WO2012173130A1 - Liquid analyser - Google Patents

Liquid analyser Download PDF

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Publication number
WO2012173130A1
WO2012173130A1 PCT/JP2012/065072 JP2012065072W WO2012173130A1 WO 2012173130 A1 WO2012173130 A1 WO 2012173130A1 JP 2012065072 W JP2012065072 W JP 2012065072W WO 2012173130 A1 WO2012173130 A1 WO 2012173130A1
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Prior art keywords
slit
liquid
substrate
light
electrode
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PCT/JP2012/065072
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French (fr)
Japanese (ja)
Inventor
ケネディ オケヨ
足立 作一郎
原田 邦男
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株式会社日立製作所
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Publication of WO2012173130A1 publication Critical patent/WO2012173130A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59Transmissivity

Definitions

  • the invention relates to a system for operating a liquid on a substrate.
  • the present invention relates to a liquid analyzer or reaction system for conveying and analyzing a large number of liquids.
  • One method of manipulating a small amount of liquid is to place a droplet on an electrode formed on a flat substrate and transport it by electrical control.
  • two substrates on which a plurality of electrodes are formed are arranged facing each other at a constant interval, a droplet to be conveyed is sandwiched between both substrates, and a voltage is applied to the electrodes.
  • There is a method of conveying a liquid by applying for example, Non-Patent Documents 1 and 2).
  • a plurality of electrodes are formed on the surface of the two substrates in contact with the droplets along the liquid conveyance path formed of the electrode array for conveying the droplets.
  • the electrowetting phenomenon improves the wettability of the electrode to which the ground and voltage are applied, and the droplet Move.
  • a liquid transport device such a device for transporting droplets.
  • the liquid transfer device has advantages such as being less susceptible to air bubbles because it uses a substrate than a container surrounded by a wall.
  • An analyzer that detects and analyzes the amount of components contained in a sample generally irradiates the reaction solution, which is a mixture of the sample and reagent, with white light from a halogen lamp or the like, and uses the light transmitted through the reaction solution.
  • a configuration is widely used in which a necessary wavelength component is extracted by spectroscopic analysis with a diffraction grating and the absorbance is calculated.
  • the reaction solution may be irradiated after white light is separated by a diffraction grating.
  • the optical path length which is the light transmission distance of the liquid in this analyzer, is usually about 5 to 10 mm.
  • Non-patent Document 3 Patent Document 1 (Patent Document 2) (Patent Document 3) (Patent Document 4).
  • the distance between the two substrates arranged opposite to each other is as narrow as 1 mm or less, and when measuring absorbance, the optical path length is short, so that the amount of signal obtained is reduced. For this reason, an optical system is built that increases the irradiation angle width of the light that irradiates the sample and the light reception angle width that captures the light from the sample so that the light receiver can receive more light from the light source.
  • a mechanism has been reported in which an opening is provided in a part of the electrode of the substrate on the light source side and the substrate on the light receiver side is made transparent. With this configuration, a large amount of light can be secured, so that variations in measurement can be reduced.
  • the configuration in which the opening is provided in the electrode of the substrate on the light source side can cut the stray light derived from the light source, but cannot reduce the scattered stray light generated in the sample. Therefore, there are immunoturbidimetric measurement, latex immunoturbidimetric measurement, and turbidity measurement including Escherichia coli among the applications of the liquid transport device as an analyzer, but in the case of measurement of samples containing these scatterers, Then, the transmitted light should be received and the absorbance measurement should be performed, but the scattered light once scattered enters the light receiver, and the correct absorbance cannot be obtained.
  • an electrode with a slit in which an electrode and a slit are integrated is provided on both the substrate on the light source side and the substrate on the light receiver side as a configuration capable of obtaining an accurate absorbance measurement.
  • the basic configuration is shown in FIG. Specifically, the lower substrate 20 on the light source 101 side has a plurality of control electrodes 21, and at least one of the control electrodes is provided with an electrode 22 with a slit including the first slit 1.
  • the insulating film 23 is disposed between the attached control electrode 22 and the liquid 30, and the first slit 1 and at least a part thereof are also formed on the upper substrate 10 on the side of the light receiver 102 that receives the light transmitted through the liquid 30.
  • a counter electrode 12 with a slit including the second slit 2 that faces is provided.
  • the droplet 30 is irradiated through the first slit 1 of the electrode 22 with the slit, and the transmitted light from the sample passes through the second slit 2 and enters the light receiver 102.
  • the lower substrate 20 and the upper substrate 10 transmit light, they are basically transparent to the light from the light source. However, the entire substrate does not need to be transparent, and a portion necessary for light transmission is transparent. I just need it.
  • the control electrode with the slit and the counter electrode 12 do not transmit light and are not easily reflected.
  • FIG. 1 A comparative example is shown in FIG.
  • a control electrode 21 and a slit electrode 22 having a first slit 1 are arranged on a substrate 20 on the light source 101 side, and light emitted from the light source 101 through the first slit 1 is passed through a liquid 30. Irradiate the through light receiver 102.
  • An insulating film 23 is disposed between the control electrode 21 and the control electrode 22 with slits and the liquid 30.
  • the counter electrode 11 disposed on the upper substrate 10 on the light receiver 102 side is made entirely transparent, and the transmitted light of the liquid 30 as a sample is detected by the light receiver 102. In this configuration, the scattered stray light derived from the sample cannot be reduced, so the absorbance of the liquid containing the scatterer could not be measured accurately.
  • FIGS. 3 (A) and 3 (B) A comparative example is described as a one-side slit and the configuration of the present invention as a two-sided slit.
  • FIG. 0 mm is the position of the counter electrode 12 with a slit in which the second slit 2 is integrated with the counter electrode 11. That is, 0 mm is the position where the second slit 2 is in contact with the liquid 30. From FIG. 4, it is clear that the amount of light decreases as the position of the second slit 2 moves away from the liquid. It can be seen that the absorbance does not change much even if the distance increases, but decreases if the distance is excessive.
  • the second slit 2 is preferably integrated with the counter electrode or as close as possible when it is desired to increase the amount of light and the absorbance. For example, if it is acceptable even if the absorbance is reduced to 2%, the position of the second slit 2 is desirably arranged within 1 mm. However, since the thickness of the upper substrate 10 is required to be approximately 1 mm, when the slits are arranged outside the upper substrate 10, the point that the amount of light decreases is disadvantageous.
  • the second slit 2 is provided not only on the light source side but also on the light receiver side, the accuracy of absorbance measurement is improved. Furthermore, it can be seen that when the second slit 2 is integrated with the counter electrode 11, more accurate light absorbance measurement can be performed with more light. Similar results are obtained for the first slit 1. Further, the thickness of the insulating film is about several hundred nanometers, and the integrated electrode 22 with slits as shown in FIG. 1 is optically the same state that the electrode with slits is almost in contact with the liquid 30. You may think.
  • the alignment of the slits on both sides is important.
  • the size of the slit is reduced to about 100 ⁇ m square by reducing the size of the slit due to the miniaturization.
  • the alignment accuracy of the second slits 2 and the first slits 1 on both substrates must be approximately 10 ⁇ m or less in order to ensure the light quantity and perform accurate measurement.
  • the slit is integrated with the electrode, it is possible to provide an alignment mechanism for the semiconductor process used to form the electrode array on the same substrate, and the slit position can be adjusted simultaneously when aligning the substrate. In addition, the position can be easily adjusted, the amount of light is ensured, and an accurate absorbance measurement is possible.
  • the accuracy of absorbance measurement is improved by providing slits on both the light source side and the light receiver side.
  • a slit integrated with the electrode on the substrate on the light receiver side the absorbance of the sample including the scatterer can be accurately measured. Furthermore, it becomes possible to perform highly accurate slit alignment.
  • Fig. 5 shows the configuration of the aforementioned analysis system.
  • the liquid analyzer measures the components inside the liquid transport device 100, the introduction unit 80 for introducing the specimen 28 and the reagent 29 into the liquid transport device 100, and the sample (droplet 30) in which the specimen 28 and the reagent 29 are mixed.
  • a specimen 28 and a reagent 29 containing a latex reagent as a scatterer are accommodated in a reagent tank, and the specimen 28 and the reagent 29 are sequentially introduced into the liquid transport device 100 from the introduction port 82 by the probe 81. 28 and the reagent 29 are mixed and stirred to form a droplet 30 as a sample.
  • the detection unit 90 is installed adjacent to the detection unit installed in at least a part of the liquid transport path through which the liquid droplet 30 is transported and discharged to the liquid transport device 100.
