WO2006115079A1 - Thermal lens spectrum analysis system and thermal lens signal correction method - Google Patents

Thermal lens spectrum analysis system and thermal lens signal correction method Download PDF

Info

Publication number
WO2006115079A1
WO2006115079A1 PCT/JP2006/307889 JP2006307889W WO2006115079A1 WO 2006115079 A1 WO2006115079 A1 WO 2006115079A1 JP 2006307889 W JP2006307889 W JP 2006307889W WO 2006115079 A1 WO2006115079 A1 WO 2006115079A1
Authority
WO
WIPO (PCT)
Prior art keywords
light
thermal lens
intensity
excitation light
analysis system
Prior art date
Application number
PCT/JP2006/307889
Other languages
French (fr)
Japanese (ja)
Inventor
Jun Yamaguchi
Takashi Fukuzawa
Original Assignee
Nippon Sheet Glass Company, Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nippon Sheet Glass Company, Limited filed Critical Nippon Sheet Glass Company, Limited
Publication of WO2006115079A1 publication Critical patent/WO2006115079A1/en

Links

Classifications

    • 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
    • G01N21/171Systems in which incident light is modified in accordance with the properties of the material investigated with calorimetric detection, e.g. with thermal lens detection
    • 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
    • G01N21/171Systems in which incident light is modified in accordance with the properties of the material investigated with calorimetric detection, e.g. with thermal lens detection
    • G01N2021/1712Thermal lens, mirage effect

Definitions

  • the present invention relates to a thermal lens spectroscopic analysis system and a thermal lens signal correction method.
  • thermal lens spectroscopic system that uses a microchemical chip to mix, react, separate, extract, and detect liquid samples.
  • the thermal lens spectroscopic analysis system 100 has a plate-like member 1 2 0 with a flow path in which a sample in liquid is filled, and a plate-like member 1 with a flow path.
  • the liquid in the flow path of the plate-like member 1 2 0 with a flow path is connected to the optical fiber with a lens 1 0 0 and the optical fiber 1 0 0 with a lens that is disposed above the 2 0 and has a lens attached to the tip.
  • the optical fiber with lens 1 0 0 has a lens 1 0 2 and one end of the lens 1 0 2 is connected to the light source unit 1 1 0 and the other end is connected to the light source unit 1 1 0 1 and the optical fiber 1 1 0 1 is fixed to the optical fiber 1 1 0 1 via the ferrule 1 0 3 and force It consists of
  • the light source unit 1 1 0 is connected to the excitation light source 1 0 5 that outputs the excitation light and the excitation light source 1 0 5 and modulates the excitation light output from the excitation light source 1 0 5.
  • it is connected to the optical fiber 1 0 1 of the optical fiber 10 0 with a lens, and combines the excitation light output from the excitation light source 1 0 5 and the detection light output from the detection light source 1 0 6.
  • an optical multiplexer 1 0 8 for making these pumping light and detection light incident on the optical fiber 1 0 1 enter, respectively.
  • the plate-like member with a channel 1 2 0 is composed of an upper glass substrate 2 0 1, a middle glass substrate 2 0 2, and a lower glass substrate 2 which are laminated and adhered in three layers in order from the optical fiber 1 0 0 with lens. 0 consists of three.
  • the middle glass substrate 20 2 which is the middle layer of the plate-like member 1 2 0 with a flow path, is mixed with a sample in liquid, stirred, synthesized, separated, extracted by a thermal lens spectroscopic analysis system 1 0 0 0 And a flow path 20 4 through which the sample in the liquid flows during operation such as detection.
  • the detection device 1 30 is located at a position facing the flow path 20 4 of the plate-like member 1 2 0 with flow path with a predetermined interval and facing the optical fiber with lens 1 100.
  • a wavelength filter 4 0 2 that separates the combined excitation light and detection light and selectively transmits only the detection light, and a channel 2 0 4 below the wavelength filter 1 4 0 2.
  • a computer connected to the photoelectric converter 4 0 1 via a plug-in amplifier 4 0 4 for detecting the detection light disposed at a position facing the 2 4 0 5 and force (for example, see Japanese Laid-Open Patent Publication No. 2 0 2-3 6 5 2 52).
  • the excitation light and detection light output from the excitation light source 1 0 5 and detection light source 1 0 6 are affected by changes in the external environment such as temperature change.
  • Lens 1 0 2 due to changes in the amount of light, changes in the loss of optical multiplexer 10 0 8, expansion of the stage (not shown) on which thermal lens spectroscopic analysis system 1 0 0 0 is mounted, etc. Misalignment between the lens and the plate-like member with flow path 120 and misalignment between the lens 10 0 2 and the photoelectric converter 4 0 1 occurred.
  • the amount of excitation light incident on the sample in the liquid in the flow path 20 4 to form a thermal lens changes, or the amount of detection light incident on the photoelectric converter 4 0 1 changes.
  • the thermal lens spectroscopic method executed by the thermal lens spectroscopic analysis system 100 is usually an analog measurement, the excitation light incident on the liquid sample in the channel 20 4 described above is used.
  • the change in the amount of light and the change in the amount of the detection light incident on the photoelectric converter 4 0 1 appear as a change in the intensity of the thermal lens signal finally measured, and the reproducibility in the measurement of the thermal lens signal intensity is reduced. It was.
  • thermo lens spectroscopic analysis system 10 00 In order to improve the reproducibility of thermal lens signal intensity measurement, electronic components such as Peltier elements are added to the light source unit 110 to control the temperature, and the measurement environment of the thermal lens spectroscopic analysis system 10 00 is controlled. It may be possible to remove changes in the external environment such as temperature changes that are the root cause of the decrease in reproducibility in thermal lens signal intensity measurement by strictly controlling the temperature, but in this case, electronic components such as Peltier elements There are problems such as increasing the size and cost of the thermal lens spectroscopic analysis system due to the addition of 100, and lack of versatility in the measurement environment.
  • the thermal lens signal is changed in accordance with the change in the amount of excitation light incident on the sample in the liquid in the channel 20 4 and the change in the amount of detection light incident on the photoelectric converter 4 0 1. It may be considered to correct the intensity.
  • a radiant heat sensor that corrects the amount of laser light measured by using two photosensitive detectors (for example, US Pat. No. 5,51,13). 0 0 6).
  • the light can be branched by a filter installed in the middle of the optical path. The amount of light can be easily corrected.
  • branch modules that split light in the visible region are often susceptible to temperature changes and the light branch ratio varies. Therefore, in the branch light detection for correcting the thermal lens signal intensity, it is possible to distinguish whether the change in the light branch ratio is detected or the change in the light amount of the excitation light and the detection light is detected. I can't.
  • the thermal lens spectroscopic analysis system uses two types of light, excitation light and detection light, at least two detectors are required to detect the amount of excitation light and detection light.
  • the lens spectroscopic analysis system will become larger.
  • An object of the present invention is to provide a small thermal lens spectroscopic analysis system and a thermal lens signal correction method capable of accurately measuring a sample even if the thermal lens signal intensity changes due to a change in the external environment. It is in.
  • a chip having a groove into which a liquid sample is injected and excitation excited from a light source to the liquid sample via an optical transmission path are provided.
  • a thermal lens spectroscopic analysis system including an objective lens that collects light and detection light to generate a thermal lens signal, a light amount measurement unit that measures the light amount of the excitation light and the detection light, and the thermal lens signal
  • a thermal lens signal intensity measuring unit for measuring the intensity; a first ratio between the predetermined light amount of the excitation light and the measured light amount of the excitation light; and the predetermined light amount of the detection light and the measured detection light
  • a ratio calculation unit for calculating a second ratio with the light amount; and the measured thermal lens signal intensity, the first ratio, and the Z or the second ratio.
  • Thermal lens signal to correct the intensity of the thermal lens signal Intensity detecting correcting part and Bei Ru thermal lens spectrometry system is provided.
  • the light quantity measuring unit for measuring the light quantity of the d excitation light and the detection light comprises one detector force.
  • the light amount measuring unit for measuring the light amount of the eye U excitation light and the detection light, and the thermal lens signal intensity measuring unit for measuring the intensity of the thermal lens signal are one detector. It is preferable to consist of
  • the detector includes a light transmission filter in which an excitation light transmission filter that transmits only BU sti excitation light and a detection light transmission filter that transmits only the detection light are interchangeable, and the detector It is preferable to measure the amount of excitation light and detection light transmitted through the light transmission filter.
  • the intensity of the thermal lens signal based on the output value of the detector.
  • the output value of the detector is a current value. Is preferred.
  • the output value of the detector is preferably a voltage value.
  • an audio input terminal for measuring the voltage value is provided.
  • the optical transmission path is preferably one optical fiber.
  • the objective lens is preferably a rod lens.
  • the thermal lens signal is preferably obtained by high-speed Fourier transform processing.
  • the thermal lens signal generated by irradiating the liquid sample injected into the groove in the chip with excitation light and detection light is generated.
  • a thermal lens signal correction method for correcting a light quantity measurement step for measuring the light quantity of the excitation light and the detection light, a thermal lens signal intensity measurement step for measuring the intensity of the thermal lens signal, and a predetermined light quantity of the excitation light
  • a ratio calculating step for calculating a first ratio between the measured light amount of the excitation light and a second ratio between the predetermined light amount of the detected light and the measured light amount of the detected light
  • a thermal lens signal intensity detection correction step for correcting the intensity of the measured thermal lens signal by integrating the intensity of the thermal lens signal, the first ratio, and / or the second ratio.
  • Heat lens Correction method is provided. Brief Description of Drawings
  • FIG. 1 is a diagram schematically showing a configuration of a thermal lens spectroscopic analysis system according to an embodiment of the present invention.
  • FIG. 2 is a diagram schematically showing the configuration of the detection apparatus in FIG.
  • FIGS. 3A, B, and C are diagrams showing the relationship between the change in the light intensity of the excitation light and detection light and the change in the thermal lens signal intensity in the thermal lens spectroscopic analysis system of FIG. 1, and FIG. 3A shows only the light intensity of the excitation light.
  • FIG. 3B is a diagram showing the relationship between the excitation light measurement intensity and the thermal lens signal intensity when only the light intensity of the detection light changes.
  • FIG. 3C is a diagram showing the relationship between the integrated value of the measured intensity of the excitation light and the detection light and the thermal lens signal intensity when the light intensity of the excitation light and the light intensity of the detection light change simultaneously. .
