the water enters the flow of the sample, causing a dilution phenomenon of the sample. occurs. In conventional apparatuses, in order to eliminate the influence of thinning of the sample, as described above, a small amount of air is interposed between the water and the sample, and 1. The amount of sample to be aspirated was slightly larger than the amount to be discharged. A second cause of thinning of the sample is wetting of the inner surface of the probe by the sample and water. Before the sample was aspirated, the inner surface of the probe was in contact with water, and even after the water flows to the syringe pump side to aspirate the sample, a thin layer remains on the inner surface due to wetness, and the sample flows over it. , thinning of the sample occurs. The effect of dilution of the sample due to these factors on sampling accuracy becomes larger as the amount dispensed becomes smaller. For example, in the conventional example, the sampling accuracy when dispensing 3 μA is 2 μA compared to when dispensing 20 μQ. ~3 times worse. It is also obvious that the sampling rate increases as the flow rate of the liquid within the probe increases.

If the above-mentioned conventional sampling device is applied to a device with a smaller sample dispensing amount and faster speed, it will not be possible to maintain or ensure the accuracy, and in order to solve this problem, the above-mentioned amount of air may have been increased. , lacks accuracy in reducing the amount of sample, and
Increasing the difference between the suction amount and the ejection amount is not acceptable because it goes against the grain size of the sample.

[Problem that the invention seeks to solve]

As is clear from the above explanation, conventional sampling devices have a limit in operating speed to ensure sample dispensing accuracy, and this device can be used to miniaturize and speed up sample dispensing. With regard to dilution of the sample, the suction and discharge speeds of the sample are constant regardless of the amount dispensed, and therefore, there is a problem in that sampling accuracy cannot be ensured when dispensing a small amount of sample quantitatively.

The purpose of the present invention is to ensure the dispensing accuracy and the performance of the device when used in a multi-item automatic analyzer, etc., in which the required sample amount is extremely small and wide, and the dispensing speed is significantly increased. The object of the present invention is to provide a high-performance liquid dispensing device that can increase reliability.

[Means for solving problems]

The above objective is that the biggest factor that affects sample sampling accuracy is the dilution of the sample by water inside the probe, and this dilution increases as the amount of liquid dispensed becomes smaller and the flow rate of the liquid within the probe increases. , we focused on the fact that when the amount of sample dispensed is close to the upper limit of 20μQ, there is no practical impact on sampling accuracy even if this flow rate is doubled, and for pipetting liquid samples, etc. probe and inhalation of the above sample with this probe.

It consists of a syringe pump whose piston that performs the dispensing operation is driven by a pulse motor, a drive circuit for the above-mentioned pulse motor, and a control circuit that controls this drive circuit. This is achieved by controlling the rotational speed of the pulse motor via the drive circuit in accordance with the dispensed amount.

[Effect]

The suction and discharge of the sample is obtained by the operation of the syringe pump. Therefore, in order to control the suction and discharge speed according to the dispensed amount, it is necessary to adjust the rotation speed of the pulse motor that drives the piston of the syringe pump. This control is performed by the control circuit of the pulse motor that generates the pulse speed according to the amount to be dispensed, so it is possible to eliminate the dilution of the sample due to water when dispensing a small amount. Near the maximum dispensing amount, the moving speed can be doubled compared to the conventional method.

〔Example〕

The present invention will be explained in detail below using the embodiments shown in FIGS. 1 and 2.

FIG. 1 is a configuration diagram showing an embodiment of a liquid dispensing device of the present invention. In FIG. 1, 1 is a microsyringe pump, cylinder 2. Vinton 3. It consists of a sealing 4 of a piston 3. 5 is a rack and pinion mechanism; 6 is a pulse motor; the rotational motion of the pulse motor 6 is converted into linear motion by the rack and pinion mechanism to drive the piston 3; 7 is a flexible tube, 8 is a probe, 9 is a probe moving mechanism that gives rotation and vertical movement to the probe 8, 10 is a solenoid valve, and the cylinder 2 stores purified water through the solenoid valve 10 on one side and the pump 11, etc. The other end is connected to a bottle 12 and the other end is connected to a probe 8 by a flexible tube 7, and the purified water from the storage bottle 12 is filled up to the tip of the probe 8. 13 is a sample container containing a sample, 14 is a reaction container, 15 is an input device for inputting analysis items, amounts of samples and reagents, etc., and 16 is a rotation speed (rotation angle) corresponding to the input sample dispensing amount. ) is a control circuit that controls the pulse motor 6, and 17 is a drive circuit that drives the pulse motor 6 with a signal from the control circuit 16.

