JP2001056286A - Measuring cell - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a measuring cell having a measurement chamber having a sufficiently small sectional area of a passage and capable of keeping gastightness surely, and having chemical stability and high measurement sensitivity. SOLUTION: This cell is composed by jointing glass substrates 1, 2, and a passage groove 6 is formed on the joint surface of the glass substrate 1 by a photo-fabrication technique and a wet etching technique, and through holes 9, 10 for introduction and discharge of a liquid sample are formed on the glass substrate 2. The joint interface other than the passage groove 6 on a joint surface of the glass substrate 1 is covered by an SiO2 film 4 formed by a sputtering method, and joint is executed so as to expose raw material of the substrate 1 on the internal surface of the passage groove 6. And, an optically opaque Si film 3 is formed as a slit on the joint surface by the sputtering method or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a measuring cell used in an optical measuring instrument for measuring the absorption or emission of light in the ultraviolet or visible region, which is used when measuring components in a very small amount of liquid sample. .

[0002]

2. Description of the Related Art A measuring cell for measuring the light absorption or emission of a fluid sample in the ultraviolet or visible region includes:
In the field of analytical chemistry (particularly environmental analytical chemistry, clinical field, pharmaceutical field, etc.), techniques for accurately and quickly analyzing very small amounts of components (for example, capillary electrophoresis (CE), high performance liquid chromatography (HPLC), capillary electrochromatography) It is often used as a detector for chromatography (CEC) or flow injection analysis (FIA). This measuring cell usually has a sample inlet for introducing a liquid sample to be analyzed, a flow path for the liquid sample, and an outlet for discharging the liquid sample. Alternatively, it is used by having a measurement chamber serving as an interaction region with light rays in the visible region, and connecting to an outlet of an analysis column used in the above-mentioned analysis method.
Further, the measurement chamber is provided with an entrance window and an exit window for measurement light, and light rays in the ultraviolet or visible region pass through the entrance window, pass through the liquid sample present in the measurement chamber, and then exit from the exit window. It is measured by a photometric optical system. In recent years, for example, "Sc
ience, Vol. 261, p. 895-897 (1993) ”, a flow path and a liquid for introducing a liquid material onto an electrophoretic member made of a glass (eg, Pyrex glass) substrate. An electrophoresis device has been developed in which a channel for separating a sample is formed using micromachining technology based on semiconductor manufacturing technology.Compared with conventional capillary electrophoresis devices, high-speed analysis is possible. It has advantages such as extremely low consumption, a very small amount of required sample, and downsizing of the apparatus. These features make it possible to perform on-site (on-site, bedside) analysis, which has been difficult to achieve with conventional analyzers in the field of analytical chemistry, and high-speed analysis in the field of DNA analysis and the like. From an analytical point of view, it is promising as an advantage for screening.

[0003]

In the measuring cell used in the field of analytical chemistry described above, the volume of the measuring chamber does not impair the separation capacity of various analytical techniques, that is, the cross-sectional area of the flow channel is different from that of the separation capillary column. Must be comparable. As the separation capillary column, a fused silica capillary having an inner diameter of about 100 μm is usually used. In order to produce a measurement chamber having a flow channel cross-sectional area having a cross-sectional area similar to the above, a glass substrate having a flow channel formed on the surface thereof is applied to the glass substrate by applying the micromachining technology described above.
There has been proposed a method of manufacturing a measurement cell to be joined together.

In this case, it is important that the surface of the flow path is chemically stable in consideration of the fact that the two substrates can be bonded securely and the influence on the analysis. In a bonding method using a thermal oxide film of a Si thin film, which is frequently used in a semiconductor device, stress and strain remain on the substrate due to a high-temperature processing step for obtaining a thermal oxide film, and the bonding becomes uncertain and the airtightness of the measurement chamber is reduced. There was a problem that I could not keep. In the method using the bonding which was deposited on the entire surface of the glass substrate a silicon dioxide (SiO ₂₎ film by a sputtering method, although the influence of stress is avoided because there is no high temperature treatment process, SiO ₂ in the flow path for analysis Due to the presence of the thin film, there was a problem with chemical stability.

In addition, of the incident light that enters the measurement chamber, light that does not interact with the liquid sample to be measured (stray light) enters the measuring instrument, causing a reduction in measurement sensitivity.

The present invention has been made to solve such a problem, and has a flow path cross-sectional area similar to that of a separation capillary column, has sufficient airtightness, is chemically stable, It is an object of the present invention to provide a measuring cell in which stray light does not enter a measuring instrument.