  • Fig. 4 is a diagram schematically showing the configuration of a conventional thermal lens spectroscopic analysis system. BEST MODE FOR CARRYING OUT THE INVENTION
  • FIG. 1 is a diagram schematically showing a configuration of a thermal lens spectroscopic analysis system according to an embodiment of the present invention.
  • the thermal lens spectroscopic analysis system 10 includes a microchemical chip 2 having a groove 1 into which a sample in liquid is poured, and a microchemical chip 2 above the groove 1 on the micro-mouth chemical chip 2.
  • a refractive index distribution type sensor such as a cylindrical self-lock (registered trademark) that is arranged at intervals and collects light propagating from an optical fiber 5 (described later) in a groove 1 to generate a thermal lens signal.
  • the ferrule 4 holding the eye bar 5, the sleeve 6 that fixes the gradient index rod lens 3 and the optical fiber 5 through the ferrule 4, and the optical fiber 1 5 are connected to the optical fiber 1.
  • a light source unit 7 irradiates the sample in liquid in the groove 1 of the chemical chip 2 with excitation light and irradiates detection light to the thermal lens generated in the sample in liquid by the irradiated excitation light, and a microphone.
  • the detection light is detected via the thermal lens generated in the sample in the liquid in the groove 1 of the microchemical chip 2 by the excitation light emitted from the light source unit 7 and placed under the chemical chip 2.
  • a detecting device 8 for performing the above operation is performed via the thermal lens generated in the sample in the liquid in the groove 1 of the microchemical chip 2 by the excitation light emitted from the light source unit 7 and placed under
  • the microchemical chip 2 has a groove 1 through which the sample in the liquid flows during operations such as mixing, stirring, synthesis, separation, extraction, and detection of the sample in the liquid by the thermal lens spectroscopic analysis system 10. is doing.
  • the material of the microchemical chip 2 is desirably glass from the viewpoint of durability and chemical resistance, and, in view of its use for biological samples such as cells, for example, DNA analysis, acid resistance, Glass having high alkali resistance, specifically, borosilicate glass, soda lime glass, aluminoborosilicate glass, and quartz glass are preferred.
  • biological samples such as cells, for example, DNA analysis, acid resistance, Glass having high alkali resistance, specifically, borosilicate glass, soda lime glass, aluminoborosilicate glass, and quartz glass are preferred.
  • organic substances such as plastic can be used by limiting the application.
  • the light source unit 7 is connected to the excitation light source 14 that outputs the excitation light, and the excitation light source 14 that is connected to the excitation light source 14, for example, emits excitation light having a wavelength of 6 58 nm, for example.
  • Modulator 15 that modulates to On and Off with a period of 1 kHz, for example, a detection light source 16 that outputs detection light with a wavelength of 785 nm, a pump light source 14 and
  • the excitation light source 1 and the detection light source 1 output from the excitation light source 1 4 connected to the detection light source 1 6 via optical fibers — 1 7 and 1 8, respectively, and connected to the optical fiber 1 5.
  • 6 includes a multiplexer 19 that multiplexes the detection light output from 6 and multiplexes the detection light and the detection light into the optical fiber 5.
  • the detection light output from 16 may be combined, and the excitation light and detection light combined in the optical fiber may be incident.
  • the detection device 8 is a position facing a transmission member 20 having a pinhole 20 a through which only a part of light is transmitted and a groove 1 of the microchemical chip 2 through a predetermined interval.
  • a filter 2 1 disposed at a position opposite to the optical fiber 1 and separating and selectively transmitting the combined excitation light and detection light;
  • a photoelectric converter (silicon diode) for detecting the amount of excitation light and detection light and the intensity of the thermal lens signal 2 2 (detector) )
  • PC personal computer
  • thermo lens signal intensity detection correction unit connected to the photoelectric converter 2 2 via an IV amplifier (current-voltage conversion amplifier) 2 3 and a voltmeter 2 4 Consists of.
  • FIG. 2 is a diagram schematically showing the configuration of the detection apparatus in FIG.
  • the filter 2 1 has a band width of 20 nm that transmits only excitation light with a wavelength of 6 58 nm, a diameter of 1 2.5 mm ( ⁇ and a band pass filter for excitation light of 3.0 and a wavelength of 7 8
  • 3 1, 3 1 Can be replaced by a left-right replacement method, a rotation method, a sampling method, or the like.
  • the measurement of the thermal lens signal intensity was performed in a state where the detection light bandpass filter 31 was placed at a position facing the pinhole 20 a formed in the transmission member 20 (FIG. 2). This is done by inputting the output signal of the IV amplifier 23 to the PC 25 via the voltmeter 24. Also to PC 2 5 The output signal is input via a DA converter (not shown) or an audio input terminal (not shown). The output signal input to PC 25 is subjected to high-speed Fourier transform (FFT) processing and detected as a thermal lens signal.
  • FFT high-speed Fourier transform
  • the amount of light absorbed by the detection target substance is measured via the thermal lens phenomenon, so the amount (concentration) of the substance cannot be calculated directly from the thermal lens signal alone. Therefore, by measuring the thermal lens signals of various sample solutions containing the detection target substance at various known concentrations, and using a calibration curve drawn based on the measured thermal lens signals, it is contained in the sample solution of unknown concentration. The concentration of the detection target substance will be calculated. In this case, since the concentration is determined by the ratio with the measurement result when the calibration curve is drawn, it is important to measure the thermal lens signal of the sample solution of unknown concentration under the same conditions as when the calibration curve is drawn. Become.
  • the amount of light output from the excitation light source and the detection light source changes due to the influence of changes in the external environment such as a temperature change, or the loss of the optical multiplexer 108 (in each of the excitation light and the detection light).
  • the ratio of the amount of light that is input to the multiplexer and the amount of light that is output) or the relative position of the lens 1002, the plate member 120, and the photoelectric converter 4001 The fluctuation of the thermal lens signal strength due to the.
  • the thermal lens signal intensity includes changes due to external fluctuation factors. It is not possible to obtain the correct concentration. Therefore, it is necessary to correct the thermal lens signal intensity changed due to the influence of external environmental changes to the value when measured under the conditions of the calibration curve.
  • FIG. 3A is a diagram showing the relationship between the change in the light intensity of the electromotive light and the detection light and the change in the thermal lens signal intensity.
  • FIG. 3A shows the relationship between the excitation light measurement intensity and the thermal lens signal intensity when only the excitation light intensity changes.
  • FIG. 3B is a diagram showing the relationship between the detected light measurement intensity and the thermal lens signal intensity when only the detection light quantity changes, and
  • FIG. 3C is the excitation light quantity and detection light.
  • FIG. 6 is a diagram showing the relationship between the integrated value of the measured intensity of excitation light and detection light and the thermal lens signal intensity when the amount of light changes simultaneously.
  • the vertical axis shows the thermal lens signal intensity (mV)
  • the horizontal axis shows the output of the IV amplifier 23 (the first IV output) (V), which represents the measured light intensity of the excitation light
  • the thermal lens signal The intensity (mV) is proportional to the first IV output (V).
  • the vertical axis shows the thermal lens signal intensity (mV)
  • the horizontal axis shows the output of the IV amplifier 23 (second IV output) (V), which represents the measured light intensity of the detected light.
  • the thermal lens signal strength (mV) is proportional to the second IV output (V). That is, when one of the excitation light and the detection light changes, the thermal lens signal intensity (mV) is proportional to the first or second IV output (V).
  • the measurement value of the excitation light used when drawing the calibration curve is 2.4 V
  • the measurement value of the excitation light when measuring a sample solution of unknown concentration is 2.2 V
  • the thermal lens signal intensity of the unknown sample solution is corrected to 3.4 mV in consideration of the change in the amount of excitation light.
  • 3.4 mV is the first ratio (measured light intensity of excitation light / measured light intensity of excitation light) to the measured value of thermal lens signal intensity in a sample solution of unknown concentration. That is, the value calculated from 3. IX (2.4 / 2.2).
  • the thermal lens signal intensity is corrected in the same way for changes in the amount of detection light.
  • the vertical axis shows the thermal lens signal intensity (mV)
  • the horizontal axis shows the integrated value of the first IV output (V) and the second IV output (V). It is proportional to the lens signal strength (mV). That is, when the amount of excitation light and detection light changes, the thermal lens signal intensity (mV) is proportional to the integrated value of the first I V output (V) and the second I V output (V).
  • the thermal lens signal intensity is proportional to the excitation light intensity or detection light intensity incident on the sample.
  • the light amounts of the excitation light and the detection light are changed at the same time, it has not been understood what relationship exists between the respective light amounts and the thermal lens signal intensity.
  • Fig. 3C it was found that the value obtained by multiplying the measured light intensity of the excitation light and the measured light intensity of the detection light is proportional to the thermal lens signal intensity.
  • the excitation light used when measuring a sample solution with an unknown concentration is 2.5 V
  • the detection light measurement value is 5.4 V
  • the detection light is 5.4 V.
  • the measured light intensity is 2.2 V
  • the detected light intensity is 4.8 V
  • the thermal lens signal intensity is 2.75 mV.
  • the intensity of the thermal lens of the sample solution of unknown concentration is corrected to 3.5 mV in consideration of the amount of change in the excitation light and detection light.
  • 3.5 mV is the first ratio (measured light intensity of the excitation light) and the ratio of the first to the measured value of the thermal lens signal intensity in the sample solution of unknown concentration and The value multiplied by the integrated value of the second ratio (predetermined light intensity measurement value of the detection light and measurement light intensity measurement value of the detection light), that is, 2.75 x (2.5 no 2.2) x (5.4 / 4.8) This is a calculated value.
  • the amount of excitation light and detection light when measuring a sample of unknown concentration (measurement light amount)
  • predetermined light amount the light amount when measuring the force calibration curve
  • the measured value of the thermal lens signal intensity, the first ratio (predetermined light amount of excitation light Z, measured light amount of excitation light), and the second ratio (predetermined light amount of detection light, measurement of detection light) Since the measured value of the thermal lens signal intensity is corrected by integrating the (light quantity), the sample can be accurately measured even if the thermal lens signal intensity changes due to changes in the external environment.
  • the light quantity measurement of the excitation light and the detection light and the measurement of the thermal lens signal are performed by one photoelectric converter 2 2 (detector). Only one detector is required, and the thermal lens spectroscopic analysis system 10 can be simplified and miniaturized.