Quantitative dispensing of a sample using the liquid dispensing device having the above configuration, that is, the liquid sample sampling device, can be performed as follows. First, the piston 3, which was located at the top dead center, is slightly lowered to suck a small amount of air into the tip of the probe 8. Then, the probe 8 is moved to the position of the sample container 13 by the probe moving mechanism 9, and the probe 8 is moved to the position of the sample container 13. Descend into the sample. Here, the pulse motor 6 is operated by the output of the control circuit 16 to determine the suction amount V, which is the sum of the predetermined dispensing amount Vo, which has been input and stored in advance by the input device IS, and the extra suction amount v1.
The piston 3 is pulled out from the cylinder 2 and the sample is sucked into the probe 8. Thereafter, the probe 8 is raised, moved to the position of the reaction vessel 14, and lowered into the reaction vessel 14 to maintain the speed t set during inhalation.
At Lf, the pulse motor 6 is rotated in a direction to push in the piston 3 by an amount corresponding to the predetermined dispensing amount Vθ, and the sample is discharged from the probe 8. After the discharge is completed, the probe 8 is moved to the cleaning position (not shown), the Vinton 3 is returned to the top dead center and the remaining sample Vl is discharged, the solenoid valve 10 is opened, and the pump 11 is operated for a predetermined time. Probe 8 with purified water.
Discharged from the tip of the probe 8 to clean the inner surface of the probe 8, and
At the same time, the outer surface of the probe 8 is also washed with water, and the solenoid valve 10 is closed.

In this state, wait for the next dispensing request.

Here, the suction and discharge speeds of the sample are determined by the amount dispensed, and this is done by the control circuit 17. The details will be explained using FIG. 2.

FIG. 2 is a block diagram showing one embodiment of the control circuit 16 of FIG. 1. In FIG. 2, 18 is a basic clock generation circuit consisting of a crystal oscillator, etc., and 19 is an arithmetic unit that determines the rotational speed f and movement amount n of the pulse motor 6 according to the suction amount V of the sample, and is composed of a computer, for example. , the rotational speed f is determined by calculating the following equation.

Here, V: the suction or discharge amount of the sample per pulse applied to the pulse motor 6, t; the predetermined dispensing time 20 is a pulse generator that generates a pulse train with a rotational speed f and a movement amount n, and the frequency of the basic clock is fo'a-f
/fo and rotation speed J! Obtain 1f.

21 is a distribution circuit that distributes the pulse train obtained by the pulse generator 20 to each phase winding of the pulse motor 6. All of these can be constructed using known circuits or computers.

According to equation (1), the moving speed of the liquid within the probe 8 can be controlled at a speed approximately proportional to the inhalation of the sample iv,
Near the minimum dispensed volume, which is most susceptible to sample dilution, the moving speed is extremely small, so no dilution occurs, and near the maximum dispensed volume, which is almost unaffected by sample dilution, the dispensing speed is extremely low. The speed can be increased and high-speed operation can be made possible. In order to obtain the rotational speed f corresponding to the suction amount ■, in addition to using the calculation unit 19, the suction amount V is divided into several stages by dividing it into an appropriate range in advance.
The rotational speed f may be determined for each of them, and this may be prepared as a table.

Note that the control circuit 16 can be realized by changing the contents of the computer part of a conventional device, and does not cause an economic burden.

In addition, although all of the above explanations have been made only regarding sample dispensing, the miniaturization of reagent dispensing is also important.

The need for speeding up is exactly the same as in the case of samples, and it goes without saying that the same effects can be obtained even when the present invention is applied to reagent dispensing.

〔Effect of the invention〕

As explained above, according to the present invention, the moving speed of the sample, etc. and water within the probe can be controlled according to the amount of the sample, etc., which affects the dispensing accuracy when dispensing a small amount. It is possible to eliminate the dilution of samples, etc. in water, and in the vicinity of the maximum dispensing amount, where the effect of dilution is short, the moving speed can be doubled compared to conventional methods, enabling high-speed dispensing. The present invention has the effect that it can be applied to multi-item automatic analysis devices such as those used in the past, contributing to faster and more accurate device operation.

[Brief explanation of drawings]

FIG. 1 is a block diagram showing an embodiment of the liquid dispensing device of the present invention, and FIG. 2 is a block diagram showing an embodiment of the control circuit of FIG. 1... Micro syringe pump, 2... Cylinder,
3... Piston, 6... Pulse motor, 8... Probe, 9... Probe moving mechanism, 12... Purified water storage bottle, 13... Sample container, 14... Reaction container,
15... Input device, 16... Control circuit, 17...
Drive circuit, 18... Basic clock generation circuit, 19...
Arithmetic unit, 2o... pulse generator, 21... distribution circuit.

Claims (1)

[Claims] 1. A probe for pipetting a liquid sample, etc.;
The syringe pump includes a syringe pump in which a piston for inhaling and discharging the sample with the probe is driven by a pulse motor, a drive circuit for the pulse motor, and a control circuit for controlling the drive circuit. A liquid dispensing device for a multi-item automatic analyzer, etc., characterized in that the circuit is configured to control the rotational speed of the pulse motor via the drive circuit in accordance with the aspiration or discharge speed of the sample, etc., depending on the amount dispensed. Note device. 2. The control circuit is configured to control the rotation speed of the pulse motor so that the suction or discharge speed of the sample, etc. changes approximately in proportion to the amount dispensed. Liquid dispensing device as described. 3. The control circuit is configured to control the rotation speed of the pulse motor so that the suction or discharge speed of the sample etc. changes stepwise according to the amount dispensed. Liquid dispensing device described in section.