JPH075157A - Liquid chromatography - Google Patents

Abstract

PURPOSE:To provide a liquid chromatography equipped with a current sensor which can measure the current velocity even in a microregion without touching the solvent. CONSTITUTION:Capillary liquid discharge pipes 14, 16 are coupled through an exchange valve 12 in the downstream of a detector 10 and the liquid discharge pipe 16 is provided with two optical bubble detectors 18, 20 while spaced apart in the axial direction. A bubble 44 can be introduced into the pipe 16 by switching the valve 12. The bubble 44 is detected by two bubble detectors 18, 20 and the current velocity of solvent is determined based on the difference between detection times.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatograph used for separation and analysis of various chemical substances.

[0002]

2. Description of the Related Art A liquid chromatograph comprises a column for separating sample components, a liquid feed pump for feeding a solvent to the column, a sample injection injector provided in a flow path between the liquid feed pump and the column, and a column. It is equipped with a detector for detecting the eluate component of. In order to perform accurate quantitative analysis and qualitative analysis in liquid chromatography, the flow rate of the solvent flowing through the column must be constant. To keep the flow velocity constant, flow velocity measurement is necessary. As a flow velocity sensor that can be used in a liquid chromatograph, turbine type, heat difference type, Hall element type flow velocity sensors, etc. are known.

[0003]

The flow velocity range which must be measured by a liquid chromatograph is 0.1 to 1000 μm.
1 / min. The conventional flow velocity sensor can measure the flow rate in a large range, and it is difficult to measure the flow velocity in a minute amount range of 50 μl / min or less. Therefore, a capillary liquid chromatograph cannot measure an accurate flow velocity when a conventional flow velocity sensor is used.

Many of the solvents used in liquid chromatography are corrosive. In a conventional sensor structure in which a solvent is brought into contact with a solvent in a flow velocity sensor, the sensor is corroded. Therefore, a non-contact type sensor is desirable. An object of the present invention is to provide a liquid chromatograph equipped with a flow velocity measuring means which is not in contact with a solvent and is capable of measuring flow velocity in a trace amount range.

[0005]

In the present invention, in order to measure the flow rate of the solvent, a drainage pipe is provided at the detector outlet of the liquid chromatograph main body passage through a valve, and the valve is the detector outlet. Is a valve that has a connection flow path that can be switched between a position for connecting to the drain pipe and a position for taking in gas, and supplies gas as bubbles to the drain pipe by switching the connection position of the connection flow passage. . The drain pipe is light-transmissive, and bubble detectors are provided at two positions separated from each other along the axial direction of the drain pipe, and the two bubble detectors generate the same bubble. The flow velocity of the solvent flowing through the liquid chromatograph main body flow path was determined from the time difference at the time of detection and the inner diameter of the drainage pipe and the distance between the two bubble detectors which were previously obtained. The bubble detector is, for example, an optical detector, specifically, a light source that emits light in a direction intersecting with the drain pipe, and a light receiving device that detects light from the light source that has passed through the drain pipe. Examples of the device include, but are not limited to, those including an element.

[0006]

When the flow velocity is measured by the bubble detector, bubbles are supplied to the drain pipe by switching the valve.
Since the drainage pipe is provided with two bubble detectors at positions distant along the axial direction, the supplied bubble is detected by the upstream bubble detector and then by the downstream bubble detector. Measure the time to be detected. Since the inner diameter of the drainage pipe and the distance between the two bubble detectors are obtained in advance, the flow velocity of the solvent can be obtained. The drainage pipe has an inner diameter of 10
By using a capillary of ~ 200 μm, 50
A minute flow rate of μl / min or less can be measured.

Both the valve and the bubble detector are provided downstream of the detector of the liquid chromatograph. Therefore, it does not affect the chromatogram data. The bubble detector is of the type that uses light, as the sensor does not come into contact with the solvent,
A mass spectrometer can be located further downstream of the valve. The mass spectrometer can be used as a means for analyzing the substance structure of the eluted component. If the measured flow rate is fed back to the control circuit of the liquid delivery pump, the flow rate can be automatically controlled.