  • the thermal lens spectroscopic analysis system 10 can be simplified and miniaturized, since changes in the amount of excitation light and detection light are measured after the excitation light and detection light have passed through the sample, there is no need to place a measurement optical system in the middle of the optical fiber that is the optical transmission path, and heat
  • the lens spectroscopic analysis system 10 can be simplified and miniaturized, and the change in the light amount of the excitation light and detection light can be accurately measured.
  • the light quantity measurement of the excitation light and the detection light is performed by using the bandpass filters 30 and 31 that allow only one of the lights to pass through. Correction can be made only by adding a mechanism that replaces the two filters to the detection device 8 used in the 10 so that the thermal lens spectroscopic analysis system 10 can be simplified and downsized.
  • band-pass fino-letters 3 0 and 3 1 were used as the filter to be used. Moyore.
  • the gradient index rod lens 3 is arranged above the groove 1 on the microchemical chip 2 with a predetermined interval, but the present invention is not limited to this. It may be placed on the microchemical chip 2 or may be adhered on the microchemical chip 2.
  • the output voltage value of the IV amplifier 23 is read by the voltmeter 24.
  • the present invention is not limited to this, and the voltage is measured by measuring the input value to the audio input terminal. The value may be measured. This eliminates the need to install the voltmeter 2 4 between the I V amplifier 2 3 and the PC 2 5.
  • the transmissive member 20 is provided.
  • the present invention is not limited to this, and the transmissive member 20 may not be provided.
  • the intensity of the measured thermal lens signal, the predetermined amount of excitation light, and the measured excitation Correct the intensity of the measured thermal lens signal by integrating the first ratio with the light intensity and the second ratio between the predetermined detection light intensity and the measured detection light intensity. Therefore, the sample can be accurately measured even if the heat lens signal intensity changes due to external environmental changes.
  • the amount of excitation light and the amount of detection light used to correct the intensity of the measured thermal lens signal are measured by a single detector.
  • the thermal lens spectroscopic analysis system can be miniaturized.
  • the intensity of the thermal lens signal is measured by one detector in addition to the light amount of the excitation light and the light amount of the detection light. The structure can be made simpler and smaller.
  • the mechanism that measures the light amount of the excitation light and the light amount of the detection light by replacing the filter that transmits only the excitation light and the filter that transmits only the detection light.
  • the structure of the detector can be simplified and the thermal lens spectroscopic analysis system can be further miniaturized, and the change in the amount of excitation light and detection light can be reliably measured to reliably correct the thermal lens signal. can do.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials Using Thermal Means (AREA)

Abstract

There are provided a thermal lens spectrum analysis system and a thermal lens signal correction method capable of accurately measuring a sample even if the thermal lens signal intensity is changed by an external environment change. The thermal lens spectrum analysis system (10) includes: a micro chemical chip (2) having a groove (1) into which a sample-in-liquid has been introduced; a refractivity distribution type rod lens (3) for converging excitation light propagating from a light source unit (7) via an optical fiber (5) and detection light into the sample-in-liquid so as to generate a thermal lens signal; a photo-electric converter (22) for detecting the light quantity of the excitation light and the detection light and the thermal lens signal intensity; and a personal computer (25) for correcting the measurement value of the thermal lens signal intensity by accumulating the thermal lens signal intensity measurement values, (a predetermined light quantity of excitation light/a measured light quantity of excitation light), and/or a second radio (a predetermined light quantity of detection light/ a measured light quantity of detection light).

Description

明 細 書 熱レンズ分光分析システム及び熱レンズ信号補正方法  MEANS TO USE THERMAL LENS SPECTRUM ANALYSIS SYSTEM AND THERMAL LENS SIGNAL CORRECTION METHOD
技術分野 Technical field
本発明は、 熱レンズ分光分析システム及び熱レンズ信号捕正方法に関 する。 背景技術  The present invention relates to a thermal lens spectroscopic analysis system and a thermal lens signal correction method. Background art
従来から、 化学反応の高速化や微少量でめ反応、 オンサイ ト分析等の 観点から、 化学反応を微小空間で行うための集積化技術が注目 されてお り、 そのため研究が精力的に進められている。  Conventionally, integration technology for conducting chemical reactions in a minute space has attracted attention from the viewpoints of speeding up chemical reactions, reaction in small amounts, on-site analysis, etc. ing.
このよ うな集積化技術の 1つと して、 マイ ク ロ化学チップを用いて、 液体試料の混合、 反応、 分離、 抽出、 検出等を行う熱レンズ分光分析シ ステムがある。  One such integration technology is a thermal lens spectroscopic system that uses a microchemical chip to mix, react, separate, extract, and detect liquid samples.
例えば、 図 4 に示すよ う に、 熱レンズ分光分析システム 1 0 0 0は、 流路内に液中試料が満たされた流路付き板状部材 1 2 0 と、 流路付き板 状部材 1 2 0 の上方に配設され、 先端にレンズを取り付けたレンズ付き 光ファイバ一 1 0 0 と、 レンズ付き光ファイバー 1 0 0 に接続され、 流 路付き板状部材 1 2 0の流路内の液中試料に励起光を照射する と共に、 当該照射された励起光によって液中試料に生成される熱レンズに検出光 を照射する光源ュニッ ト 1 1 0 と、 流路付き板状部材 1 2 0の下方に配 設され、 励起光によって流路付き板状部材 1 2 0の流路内の液中試料に 生成された熱レンズを介して検出光を検出する検出装置 1 3 0 と を備え る。  For example, as shown in FIG. 4, the thermal lens spectroscopic analysis system 100 has a plate-like member 1 2 0 with a flow path in which a sample in liquid is filled, and a plate-like member 1 with a flow path. The liquid in the flow path of the plate-like member 1 2 0 with a flow path is connected to the optical fiber with a lens 1 0 0 and the optical fiber 1 0 0 with a lens that is disposed above the 2 0 and has a lens attached to the tip. A light source unit 110 for irradiating a medium sample with excitation light and irradiating detection light to a thermal lens generated in the liquid sample by the irradiated excitation light; and a plate-like member with flow path 120 And a detection device 1300 which is arranged below and detects detection light via a thermal lens generated in the sample in liquid in the flow path of the plate-like member 120 with flow path by excitation light.
レンズ付き光ファ バ— 1 0 0は、 レンズ 1 0 2 と、 一端がレシズ 1 0 2 に接続され、 他端が光源ユニッ ト 1 1 0 に接続される光ファイバ一 1 0 1 と、 光ファイバ一 1 0 1 をフヱルール 1 0 3 を介して固定するス リーブ 1 0 4 と力 ら成る。 The optical fiber with lens 1 0 0 has a lens 1 0 2 and one end of the lens 1 0 2 is connected to the light source unit 1 1 0 and the other end is connected to the light source unit 1 1 0 1 and the optical fiber 1 1 0 1 is fixed to the optical fiber 1 1 0 1 via the ferrule 1 0 3 and force It consists of
光源ユニッ ト 1 1 0は、 励起光を出力する励起光用光源 1 0 5 と、 励 起光用光源 1 0 5 に接続され、 励起光用光源 1 0 5から出力される励起 光を変調するモジュ レーター 1 0 7 と、 検出光を出力する検出光用光源 1 0 6 と、 励起光用光源 1 0 5及び検出光用光源 1 0 6 に夫々光フアイ バー 1 1 4 を介して接続され、 且つレンズ付き光フアイバー 1 0 0 の光 ファイバ一 1 0 1 に接続され、 励起光用光源 1 0 5から出力される励起 光及び検出光光源 1 0 6から出力される検出光を合波して光ファイバ一 1 0 1 に合波したこれらの励起光及び検出光を夫々入射させる光合波器 1 0 8 とから成る。  The light source unit 1 1 0 is connected to the excitation light source 1 0 5 that outputs the excitation light and the excitation light source 1 0 5 and modulates the excitation light output from the excitation light source 1 0 5. A modulator 1 0 7, a detection light source 1 0 6 that outputs detection light, an excitation light source 1 0 5 and a detection light source 1 0 6 via optical fibers 1 1 4, respectively. In addition, it is connected to the optical fiber 1 0 1 of the optical fiber 10 0 with a lens, and combines the excitation light output from the excitation light source 1 0 5 and the detection light output from the detection light source 1 0 6. And an optical multiplexer 1 0 8 for making these pumping light and detection light incident on the optical fiber 1 0 1 enter, respectively.
流路付き板状部材 1 2 0 は、 レンズ付き光フ アイバー 1 0 0側から順 に 3層に重ねて接着された上部ガラス基板 2 0 1 、 中部ガラス基板 2 0 2、 及び下部ガラス基板 2 0 3から成る。 流路付き板状部材 1 2 0 の中 間層である中部ガラス基板 2 0 2 には、 熱レンズ分光分析システム 1 0 0 0 によ り液中試料の混合、 攪拌、 合成、 分離、 抽出、 及び検出等の操 作の際に液中試料を流す流路 2 0 4 を有する。  The plate-like member with a channel 1 2 0 is composed of an upper glass substrate 2 0 1, a middle glass substrate 2 0 2, and a lower glass substrate 2 which are laminated and adhered in three layers in order from the optical fiber 1 0 0 with lens. 0 consists of three. The middle glass substrate 20 2, which is the middle layer of the plate-like member 1 2 0 with a flow path, is mixed with a sample in liquid, stirred, synthesized, separated, extracted by a thermal lens spectroscopic analysis system 1 0 0 0 And a flow path 20 4 through which the sample in the liquid flows during operation such as detection.