[0007]

In order to solve the above problems, a measuring cell according to the present invention comprises a sample inlet for introducing a liquid sample, a flow path of the introduced liquid sample, and a liquid sample. A measurement cell using a sample discharge port for discharging, and using at least a part of the flow path as a measurement chamber, wherein the measurement cell is bonded using a silicon dioxide (SiO ₂ ) thin film; And a groove portion serving as the flow path is formed on a joint surface of at least one of the glass substrates. In the measuring cell of the present invention, in order to join two glass substrates,
SiO formed by sputtering on the bonding interface other than the flow path
_The flow path is covered with _two thin films, and the inner surface of the channel is not exposed to the SiO ₂ thin film, exposing the material of the substrate. This allows
A glass cell can be reliably bonded without including a high heat treatment step for generating stress on the substrate, and since a SiO ₂ thin film does not face the inner surface of the flow path, a cell for measurement having chemical stability is produced. It becomes possible.

Further, in order to form a groove serving as a flow path at a bonding interface of a glass substrate, a known photofabrication technique and a wet etching technique can be used, and an arbitrary width and depth (both are several hundred μm or less) ) Can be formed. As a result, it is possible to use a micro flow channel with a flow channel cross-sectional area almost the same as that of a separation capillary column as a measurement chamber, and to realize a measurement chamber whose volume is small enough not to impair the separation ability of various separation and analysis means. it can. Further, for example, Si
By forming an optically opaque portion such as a thin film, the sample flow path has optically opaque portions on both sides in the sample flow direction, and does not interact with the liquid sample to be measured. A stray light does not impinge on a measuring instrument, and a measuring cell having high measuring sensitivity can be manufactured.

Here, the thickness of the glass substrate is desirably as thin as possible in order to suppress the absorption of the measuring light by the glass, and is desirably about 100 μm to 1 mm.
The size of the measuring cell is not particularly limited, but the length of the measuring chamber is desirably about several hundred μm or more so as not to lower the resolution.

When a liquid sample is measured by absorption of ultraviolet light, an ultraviolet transmitting glass (for example, UV-22 of HOYA Corp., # 9741 of Corning Corp.) having a good transmittance up to the ultraviolet region is used as a glass substrate. If the above configuration is realized by using the above, a measurement cell that can be used for measuring light absorption in the ultraviolet region can be obtained. If it is desired to further increase the ultraviolet transmittance, if the above-described configuration is realized using quartz glass as a glass substrate, an ideal measuring cell for measuring light absorption in the ultraviolet region can be obtained.

According to the present invention, a flow channel formed by photofabrication technology and wet etching technology and having a very small width and depth and a channel cross-sectional area similar to that of a separation capillary column is used as a measurement chamber. A sufficiently small measuring chamber can be realized, and the separation capacity of various separation and analysis means does not decrease. Also, when joining two glass substrates, the joining interface other than the flow path was covered with a SiO ₂ thin film formed by sputtering, and the inner surface of the flow path was exposed such that the material of the substrate was exposed. Therefore, there is no distortion or thermal stress in the substrate, and reliable bonding can be achieved. Furthermore, the chemically unstable SiO 2
_Since there are no thin films and the chemical stability is determined only by the properties of the substrate glass, a chemically stable measuring cell can be obtained. In addition, since an optically opaque portion such as a Si thin film is formed on the bonding surface by sputtering or the like, stray light does not enter the detector, and the detector measures only light interacting with the sample as a signal. And a measurement cell having high measurement sensitivity. Furthermore, since the measurement cell is manufactured using semiconductor manufacturing technology, the entire measurement cell is processed with small size and high precision, and furthermore, a plurality of measurement cells can be produced at a time, thereby facilitating cost reduction. Can be done.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a configuration diagram of one embodiment of a measuring cell realized by the present invention. In the figure, reference numerals 1 and 2 denote glass substrates, for example, a quartz glass substrate. On one surface of the glass substrate 1, a minute flow channel groove 6 having a width and a depth of several hundreds μm or less and used as a liquid sample flow channel is formed.
A portion of the glass substrate 1 other than the flow channel 6 is provided with, for example, an optically opaque S for blocking light in the ultraviolet or visible region.
An SiO ₂ film 4 for bonding the i film and the glass substrates 1 and ₂ is formed. On the other hand, through holes 9 and 10 for introducing and discharging a sample liquid are formed in the glass substrate 2. The surfaces to be bonded of the glass substrates 1 and 2 are brought into close contact with each other, and airtightly bonded by means such as bonding using a hydrofluoric acid solution, which will be described later, to form a flow channel 6 for a liquid sample.