  • a sipper 71 and a waste liquid tank 73 are disposed in the discharge unit 70, and the droplets 30 conveyed to the discharge port 72 can be discharged from the liquid transfer device 100 to the waste liquid tank 73 by the sipper 71.
  • the introduction port 82 and the discharge port 72 may be holes provided on both sides of the upper substrate 10 as shown in FIG.
  • the liquid transport device 100 is configured by arranging a lower substrate 20 having a thickness of 2 mm and an upper substrate 10 having a thickness of 1 mm so as to form a gap 31 having a spacing of 0.5 mm.
  • the gap 31 was filled with a silicone oil 40 having a viscosity of 2 cSt as a medium. Since the silicone oil 40 can prevent the droplets 30 from evaporating, the silicone oil 40 is preferably used in the case of a solution in which the droplets 30 are easily evaporated.
  • a plurality of square control electrodes 21 each having a size of 1.5 mm square were disposed on the lower substrate 20, and the surface of these control electrodes 21 was covered with an insulating film 23 having a thickness of 300 mm.
  • One or more counter electrodes 11 are arranged on the upper substrate 10. The thicknesses of the control electrode 21 and the counter electrode 11 were 200 nm.
  • a voltage control unit including a power source 121, a wiring 122, and a switch 120 for controlling ON / OFF of the voltage to each control electrode 21 is also provided. Normally, by applying the voltage to the control electrode 21 with the counter electrode 11 as the ground, a voltage difference is generated between the upper substrate and the lower substrate, so that the droplet 30 can be transported.
  • the droplet 30 to be conveyed was placed on one or more control electrodes 21 and moved by sequentially applying a voltage of 25 V to the control electrode 21.
  • the surfaces of the insulating film 23 and the counter electrode 11 were subjected to a water repellency treatment so that the droplets 30 were easy to move.
  • quartz is used for the lower substrate 20 and the upper substrate 10, but silicon may also be used.
  • silicon when silicon is used for the lower substrate 20, it is necessary to provide the silicon substrate with an opening leading to the first slit 1.
  • silicon dioxide is formed on the silicon surface by using a generally known semiconductor technology.
  • the silicon at the location of the opening is locally removed by anisotropic etching or the like to leave the light-transmitting film as the opening.
  • the control electrode 21 and the counter electrode 11 are made of chrome having a thickness of 200 nm and formed by a semiconductor technique represented by a lithography method.
  • Silicon dioxide (SiO 2 ) was used for the insulating film 23 and was formed by CVD (Chemical Vapor Deposition). In this embodiment, silicon dioxide is used, but insulating materials such as parylene C, silicon nitride, and amorphous fluororesin (amorphous fluoropolymer) may be used.
  • the specimen 28 and the reagent 29 containing latex particles having a diameter of 2 ⁇ m are introduced into the transport device 100, the voltage is applied to the control electrode 21 to control the introduced liquid, and the specimen 28 and the reagent 29 are transported within the device. Mixing and reaction were performed to form droplets 30.
  • the liquid up to the detection unit 90 including the light source 101, the light receiver 102, and the electrode 22 with the slit is obtained. Drop 30 was conveyed.
  • FIG. 7 is a cross-sectional view showing the positional relationship between the detection unit 90 and the liquid transport device 100.
  • the detection unit 90 includes a light source 101, a light receiver 102, and a lens 103.
  • the upper substrate 10 provided with the second slit 2 and the counter electrode 12 with slit is disposed on the light receiver 102 side
  • the lower substrate 20 provided with the first slit 1 and the electrode 22 with slit is disposed on the light source 101 side.
  • the two substrates sandwiching the droplet 30 are arranged between the light source 101 and the light receiver 102, and the light 104 from the light source 101 is collected by the lens 103 and is provided on the electrode 22 with the slit.
  • the light 104 that has passed through the droplet 30 passes through the second slit 2 provided in the counter electrode 12 with slit, and is condensed by the lens 103 and reaches the light receiver 102.
  • the absorbance of the liquid 30 obtained by mixing and stirring the specimen 28 containing latex particles having a diameter of 2 ⁇ m and the reagent 29 was measured.
  • the voltage controller fixes the liquid 30 by applying a voltage between the electrode 22 with the slit and the counter electrode 12 with the slit at least while the liquid 30 is irradiated with light. 30 did not move carelessly, and stable measurement became possible.
  • first slit 1 and the second slit 2 are paired, and a plurality of both the slit electrode 22 and the slit electrode 22 and the slit electrode 12 may be provided.
  • first slit electrode is provided on the light source side and the second counter electrode with a slit is provided on the light receiver side is shown here, measurement is possible even if the positions of the light source and the light receiver are switched.
  • the electrode 22 with the slit is a square having a thickness of 200 nm and a size of 1.5 mm square, and is the same as the adjacent control electrode 21.
  • the size of the first slit 1 is set to 1/3 of the area of the electrode 22 with a slit and a square with a width of 0.5 mm square so that the electrode 22 with the slit can be used for both conveyance and measurement.
  • the size of the second slit 2 is the same as that of the first slit 1 and is a square of 0.5 mm square.
  • the shape of the slit is not limited to a square, but may be a rectangle, other polygons, or a circle. As a result, both conveyance and measurement were realized.
  • Chrome is used for the electrode 22 with slit and the counter electrode 12 with slit, but other opaque metal materials such as aluminum may be used. Other opaque conductive materials may also be used.
  • a transparent electrode may be used so that the position of the liquid can be seen from the substrate.
  • the fitting opening 200 is formed at an arbitrary tip of the lower substrate 20 including the first slit 1 by a semiconductor process used for electrode formation. Further, the fitting opening 200 was formed at an arbitrary tip of the upper substrate 10 including the second slit 2 by the same semiconductor process.
  • a semiconductor process such as wet etching or dicing may be used.
  • a spacer 201 having a shape that fits into the fitting opening 200 was fitted into the fitting openings of the substrates on both sides, and the positions of the slits were adjusted.
  • the slit position error ⁇ L defined by the shift of the vertical center line of each of the two first slits 1 and the second slit 2 can be suppressed to 10 ⁇ m or less.
  • the spacer 201 also serves to make the gap 31 constant.
  • a spacer having a step may be used for positioning the upper and lower substrates. Details are shown in FIGS. 9A to 9C.
  • this alignment mechanism the two sides of the upper substrate and the lower substrate were processed with high accuracy and used for alignment. This time, dicing was used for processing, but the substrate may be gradually sharpened with a scissors or the like to finally match with accuracy.
  • FIG. 9A out of the four sides of the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit, the two sides 306 and 307 constituting one end of the substrate are accurately defined. processed.
  • the processing positions of the sides 306 and 307 are set to positions where the distances XE and YE are determined with reference to two sides that form the second slit 2 and are orthogonal to each other.
  • the width distances XE and YE were 10 mm and 5 mm respectively.
  • the horizontal axis 305 and the vertical axis 304 passing through the center of the slit may be used as a reference.
  • the sides 306 and 307 corresponding to the distances may be processed at the positions of the distances XC and YC shown in FIG.
  • the two sides 308 and 309 were processed for the lower substrate 20 shown in FIG. 9B by the same procedure as that for the upper substrate 10. Again, the center line of the slit may be used as a reference. In this case, the side 308 and the side 309 may be processed based on the distance XC and the distance YC shown in FIG.
  • the spacers 310 are placed in contact with two processed sides (for example, the side 306 and the side 308) of the substrates on both sides, so that the upper substrate 10 and the lower substrate 20 are formed.
  • the positions of the two sides coincide vertically, and the first slit 1 and the second slit 2 can be aligned.
  • the spacers 310 may be installed on both sides to serve as a constant substrate interval.
  • FIGS. 10 (A) to 10 (C) are shown in FIGS. 10 (A) to 10 (C).
  • 10A is a plan view of the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit
  • FIG. 10B includes the first slit 1, the electrode 22 with the slit, and the control electrode 21.
  • substrate is shown.
  • 210 and 211 are provided as two or more alignment marks for positioning the slit in the upper substrate 10, and similarly, two or more alignment marks 212 are also provided in the lower substrate 20. And 213, which correspond to the alignment marks on the upper substrate.
  • the alignment marks of the upper substrate 10 and the lower substrate 20 form a pair (210 ⁇ 213, 211 ⁇ 212).
  • the alignment mark may be formed by a process similar to that of the counter electrode 11 or the control electrode 21, and may be formed by a general semiconductor process (dry etching, wet etching, etc.) used for forming the electrode. Since the vertical direction and the horizontal direction are easily determined, the shape of the alignment mark is a cross shape here, but other shapes (circular shape, polygonal shape, etc.) may be used.