検出装置 1 3 0 は、 流路付き板状部材 1 2 0の流路 2 0 4 に所定間隔 を介して面する位置であって、 レンズ付き光ファイバ一 1 0 0に対向す る位置に配設され、 合波された励起光及び検出光を分離して検出光のみ を選択的に透過させる波長フィルター 4 0 2 と、 波長フィルタ一 4 0 2 の下側であって、 流路 2 0 4 に所定間隔を介して面する位置に配設され た検出光を検出するための光電変換器 4 0 1 と 、 光電変換器 4 0 1 に口 ックイ ンアンプ 4 0 4 を介して接続されたコ ンピュータ 4 0 5 と力 ら成 る (例えば、 特開 2 0 0 2 — 3 6 5 2 5 2号公報参照) 。 この熱レンズ分光分析システム 1 0 0 0 において、 温度変化等の外部 環境変化の影響を受けて、 励起光用光源 1 0 5及び検出光用光源 1 0 6 から出力された励起光及び検出光の光量が変化したり、 光合波器 1 0 8 の損失が変化したり、 熱レンズ分光分析システム 1 0 0 0が載置された ステージ (不図示) の膨張等に起因して、 レンズ 1 0 2 と流路付き板状 部材 1 2 0 と の位置ずれやレンズ 1 0 2 と光電変換器 4 0 1 と の位置ず れが発生したり していた。 The detection device 1 30 is located at a position facing the flow path 20 4 of the plate-like member 1 2 0 with flow path with a predetermined interval and facing the optical fiber with lens 1 100. A wavelength filter 4 0 2 that separates the combined excitation light and detection light and selectively transmits only the detection light, and a channel 2 0 4 below the wavelength filter 1 4 0 2. And a computer connected to the photoelectric converter 4 0 1 via a plug-in amplifier 4 0 4 for detecting the detection light disposed at a position facing the 2 4 0 5 and force (for example, see Japanese Laid-Open Patent Publication No. 2 0 2-3 6 5 2 52). In this thermal lens spectroscopic analysis system 1 0 0 0, the excitation light and detection light output from the excitation light source 1 0 5 and detection light source 1 0 6 are affected by changes in the external environment such as temperature change. Lens 1 0 2 due to changes in the amount of light, changes in the loss of optical multiplexer 10 0 8, expansion of the stage (not shown) on which thermal lens spectroscopic analysis system 1 0 0 0 is mounted, etc. Misalignment between the lens and the plate-like member with flow path 120 and misalignment between the lens 10 0 2 and the photoelectric converter 4 0 1 occurred.
これにより、 熱レンズを形成するために流路 2 0 4内の液中試料に入 射される励起光の光量が変化したり、 光電変換器 4 0 1 に入射される検 出光の光量が変化したりすることがある。  As a result, the amount of excitation light incident on the sample in the liquid in the flow path 20 4 to form a thermal lens changes, or the amount of detection light incident on the photoelectric converter 4 0 1 changes. Sometimes.
また、 熱レンズ分光分析システム 1 0 0 0によって実行される熱レン ズ分光分析法は、 通常、 アナログ測定であるので、 上述した流路 2 0 4 内の液中試料に入射される励起光の光量変化及び光電変換器 4 0 1に入 射される検出光の光量変化は、 最終的に測定される熱レンズ信号の強度 変化となって表れ、 熱レンズ信号強度測定における再現性が低下してい た。  In addition, since the thermal lens spectroscopic method executed by the thermal lens spectroscopic analysis system 100 is usually an analog measurement, the excitation light incident on the liquid sample in the channel 20 4 described above is used. The change in the amount of light and the change in the amount of the detection light incident on the photoelectric converter 4 0 1 appear as a change in the intensity of the thermal lens signal finally measured, and the reproducibility in the measurement of the thermal lens signal intensity is reduced. It was.
熱レンズ信号強度測定における再現性を高めるために、 光源ュニッ ト 1 1 0にペルチェ素子等の電子部品を付加して温度を制御したり、 熱レ ンズ分光分析システム 1 0 0 0の測定環境を厳密に温度管理したりする ことにより、 熱レンズ信号強度測定における再現性低下の根本的な原因 である温度変化等の外部環境変化を取り除く ことが考えられるが、 この 場合、 ペルチェ素子等の電子部品の付加による熱レンズ分光分析システ ム 1 0 0 0の大型化及びコス ト増大や、 測定環境の汎用性欠如等の問題 力 ある。  In order to improve the reproducibility of thermal lens signal intensity measurement, electronic components such as Peltier elements are added to the light source unit 110 to control the temperature, and the measurement environment of the thermal lens spectroscopic analysis system 10 00 is controlled. It may be possible to remove changes in the external environment such as temperature changes that are the root cause of the decrease in reproducibility in thermal lens signal intensity measurement by strictly controlling the temperature, but in this case, electronic components such as Peltier elements There are problems such as increasing the size and cost of the thermal lens spectroscopic analysis system due to the addition of 100, and lack of versatility in the measurement environment.
よって、 流路 2 0 4内の液中試料に入射される励起光の光量変化及び 光電変換器 4 0 1 に入射される検出光の光量変化に応じて熱レンズ信号 強度 を補正す る こ と が 考 え ら れ る 。 既 に 、 2 つ の 感光検 出器 ( pho t o-s ens i t i v e d e t e c t or ) を用レヽて、 測定されたレーザー光の光量 を補正する輻射熱センサーが開示されている (例えば、 米国特許第 5 5 1 3 0 0 6号明細書参照) 。 この輻射熱センサーのよ う な光ファイバ一 を使用 しない空間光学系においては、 光路途中に設置したフ ィルタ一等 によ り光を分岐させるこ とができるので、 この分岐光の光量に基づいて レーザー光の光量を容易に補正するこ とができる。 Therefore, the thermal lens signal is changed in accordance with the change in the amount of excitation light incident on the sample in the liquid in the channel 20 4 and the change in the amount of detection light incident on the photoelectric converter 4 0 1. It may be considered to correct the intensity. There has already been disclosed a radiant heat sensor that corrects the amount of laser light measured by using two photosensitive detectors (for example, US Pat. No. 5,51,13). 0 0 6). In a spatial optical system that does not use an optical fiber, such as this radiant heat sensor, the light can be branched by a filter installed in the middle of the optical path. The amount of light can be easily corrected.
しかしながら、 光ファイバ一を使用する熱レンズ分光分析システムに おいては、 光が光ファイバ一内に閉じ込められているので、 光を分岐さ せるには特殊な分岐モジュールが必要となり、 分岐光を容易に検出する ことができない。 特に、 可視領域光を分岐する分岐モジュールは、 分岐 モジュール自体が温度変化の影響を受け易く 、 光の分岐比が変動してし ま う ものが多い。 よって、 熱レンズ信号強度を補正するための分岐光検 出において、 光の分岐比の変化分を検出しているのか、 励起光及び検出 光の光量変化を検出しているのかを区別するこ とができない。  However, in a thermal lens spectroscopic analysis system that uses an optical fiber, the light is confined within the optical fiber, so a special branch module is required to split the light, making branching easier. Cannot be detected. In particular, branch modules that split light in the visible region are often susceptible to temperature changes and the light branch ratio varies. Therefore, in the branch light detection for correcting the thermal lens signal intensity, it is possible to distinguish whether the change in the light branch ratio is detected or the change in the light amount of the excitation light and the detection light is detected. I can't.
また、 熱レンズ分光分析システムは、 励起光及び検出光の 2種の光を 用いているため、 励起光及び検出光の光量を検出するためには少なく と も 2つの検出器が必要となり 、 熱レンズ分光分析システムが大型化して しま う。  In addition, since the thermal lens spectroscopic analysis system uses two types of light, excitation light and detection light, at least two detectors are required to detect the amount of excitation light and detection light. The lens spectroscopic analysis system will become larger.
また、 光合波器 1 0 8の損失を補正するためには、 励起光及び検出光 が合波した後に光量を検出する必要があるが、 光ファイバ一内で合波し た励起光及び検出光を分離して検出するのは難しい。  In order to correct the loss of the optical multiplexer 108, it is necessary to detect the amount of light after the excitation light and the detection light are combined, but the excitation light and the detection light combined in the optical fiber. It is difficult to detect separately.
本発明の目的は、 外部環境変化によ り熱レンズ信号強度が変化しても 試料を正確に測定するこ とができる小型の熱レンズ分光分析システム及 び熱レンズ信号補正方法を提供するこ とにある。 ふ An object of the present invention is to provide a small thermal lens spectroscopic analysis system and a thermal lens signal correction method capable of accurately measuring a sample even if the thermal lens signal intensity changes due to a change in the external environment. It is in. F
発明の開示 Disclosure of the invention
上記目的を達成するために、 本発明の第 1 の態様によれば、 内部に液 体試料が注入された溝を有するチップと、 前記液体試料に光伝送経路を 介して光源から伝播された励起光及び検出光を集光して熱レンズ信号を 生成する対物レンズとを備える熱レンズ分光分析システムにおいて、 前 記励起光及び前記検出光の光量を測定する光量測定部と、 前記熱レンズ 信号の強度を測定する熱レンズ信号強度測定部と、 前記励起光の所定光 量と前記測定された励起光の光量との第 1 の比、 及び前記検出光の所定 光量と前記測定された検出光の光量との第 2の比を算出する比算出部と、 前記測定された熱レンズ信号の強度、 前記第 1 の比、 及び Z又は前記第 2の比を積算するこ とによ り前記測定された熱レンズ信号の強度を補正 する熱レンズ信号強度検出補正部とを備 る熱レンズ分光分析システム が提供される。  In order to achieve the above object, according to a first aspect of the present invention, a chip having a groove into which a liquid sample is injected and excitation excited from a light source to the liquid sample via an optical transmission path are provided. In a thermal lens spectroscopic analysis system including an objective lens that collects light and detection light to generate a thermal lens signal, a light amount measurement unit that measures the light amount of the excitation light and the detection light, and the thermal lens signal A thermal lens signal intensity measuring unit for measuring the intensity; a first ratio between the predetermined light amount of the excitation light and the measured light amount of the excitation light; and the predetermined light amount of the detection light and the measured detection light A ratio calculation unit for calculating a second ratio with the light amount; and the measured thermal lens signal intensity, the first ratio, and the Z or the second ratio. Thermal lens signal to correct the intensity of the thermal lens signal Intensity detecting correcting part and Bei Ru thermal lens spectrometry system is provided.
本発明の第 1 の態 において、 刖 d励起光及び前記検出光の光量を測 定する光量測定部は 1 つの検出器力 ら成るこ とが好ま しい。  In the first aspect of the present invention, it is preferable that the light quantity measuring unit for measuring the light quantity of the d excitation light and the detection light comprises one detector force.
本発明の第 1 の態 において、 目 U 励起光及び前記検出光の光量を測 定する光量測定部と 、 前記熱レンズ信号の強度を測定する熱レンズ信号 強度測定部とは、 1 つの検出器から成るこ とが好ま しい。  In the first aspect of the present invention, the light amount measuring unit for measuring the light amount of the eye U excitation light and the detection light, and the thermal lens signal intensity measuring unit for measuring the intensity of the thermal lens signal are one detector. It is preferable to consist of
本発明の第 1 の態 において、 BU sti励起光のみを透過する励起光透過 フィルター及び前記検出光のみを透過する検出光透過フィルターが入れ 替え可能に設置された光透過フィルターを備え、 前記検出器は前記光透 過フィルターを透過した励起光及び検出光の光量を測定するこ とが好ま しい  In the first aspect of the present invention, the detector includes a light transmission filter in which an excitation light transmission filter that transmits only BU sti excitation light and a detection light transmission filter that transmits only the detection light are interchangeable, and the detector It is preferable to measure the amount of excitation light and detection light transmitted through the light transmission filter.