In the measuring cell having such a configuration, if a part of the minute flow channel 6 of the liquid sample is used as the measuring chamber 6a, the measuring chamber 6a having a sufficiently small volume can be realized. When the measuring incident light is incident on the measuring cell, the measuring light passes only through the measuring chamber 6a which is a part of the liquid sample flow channel 6, and the other light is optically opaque which acts as a slit. Since the light is blocked by the Si film 3, the stray light can be reduced as compared with the related art, and the measurement sensitivity is improved.

Next, a process for manufacturing the above-described measuring cell will be described with reference to FIG. First, as shown in FIG. 2A, after cleaning a glass substrate 1 made of quartz glass, an etching protective film, for example, a Si film 3 (thickness 3000 Å) is formed by a thin film forming apparatus (for example, a sputtering film forming apparatus). ) And an SiO ₂ film 4 for substrate bonding (film thickness 150)
0 angstrom). At this time, the Si film 3
Serves not only as an etching protection film but also as an optically opaque slit. The material and thickness of the etching protective film are not particularly limited, and may be a material and thickness that can withstand a solution in a later etching process.
Any optically opaque material may be used.

Next, as shown in FIG. 2B, a pattern having a width slightly larger than the flow path is formed by the photoresist 5, and the SiO.sub.2 is formed by buffered hydrofluoric acid (BHF) or the like.
_{2 The} film 4 is etched. Here, the exposure of the photoresist can be performed using an aligner or a stepper generally used in semiconductor manufacturing. further,
The developer for developing the photoresist is not particularly limited as long as it is used for developing the photoresist to be used.

Subsequently, as shown in FIG. 2C, after the photoresist 5 is completely removed, the Si film 7 (thickness 30) is formed.
(00 angstrom). By this process,
Since the SiO ₂ film 4 formed in FIG. 2B has a structure completely sandwiched between the Si films 7 including the side surfaces, the SiO ₂ film 4 can be retained without being etched even in the subsequent quartz etching.

Further, as shown in FIG. 2D, photolithography for patterning the etching protection film is performed to form a pattern of the flow path by the photoresist 8, and then, for example, reactive ion etching using SF6 gas is performed. The Si films 3 and 7 are etched by (RIE) or the like. Here, the material and thickness of the photoresist 8 used as the etching protection film are not particularly limited.

Subsequently, as shown in FIG. 2E, the glass substrate 1 is immersed in a BHF solution heated to, for example, about 37 ° C. using the Si films 3, 7 and the photoresist 8 as etching protection films as masks. An etching step of etching is performed to form a sample channel groove 6. At this time, since the width of the flow path is widened with the etching, if the appropriate design is made, the S film having the width of the flow path as shown in FIG.
The width of the remaining portion of the iO ₂ film 4 can be made wider. Here, the etchant used for etching the glass substrate 1 is not particularly limited, and may be any solution that can etch the glass substrate without any problem.

Subsequently, as shown in FIG. 2F, a photoresist 7 and Si / SiO ₂ /
After completely removing the Si film by ultrasonic cleaning or the like, FIG.
As shown in (g), the Si film 7 is removed by RIE or a solution such as tetramethylammonium hydroxide.

On the other hand, for the glass substrate 2, FIG.
As shown in (h), through holes 9, 10 for introducing and discharging the liquid sample by processing such as sandblasting.
Is formed.

Finally, the glass substrate 1 having the sample flow channel 6 and the slit 3 formed in the steps (a) to (g)
And the glass substrate 2 on which the through holes 9 and 10 are formed in the step (h) are superimposed, and a 1% hydrofluoric acid aqueous solution is interposed at the interface, for example, and a load of about 1 MPa is applied as needed, and at room temperature. By holding for 24 hours, the glass substrates 1 and 2 are joined to realize the measurement cell diagram 2 (i).

In the measuring cell and the method of manufacturing the same having the above-described structure, the width and depth of the flow channel 6 formed by using the photofabrication technology and the wet etching technology are very small, and the flow channel cross-sectional area is almost the same as that of the separation capillary column. Is used as the measurement chamber 6a, so that a measurement chamber having a sufficiently small volume can be realized. When the two glass substrates 1 and 2 are joined, the joining interface other than the flow path is covered with a SiO ₂ 4 film formed by sputtering, and the inner surface of the flow path is made to expose the material of the substrate. Since the bonding is performed, there is no distortion or thermal stress on the substrate, and reliable bonding can be performed. Further, since a chemically unstable SiO ₂ thin film does not exist on the inner surface of the flow channel and the chemical stability is determined only by the properties of the substrate glass 1, it is necessary to obtain a chemically stable measuring instrument cell. it can. Further, since the optically opaque Si film 3 is formed as a slit on the bonding surface by sputtering or the like, stray light does not enter the detector, and the detector measures only light interacting with the sample as a signal. It can have high measurement sensitivity.

Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and various changes may be made within the scope of the present invention described in the appended claims. be able to. For example, the cross-sectional shape of the flow channel 6 is shown in FIG.
It does not stick to a semi-elliptical shape as shown in (g). For example, the process of FIG. 2E is performed by using CF ₄ , C ₂ F ₂ , and CHCF.
_When etching is performed using a gas such as ₃ or a mixed gas thereof, the cross-sectional shape of the flow channel 6 becomes almost rectangular.

The material of the glass substrates 1 and 2 can be selected according to the wavelength of the measuring light used. For example, Pyrex glass may be used for visible light, and when light in the ultraviolet region is used, for example, UV-22 of HOYA Co., Ltd., and Corning Co. #
It is necessary to use an ultraviolet transmitting glass substrate such as 9741 or the quartz glass of the above-described embodiment which transmits ultraviolet light almost completely. The manufacturing process when a substrate material other than quartz glass is used substantially conforms to the embodiment.

[0025]

According to the measuring cell of the present invention, the width and depth formed by photofabrication technology and wet etching technology with high precision are very small, and the cross-sectional area of the flow channel is almost the same as that of the separation capillary column. Since a part of the groove is used as a measurement chamber, it is possible to realize a measurement chamber with a small volume that does not impair the separation ability of various separation and analysis means. When joining two glass substrates, the joining interface other than the flow path was covered with an SiO ₂ film formed by sputtering, and the inner surface of the flow path was exposed such that the material of the substrate was exposed. Therefore, there is no distortion or thermal stress in the substrate, and reliable bonding can be achieved. Furthermore, since a chemically unstable SiO ₂ thin film does not exist on the inner surface of the flow channel and the chemical stability is determined only by the properties of the substrate glass, a chemically stable measuring cell can be obtained. . In addition, since the thickness and characteristics of the SiO ₂ film that plays an important role in substrate bonding can be easily adjusted by the film formation conditions, a reliable measurement cell can be manufactured. Furthermore, by realizing a measurement cell with a slit configured to block incident light other than passing through the liquid sample, stray light incident on the detector can be reduced,
Since the detector measures only the light interacting with the sample as a signal, the measurement sensitivity is improved. In addition, since the measuring cell of the present invention is manufactured using semiconductor manufacturing technology, the entire measuring cell is processed with small size and high precision, and a plurality of measuring cells can be produced at a time. Therefore, the cost can be easily reduced.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a measurement cell according to an embodiment of the present invention.

FIG. 2 is a view showing a manufacturing process of the measuring cell of FIG. 1; (A) Etching mask material (Si film) and bonding SiO ₂
Film formation. (B) Patterning of photoresist and etching of SiO ₂ film. (C) Deposition of an upper etching mask material (SiO ₂ film). (D) Patterning of photoresist and etching of Si (upper + lower) film. (E) Formation of a channel groove by etching the glass substrate. (F) Photoresist and unnecessary portions of Si / SiO ₂
/ Si film removal. (G) Removal of upper etching mask material (Si film). (H) Formation of a through hole in the second substrate. (I) Completed view of the present embodiment.

[Explanation of symbols]

Reference numerals 1, 2, glass substrate 3, Si film (slit) 4, SiO ₂ film 5, 8, photoresist 6, flow channel 6a, measuring chamber 7, Si film 9, 10, through hole

Claims (3)

[Claims] 1. A sample introduction port for introducing a liquid sample, a flow path for the introduced liquid sample, and a discharge port for discharging the liquid sample are provided, and at least a partial area of the flow path is provided. A measurement cell used as a measurement chamber, wherein a measurement flow path of the measurement cell is formed by two substrates joined using a silicon oxide thin film, and a silicon oxide thin film is formed on an inner surface of the flow path. Has a structure that does not face the measurement. 2. The measuring cell according to claim 1, wherein the measuring cell has optically opaque joining surfaces on both sides in the flow direction of the flow channel used as a measuring chamber. 3. The measuring cell according to claim 1, wherein the flow path is formed by using wet etching.