  • FIG. 10C shows a cross-sectional view of the liquid transport device including the droplets 30, and the alignment will be described based on the cross-sectional view.
  • the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit and the lower substrate 20 including the first slit 1, the electrode 22 with the slit, and the control electrode 21 are faced to each other. Arranged.
  • the alignment marks of the paired substrates are arranged in a straight line.
  • the alignment mark 210 of the upper substrate and the alignment mark 212 of the lower substrate are aligned, and similarly, the alignment mark 211 of the upper substrate 10 and the alignment mark 213 of the lower substrate 20 corresponding thereto are aligned.
  • the alignment mark is small, the alignment marks on both substrates may be matched using a microscope or the like, but it is usually sufficient to form the alignment mark large so that the alignment can be made visually.
  • the alignment mark as described above, the alignment of the first slit 1 and the second slit 2 can be easily performed with high accuracy, and accurate absorbance measurement can be performed.
  • Light source 102 ... Light receiver, 103 ... Lens, 104 ... Light, 121 ... Power supply, 122 ... Wiring, 120 ... Switch, 200 ... Insertion port, 201 ... spacer, 210 ... alignment mark, 211 ... alignment mark, 212 ... alignment mark, 213 ... alignment mark, 214 ... arrow, 304 ... vertical axis , 305 ... horizontal axis, 306 ... of the upper substrate side, 307 ... of the upper substrate side, 308 ... of the lower substrate side, 309 ... of the lower substrate side, 310 ... spacer

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Abstract

There is a problem with scattering light when an absorbance measurement is conducted on a scattering substance in a liquid transport device, and an accurate absorbance measurement is difficult to perform. In order to solve this problem, an embodiment of the present invention is configured to be able to reduce scattering light and conduct an accurate absorbance measurement by providing an electrode with a measuring slit on two substrates making up the liquid transport device. This embodiment of the present invention is also configured to provide a positioning mechanism for the slits on the two substrates. In this way, the absorbance of a sample including a scattering substance can be measured accurately. Highly accurate slit positioning can also be performed.

Description

液体分析装置Liquid analyzer
 発明は基板上で液体を操作するシステムに関する。特に多数の液体を搬送し,分析する液体分析装置または反応システムに関する。 The invention relates to a system for operating a liquid on a substrate. In particular, the present invention relates to a liquid analyzer or reaction system for conveying and analyzing a large number of liquids.
 生化学分析装置においては、従来、プラスチックやガラスの反応容器内に検体と試薬とを分注し、これらを混合してできた反応液に光を照射し、成分量を測定していた。しかし近年、試薬コストの削減や、環境への負荷低減のため、分析に用いる反応液の微少量化が求められており、従来方式での反応液微少量化では液の取り扱いが困難になり、また分注、混合時に発生する気泡等により正確な測定ができなくなるという問題があった。そのため、微少量の液体を的確に操作し、精度良く分析する技術が求められていた。 In biochemical analyzers, conventionally, specimens and reagents are dispensed in a plastic or glass reaction vessel, and light is applied to a reaction solution obtained by mixing these to measure the amount of components. However, in recent years, in order to reduce reagent costs and reduce the burden on the environment, it has been required to reduce the amount of reaction solution used for analysis. Note: There was a problem that accurate measurement could not be performed due to bubbles generated during mixing. Therefore, there has been a demand for a technique for accurately operating a minute amount of liquid and analyzing it with high accuracy.
 微少量の液体(液滴)を操作する一つの方法として、平面基板に形成された電極上に液滴を置き,電気的な制御により搬送する方法がある。代表的な方法として、表面に沿って複数の電極が形成された2つの基板を一定の間隔をなすように対向して配置し,搬送する液滴を両基板間に挟みこみ,電極に電圧を印加することで液体を搬送する方法がある(例えば非特許文献1、2)。この方法では、通常、液滴を搬送する電極配列からなる液体搬送路に沿って、2つの基板の液滴が接する面に複数の電極が形成されている。2つの基板の片方の電極をグランドに、もう片方の基板側の電極に一定電圧を印加すると、エレクトロウェッティング現象により、グランドおよび電圧を印加した電極の上の濡れ性が良くなり、その液滴が移動する。このプロセスを繰りかえすことで、電極配列に沿って液滴を搬送できる。ここではこのような,液滴を搬送するデバイスを液体搬送デバイスと呼ぶ。液体搬送デバイスは微量の液体を自由度高く操作できるほか,周囲が壁に囲まれた容器に比べ、基板を利用するため気泡の影響を受けにくいことなどが利点として挙げられる。 One method of manipulating a small amount of liquid (droplet) is to place a droplet on an electrode formed on a flat substrate and transport it by electrical control. As a typical method, two substrates on which a plurality of electrodes are formed are arranged facing each other at a constant interval, a droplet to be conveyed is sandwiched between both substrates, and a voltage is applied to the electrodes. There is a method of conveying a liquid by applying (for example, Non-Patent Documents 1 and 2). In this method, normally, a plurality of electrodes are formed on the surface of the two substrates in contact with the droplets along the liquid conveyance path formed of the electrode array for conveying the droplets. When a constant voltage is applied to the electrode on one side of the two substrates and the electrode on the other side of the substrate, the electrowetting phenomenon improves the wettability of the electrode to which the ground and voltage are applied, and the droplet Move. By repeating this process, droplets can be transported along the electrode array. Here, such a device for transporting droplets is called a liquid transport device. In addition to being able to operate a small amount of liquid with a high degree of freedom, the liquid transfer device has advantages such as being less susceptible to air bubbles because it uses a substrate than a container surrounded by a wall.
 検体中に含まれる成分量を検出し分析する分析装置には、一般的にハロゲンランプ等からの白色光を検体と試薬の混合液である反応液に照射し、反応液を透過してきた光を回折格子で分光して必要な波長成分を取り出し、その吸光度を割り出す構成が広く用いられている。あるいは、白色光を回折格子で分光した後、反応液に照射する場合もある。この分析装置の液体の光透過距離である光路長は通常、5~10 mm程度である。一方,液体搬送デバイスを用いた液体分析装置では,光路長が1 mm未満と短く,当該デバイスを上述の分析装置として用いる際に光量および吸光度の確保が課題となる。これまでに液体搬送デバイスを適用した液体分析装置が報告されている(非特許文献3)(特許文献1)(特許文献2)(特許文献3)(特許文献4)。 An analyzer that detects and analyzes the amount of components contained in a sample generally irradiates the reaction solution, which is a mixture of the sample and reagent, with white light from a halogen lamp or the like, and uses the light transmitted through the reaction solution. A configuration is widely used in which a necessary wavelength component is extracted by spectroscopic analysis with a diffraction grating and the absorbance is calculated. Alternatively, the reaction solution may be irradiated after white light is separated by a diffraction grating. The optical path length, which is the light transmission distance of the liquid in this analyzer, is usually about 5 to 10 mm. On the other hand, in a liquid analyzer using a liquid transport device, the optical path length is as short as less than 1 mm, and securing the light amount and absorbance is a problem when the device is used as the above-described analyzer. So far, a liquid analyzer using a liquid transport device has been reported (Non-patent Document 3) (Patent Document 1) (Patent Document 2) (Patent Document 3) (Patent Document 4).
特表2010-521676号Special table 2010-521676 特表2010-503516号Special table 2010-503516 特表2009-534653号Special table 2009-534653 特開2006-317363号公報JP 2006-317363 A
 上記液体分析装置では、対向して配置する2つの基板が形成する間隔がおおむね1mm以下と狭く、吸光度測定を行う際、光路長が短いため、得られるシグナルの量が少なくなる。そのため光源からの光量をより多く受光器で受光できるよう、試料に照射する光の照射角度幅および、試料からの光を取り込む受光角度幅を大きくとる光学系が組まれている。例えば上述した液体分析装置では光源側の基板の電極の一部に開口部を設け,さらに受光器側の基板を透明にした仕組みが報告されている。この構成であれば光量は多く確保できるために測定のばらつきは低減できる。しかしながらこのような光源側の基板の電極に開口部を設けた構成は,光源由来の迷光はカットできるが,試料内で生じる散乱迷光を低減できなかった。そのため、液体搬送デバイスの分析装置としての用途の中には免疫比濁測定やラテックス免疫比濁測定、大腸菌などを含む濁度測定があるが、これらの散乱体を含む試料の測定の場合,本来ならば透過した光を受光し吸光度測定を行うべきところ、一度散乱された散乱光も受光器に入り込み,正しい吸光度を得ることができないのが問題となっていた。 In the above-described liquid analyzer, the distance between the two substrates arranged opposite to each other is as narrow as 1 mm or less, and when measuring absorbance, the optical path length is short, so that the amount of signal obtained is reduced. For this reason, an optical system is built that increases the irradiation angle width of the light that irradiates the sample and the light reception angle width that captures the light from the sample so that the light receiver can receive more light from the light source. For example, in the liquid analyzer described above, a mechanism has been reported in which an opening is provided in a part of the electrode of the substrate on the light source side and the substrate on the light receiver side is made transparent. With this configuration, a large amount of light can be secured, so that variations in measurement can be reduced. However, the configuration in which the opening is provided in the electrode of the substrate on the light source side can cut the stray light derived from the light source, but cannot reduce the scattered stray light generated in the sample. Therefore, there are immunoturbidimetric measurement, latex immunoturbidimetric measurement, and turbidity measurement including Escherichia coli among the applications of the liquid transport device as an analyzer, but in the case of measurement of samples containing these scatterers, Then, the transmitted light should be received and the absorbance measurement should be performed, but the scattered light once scattered enters the light receiver, and the correct absorbance cannot be obtained.