本発明の第 1 の態様において、 前記検出器の出力値に基づいて前記熱 レンズ信号の強度を捕正するこ とが好ま しい。  In the first aspect of the present invention, it is preferable to correct the intensity of the thermal lens signal based on the output value of the detector.
本発明の第 1 の態様において、 前記検出器の出力値は電流値であるこ とが好ま しい。 In the first aspect of the present invention, the output value of the detector is a current value. Is preferred.
本発明の第 1 の態様において、 前記検出器の出力値は電圧値であるこ とが好ま しい。  In the first aspect of the present invention, the output value of the detector is preferably a voltage value.
本発明の第 1 の態様において、 前記電圧値を測定する音声入力端子を 備えるこ とが好ま しい。  In the first aspect of the present invention, it is preferable that an audio input terminal for measuring the voltage value is provided.
本発明の第 1 の態様において、 前記光伝送経路は光ファイバ一である ことが好ま しい。  In the first aspect of the present invention, the optical transmission path is preferably one optical fiber.
本発明の第 1 の態様において、 前記対物レンズはロ ッ ドレンズである ことが好ま しい。  In the first aspect of the present invention, the objective lens is preferably a rod lens.
本発明の第 1 の態様において、 前記熱レンズ信号は高速フ一リ エ変換 処理によって得られるこ とが好ま しい。  In the first aspect of the present invention, the thermal lens signal is preferably obtained by high-speed Fourier transform processing.
上記目的を達成するために、 本発明の第 2の態様によれば、 チップに おける溝内部に注入された液体試料に励起光及び検出光を照射するこ と によ り生成した熱レンズ信号を補正する熱レンズ信号補正方法において、 前記励起光及び前記検出光の光量を測定する光量測定ステクプと、 前記 熱レンズ信号の強度を測定する熱レンズ信号強度測定ステ クプと、 前記 励起光の所定光量と前記測定された励起光の光量との第 1 の比、 及び前 記検出光の所定光量と前記測定された検出光の光量との第 2の比を算出 する比算出ステップと、 前記測定された熱レンズ信号の強度 、 前記第 1 の比、 及び 又は前記第 2の比を積算するこ とによ り前記測定された熱 レンズ信号の強度を補正する熱レンズ信号強度検出補正ステップとを備 える熱レンズ信号補正方法が提供される。 図面の簡単な説明  In order to achieve the above object, according to the second aspect of the present invention, the thermal lens signal generated by irradiating the liquid sample injected into the groove in the chip with excitation light and detection light is generated. In the thermal lens signal correction method for correcting, a light quantity measurement step for measuring the light quantity of the excitation light and the detection light, a thermal lens signal intensity measurement step for measuring the intensity of the thermal lens signal, and a predetermined light quantity of the excitation light And a ratio calculating step for calculating a first ratio between the measured light amount of the excitation light and a second ratio between the predetermined light amount of the detected light and the measured light amount of the detected light; and A thermal lens signal intensity detection correction step for correcting the intensity of the measured thermal lens signal by integrating the intensity of the thermal lens signal, the first ratio, and / or the second ratio. Heat lens Correction method is provided. Brief Description of Drawings
図 1 は、 本発明の実施の形態に係る熱レンズ分光分析システムの構成 を概略的に示す図である。 図 2 は、 図 1 における検出装置の構成を概略的に示す図である。 FIG. 1 is a diagram schematically showing a configuration of a thermal lens spectroscopic analysis system according to an embodiment of the present invention. FIG. 2 is a diagram schematically showing the configuration of the detection apparatus in FIG.
図 3 A , B , Cは、 図 1 の熱レンズ分光分析システムにおける励起光 及び検出光の光量変化と熱レンズ信号強度変化との関係を示す図であり 、 図 3 Aは励起光の光量のみが変化した場合における励起光測定強度と熱 レンズ信号強度との関係を示す図であり 、 図 3 Bは検出光の光量のみが 変化した場合における検出光測定強度と熱レンズ信号強度との関係を示 す図であり、 図 3 Cは励起光の光量及ぴ検出光の光量が同時に変化した 場合における励起光及び検出光の測定強度の積算値と熱レンズ信号強度 との関係を示す図である。  3A, B, and C are diagrams showing the relationship between the change in the light intensity of the excitation light and detection light and the change in the thermal lens signal intensity in the thermal lens spectroscopic analysis system of FIG. 1, and FIG. 3A shows only the light intensity of the excitation light. FIG. 3B is a diagram showing the relationship between the excitation light measurement intensity and the thermal lens signal intensity when only the light intensity of the detection light changes. FIG. 3C is a diagram showing the relationship between the integrated value of the measured intensity of the excitation light and the detection light and the thermal lens signal intensity when the light intensity of the excitation light and the light intensity of the detection light change simultaneously. .
図 4 は、 従来の熱レンズ分光分析システムの構成を概略的に示す図で ある。 発明を実施するための最良の形態  Fig. 4 is a diagram schematically showing the configuration of a conventional thermal lens spectroscopic analysis system. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 本発明の実施の形態を図面を参照しながら詳説する。  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
図 1 は、 本発明の実施の形態に係る熱レンズ分光分析システムの構成 を概略的に示す図である。  FIG. 1 is a diagram schematically showing a configuration of a thermal lens spectroscopic analysis system according to an embodiment of the present invention.
図 1 において、 熱レンズ分光分析システム 1 0は、 中に液中試料が注 入された溝 1 を有するマイ ク ロ化学チップ 2 と、 溝 1 の上方においてマ イ ク 口化学チップ 2上に所定間隔を介して配設され、 後述する光フアイ バー 5から伝播された光を溝 1 に集光して熱レンズ信号を生成する円柱 状のセルフオ ック (登録商標) 等の屈折率分布型ロ ッ ドレンズ 3 と、 屈 折率分布型口 ッ ドレンズ 3 の上方に配設され、 屈折率分布型口 ッ ドレン ズ 3 に光を伝播する可視光用シングルモー ドの光ファイバ一 5 と、 光フ アイバー 5 を保持するフエルール 4 と、 屈折率分布型ロ ッ ドレンズ 3 を 固定する と共に光ファイバ一 5 をフエルール 4 を介して固定するス リ 一 ブ 6 と、 光ファイバ一 5 に接続され、 光ファイバ一 5 を介してマイ ク ロ 化学チップ 2の溝 1 内の液中試料に励起光を照射する と共に、 当該照射 された励起光によって液中試料に生成される熱レンズに検出光を照射す る光源ユニッ ト 7 と、 マイ ク ロ化学チップ 2 の下方に配設され、 光源ュ ニッ ト 7から照射された励起光によってマイ ク ロ化学チップ 2の溝 1 内 の液中試料に生成された熱レンズを介して検出光を検出する検出装置 8 とを備える。 In FIG. 1, the thermal lens spectroscopic analysis system 10 includes a microchemical chip 2 having a groove 1 into which a sample in liquid is poured, and a microchemical chip 2 above the groove 1 on the micro-mouth chemical chip 2. A refractive index distribution type sensor such as a cylindrical self-lock (registered trademark) that is arranged at intervals and collects light propagating from an optical fiber 5 (described later) in a groove 1 to generate a thermal lens signal. A single-mode optical fiber 5 for visible light that is disposed above the refractive index distribution type lens 3 and propagates light to the refractive index distribution type lens 3; The ferrule 4 holding the eye bar 5, the sleeve 6 that fixes the gradient index rod lens 3 and the optical fiber 5 through the ferrule 4, and the optical fiber 1 5 are connected to the optical fiber 1. 1 through 5 A light source unit 7 irradiates the sample in liquid in the groove 1 of the chemical chip 2 with excitation light and irradiates detection light to the thermal lens generated in the sample in liquid by the irradiated excitation light, and a microphone. The detection light is detected via the thermal lens generated in the sample in the liquid in the groove 1 of the microchemical chip 2 by the excitation light emitted from the light source unit 7 and placed under the chemical chip 2. And a detecting device 8 for performing the above operation.
マイ ク ロ化学チップ 2 は、 熱レンズ分光分析システム 1 0によ り液中 試料の混合、 攪拌、 合成、 分離、 抽出、 及び検出等の操作の際に液中試 料を流す溝 1 を有している。  The microchemical chip 2 has a groove 1 through which the sample in the liquid flows during operations such as mixing, stirring, synthesis, separation, extraction, and detection of the sample in the liquid by the thermal lens spectroscopic analysis system 10. is doing.
マイ ク ロ化学チップ 2の材料は耐久性、 耐薬品性の面からガラスが望 ま しく 、 ざちに、 細胞等の生体試料、 例えば D N A解析用と しての用途 を考慮する と、 耐酸性、 耐アルカ リ性の高いガラス、 具体的には、 硼珪 酸ガラス、 ソーダライムガラス、 アルミ ノ硼珪酸ガラス、 及び石英ガラ ス等が好ま しい。 しかし、 用途を限定するこ とによってプラスチック等 の有機物を用いること もできる。  The material of the microchemical chip 2 is desirably glass from the viewpoint of durability and chemical resistance, and, in view of its use for biological samples such as cells, for example, DNA analysis, acid resistance, Glass having high alkali resistance, specifically, borosilicate glass, soda lime glass, aluminoborosilicate glass, and quartz glass are preferred. However, organic substances such as plastic can be used by limiting the application.
光源ユニッ ト 7 は、 励起光を出力する励起光用光源 1 4 と、 励起光用 光源 1 4に接続され、 励起光用光源 1 4から出力される例えば波長 6 5 8 n mの励起光を例えば 1 k H z の周期で O n、 O f f するよ うに変調 する変調器 1 5 と、 例えば波長 7 8 5 n mの検出光を出力する検出光用 光源 1 6 と、 励起光用光源 1 4及び検出光用光源 1 6 に夫々光ファイバ — 1 7 , 1 8 を介して接続され、 且つ光ファイバ一 5 に接続された、 励 起光用光源 1 4から出力される励起光及び検出光光源 1 6から出力され る検出光を合波して光ファイバ一 5 に合波したこれらの励起光及び検出 光を夫々入射させる合波器 1 9 とから成る。  The light source unit 7 is connected to the excitation light source 14 that outputs the excitation light, and the excitation light source 14 that is connected to the excitation light source 14, for example, emits excitation light having a wavelength of 6 58 nm, for example. Modulator 15 that modulates to On and Off with a period of 1 kHz, for example, a detection light source 16 that outputs detection light with a wavelength of 785 nm, a pump light source 14 and The excitation light source 1 and the detection light source 1 output from the excitation light source 1 4 connected to the detection light source 1 6 via optical fibers — 1 7 and 1 8, respectively, and connected to the optical fiber 1 5. 6 includes a multiplexer 19 that multiplexes the detection light output from 6 and multiplexes the detection light and the detection light into the optical fiber 5.
