JPH11264814A - Sample separating apparatus and chemical analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a sample separating apparatus in which flows of a sample liquid are made uniform in a gap inside a chromatographic column, in which separated components are not mixed again and whose separating capability is high, by branching the sample liquid into a plurality of flow passages for separation, which are formed on a flat board and whose cross-sectional shape and length are equal. SOLUTION: A sample liquid of a set amount is put on the flow of a carrier liquid, and it is introduced into the inside from the entrance of a sample separating apparatus. At this time, since both the cross-sectional shape and the length of respective separating flow passages are equal, pressure drags in flow passages which are continued to respective separating flow passages 451, 461 are equal. Consequently, the carrier liquid which contains the sample liquid is branched equally into the flow passages 451, 461 at an equal flow rate so as to flow. In this manner, the flow of the sample liquid which approaches the branch part 452 of the flow passage 451 is branched into flow passages 453, 454, which are continued to it, at an equal flow rate so as to flow because a flow passage resistance is equal. In the same manner, the sample liquid is branched at an equal flow rate even in the flow passage 461 through a branch part 462 to flow passages 463, 464. Components which are separated in the respective flow passages are joined without being mixed with each other, and they go out from an exit 43 to be sent to a flow cell.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample separation device for separating components dissolved in a sample liquid and a chemical analyzer for quantifying the concentration of each separated component, and more particularly to the analysis of components such as biological fluids and water. Do chromatographs.

[0002]

2. Description of the Related Art As a prior art corresponding to the chemical analyzer of the present invention, reference is made to Gregor Ocvirk, "Integration of am
icro liquid chromatograph onto a silicon chip ", Pr
oc .. of Transducers '95 pp. 756-759 (1995) describes a chromatographic column and a flow cell for optical measurement formed on a silicon substrate.

The present chromatographic column is obtained by etching a silicon substrate to a width of 300 μm, a depth of 100 μm, and a length of 2 μm.
It is formed by bonding a glass plate from above a groove carved to 0 mm and then filling it with fine particles having a diameter of 5 μm (coated with an adsorbing substance). Immediately after the outlet of the chromatographic column, a flow cell for optical measurement is also formed by etching. When the sample solution passes through this column,
Since the degree of adsorption on the surface of the fine particles differs for each component in the sample solution, components having lower adsorption come out in order from the column outlet. This separated component is detected by a flow cell for optical measurement provided immediately after the column. According to this conventional technique, it is possible to provide a chromatographic column and a flow cell closer to each other by etching, so that diffusion of a separation component is suppressed in a flow path therebetween, and high separation performance can be maintained.

[0004]

In order to analyze each dissolved component with high sensitivity and speed, it is necessary that the detection peaks of the separated components in the detection section are sufficiently separated without overlapping each other. When the chromatographic column is shortened with the same separation capacity, there are effects such as shortening of measurement time and simplification of the liquid sending pump by reducing liquid sending pressure. However, in order to increase the degree of separation at the detector, it is necessary to further improve the separation capacity of the chromatographic column, and it is necessary to prevent the separation components from mixing again in the flow path from the column to the detector. There is.

[0005] In the above prior art, the flow path from the chromatographic column to the flow cell is shortened in order to improve the separation performance, and the remixing of the separated components due to the diffusion occurring during transportation is minimized. On the other hand, the chromatographic column that controls the separation performance is not much different from the conventional tubular column packed with fine particles functionally, and the separation performance is not particularly improved. Microscopically, the principle of the separation in the chromatography column filled with the fine particles is as follows.

The sample solution sent into the chromatography column is
First, the column spreads completely, enters the gaps between the fine particles, and flows. At this time, the molecules of the dissolved chemical components in the sample liquid reach the fine particle surface by local flow in the gap or by molecular diffusion, and cause an adsorption reaction with the adsorbed substance coated on the fine particle surface. . Since the degree of adsorption differs for each component molecule, separation occurs for each component when passing through the gap. However, the separation technique using the fine particles has the following problems.