 本発明では,正確な吸光度測定が得られる構成として,電極とスリットを一体化したスリット付き電極(スリット電極)を光源側の基板および受光器側の基板の両方に設けた。基本構成を図1に示す。具体的には,光源101側の下部基板20に複数の制御電極21を有し、その制御電極の少なくとも1つに第1のスリット1を含むスリット付き電極22を設け,これら制御電極21およびスリット付き制御電極22と液体30の間に絶縁膜23を配置し、さらに,液体30を透過した光を受光する受光器102側の上部基板10にも、第1のスリット1とその少なくとも一部が対面するような第2のスリット2を含むスリット付き対向電極12を設ける。スリット付き電極22の第1のスリット1を通して液滴30を照射し,試料からの透過光は第2のスリット2を通過して受光器102に入る。第1のスリット1を含むスリット付き電極22と第2のスリット2を含むスリット付き電極12は複数であってもよい。また,下部基板20および上部基板10は光を透過させるため、基本的に光源からの光に対して透明であるが、全体が透明である必要は無く、光の透過に必要な部分が透明であればよい。スリット付きの制御電極および対向電極12は光を通さず,かつ反射しにくいものとする。 In the present invention, an electrode with a slit (slit electrode) in which an electrode and a slit are integrated is provided on both the substrate on the light source side and the substrate on the light receiver side as a configuration capable of obtaining an accurate absorbance measurement. The basic configuration is shown in FIG. Specifically, the lower substrate 20 on the light source 101 side has a plurality of control electrodes 21, and at least one of the control electrodes is provided with an electrode 22 with a slit including the first slit 1. The insulating film 23 is disposed between the attached control electrode 22 and the liquid 30, and the first slit 1 and at least a part thereof are also formed on the upper substrate 10 on the side of the light receiver 102 that receives the light transmitted through the liquid 30. A counter electrode 12 with a slit including the second slit 2 that faces is provided. The droplet 30 is irradiated through the first slit 1 of the electrode 22 with the slit, and the transmitted light from the sample passes through the second slit 2 and enters the light receiver 102. There may be a plurality of electrodes with slits 22 including the first slits 1 and electrodes 12 with slits including the second slits 2. Further, since the lower substrate 20 and the upper substrate 10 transmit light, they are basically transparent to the light from the light source. However, the entire substrate does not need to be transparent, and a portion necessary for light transmission is transparent. I just need it. The control electrode with the slit and the counter electrode 12 do not transmit light and are not easily reflected.
 比較例を図2に示す。この構成では,光源101側の基板20に制御電極21および第1のスリット1を備えたスリット付き電極22を配置し,第一のスリット1を通して,光源101から出射される光を,液体30を通し受光器102に照射する。制御電極21およびスリット付き制御電極22と液体30の間には絶縁膜23が配置される。一方,受光器102側の上部基板10に配置する対向電極11を全面透明とし,試料である液体30の透過光を受光器102で検出する。この構成では試料由来の散乱迷光は低減できないため,散乱体を含む液体の吸光度測定を正確にできなかった。 A comparative example is shown in FIG. In this configuration, a control electrode 21 and a slit electrode 22 having a first slit 1 are arranged on a substrate 20 on the light source 101 side, and light emitted from the light source 101 through the first slit 1 is passed through a liquid 30. Irradiate the through light receiver 102. An insulating film 23 is disposed between the control electrode 21 and the control electrode 22 with slits and the liquid 30. On the other hand, the counter electrode 11 disposed on the upper substrate 10 on the light receiver 102 side is made entirely transparent, and the transmitted light of the liquid 30 as a sample is detected by the light receiver 102. In this configuration, the scattered stray light derived from the sample cannot be reduced, so the absorbance of the liquid containing the scatterer could not be measured accurately.
 次に散乱体として直径2 μmの球体を用い,それぞれの構成における吸光度と光量を吸光度測定のシミュレーションで求めた。本シミュレーションでは,吸光度0.5 absを目標値とし,散乱体の濃度および光路設定を行った。その結果を図3(A)(B)に示す。比較例を片側スリット、本発明の構成を両側スリットとして記載する。 Next, a sphere having a diameter of 2 μm was used as a scatterer, and the absorbance and the amount of light in each configuration were obtained by a simulation of absorbance measurement. In this simulation, the absorbance of 0.5 abs was set as the target value, and the scatterer concentration and optical path were set. The results are shown in FIGS. 3 (A) and 3 (B). A comparative example is described as a one-side slit and the configuration of the present invention as a two-sided slit.
 図3(A)より,片側スリットの場合の方が両側スリットの場合よりも光量が得られるが、図3(B)から明らかなように,片側スリットでは吸光度が0.17 absであるのに対し、両側スリットでは吸光度が0.5 absとより正確に測定できていることがわかった。 From FIG. 3 (A), the amount of light is obtained in the case of the one-side slit than in the case of the both-side slit, but as is clear from FIG. 3 (B), the absorbance in the one-side slit is 0.17 abs, It was found that the absorbance at both side slits could be measured more accurately at 0.5 abs.
 次に,受光器側の第2のスリット2の位置を液体30から受光器の方向へ徐々に遠ざけた場合の、光量と吸光度のスリット位置依存性を計算した。その結果を図4に示す。0 mmは第2のスリット2を対向電極11と一体化したスリット付き対向電極12の位置である。すなわち,0 mmとは第2のスリット2が液体30に接している位置である。図4より,第2のスリット2の位置が液体から離れるにつれて光量が減少していることが明らかである。吸光度については距離が離れてもあまり変わらないが、離れすぎると減少することが分かる。そのため,光量と吸光度を共にかせぎたい場合には、第2のスリット2は対向電極と一体化しているか、できるだけ近い方がよいことがわかる。例えば,吸光度が2%まで低減しても許容できるとすると、第2のスリット2の位置は1mm以内に配置することが望ましい。しかしながら,上部基板10の厚みは概ね1mm程度必要であるため、上部基板10よりも外側にスリットを配置した場合には光量が減少する点が不利になる。 Next, the dependency of the light amount and absorbance on the slit position when the position of the second slit 2 on the receiver side is gradually moved away from the liquid 30 toward the receiver was calculated. The result is shown in FIG. 0 mm is the position of the counter electrode 12 with a slit in which the second slit 2 is integrated with the counter electrode 11. That is, 0 mm is the position where the second slit 2 is in contact with the liquid 30. From FIG. 4, it is clear that the amount of light decreases as the position of the second slit 2 moves away from the liquid. It can be seen that the absorbance does not change much even if the distance increases, but decreases if the distance is excessive. For this reason, it is understood that the second slit 2 is preferably integrated with the counter electrode or as close as possible when it is desired to increase the amount of light and the absorbance. For example, if it is acceptable even if the absorbance is reduced to 2%, the position of the second slit 2 is desirably arranged within 1 mm. However, since the thickness of the upper substrate 10 is required to be approximately 1 mm, when the slits are arranged outside the upper substrate 10, the point that the amount of light decreases is disadvantageous.
 以上から,光源側のみならず,受光器側にも第2のスリット2を設けると、吸光度測定の精度が向上することわかる。さらに、第2のスリット2を対向電極11と一体化した場合のほうがより光量をかせいで正確な吸光度測定ができることがわかる。尚、第1のスリット1についても同様の結果が得られる。また、絶縁膜の厚みは数百ナノ程度であり、図1のような一体化したスリット付き電極22であれば、光学的にはスリット付き電極が液体30にほぼ接触しているのと同じ状態と考えてよい。 From the above, it can be seen that if the second slit 2 is provided not only on the light source side but also on the light receiver side, the accuracy of absorbance measurement is improved. Furthermore, it can be seen that when the second slit 2 is integrated with the counter electrode 11, more accurate light absorbance measurement can be performed with more light. Similar results are obtained for the first slit 1. Further, the thickness of the insulating film is about several hundred nanometers, and the integrated electrode 22 with slits as shown in FIG. 1 is optically the same state that the electrode with slits is almost in contact with the liquid 30. You may think.