光源ュニッ ト 7においては、 合波器 1 9 の代わり にダイ ク ロイ ツク ミ ラーを用いて励起光用光源 1 4から出力される励起光及び検出光用光源 1 6から出力される検出光を合波し、 光ファイバ一 5 に合波したこれら の励起光及び検出光を入射させてもよい。 In the light source unit 7, pump light and detection light source output from the pump light source 14 using a dichroic mirror instead of the multiplexer 19 The detection light output from 16 may be combined, and the excitation light and detection light combined in the optical fiber may be incident.
検出装置 8 は、 光の一部のみを透過させる ピンホール 2 0 aが形成さ れた透過部材 2 0 と、 マイ ク ロ化学チップ 2の溝 1 に所定間隔を介して 面する位置であって、 光ファイバ一 5に対向する位置に配設され、 合波 された励起光及び検出光を分離して選択的に透過させるフ ィルター 2 1 と、 フィルター 2 1 の下側であって、 溝 1 に所定間隔を介して面する位 置に配設され、 励起光及び検出光の光量及び熱レンズ信号強度を検出す るための光電変换器 (シリ コ ンフォ トダイ オー ド) 2 2 (検出器) と、 光電変換器 2 2 に I Vアンプ (電流一電圧変換アンプ) 2 3及び電圧計 2 4 を介して接続されたパーソナルコ ンピュータ ( P C ) 2 5 (熱レン ズ信号強度検出補正部) とから成る。 電圧計 2 4 は I Vアンプ 2 3 と P C 2 5 と の間に挿入してもよレ、 し、 独立して I Vアンプ 2 3 と接続して もよレ、。 この場合、 I Vアンプ 2 3 と P C 2 5は直接接続される。 光電 変換器 2 2から得られた信号は、次いで、 P C 2 5 において分析される。 図 2は、 図 1 における検出装置の構成を概略的に示す図である。  The detection device 8 is a position facing a transmission member 20 having a pinhole 20 a through which only a part of light is transmitted and a groove 1 of the microchemical chip 2 through a predetermined interval. A filter 2 1 disposed at a position opposite to the optical fiber 1 and separating and selectively transmitting the combined excitation light and detection light; A photoelectric converter (silicon diode) for detecting the amount of excitation light and detection light and the intensity of the thermal lens signal 2 2 (detector) ) And a personal computer (PC) 2 5 (thermal lens signal intensity detection correction unit) connected to the photoelectric converter 2 2 via an IV amplifier (current-voltage conversion amplifier) 2 3 and a voltmeter 2 4 Consists of. The voltmeter 2 4 can be inserted between the I V amplifier 2 3 and P C 2 5, or it can be connected to the I V amplifier 2 3 independently. In this case, the I V amplifier 2 3 and PC 25 are directly connected. The signal obtained from the photoelectric converter 22 is then analyzed at P C 25. FIG. 2 is a diagram schematically showing the configuration of the detection apparatus in FIG.
図 2において、 フィルター 2 1 は、 波長 6 5 8 n mの励起光のみを透 過するバン ド幅 2 0 n m、 直径 1 2. 5 m m (^の励起光用バン ドパスフ ィルター 3.0 と、 波長 7 8 5 n mの検出光のみを透過するバン ド幅 2 0 n m、 直径 1 2. 5 πιιη φの検出光用バン ドパスフィルター 3 1 とを備 え、 これらのバン ドパスフィルタ一 3 0 , 3 1 は、 左右入替方式、 回転 方式、 抜き取り方式等によって入れ替え可能な構成となっている。  In Fig. 2, the filter 2 1 has a band width of 20 nm that transmits only excitation light with a wavelength of 6 58 nm, a diameter of 1 2.5 mm (^ and a band pass filter for excitation light of 3.0 and a wavelength of 7 8 A bandpass filter 3 1 for detecting light with a band width of 20 nm that transmits only 5 nm of detection light and a diameter of 12.5 πιιηφ. 3 1, 3 1 Can be replaced by a left-right replacement method, a rotation method, a sampling method, or the like.
なお、 熱レンズ信号強度の測定は、 検出光用バン ドパスフ ィルタ一 3 1 が、 透過部材 2 0に形成されたピンホール 2 0 a に対向する位置に配 設された状態 (図 2 ) で、 I Vアンプ 2 3の出力信号を電圧計 2 4 を介 して P C 2 5に入力させるこ とによって行われる。 また、 P C 2 5への 出力信号の入力は D Aコンバーター (不図示) 又は音声入力端子 (不図 示) を介して行われる。 P C 2 5 に入力された出力信号は、 高速フ一リ ェ変換 ( F F T ) 処理が施されて熱レンズ信号と して検出される。 以下、 熱レンズ分光分析システム 1 0における励起光及び検出光の光 量変化と熱レンズ信号の強度変化との関係について説明する。 The measurement of the thermal lens signal intensity was performed in a state where the detection light bandpass filter 31 was placed at a position facing the pinhole 20 a formed in the transmission member 20 (FIG. 2). This is done by inputting the output signal of the IV amplifier 23 to the PC 25 via the voltmeter 24. Also to PC 2 5 The output signal is input via a DA converter (not shown) or an audio input terminal (not shown). The output signal input to PC 25 is subjected to high-speed Fourier transform (FFT) processing and detected as a thermal lens signal. Hereinafter, the relationship between the change in the light amount of the excitation light and the detection light and the change in the intensity of the thermal lens signal in the thermal lens spectroscopic analysis system 10 will be described.
熱レンズ分光分析法では検出対象物質が吸収した光の量を熱レンズ現 象を介して測定しているため、 熱レンズ信号のみから物質の量 (濃度) を直接計算することはできない。 そのため、 検出対象物質が種々の既知 濃度で含まれている種々の試料溶液の熱レンズ信号を測定し、 それに基 づいて引いた検量線を使用するこ とで、 未知濃度の試料溶液に含まれる 検出対象物質の濃度を計算するこ とになる。 この場合、 検量線を引いた ときの測定結果との比によって濃度を決定するため、 検量線を引いたと き と同じ条件で未知濃度の試料溶液の熱レンズ信号を測定するこ とが重 要となる。  In thermal lens spectroscopy, the amount of light absorbed by the detection target substance is measured via the thermal lens phenomenon, so the amount (concentration) of the substance cannot be calculated directly from the thermal lens signal alone. Therefore, by measuring the thermal lens signals of various sample solutions containing the detection target substance at various known concentrations, and using a calibration curve drawn based on the measured thermal lens signals, it is contained in the sample solution of unknown concentration. The concentration of the detection target substance will be calculated. In this case, since the concentration is determined by the ratio with the measurement result when the calibration curve is drawn, it is important to measure the thermal lens signal of the sample solution of unknown concentration under the same conditions as when the calibration curve is drawn. Become.
しかしながら、 温度変化等の外的環境変化の影響によ り 、 励起光光源 及び検出光光源から出力される光量が変化したり 、 光合波器 1 0 8の損 失 (励起光及び検出光それぞれにおいて、 合波器に入力する光量と出力 される光量の比) が変化した り 、 レンズ 1 0 2、 板状部材 1 2 0 、 及び 光電変換器 4 0 1 の相対位置がずれた りするこ と による熱レンズ信号強 度の変動が発生する。 このよ う な変動が発生し、 検量線を測定したとき と異なる条件で未知濃度の試料溶液を測定した場合、 熱レンズ信号強度 に外的変動要因による変化分が含まれて しま うため、 正確な濃度を得る ことができない。 よって、 外的環境変化の影響によって変化した熱レン ズ信号強度を、 検量線を測定した条件で測定した場合の値へ補正するこ とが必要となる。  However, the amount of light output from the excitation light source and the detection light source changes due to the influence of changes in the external environment such as a temperature change, or the loss of the optical multiplexer 108 (in each of the excitation light and the detection light). The ratio of the amount of light that is input to the multiplexer and the amount of light that is output) or the relative position of the lens 1002, the plate member 120, and the photoelectric converter 4001 The fluctuation of the thermal lens signal strength due to the. When such fluctuations occur and a sample solution with an unknown concentration is measured under conditions different from those when the calibration curve is measured, the thermal lens signal intensity includes changes due to external fluctuation factors. It is not possible to obtain the correct concentration. Therefore, it is necessary to correct the thermal lens signal intensity changed due to the influence of external environmental changes to the value when measured under the conditions of the calibration curve.
図 3 A , B , Cは'、 図 1 の熱レンズ分光分析システム 1 0 における励 起光及び検出光の光量変化と熱レンズ信号強度変化との関係を示す図で あり 、 図 3 Aは励起光の光量のみが変化した場合における励起光測定強 度と熱レンズ信号強度との関係を示す図であり、 図 3 Bは検出光の光量 のみが変化した場合における検出光測定強度と熱レンズ信号強度との関 係を示す図であり 、 図 3 Cは励起光の光量及び検出光の光量が同時に変 化した場合における励起光及び検出光の測定強度の積算値と熱レンズ信 号強度との関係を示す図である。 Fig. 3 A, B, and C 'are excitations in the thermal lens spectroscopic system 10 of Fig. 1. FIG. 3A is a diagram showing the relationship between the change in the light intensity of the electromotive light and the detection light and the change in the thermal lens signal intensity. FIG. 3A shows the relationship between the excitation light measurement intensity and the thermal lens signal intensity when only the excitation light intensity changes. FIG. 3B is a diagram showing the relationship between the detected light measurement intensity and the thermal lens signal intensity when only the detection light quantity changes, and FIG. 3C is the excitation light quantity and detection light. FIG. 6 is a diagram showing the relationship between the integrated value of the measured intensity of excitation light and detection light and the thermal lens signal intensity when the amount of light changes simultaneously.