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 shows an embodiment. The liquid chromatograph body is a capillary liquid chromatograph, and is provided in a capillary column 2 for separating sample components, a liquid feed pump 6 for feeding a solvent 4 to the column 2, and a flow passage between the liquid feed pump 6 and the column 2. The sample injection injector 8 and the spectrophotometer detector 10 for detecting the eluate component from the column 2 are provided.

Downstream of the detector 10, a first pipe 14 and a second pipe 16 are connected via a switching valve 12.
The tubes 14 and 16 are translucent or transparent capillaries having an inner diameter of 10 to 200 μm, and are, for example, quartz glass capillaries whose outer surfaces are covered with a polyimide coating for protection or whose polyimide coating is peeled off in a flame. .

The switching valve 12 has a detector 10 at the connection port a.
, And the pipes 14 and 16 are connected to the connection ports b and e on both sides thereof, respectively. Tube 14f is connected to the mass spectrometer and tube 16 is a drainage tube. 2 remaining
A syringe 16 for supplying gas is connected to one of the two connection ports c and d, and the other connection port d is open to the atmosphere. The connection ports a to e are arranged on the same circumference, and the arcs ab, cd, and ea have the same length. Switching valve 12
Has two connecting channels 13a, 13b in its rotor,
When one of the connection flow paths 13a (or 13b) is connected between the outlet of the column 10 and the pipe 14, the other connection flow path 13b (or 13a) takes in gas and the flow paths are switched. The other connection channel 13b (or 13a)
When the column is connected between the outlet of the column 10 and the pipe 16, the gas taken in the connection flow path 13b (or 13a) is supplied to the pipe 16 as bubbles.

Two optical bubble detectors 18, 20 are arranged in the tube 16 at positions separated from each other along the axial direction. Bubble detectors 18 and 20 are photo-interrupters as shown in FIG. The bubble detectors 18 and 20 are provided with light sources 22 and 26 and light receiving elements 24 and 28, respectively, and the light from the light sources 22 and 26 is slit 30, respectively.
The light is emitted toward the light receiving elements 24 and 28 via 32. The bubble detectors 18 and 20 are arranged so that the respective measuring luminous fluxes intersect the tube 16. Bubble detector 18, 20
The photo interrupter of FIG. 2 is supported by respective support plates 34 and 36, and the support plates 34 and 36 move in the directions indicated by double-headed arrows in FIG. 2 so that the position where the measurement light beam intersects the tube 16 can be adjusted. Optical axis adjustment micrometer 3
8 and 40 are provided, respectively.

The diameter of the light beam from the light emitting portion of the photo interrupter of the bubble detectors 18 and 20 is about 1 mm. The tube 16 used in the embodiment is, for example, a capillary having an inner diameter of 70 μm. In order to correctly transmit the light beam of the photo interrupter through the tube 16, the micrometers 38 and 40 are capable of adjusting the optical axis in one axis with an accuracy of the order of several tens of μm. The optical axis adjustment can be easily set by monitoring the voltage signals V ₁ and V ₂ from the light receiving portion of the photointerrupter and finding the point where the respective signal intensities become maximum.

In FIG. 1, reference numeral 42 designates both bubble detectors 18, 20.
In a calculation circuit for calculating the time difference between the detection of bubbles and the detection time of the bubbles, and calculating the flow velocity of the solvent from the volume determined from the inner diameter of the pipe 16 and the distance between the two bubble detectors 18 and 20 which are obtained in advance. is there.

Next, the operation of this embodiment will be described. When the switching valve 12 does not measure the flow velocity,
As shown in (A), the connection channel 13a is set at a position where the connection port a is connected to the connection port b. At this time, gas is sent from the syringe 16 to the connection flow path 13b connecting the connection ports c and d.