 一方、下部基板20と上部基板10のそれぞれにスリットを設けた場合では両側のスリットの位置合わせが重要となる。上述の通り,微量化に伴うスリットの縮小化により、スリットの大きさは100 μm角程度にまでなる。その際光量を確保し正確な測定をするには両側基板の第2のスリット2および第1のスリット1の位置あわせ精度は概ね10 μm以下にしなければならないと考えられる。スリットを電極と一体化させた場合では、電極配列の形成に用いる半導体プロセス等での位置あわせ機構を同一基板に設けることができ,基板を合わせる際にスリット位置を同時に合わせることができるため高精度にかつ簡易に位置あわせでき、光量を確保し、正確な吸光度測定が可能となる。 On the other hand, when slits are provided in each of the lower substrate 20 and the upper substrate 10, the alignment of the slits on both sides is important. As described above, the size of the slit is reduced to about 100 μm square by reducing the size of the slit due to the miniaturization. In that case, it is considered that the alignment accuracy of the second slits 2 and the first slits 1 on both substrates must be approximately 10 μm or less in order to ensure the light quantity and perform accurate measurement. When the slit is integrated with the electrode, it is possible to provide an alignment mechanism for the semiconductor process used to form the electrode array on the same substrate, and the slit position can be adjusted simultaneously when aligning the substrate. In addition, the position can be easily adjusted, the amount of light is ensured, and an accurate absorbance measurement is possible.
 光源側と受光器側の両方にスリットを設けることで、吸光度測定の精度が向上する。受光器側の基板に電極と一体化したスリットを設けることにより、散乱体を含む試料の吸光度を正確に測定できる。さらに高精度なスリットの位置あわせを実施することが可能となる。 The accuracy of absorbance measurement is improved by providing slits on both the light source side and the light receiver side. By providing a slit integrated with the electrode on the substrate on the light receiver side, the absorbance of the sample including the scatterer can be accurately measured. Furthermore, it becomes possible to perform highly accurate slit alignment.
電極スリット両側構成の説明図Illustration of electrode slits on both sides 電極スリット片側構成の説明図Illustration of electrode slit one side configuration 吸光度および光量のシミュレーション結果Absorbance and light intensity simulation results 吸光度および光量のスリット位置依存性のシミュレーション結果Simulation results of the dependency of absorbance and light quantity on slit position 液体分析装置の概要図Overview of liquid analyzer 液体デバイスの搬送経路の断面図Cross-sectional view of liquid device transport path 液体分析装置の検出ユニットの断面図Cross section of detection unit of liquid analyzer はめ込み口を用いたスリット位置合わせ機構の説明図Explanatory drawing of slit alignment mechanism using fitting port デバイスの2つの辺を基準とするスリット位置合わせ機構の説明図Explanatory drawing of slit alignment mechanism based on two sides of device 位置合わせマークを用いたスリット位置合わせ機構の説明図Explanatory drawing of slit alignment mechanism using alignment marks
 本実施例では、吸光度測定を行う分析システムにおける計測部ユニットの構成について説明する。 In the present embodiment, the configuration of a measurement unit in an analysis system that performs absorbance measurement will be described.
 図5に前述分析システムの構成を示す。液体分析装置は液体搬送デバイス100と、検体28と試薬29を液体搬送デバイス100に導入するための導入ユニット80と、検体28と試薬29を混合した試料(液滴30)の内部の成分を測定するための検出ユニット90と、液滴30を液体搬送デバイス100から排出するための排出ユニット70から構成される。 Fig. 5 shows the configuration of the aforementioned analysis system. The liquid analyzer measures the components inside the liquid transport device 100, the introduction unit 80 for introducing the specimen 28 and the reagent 29 into the liquid transport device 100, and the sample (droplet 30) in which the specimen 28 and the reagent 29 are mixed. A detection unit 90 for discharging the liquid droplets 30 and a discharge unit 70 for discharging the droplets 30 from the liquid transport device 100.
 導入ユニット80には検体28と散乱体としてラテックス試薬を含む試薬29が試薬槽に収容等され、プローブ81により導入口82から検体28及び試薬29を順番に液体搬送デバイス100内に導入し,検体28と試薬29を混合・撹拌して試料となる液滴30ができる。検出ユニット90は、液体搬送デバイス100に液滴30が搬送され排出されるまでに通過する液体搬送路の少なくとも一部に設置された検出ユニットに隣接して設置される。排出ユニット70にはシッパー71と廃液タンク73が配置され、排出口72に搬送された液滴30をシッパー71により液体搬送デバイス100内から廃液タンク73へ排出できる。導入口82および排出口72は,図5に示すように,上部基板10の両側に設けた穴であってもよい。 In the introduction unit 80, a specimen 28 and a reagent 29 containing a latex reagent as a scatterer are accommodated in a reagent tank, and the specimen 28 and the reagent 29 are sequentially introduced into the liquid transport device 100 from the introduction port 82 by the probe 81. 28 and the reagent 29 are mixed and stirred to form a droplet 30 as a sample. The detection unit 90 is installed adjacent to the detection unit installed in at least a part of the liquid transport path through which the liquid droplet 30 is transported and discharged to the liquid transport device 100. A sipper 71 and a waste liquid tank 73 are disposed in the discharge unit 70, and the droplets 30 conveyed to the discharge port 72 can be discharged from the liquid transfer device 100 to the waste liquid tank 73 by the sipper 71. The introduction port 82 and the discharge port 72 may be holes provided on both sides of the upper substrate 10 as shown in FIG.
 次に本実施例に用いた液体搬送デバイス100の構成を図6に示す。液体搬送デバイス100は厚み2 mmの下部基板20及び厚み1mmの上部基板10を間隔0.5 mmの隙間31を形成するように配置して構成された。隙間31は媒体となる粘度2cStのシリコーンオイル40で満たした。このシリコーンオイル40は液滴30の蒸発を防ぐことができるため、液滴30が蒸発しやすい溶液の場合には使うとよい。下部基板20にはサイズ1.5 mm角の正方形制御用電極21を複数配置し、さらにそれらの制御電極21の表面を厚み300 nmの絶縁膜23で覆った。上部基板10には,1つ以上の対向電極11を配置した。制御電極21および対向電極11の厚みを200 nmとした。液体搬送の制御のため,電源121,配線122,及び各制御用電極21への電圧のON/OFFを制御するスイッチ120を含む電圧制御部も備えた。通常,対向電極11をグラウンドにし,制御用電極21に電圧をかけることで,上部基板と下部基板との間に電圧差が生じて液滴30を搬送できる。搬送する液滴30を1つ以上の制御用電極21の上に配置し,制御電極21に25Vの電圧を順次印加することにより移動させた。液滴30が移動し易いように,絶縁膜23および対向電極11の表面を撥水性処理した。 Next, the configuration of the liquid transport device 100 used in the present embodiment is shown in FIG. The liquid transport device 100 is configured by arranging a lower substrate 20 having a thickness of 2 mm and an upper substrate 10 having a thickness of 1 mm so as to form a gap 31 having a spacing of 0.5 mm. The gap 31 was filled with a silicone oil 40 having a viscosity of 2 cSt as a medium. Since the silicone oil 40 can prevent the droplets 30 from evaporating, the silicone oil 40 is preferably used in the case of a solution in which the droplets 30 are easily evaporated. A plurality of square control electrodes 21 each having a size of 1.5 mm square were disposed on the lower substrate 20, and the surface of these control electrodes 21 was covered with an insulating film 23 having a thickness of 300 mm. One or more counter electrodes 11 are arranged on the upper substrate 10. The thicknesses of the control electrode 21 and the counter electrode 11 were 200 nm. In order to control the liquid conveyance, a voltage control unit including a power source 121, a wiring 122, and a switch 120 for controlling ON / OFF of the voltage to each control electrode 21 is also provided. Normally, by applying the voltage to the control electrode 21 with the counter electrode 11 as the ground, a voltage difference is generated between the upper substrate and the lower substrate, so that the droplet 30 can be transported. The droplet 30 to be conveyed was placed on one or more control electrodes 21 and moved by sequentially applying a voltage of 25 V to the control electrode 21. The surfaces of the insulating film 23 and the counter electrode 11 were subjected to a water repellency treatment so that the droplets 30 were easy to move.