図 3 Aにおいて、 縦軸は熱レンズ信号強度 (mV) を示し、 横軸は励起 光の測定光量を表す I Vアンプ 2 3の出力 (第 1 の I V出力) (V) を 示し、 熱レンズ信号強度 (mV) は第 1 の I V出力 (V) と比例する。 ま た、 図 3 Bにおいて、 縦軸は熱レンズ信号強度 (mV) を示し、 横軸は検 出光の測定光量を表す I Vアンプ 2 3の出力 (第 2の I V出力) (V) を示し、 熱レンズ信号強度 (mV) は第 2の I V出力 (V) と比例する。 即ち、 励起光及び検出光のう ちいずれか 1 つの光量が変化した場合、 熱 レンズ信号強度 ( m V) は第 1又は第 2の I V出力 ( V ) と比例する。 こ こで、 励起光又は検出光の光量が変化した場合の熱レンズ信号強度 の補正方法を説明する。 例えば、 検量線を引いたときに用いた励起光の 所定光量測定値が 2. 4 Vで、 未知濃度の試料溶液を測定したと きの励 起光の光量測定値が 2. 2 V、 熱レンズ信号強度が 3. l m Vであった とする。 この場合、 このままの熱レンズ信号強度で検量線に照ら し合わ すと、 得られる濃度は励起光の光量低下分だけ低い値となってしま う。 よって、 励起光の光量変化分に鑑み、 未知試料溶液の熱レンズ信号強度 を 3. 4 mVに補正する。 こ こで、 3. 4 mVは、 未知濃度の試料溶液で の熱レンズ信号強度の測定値に対して、 第 1 の比 (励起光の所定光量測 定値/励起光の測定光量測定値) を乗じた値、 即ち、 3. I X ( 2. 4 / 2. 2 ) よ り算出された値である。 検出光の光量変化についても同様の方法で、 熱レンズ信号強度を補正 する。 In Fig. 3A, the vertical axis shows the thermal lens signal intensity (mV), the horizontal axis shows the output of the IV amplifier 23 (the first IV output) (V), which represents the measured light intensity of the excitation light, and the thermal lens signal The intensity (mV) is proportional to the first IV output (V). In Fig. 3B, the vertical axis shows the thermal lens signal intensity (mV), and the horizontal axis shows the output of the IV amplifier 23 (second IV output) (V), which represents the measured light intensity of the detected light. The thermal lens signal strength (mV) is proportional to the second IV output (V). That is, when one of the excitation light and the detection light changes, the thermal lens signal intensity (mV) is proportional to the first or second IV output (V). Here, a method of correcting the thermal lens signal intensity when the amount of excitation light or detection light changes will be described. For example, the measurement value of the excitation light used when drawing the calibration curve is 2.4 V, the measurement value of the excitation light when measuring a sample solution of unknown concentration is 2.2 V, and heat Assume that the lens signal strength is 3. lm V. In this case, if the calibration curve is compared with the thermal lens signal intensity as it is, the concentration obtained will be as low as the amount of excitation light decreases. Therefore, the thermal lens signal intensity of the unknown sample solution is corrected to 3.4 mV in consideration of the change in the amount of excitation light. Here, 3.4 mV is the first ratio (measured light intensity of excitation light / measured light intensity of excitation light) to the measured value of thermal lens signal intensity in a sample solution of unknown concentration. That is, the value calculated from 3. IX (2.4 / 2.2). The thermal lens signal intensity is corrected in the same way for changes in the amount of detection light.
図 3 Cにおいて、 縦軸は熱レンズ信号強度 (mV) を示し、 横軸は第 1 の I V出力 (V) と第 2の I V出力 (V) の積算値を示すが、 この積算 値は熱レンズ信号強度 (mV) と比例している。 即ち、 励起光及び検出光 の光量が変化した場合、 熱レンズ信号強度 (mV) は第 1 の I V出力 ( V) と第 2 の I V出力 (V) の積算値と比例している。  In Fig. 3C, the vertical axis shows the thermal lens signal intensity (mV), and the horizontal axis shows the integrated value of the first IV output (V) and the second IV output (V). It is proportional to the lens signal strength (mV). That is, when the amount of excitation light and detection light changes, the thermal lens signal intensity (mV) is proportional to the integrated value of the first I V output (V) and the second I V output (V).
一般的に、 熱レンズ信号強度は試料に入射する励起光強度又は検出光 強度と比例することが知られている。 しかしながら、 励起光と検出光の 光量が同時に変化した場合、 それぞれの光量と熱レンズ信号強度との間 にどのよ うな関係があるかは分かっていなかった。 そこで検討を重ねた 結果、 図 3 Cで示したよ うに、 励起光の測定光量強度と検出光の測定光 量強度を乗じた値と熱レンズ信号強度が比例しているこ と を見出した。  In general, it is known that the thermal lens signal intensity is proportional to the excitation light intensity or detection light intensity incident on the sample. However, when the light amounts of the excitation light and the detection light are changed at the same time, it has not been understood what relationship exists between the respective light amounts and the thermal lens signal intensity. As a result of repeated studies, as shown in Fig. 3C, it was found that the value obtained by multiplying the measured light intensity of the excitation light and the measured light intensity of the detection light is proportional to the thermal lens signal intensity.
ここで励起光及び検出光の光量が同時に変化した場合の熱レンズ信号 強度の捕正方法を説明する。 例えば、 検量線を引いたときに用いた励起 光の所定光量測定値が 2. 5 V、 検出光の所定光量測定値が 5. 4 V、 未知濃度の試料溶液を測定したと きの励起光の光量測定値が 2. 2 V、 検出光の光量測定値が 4. 8 Vで熱レンズ信号強度が 2. 7 5 m Vであつ たとする。 この場合、 このままの熱レンズ信号強度で検量線に照ら し合 わすと、 得られる濃度は励起光及び検出光の光量低下分低い値となって しま う。 よって、 励起光及び検出光の光量変化分に鑑み、 未知濃度の試 料溶液の熱レンズ信号強度を 3. 5 mVへ補正する。 こ こで、 3. 5 mV は、 未知濃度の試料溶液での熱レンズ信号強度の測定値に対して、 第 1 の比 (励起光の所定光量測定値ノ励起光の測定光量測定値) 及び第 2の 比 (検出光の所定光量測定値 検出光の測定光量測定値) の積算値を乗 じた値、 即ち、 2. 7 5 X ( 2. 5ノ 2. 2 ) X ( 5 . 4 / 4. 8 ) よ り算出された値である。 Here, a method for correcting the thermal lens signal intensity when the light amounts of the excitation light and the detection light are simultaneously changed will be described. For example, the excitation light used when measuring a sample solution with an unknown concentration is 2.5 V, the detection light measurement value is 5.4 V, and the detection light is 5.4 V. Suppose that the measured light intensity is 2.2 V, the detected light intensity is 4.8 V, and the thermal lens signal intensity is 2.75 mV. In this case, if the calibration curve is compared with the thermal lens signal intensity as it is, the resulting concentration will be lower due to the decrease in the amount of excitation light and detection light. Therefore, the intensity of the thermal lens of the sample solution of unknown concentration is corrected to 3.5 mV in consideration of the amount of change in the excitation light and detection light. Here, 3.5 mV is the first ratio (measured light intensity of the excitation light) and the ratio of the first to the measured value of the thermal lens signal intensity in the sample solution of unknown concentration and The value multiplied by the integrated value of the second ratio (predetermined light intensity measurement value of the detection light and measurement light intensity measurement value of the detection light), that is, 2.75 x (2.5 no 2.2) x (5.4 / 4.8) This is a calculated value.
以上の説明では未知濃度の試料を測定したと きの励起光及.び検出光の 光量 (測定光量) 力 検量線を測定したと きの光量 (所定光量) よ り も 低く なった場合を説明したが、 測定光量が所定光量よ り も高く なった場 合も同じ式で同様に計算される。  In the above explanation, the amount of excitation light and detection light when measuring a sample of unknown concentration (measurement light amount) The case where the light amount when measuring the force calibration curve (predetermined light amount) is lower However, if the measured light intensity is higher than the predetermined light intensity, it is calculated in the same way using the same formula.
本実施の形態によれば、 熱レンズ信号強度の測定値、 第 1 の比 (励起 光の所定光量 Z励起光の測定光量) 、 及び第 2の比 (検出光の所定光量 ノ検出光の測定光量) を積算するこ とによ り熱レンズ信号強度の測定値 を補正するので、 外部環境変化によ り熱レンズ信号強度が変化しても試 料を正確に測定するこ とができる。  According to the present embodiment, the measured value of the thermal lens signal intensity, the first ratio (predetermined light amount of excitation light Z, measured light amount of excitation light), and the second ratio (predetermined light amount of detection light, measurement of detection light) Since the measured value of the thermal lens signal intensity is corrected by integrating the (light quantity), the sample can be accurately measured even if the thermal lens signal intensity changes due to changes in the external environment.
本実施の形態によれば、 励起光及び検出光の光量測定と熱レンズ信号 の測定を 1つの光電変換器 2 2 (検出器) にて行っているため、 熱レン ズ分光分析システム 1 0 に必要な検出器は 1 つだけとな り 、 熱レンズ分 光分析システム 1 0 を簡単にして小型化するこ とができる。 また、 励起 光及び検出光の光量変化を励起光及び検出光が試料を透過した後に測定 しているため、 光伝送経路である光ファイバ一の途中に測定光学系を入 れる必要がなく 、 熱レンズ分光分析システム 1 0 を簡単にして小型化す るこ とができる と共に、 正確に励起光及び検出光の光量変化を測定する ことができる。  According to the present embodiment, the light quantity measurement of the excitation light and the detection light and the measurement of the thermal lens signal are performed by one photoelectric converter 2 2 (detector). Only one detector is required, and the thermal lens spectroscopic analysis system 10 can be simplified and miniaturized. In addition, since changes in the amount of excitation light and detection light are measured after the excitation light and detection light have passed through the sample, there is no need to place a measurement optical system in the middle of the optical fiber that is the optical transmission path, and heat The lens spectroscopic analysis system 10 can be simplified and miniaturized, and the change in the light amount of the excitation light and detection light can be accurately measured.