[0007] The sample liquid flowing out of each gap merges with the sample liquid flowing in another gap downstream thereof.
In the separation state of the sample liquid that has passed through different gaps, since the size and distance of each gap are not uniform, the same separated components do not necessarily join at the same timing, and different separated components may join again and mix. become.

Further, if there is a flow that stagnates at the merging position, the separated components are mixed again there. In the chromatographic column packed with fine particles as described above, the shape of the gap between the fine particles is not uniform, and thus there is a limit in improving the separation ability. In order to solve this problem, improvements were made such as reducing the cross-sectional area of the chromatographic column, reducing the uneven distribution of the flow in the cross-section, and reducing the size of the fine particles packed in the column to increase the uniformity of the gap. However, the fundamental solution has not been reached.

An object of the present invention is to provide a sample separation device and a chemical analysis device having a high separation ability, in which the flow in the gap is uniform in the chromatographic column and the component separated once does not mix with other separated components again. It is to be.

[0010]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a sample separation apparatus or a chemical analysis apparatus, in which a sample liquid inlet, a subsequent inlet flow path, and a plurality of separation flow paths having the same cross-sectional shape and the same length. And an outlet for the separated liquid, an outlet channel connected to the outlet, a branch portion for branching from the inlet channel to a plurality of separating channels, and a merging for joining the plurality of separating channels to one outlet channel. The problem is solved by forming the part on a flat plate.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described with reference to FIGS. FIG. 1 is an overall configuration diagram of a chemical analyzer provided with a sample separation device of the present invention, FIG. 2 is a detailed explanatory view of the sample separation device of the present invention, and FIGS. 3 and 4 are explanatory diagrams of another sample separation device of the present invention. FIG. 5 shows an overall configuration diagram of another chemical analyzer according to the present invention. FIG. 6 is a schematic diagram for explaining the principle of separation in the separation channel according to the present invention.

Referring to FIG. 1, the configuration of the chemical analyzer of the present invention will be described in order from upstream to downstream.

Carrier liquid 11 used as a transfer medium
Are held in the carrier liquid tank 10. Carrier liquid tank 1
0 to the sample separation device 40 are connected by a pipe 12, a pump 20 for pumping up the carrier liquid 11 and sending it to the sample separation device, and a sample liquid in the carrier liquid 11. An injection valve 31 for injecting 30 is provided in order. In the injection valve 31,
There is a hole for injecting the sample liquid 30, and the syringe 3
2 can be attached. The sample liquid 30 is suction-held in the syringe 32.

The sample separator 40 has an inlet 41 connected to the pipe 12 and an outlet 42 for the sample liquid separated by the sample separator 40. The pipe 1 extends from the outlet 42 to the waste liquid tank 70.
3, and a flow cell 50 for measuring the absorption spectrum of the liquid is provided in the middle. Further, a light source 51 for irradiating light to the flow cell 50 and a detector 52 for detecting light transmitted through the flow cell 50 are provided. From the signal processing / operation control unit 60 to the pump 20,
A control signal is connected to the light source 51, and a detection signal cable is connected to the detector 52.

Next, the structure of the sample separation device 40 will be described with reference to FIG. The sample liquid 30
An inlet 41 for introducing the carrier liquid 11 and an outlet 42 for discharging the separated sample liquid 30 are provided. 2 of equal cross-sectional shape and equal length from inlet 42
The two separation channels 451 and 461 are branched. Each of the separation channels 451, 461 is divided into separation channels 453, 454 and 463, 464 having the same cross-sectional shape and the same length, respectively, via the branch portions 452, 462.
The branch channels 453, 454 and 463, 464
Are integrated again into separation channels 456 and 466 having the same cross-sectional shape and the same length via the junctions 455 and 465, respectively. Further, these channels 456, 466 join together and are connected to the outlet 42. The inner walls of all these separation channels are coated with an adsorbent for separation.

The chemical analyzer having the above configuration operates as follows.