When measuring the flow velocity, the switching valve 12
As shown in FIG. 3B, the connection flow path 13b is positioned so that the connection flow paths 13a connect the connection openings a and e, and the connection flow path 13a connects the connection openings c and d as shown in FIG. 3B. As a result, the solvent eluted from the detector 10 is transferred to the flow path 13
The gas in b is pushed out to the pipe 16, and the gas becomes bubbles 44 and flows in the pipe 16. The bubbles 44 are first detected by the upstream bubble detector 18, and subsequently detected by the downstream bubble detector 20. The distance between the bubble detectors 18 and 20 is Dc
m, the volume of the tube 16 is C μl / cm, and the detection time difference of the bubbles detected by the bubble detectors 18 and 20 is T minutes, the solvent flow rate A μl / min is calculated by A = C · D / T be able to.

In the field of microcapillary liquid chromatography in which the present invention is most effectively used, the solvent flow rate is 1 to 50 μl / min. If the pipe 16 has an inner diameter of 7
When the solvent is made to flow at a flow rate of 50 μl / min with a capillary of 0 μm, bubbles move at a speed of about 4.5 × 10 ⁻² sec / cm, so A / D conversion in the arithmetic circuit 10 and other There is enough time to process the signal.

The detector 18 using the bubbles 44 was used for the case of using acetonitrile as a solvent and the case of using water as a solvent.
Table 1 shows the comparison results of the detection signals at 20 in the case where the tube 16 is a capillary having a polyimide coating and in the case where the capillary is a capillary having the polyimide coating removed.

[0018]

[Table 1] Bubble detector output (V) Bubble detector output (V) Polyimide film Bubble Water S / N Bubble acetonitrile S / N Yes 3.70 4.05 8.6 3.70 4.04 8.4 None 3.95 4.37 9.6 3.91 4.38 10.7

In Table 1, the definition of the S / N ratio is S / N = (X−Y) × 100 / X (%). Here, X is a signal voltage when the detector is detecting the solvent, and Y is a signal voltage when the detector is detecting bubbles. In the embodiment of FIG. 1, two tubes 14 and 16 are provided, but the tube may be only the tube 16 on the side where the bubble detectors 18 and 20 are provided.

[0020]

According to the present invention, in order to measure the flow rate of the solvent flowing through the liquid chromatograph, a drainage pipe is provided at the column outlet via a valve, and bubbles are introduced into the drainage pipe by switching the valve. At the same time, the bubbles are optically detected at two positions separated from each other along the drainage pipe, and the flow velocity of the solvent is obtained from the time difference between the detections. can do. For example, the drainage pipe has an inner diameter of 10 to 200 μm.
By using the capillary of (1), a minute flow rate of 50 μl / min or less can be measured. The bubble detector in the present invention is of a type using light, and since the sensor does not come into contact with the solvent, a mass spectrometer can be arranged downstream of the valve. If the measured flow rate is fed back to the control circuit of the liquid delivery pump, the flow rate can be automatically controlled.

[Brief description of drawings]

FIG. 1 is a schematic configuration diagram showing an embodiment.

FIG. 2 is a perspective view showing a bubble detector in the same embodiment.

FIG. 3 is a view showing the operation of the switching valve in the same embodiment.

[Explanation of symbols]

 2 column 4 solvent 6 liquid feed pump 8 injector 10 spectrophotometer detector 12 switching valve 14, 16 drainage pipe 16 syringe 18, 20 bubble detector

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Rintaro Yamamoto 1 Nishinokyo Kuwabaracho, Nakagyo-ku, Kyoto City, Kyoto Prefecture Shimazu Corporation Sanjo Factory

Claims (1)

[Claims] 1. A column for separating sample components, a liquid feed pump for feeding a solvent to the column, a sample injection injector provided in a flow path between the liquid feed pump and the column, and from the column. Of the liquid chromatograph main body provided with a detector for detecting the eluate component of the above, a drainage pipe is provided through a valve at the detector outlet, and the valve is a position where the detector outlet is connected to the drainage pipe. Is a valve that supplies a gas as bubbles to the drainage pipe by switching the connection position of the connection flow path, and the drainage pipe is connected to the drainage pipe. Two bubble detectors are provided, and from the time difference when the two bubble detectors detect the same bubble, and the predetermined inner diameter of the drainage pipe and the distance between the two bubble detectors. Liquid chromatograph A liquid chromatograph designed to determine the flow velocity of the solvent flowing through the main body flow path.