 本実施例では下部基板20および上部基板10に石英を用いたが,シリコンを用いてもよい。例えば,下部基板20にシリコンを用いた場合,第1スリット1に通じる開口部をシリコン基板に設ける必要があり,その方法として,一般的に知られている半導体技術を使ってシリコン表面に二酸化ケイ素等の光透過性を持つ膜を成膜した後,異方性エッチング等で開口部となる場所のシリコンを局所的に除去し,前記光透過性膜を開口部として残すなどの方法がある。上部基板10にシリコンを用いた場合でも同様である。また,制御用電極21及び対向電極11には厚み200 nmのクロームを用い、リソグラフィー法で代表される半導体技術で形成した。絶縁膜23に二酸化ケイ素(SiO)を用い,CVD(Chemical Vapor Deposition)で成膜した。本実施例では,二酸化ケイ素を用いたが,パリレンC,窒化ケイ素,非晶性フッ素樹脂(アモルファスフロロポリマー)、等の絶縁性材用を用いてもよい。 In this embodiment, quartz is used for the lower substrate 20 and the upper substrate 10, but silicon may also be used. For example, when silicon is used for the lower substrate 20, it is necessary to provide the silicon substrate with an opening leading to the first slit 1. As a method for this, silicon dioxide is formed on the silicon surface by using a generally known semiconductor technology. There is a method in which after forming a light-transmitting film such as silicon, the silicon at the location of the opening is locally removed by anisotropic etching or the like to leave the light-transmitting film as the opening. The same applies when silicon is used for the upper substrate 10. Further, the control electrode 21 and the counter electrode 11 are made of chrome having a thickness of 200 nm and formed by a semiconductor technique represented by a lithography method. Silicon dioxide (SiO 2 ) was used for the insulating film 23 and was formed by CVD (Chemical Vapor Deposition). In this embodiment, silicon dioxide is used, but insulating materials such as parylene C, silicon nitride, and amorphous fluororesin (amorphous fluoropolymer) may be used.
 測定に先立ち,検体28と直径2 μmのラテックス粒子を含む試薬29をそれぞれ搬送デバイス100に導入し,制御電極21に電圧を印加し導入液体を制御し,デバイス内で検体28と試薬29を搬送・混合・反応させ,液滴30とした。次に,下部基板20と上部基板10の間に挟み,下部基板20に配置する制御用電極21に電圧を印加することで光源101、受光器102、スリット付き電極22を含む検出ユニット90まで液滴30を搬送した。 Prior to the measurement, the specimen 28 and the reagent 29 containing latex particles having a diameter of 2 μm are introduced into the transport device 100, the voltage is applied to the control electrode 21 to control the introduced liquid, and the specimen 28 and the reagent 29 are transported within the device. Mixing and reaction were performed to form droplets 30. Next, by sandwiching the voltage between the lower substrate 20 and the upper substrate 10 and applying a voltage to the control electrode 21 disposed on the lower substrate 20, the liquid up to the detection unit 90 including the light source 101, the light receiver 102, and the electrode 22 with the slit is obtained. Drop 30 was conveyed.
 図7は検出ユニット90と液体搬送デバイス100の位置関係を示す断面図である。検出ユニット90は,光源101,受光器102およびレンズ103によって構成させている。第2のスリット2およびスリット付き対向電極12を設けた上部基板10が受光器102側に配置され,さらに第1のスリット1およびスリット付き電極22を設けた下部基板20が光源101側に配置されている。また,光路設計では,液滴30を挟む2つの基板は光源101と受光器102の間に配置し、光源101からの光104はレンズ103で集光され,スリット付き電極22に設けた第1のスリット1を通過して液滴30に入射するようにした。さらに、液滴30を通過した光104がスリット付き対向電極12に設ける第2のスリット2を通り、レンズ103で集光されて受光器102に到達する。実際,図7に示す構成を用い,直径2 μmのラテックス粒子を含む検体28と試薬29を混合・撹拌してできた液体30の吸光度測定を実施した。測定の際、前記電圧制御部により、少なくとも液体30に光を照射している間はスリット付き電極22とスリット付き対向電極12の電極間に電圧を印加して液体30を固定することによって,液体30が不用意に移動せず,安定した測定が可能となった。なお,第1のスリット1および第2のスリット2は対をなしており,両方のスリット及びそれぞれを含むスリット付き電極22およびスリット付き電極12を複数設けてもよい。また、ここでは光源側に第1のスリット電極、受光器側に第2のスリット付き対向電極を設けた場合を示しているが、光源と受光器の位置は入れ替えても測定は可能である。 FIG. 7 is a cross-sectional view showing the positional relationship between the detection unit 90 and the liquid transport device 100. The detection unit 90 includes a light source 101, a light receiver 102, and a lens 103. The upper substrate 10 provided with the second slit 2 and the counter electrode 12 with slit is disposed on the light receiver 102 side, and the lower substrate 20 provided with the first slit 1 and the electrode 22 with slit is disposed on the light source 101 side. ing. In the optical path design, the two substrates sandwiching the droplet 30 are arranged between the light source 101 and the light receiver 102, and the light 104 from the light source 101 is collected by the lens 103 and is provided on the electrode 22 with the slit. It was made to enter the droplet 30 through the slit 1. Further, the light 104 that has passed through the droplet 30 passes through the second slit 2 provided in the counter electrode 12 with slit, and is condensed by the lens 103 and reaches the light receiver 102. Actually, using the configuration shown in FIG. 7, the absorbance of the liquid 30 obtained by mixing and stirring the specimen 28 containing latex particles having a diameter of 2 μm and the reagent 29 was measured. At the time of measurement, the voltage controller fixes the liquid 30 by applying a voltage between the electrode 22 with the slit and the counter electrode 12 with the slit at least while the liquid 30 is irradiated with light. 30 did not move carelessly, and stable measurement became possible. Note that the first slit 1 and the second slit 2 are paired, and a plurality of both the slit electrode 22 and the slit electrode 22 and the slit electrode 12 may be provided. Although the case where the first slit electrode is provided on the light source side and the second counter electrode with a slit is provided on the light receiver side is shown here, measurement is possible even if the positions of the light source and the light receiver are switched.
 本実施例では,スリット付き電極22は厚み200 nm,大きさ1.5 mm角の正方形で,隣り合う制御用電極21と同じにした。また,スリット付き電極22は搬送にも測定にも利用できるように,第1のスリット1のサイズをスリット付き電極22の面積の1/3にし,幅0.5 mm角の正方形にした。さらに,第2のスリット2の大きさを第1のスリット1と同じで0.5 mm角の正方形にした。スリットの形は正方形に限らず、長方形やその他の多角形、円形などでもよい。これにより搬送および測定の両方を実現できた。スリット付き電極22およびスリット付き対向電極12にはクロームを用いたが、アルミなど他の不透明な金属材料を用いてもよい。また、他の不透明な導電性材料を用いてもよい。また、スリットの付いていない電極については、基板上から液体の位置が見えるように透明な電極を用いてもよい。受光器側の基板に電極と一体化したスリットを設けることにより、散乱体を含む試料の吸光度を正確に測定できた。 In this embodiment, the electrode 22 with the slit is a square having a thickness of 200 nm and a size of 1.5 mm square, and is the same as the adjacent control electrode 21. In addition, the size of the first slit 1 is set to 1/3 of the area of the electrode 22 with a slit and a square with a width of 0.5 mm square so that the electrode 22 with the slit can be used for both conveyance and measurement. Further, the size of the second slit 2 is the same as that of the first slit 1 and is a square of 0.5 mm square. The shape of the slit is not limited to a square, but may be a rectangle, other polygons, or a circle. As a result, both conveyance and measurement were realized. Chrome is used for the electrode 22 with slit and the counter electrode 12 with slit, but other opaque metal materials such as aluminum may be used. Other opaque conductive materials may also be used. As for the electrode without a slit, a transparent electrode may be used so that the position of the liquid can be seen from the substrate. By providing a slit integrated with the electrode on the substrate on the light receiver side, the absorbance of the sample containing the scatterer could be accurately measured.
 搬送液体の微量化に伴うスリットサイズの縮小化により,機械的な組み立てによるスリットの位置合わせは困難となる。本実施例では,両側基板のスリットが幅0.1 mm角の正方形の場合において,スリット位置誤差を10 μm以下に抑えて調節するための位置合わせ機構について説明する。スリット付き電極22,第1のスリット1および第2のスリット2の大きさは上記と同じにした。 Alignment of the slits by mechanical assembly becomes difficult due to the reduction of the slit size due to the small amount of liquid transported. In this embodiment, a description will be given of an alignment mechanism for adjusting the slit position error to 10 μm or less when the slits on both substrates are 0.1 mm square square. The size of the electrode 22 with slits, the first slit 1 and the second slit 2 was the same as described above.