First, upon receiving a control signal from the signal processing / operation control unit 60, the pump 20 starts liquid supply. Pump 2
At 0, the carrier liquid 11 is pumped from the carrier liquid tank 10 at a constant flow rate and supplied to the sample separation device 40 through the pipe 12. When the flow is stabilized, the sample liquid 3 is supplied to the injection valve 31.
A syringe 32 containing 0 is inserted, and a fixed amount of the sample liquid 30 is injected into the pipe 12. The sample liquid 30 is introduced into the sample separation device 40 from the inlet 41 along with the flow of the carrier liquid 11. Here, since the cross-sectional shape and length of each separation channel are equal, the pressure resistance of the channel following the sample separation channel 451,
The pressure resistance of the flow path following 61 is equal. Therefore, sample liquid 3
The carrier liquid 11 containing 0 flows equally into the flow paths 451 and 461 at equal flow rates. Similarly, the flow approaching the branch portion 452 from the flow path 451 is branched and flows at an equal flow rate, because the flow resistances of the subsequent flow paths 463 and 464 are equal. The same applies to the following channel 461-branch 462-channels 463, 464.
Branch at equal flow rate.

FIG. 6 shows the separation step of the present invention. First, in each of the separation channels 453 and 454, the components in the sample liquid are changed from the first to the first by the interaction with the adsorbed substance on the channel walls. It is separated into three components 33, 34 and 35 up to the third. The separation patterns occurring in the two flow paths show the same pattern as shown in the figure if the two flow paths have the same shape and flow conditions. If the lengths of the two channels are the same,
Similarly, as shown in the figure, the components merge at the same timing at the junction. For this reason, the deterioration of the separation performance due to the unevenness of the gap between the fine particles, which is remarkable in the related art, does not occur. The components separated in the respective flow paths merge without being mixed with each other, and exit from the outlet 43, and enter the flow cell 50.
Sent to In the flow cell 50, the light source emits light in response to a signal from the signal processing / drive control unit 60, and the detector 52 detects a temporal change in the absorption spectrum of the separated component in the flow cell, and sends the signal to the signal processing / drive control unit 60. Perform feed data processing.

As described above, the present invention makes it possible to form a uniform flow in a chromatographic column, and a component having a high separation ability can be obtained, in which components once separated do not mix again with other separated components. And a chemical analyzer.

Another embodiment of the present invention will be described with reference to FIG. FIG. 3 shows another structure of the sample separation device 40. In the present embodiment, the separation channels of the sample liquid separator 40 shown in FIG. 2 have a hierarchical structure, and the same parts as those in FIG. As in the sample separation apparatus of FIG. 2, the cross-sectional shape and the flow path length of each flow path in the same layer are equal, so that a high separation capacity can be obtained as in the first embodiment. As compared with the sample separation apparatus of the embodiment shown in FIG. 1, the number of separation channels is increased, so that the probability of contact between the sample liquid and the adsorbed substance is increased, and high separation performance can be obtained in a shorter time. Further, the sample separation device of this embodiment has two sample separation units 71 and 7.
Since the two are connected in series, the components can be more finely separated.

FIG. 4 shows a sample separation apparatus according to another embodiment of the present invention.

In FIG. 4, three flow path plates 91 for separation,
The sample liquids 92 and 93 are stacked in the vertical direction, and the sample liquid entered from the inlet 41 is evenly dispersed in the three channel plates for separation. In each channel in the plate, the sample solution flows from left to right, but the channels are formed in a grid so that the distance from the inlet to the outlet is the same regardless of the route. I have. If the cross-sectional shapes of the unit flow path elements 94 corresponding to one side of the lattice are the same, different separation components will not be mixed at the merging position. Further, in this embodiment, since three separation flow path plates are overlapped and connected in parallel, a large amount of separation components can be obtained in a short time, and the measurement sensitivity is improved. The shape of the separation channel is shown in FIG.
Alternatively, it may be configured in the same shape as in FIG.

In order to form the separation channels in the sample separation device shown in FIGS. 2, 3 and 4 with the same cross-sectional shape with high precision,
A semiconductor manufacturing technique such as etching is used. By filling with conventional microparticles, a large number of fine channels with a width comparable to the gap can be formed very easily on a thin plate, and by stacking a plurality of these, a separation channel with a small volume and high density can be mounted. , Contribute to miniaturization.

Another embodiment of the present invention will be described with reference to FIG. FIG. 5 shows a chemical composition in which the carrier liquid and the sample liquid shown in FIG. 1 are mixed and suctioned and sent out by a pump 20 for feeding, and other parts are connected in series in order to obtain high separation performance. It is an analyzer.

In the case of this configuration, since the pressure loss in each sample separation device is integrated, a large-sized high-pressure pump is required as a driving pump. Therefore, in order to solve these problems, a thin small pump 20 is provided between each of the sample separation devices.
Is provided. The pump 20 according to the present embodiment includes a bimorph vibrator 21 and check valves 22 and 23. The sample and the carrier liquid sucked from the lowermost pump are sequentially pumped from below toward the flow cell 50. One pump only needs to have a pressure enough to send the sample liquid only in one sample separation device, so even a simple diaphragm type pump as shown in the figure can send the sample liquid.
It contributes to downsizing of the whole system.

[0026]

According to the present invention, there is provided a sample separation apparatus and a chemical analysis apparatus having a high separation ability, in which the flow in the gap is uniform in the chromatographic column and the component once separated does not mix again with other separated components. It is possible to do.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a chemical analyzer according to the present invention.

FIG. 2 is a configuration diagram of a sample separation device of the present invention.

FIG. 3 is a configuration diagram of another sample separation device of the present invention.

FIG. 4 is a configuration diagram of another sample separation device of the present invention.

FIG. 5 is a configuration diagram of another chemical analysis device of the present invention.

FIG. 6 is an explanatory diagram showing a state of sample separation in a separation channel of the present invention.

[Explanation of symbols]

10 ... Carrier liquid tank, 11 ... Carrier liquid, 12, 13 ...
Piping, 20 pump, 30 sample liquid, 31 injection valve, 32 syringe, 40 sample separation device, 41 inlet,
42 outlet, 50 flow cell, 51 light source, 52 detector, 60 signal processing / operation control unit, 451 to 466
Separation flow path, 71: first sample separation section, 72: second sample separation section, 91, 92, 93: separation plate, 94: unit flow path element, 21: bimorph vibrator, 22, 23: check valve .

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Mune Kato 502, Kandachicho, Tsuchiura-shi, Ibaraki Pref.

Claims (5)

[Claims] An inlet for a sample liquid, an inlet channel following the inlet,
A plurality of equal cross-sectional shapes, equal length separation channels,
An outlet for the separated liquid, an outlet flow path connected to the outlet, a branching part for branching from the inlet flow path to a plurality of separation flow paths, and a merging part for joining the plurality of separation flow paths to one outlet flow path. A sample separation device formed on a flat plate. 2. The sample separation method according to claim 1, wherein a sample separation section having a branching section, a plurality of separation flow paths and a junction section is provided in a hierarchy at a junction of the separation flow paths. apparatus. 3. The separation channel according to claim 1, wherein the separation channels from the branch portion to the junction portion intersect in a grid pattern, and all the channels between the grids have the same cross section and the same length. A sample separation device characterized in that the distance is the same regardless of the path along the downstream direction from the junction to the junction. 4. A chemical analyzer for separating a dissolved chemical component in a sample liquid and detecting the concentration of each separated component, wherein a sample liquid inlet, a subsequent inlet channel, and a plurality of equal cross-sectional shapes are equal. The length of the separation channel, the outlet of the separation liquid, the outlet channel connected to the outlet, the branch portion that branches from the inlet channel to the plurality of separation channels, and the plurality of separation channels into one A chemical analysis device comprising a sample separation device in which a merging portion for merging with an outlet channel is formed on a flat plate. 5. The chemical analyzer according to claim 4, wherein a plurality of the sample separation devices are stacked and a sample liquid sending means is provided between each of the sample separation devices.