 本実施例の一つの形態を図8に示す。図8(A)に示すように,本実施例では,電極形成に用いる半導体プロセスで,第1のスリット1を含む下部基板20の任意の先端に,はめ込み口200を形成した。また同様の半導体プロセスで,第2のスリット2を含む上部基板10の任意の先端にもはめ込み口200を形成した。上下基板の第1のスリット1及び第2のスリット2からはめ込み口200までの距離XEを10 mmと同じにした。この条件を設定する一つの方法として,スリットの一辺を基準にし,そこから基板の任意の先端に向かって距離XE=10 mmをとり,その位置にはめ込み口200を形成する。はめ込み口を精度よく形成するため,ドライエッチングを用いたが、ウェットエッチングやダイシング等の半導体プロセスを用いてもよい。次に,図8(B)に示すように,はめ込み口200に合う形状を有するスペーサ201を両側の基板のはめ込み口にはめてスリットの位置を合わせた。これにより,2つの第1のスリット1および第2のスリット2のぞれぞれの縦中心線のズレで定義するスリット位置誤差ΔLを10 μm以下に抑えることができた。当該スペーサ201は隙間31を一定にする役割も担っている。 One form of this embodiment is shown in FIG. As shown in FIG. 8A, in this embodiment, the fitting opening 200 is formed at an arbitrary tip of the lower substrate 20 including the first slit 1 by a semiconductor process used for electrode formation. Further, the fitting opening 200 was formed at an arbitrary tip of the upper substrate 10 including the second slit 2 by the same semiconductor process. The distance XE from the first slit 1 and the second slit 2 of the upper and lower substrates to the insertion opening 200 was made the same as 10 mm. As one method for setting this condition, a distance XE = 10 mm is taken from one side of the slit to an arbitrary tip of the substrate, and a fitting port 200 is formed at that position. Although dry etching is used to form the insertion hole with high accuracy, a semiconductor process such as wet etching or dicing may be used. Next, as shown in FIG. 8B, a spacer 201 having a shape that fits into the fitting opening 200 was fitted into the fitting openings of the substrates on both sides, and the positions of the slits were adjusted. As a result, the slit position error ΔL defined by the shift of the vertical center line of each of the two first slits 1 and the second slit 2 can be suppressed to 10 μm or less. The spacer 201 also serves to make the gap 31 constant.
 このようにスリット位置誤差を低減する位置あわせ機構を設けることで光量を確保し、正確な吸光度測定を行うことができた。 In this way, by providing an alignment mechanism that reduces the slit position error, the amount of light was secured and accurate absorbance measurement could be performed.
 さらに,上下基板の位置あわせは段差を有するスペーサを用いてもよい。詳細を図9(A)~(C)に示す。本位置合わせ機構では,上部基板および下部基板の2辺を高精度に加工して位置合わせに用いた。今回、加工にはダイシングを用いたが,鑢等で基板を徐々に削ることで最終的に精度よく合わせてもよい。図9(A)に示すように,第2のスリット2およびスリット付き対向電極12を含む上部基板10の4つの辺のうち,当該基板の片端を構成する2つの辺306と307を高精度に加工した。すなわち,当該辺306および307の加工位置は,第2のスリット2を構成しかつ直交する2つの辺を基準に定めた距離XE,YEとなる位置にした。幅距離XE,YEはそれぞれ10 mmと5 mmにした。第2のスリット2の辺の代わりに,当該スリットの中心を通る横軸線305および縦軸線304を基準に加工してもよい。その場合,図9(A)に示す距離XC,YCの位置に,それぞれの距離に対応する辺306および辺307を加工すればよい。 Furthermore, a spacer having a step may be used for positioning the upper and lower substrates. Details are shown in FIGS. 9A to 9C. In this alignment mechanism, the two sides of the upper substrate and the lower substrate were processed with high accuracy and used for alignment. This time, dicing was used for processing, but the substrate may be gradually sharpened with a scissors or the like to finally match with accuracy. As shown in FIG. 9A, out of the four sides of the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit, the two sides 306 and 307 constituting one end of the substrate are accurately defined. processed. In other words, the processing positions of the sides 306 and 307 are set to positions where the distances XE and YE are determined with reference to two sides that form the second slit 2 and are orthogonal to each other. The width distances XE and YE were 10 mm and 5 mm respectively. Instead of the side of the second slit 2, the horizontal axis 305 and the vertical axis 304 passing through the center of the slit may be used as a reference. In that case, the sides 306 and 307 corresponding to the distances may be processed at the positions of the distances XC and YC shown in FIG.
 また,図9(B)に示す下部基板20に対しても,上部基板10の場合と同様の手順で,2辺308および309を加工した。ここでも,スリットの中心線を基準にしても良く,この場合は,図9(B)に示す距離XCおよび距離YCを基準に辺308および辺309を加工すればよい。 Also, the two sides 308 and 309 were processed for the lower substrate 20 shown in FIG. 9B by the same procedure as that for the upper substrate 10. Again, the center line of the slit may be used as a reference. In this case, the side 308 and the side 309 may be processed based on the distance XC and the distance YC shown in FIG.
 さらに,図9(C)に示すように,両側の基板の加工された2つの辺(例えば辺306および辺308)に接触してスペーサ310を設置することによって,上部基板10および下部基板20のそれぞれの2つの辺の位置が上下で一致し,第1のスリット1および第2のスリット2の位置合わせができる。スペーサ310は両側に設置し,基板間隔を一定にする役割を兼ねてもよい。このように端面を高精度に加工することで第1のスリット1と第2のスリット2の位置あわせを高精度にかつ簡易に実施し、正確な吸光度測定を行うことができた。 Furthermore, as shown in FIG. 9C, the spacers 310 are placed in contact with two processed sides (for example, the side 306 and the side 308) of the substrates on both sides, so that the upper substrate 10 and the lower substrate 20 are formed. The positions of the two sides coincide vertically, and the first slit 1 and the second slit 2 can be aligned. The spacers 310 may be installed on both sides to serve as a constant substrate interval. Thus, by processing the end face with high accuracy, the first slit 1 and the second slit 2 can be aligned with high accuracy and simply, and accurate absorbance measurement can be performed.
 また上下基板の位置あわせには位置決めマークを用いてもよい。詳細を図10(A)~(C)に示す。図10(A)は第2のスリット2,およびスリット付き対向電極12を含む上部基板10の平面図,図10(B)は第1のスリット1,スリット付き電極22,および制御電極21を含む下部基板の平面図を示す。図10(A)に示すように,上部基板10にスリット位置決めのため,2つ以上の位置合わせマークとして210および211を設け,同様に,下部基板20にも2つ以上の位置合わせマークとして212および213を設け,上部基板の位置合わせマークと対応させた。つまり,上部基板10および下部基板20のそれぞれの位置合わせマークが対をなしている(210→213,211→212)。位置合わせマークは,対向電極11または制御電極21と同様のプロセスで形成すれば良く電極の形成に用いられている一般的な半導体プロセス(ドライエッチング,ウェットエッチング等)で形成してもよい。縦方向と横方向が簡単に定められるため,ここでは位置合わせマークの形を十字形にしているが,他の形状(円形状,多角形状等)を用いてもよい。 Also, positioning marks may be used for positioning the upper and lower substrates. Details are shown in FIGS. 10 (A) to 10 (C). 10A is a plan view of the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit, and FIG. 10B includes the first slit 1, the electrode 22 with the slit, and the control electrode 21. The top view of a lower board | substrate is shown. As shown in FIG. 10A, 210 and 211 are provided as two or more alignment marks for positioning the slit in the upper substrate 10, and similarly, two or more alignment marks 212 are also provided in the lower substrate 20. And 213, which correspond to the alignment marks on the upper substrate. That is, the alignment marks of the upper substrate 10 and the lower substrate 20 form a pair (210 → 213, 211 → 212). The alignment mark may be formed by a process similar to that of the counter electrode 11 or the control electrode 21, and may be formed by a general semiconductor process (dry etching, wet etching, etc.) used for forming the electrode. Since the vertical direction and the horizontal direction are easily determined, the shape of the alignment mark is a cross shape here, but other shapes (circular shape, polygonal shape, etc.) may be used.
 次に,液滴30を含む液体搬送デバイスの断面図を図10(C)に示し,それを元に位置合わせの様子を説明する。図10(C)のように,第2のスリット2およびスリット付き対向電極12を含む上部基板10と,第1のスリット1,スリット付き電極22および制御電極21を含む下部基板20を向き合わせて配置した。その時,図10(C)の矢印214および214で示すように,対をなしている両基板のそれぞれの位置合わせマークが一直線上に配置するようにした。すなわち,上部基板の位置合わせマーク210と下部基板の位置合わせマーク212を合わせ,同様に,上部基板10の位置合わせマーク211とそれに対応する下部基板20の位置合わせマーク213を合わせた。位置合わせマークが小さい場合は顕微鏡等を利用して両基板の位置合わせマークを一致させてもよいが、通常,目視でも位置合わせができるように位置合わせマークを大きく形成すればよい。このように位置あわせマークを用いることで第1のスリット1と第2のスリット2の位置あわせを高精度にかつ簡易に実施し、正確な吸光度測定を行うことができた。 Next, FIG. 10C shows a cross-sectional view of the liquid transport device including the droplets 30, and the alignment will be described based on the cross-sectional view. As shown in FIG. 10C, the upper substrate 10 including the second slit 2 and the counter electrode 12 with the slit and the lower substrate 20 including the first slit 1, the electrode 22 with the slit, and the control electrode 21 are faced to each other. Arranged. At that time, as indicated by arrows 214 and 214 in FIG. 10C, the alignment marks of the paired substrates are arranged in a straight line. That is, the alignment mark 210 of the upper substrate and the alignment mark 212 of the lower substrate are aligned, and similarly, the alignment mark 211 of the upper substrate 10 and the alignment mark 213 of the lower substrate 20 corresponding thereto are aligned. If the alignment mark is small, the alignment marks on both substrates may be matched using a microscope or the like, but it is usually sufficient to form the alignment mark large so that the alignment can be made visually. By using the alignment mark as described above, the alignment of the first slit 1 and the second slit 2 can be easily performed with high accuracy, and accurate absorbance measurement can be performed.
1…第1のスリット,2…第2のスリット,10…上部基板,11…対向電極,12…スリット付き対向電極,20…下部基板,21…制御電極,22…スリット付き電極,23…絶縁膜,28…検体,29…試薬,30…液体,31…隙間,40…オイル,70…排出ユニット,71…シッパー,72…排出口,73…液タンク,80…導入ユニット,81…プローブ,82…導入口,90…検出ユニット,100…液体搬送デバイス,101…光源,102…受光器,103…レンズ,104…光,121…電源,122…配線,120…スイッチ,200…はめ込み口,201…スペーサ,210…位置合わせマーク,211…位置合わせマーク,212…位置合わせマーク,213…位置合わせマーク,214…矢印,304…縦軸線,305…横軸線,306…上部基板の辺,307…上部基板の辺,308…下部基板の辺,309…下部基板の辺,310…スペーサ DESCRIPTION OF SYMBOLS 1 ... 1st slit, 2 ... 2nd slit, 10 ... Upper substrate, 11 ... Counter electrode, 12 ... Counter electrode with slit, 20 ... Lower substrate, 21 ... Control electrode, 22 ... Electrode with slit, 23 ... Insulation Membrane, 28 ... specimen, 29 ... reagent, 30 ... liquid, 31 ... gap, 40 ... oil, 70 ... discharge unit, 71 ... sipper, 72 ... discharge port, 73 ... liquid tank, 80 ... introduction unit, 81 ... probe, DESCRIPTION OF SYMBOLS 82 ... Introduction port, 90 ... Detection unit, 100 ... Liquid conveyance device, 101 ... Light source, 102 ... Light receiver, 103 ... Lens, 104 ... Light, 121 ... Power supply, 122 ... Wiring, 120 ... Switch, 200 ... Insertion port, 201 ... spacer, 210 ... alignment mark, 211 ... alignment mark, 212 ... alignment mark, 213 ... alignment mark, 214 ... arrow, 304 ... vertical axis , 305 ... horizontal axis, 306 ... of the upper substrate side, 307 ... of the upper substrate side, 308 ... of the lower substrate side, 309 ... of the lower substrate side, 310 ... spacer

Claims (10)

  1.  第1の基板と、
     前記第1の基板に設けられ、複数の制御電極と、
     前記複数の制御電極の少なくとも1つに設けられた第1のスリットと、
     前記第1の基板と一定の隙間を形成して配置される第2の基板と、
     前記第2の基板上に設けられた対向電極と、
     前記第1のスリットと少なくとも一部が対面するように前記対向電極に設けられた第2のスリットと、
     前記複数の制御電極それぞれと前記対向電極との間の電圧を制御することにより、前記第1の基板と第2の基板との間に配置される液体の搬送を制御する電圧制御部と、
     光源と、
     前記光源から出射され、前記第1のスリット及び第2のスリットを通過した光を検出する受光器とを有することを特徴とする液体分析装置。
    A first substrate;
    A plurality of control electrodes provided on the first substrate;
    A first slit provided in at least one of the plurality of control electrodes;
    A second substrate disposed with a certain gap from the first substrate;
    A counter electrode provided on the second substrate;
    A second slit provided in the counter electrode so that at least part of the first slit faces the first slit;
    A voltage control unit that controls transport of a liquid disposed between the first substrate and the second substrate by controlling a voltage between each of the plurality of control electrodes and the counter electrode;
    A light source;
    A liquid analyzer comprising: a light receiver that detects light emitted from the light source and passed through the first slit and the second slit.
  2.  前記第1のスリットを有する制御電極及び前記第2のスリットを有する前記対向電極は、前記光源からの光に対し不透明な導電性材料で形成されていることを特徴とする請求項1記載の液体分析装置。 2. The liquid according to claim 1, wherein the control electrode having the first slit and the counter electrode having the second slit are formed of a conductive material that is opaque to light from the light source. Analysis equipment.
  3.  前記電圧制御部は、前記光源から前記液体に光を照射して前記受光器で検出する間は、前記第1のスリットを有する制御電極と、前記第2のスリットを有する対向電極との間に電圧を印加することを特徴とする請求項1記載の液体分析装置。 While the voltage control unit irradiates the liquid with light from the light source and detects the light with the light receiver, the voltage control unit is provided between the control electrode having the first slit and the counter electrode having the second slit. The liquid analyzer according to claim 1, wherein a voltage is applied.
  4.  前記第1のスリットと前記第2のスリットの位置を合わせるための位置決め機構を備えたことを特徴とする請求項記載の液体分析装置。 The liquid analyzer according to claim 1, further comprising a positioning mechanism for aligning the positions of the first slit and the second slit.
  5.  前記位置決め機構は、前記第1の基板の片端又は両端に設けた第1のはめ込み口と、前記第2の基板の片端又は両端に設けた第2のはめ込み口であることを特徴とする請求項4記載の液体分析装置。 The positioning mechanism includes a first insertion port provided at one or both ends of the first substrate and a second insertion port provided at one or both ends of the second substrate. 4. The liquid analyzer according to 4.
  6.  前記第1のスリットから前記第1のはめ込み口までの距離と,前記第2のスリットから前記第2のはめ込み口までの距離が等しいことを特徴とする請求項5記載の液体分析装置。 6. The liquid analyzer according to claim 5, wherein a distance from the first slit to the first insertion port is equal to a distance from the second slit to the second insertion port.
  7.  前記第1および第2のはめ込み口の加工位置は、前記第1および第2のスリットの一辺と、前記一辺とは異なる他辺を基準に加工されていることを特徴とする請求項5記載の液体分析装置。 6. The processing positions of the first and second insertion holes are processed on the basis of one side of the first and second slits and another side different from the one side. Liquid analyzer.
  8.  前記第1および第2のはめ込み口の加工位置は、前記第1および第2のスリットの中心を基準に加工されていることを特徴とする請求項5記載の液体分析装置。 6. The liquid analyzer according to claim 5, wherein the processing positions of the first and second insertion ports are processed based on the centers of the first and second slits.
  9.  前記位置決め機構は、前記第1の基板と前記第2の基板のそれぞれに設けられた可視可能な位置合わせマークであることを特徴とする請求項4記載の液体分析装置。 5. The liquid analyzer according to claim 4, wherein the positioning mechanism is a visible alignment mark provided on each of the first substrate and the second substrate.
  10.  請求項1記載の液体分析装置であって、さらに、
     前記液体を供給する手段と、
     前記液体を供給する手段から、前記液体を第1,2の基板の間の隙間に導入する導入手段と、
     前記液体を、前記第1,2の基板の間の隙間から排出する排出する手段とを有することを特徴とする液体分析装置。
    The liquid analyzer according to claim 1, further comprising:
    Means for supplying the liquid;
    Introducing means for introducing the liquid into the gap between the first and second substrates from the means for supplying the liquid;
    And a means for discharging the liquid from a gap between the first and second substrates.
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