本実施の形態によれば、 励起光及び検出光の光量測定をいずれか一方 の光のみが透過するバン ドパスフィルター 3 0 , 3 1 を用いるこ とで行 つているため、 熱レンズ分光分析システム 1 0 に用いられている検出装 置 8 に 2つのフィルターを入れ替える機構を付加するこ とのみで補正が 可能となるので、 熱レンズ分光分析システム 1 0 を簡単にして小型化す るこ とができ る。  According to the present embodiment, the light quantity measurement of the excitation light and the detection light is performed by using the bandpass filters 30 and 31 that allow only one of the lights to pass through. Correction can be made only by adding a mechanism that replaces the two filters to the detection device 8 used in the 10 so that the thermal lens spectroscopic analysis system 10 can be simplified and downsized. The
本実施の形態では、 励起光及び検出光のいずれか一方の光のみを透過 するフイノレターと してバン ドパス フイノレター 3 0, 3 1 を用いたが、 逆 に励起光及び検出光のいずれか一方の光のみを遮断するフィルターでも よく 、 ノ ッチフィルタ一、 エッジフィルタ一等を用いてもよレ、。 In this embodiment, only one of the excitation light and the detection light is transmitted. The band-pass fino-letters 3 0 and 3 1 were used as the filter to be used. Moyore.
本実施の形態では、 屈折率分布型ロ ッ ドレンズ 3が溝 1 の上方におい てマイ ク ロ化学チップ 2上に所定間隔を介して配設されているが、 これ に限定されるものではなく 、 マイ ク ロ化学チップ 2上に載置されていて もよ く 、 またマイ ク ロ化学チップ 2上に接着されていてもよい。  In the present embodiment, the gradient index rod lens 3 is arranged above the groove 1 on the microchemical chip 2 with a predetermined interval, but the present invention is not limited to this. It may be placed on the microchemical chip 2 or may be adhered on the microchemical chip 2.
本実施の形態では、 I Vアンプ 2 3の出力電圧値を電圧計 2 4 によ り 読み取っているが、 これに限定されるものではなく 、 音声入力端子への 入力値を測定する こ とによって電圧値を測定してもよい。 これによ り 、 電圧計 2 4 を I Vアンプ 2 3及び P C 2 5間に設置する必要をなくすこ とができる。  In this embodiment, the output voltage value of the IV amplifier 23 is read by the voltmeter 24. However, the present invention is not limited to this, and the voltage is measured by measuring the input value to the audio input terminal. The value may be measured. This eliminates the need to install the voltmeter 2 4 between the I V amplifier 2 3 and the PC 2 5.
本実施の形態では、 透過部材 2 0が設けられているが、 これに限定さ れるものではなく 、 透過部材 2 0が設けられていなく てもよい。 産業上の利用可能性  In the present embodiment, the transmissive member 20 is provided. However, the present invention is not limited to this, and the transmissive member 20 may not be provided. Industrial applicability
本発明の第 1 の態様の熱レンズ分光分析システム及び本発明の第 2の 態様の熱レンズ信号補正方法によれば、測定された熱レンズ信号の強度、 励起光の所定光量と測定された励起光の光量との第 1 の比、 検出光の所 定光量と測定された検出光の光量との第 2の比を積算するこ とによ り測 定された熱レンズ信号の強度を補正するので、 外部環境変化によ り熱レ ンズ信号強度が変化しても試料を正確に測定するこ とができる。  According to the thermal lens spectroscopic analysis system of the first aspect of the present invention and the thermal lens signal correction method of the second aspect of the present invention, the intensity of the measured thermal lens signal, the predetermined amount of excitation light, and the measured excitation Correct the intensity of the measured thermal lens signal by integrating the first ratio with the light intensity and the second ratio between the predetermined detection light intensity and the measured detection light intensity. Therefore, the sample can be accurately measured even if the heat lens signal intensity changes due to external environmental changes.
本発明の第 1 の態様の熱レンズ分光分析システムによれば、 測定され た熱レンズ信号の強度を補正するために用いる、 励起光の光量及び検出 光の光量を 1 つの検出器で測定するので、 熱レンズ分光分析システムを 小型化するこ とができる。 本発明の第 1 の態様の熱レンズ分光分析システムによれば、 励起光の 光量及び検出光の光量に加えて、 熱レンズ信号の強度を 1 つの検出器で 測定するので、 熱レンズ分光分析システムの構造を簡単にして、 よ り小 型化することができる。 According to the thermal lens spectroscopic analysis system of the first aspect of the present invention, the amount of excitation light and the amount of detection light used to correct the intensity of the measured thermal lens signal are measured by a single detector. The thermal lens spectroscopic analysis system can be miniaturized. According to the thermal lens spectroscopic analysis system of the first aspect of the present invention, the intensity of the thermal lens signal is measured by one detector in addition to the light amount of the excitation light and the light amount of the detection light. The structure can be made simpler and smaller.
本発明の第 1 の態様の熱レンズ分光分析システムによれば、 励起光の みを透過するフィルター及び検出光のみを透過するフィルターを入れ替 えて励起光の光量及び検出光の光量を測定する機構であるので、 検出器 の構造を簡単にして熱レンズ分光分析システムをさ らに小型化すること ができる と共に、 励起光及び検出光の光量変化を確実に測定して熱レン ズ信号を確実に補正するこ とができる。  According to the thermal lens spectroscopic analysis system of the first aspect of the present invention, the mechanism that measures the light amount of the excitation light and the light amount of the detection light by replacing the filter that transmits only the excitation light and the filter that transmits only the detection light. As a result, the structure of the detector can be simplified and the thermal lens spectroscopic analysis system can be further miniaturized, and the change in the amount of excitation light and detection light can be reliably measured to reliably correct the thermal lens signal. can do.

Claims

請 求 の 範 囲 The scope of the claims
1 . 内部に液体試料が注入された溝を有するチップと、 前記液体試料に 光伝送経路を介して光源から伝播された励起光及び検出光を集光して熱 レンズ信号を生成する対物レンズとを備える熱レンズ分光分析システム において、 前記励起光及び前記検出光の光量を測定する光量測定部と、 前記熱レンズ信号の強度を測定する熱レンズ信号強度測定部と、 前記励 起光の所定光量と前記測定された励起光の光量との第 1 の比、 及び前記 検出光の所定光量と前記測定された検出光の光量との第 2の比を算出す る比算出部と、 前記測定された熱レンズ信号の強度、 前記第 1 の比、 及 び 又は前記第 2 の比を積算するこ とによ り前記測定された熱レンズ信 号の強度を補正する熱レンズ信号強度検出補正部とを備えるこ とを特徴 とする熱レンズ分光分析システム。 1. a chip having a groove in which a liquid sample is injected, and an objective lens that collects excitation light and detection light propagated from a light source through an optical transmission path to the liquid sample to generate a thermal lens signal; A thermal lens spectroscopic analysis system comprising: a light quantity measuring unit that measures the light quantity of the excitation light and the detection light; a thermal lens signal intensity measuring part that measures the intensity of the thermal lens signal; and a predetermined light quantity of the excitation light. A ratio calculating unit that calculates a first ratio between the measured light amount of the excitation light and a second ratio between the predetermined light amount of the detected light and the measured light amount of the detected light; A thermal lens signal intensity detection correction unit that corrects the intensity of the measured thermal lens signal by integrating the intensity of the thermal lens signal, the first ratio, and / or the second ratio. Thermal lens component characterized by comprising Analysis system.
2 . 前記励起光及び前記検出光の光量を測定する光量測定部は 1 つの検 出器から成るこ とを特徴とする請求の範囲第 1項記載の熱レンズ分光分 析システム。  2. The thermal lens spectroscopic analysis system according to claim 1, wherein the light quantity measuring unit for measuring the quantity of the excitation light and the detection light comprises a single detector.
3 . 前記励起光及び前記検出光の光量を測定する光量測定部と、 前記熱 レンズ信号の強度を測定する熱レンズ信号強度測定部とは、 1 つの検出 器から成るこ と を特徴とする請求の範囲第 1項記載の熱レンズ分光分析 システム。  3. The light quantity measurement unit that measures the light quantity of the excitation light and the detection light and the thermal lens signal intensity measurement unit that measures the intensity of the thermal lens signal are composed of one detector. The thermal lens spectroscopic analysis system according to paragraph 1 of the above.
4 . 前記励起光のみを透過する励起光透過フィ ルタ一及び前記検出光の みを透過する検出光透過フィルターが入れ替え可能に設置された光透過 フィルタ一を備え、 前記検出器は前記光透過フィルタ一を透過した励起 光及び検出光の光量を測定するこ とを特徴とする請求の範囲第 2項記載 の熱レンズ分光分析システム。  4. An excitation light transmission filter that transmits only the excitation light and a detection light transmission filter that transmits only the detection light are arranged to be interchangeable, and the detector includes the light transmission filter. The thermal lens spectroscopic analysis system according to claim 2, characterized in that the amount of excitation light and detection light transmitted through one is measured.
5 . 前記検出器の出力値に基づいて前記熱レンズ信号の強度を補正する こ と を特徴とする請求の範囲第 2項記載の熱レンズ分光分析システム。5. Correct the intensity of the thermal lens signal based on the output value of the detector The thermal lens spectroscopic analysis system according to claim 2, characterized in that this is a feature.
6 . 前記検出器の出力値は電流値であるこ と を特徴とする請求の範囲第 5項記載の熱レンズ分光分析システム。 6. The thermal lens spectroscopic analysis system according to claim 5, wherein the output value of the detector is a current value.
7 . 前記検出器の出力値は電圧値であるこ とを特徵とする請求の範囲第 5項記載の熱レンズ分光分析システム。  7. The thermal lens spectroscopic analysis system according to claim 5, wherein the output value of the detector is a voltage value.
8 . 前記電圧値を測定する音声入力端子を備えるこ とを特徵とする請求 の範囲第 7項記載の熱レンズ分光分析システム。  8. The thermal lens spectroscopic analysis system according to claim 7, further comprising an audio input terminal for measuring the voltage value.
9 . 前記光伝送経路は光ファイバ一であるこ とを特徴とする請求の範囲 第 1 項記載の熱レンズ分光分析システム。  9. The thermal lens spectroscopic analysis system according to claim 1, wherein the optical transmission path is a single optical fiber.
1 0 . 前記対物レンズはロ ッ ドレンズであるこ と を特徴とする請求の範 囲第 1項記載の熱レンズ分光分析システム。  10. The thermal lens spectroscopic analysis system according to claim 1, wherein the objective lens is a rod lens.
1 1 . 前記熱レンズ信号は高速フーリ エ変換処理によって得られるこ と を特徴とする請求の範囲第 1 項記載の熱レンズ分光分析システム。 11. The thermal lens spectroscopic analysis system according to claim 1, wherein the thermal lens signal is obtained by a high-speed Fourier transform process.
1 2 . チップにおける溝内部に注入された液体試料に励起光及び検出光 を照射するこ とによ り生成した熱レンズ信号を補正する熱レンズ信号補 正方法において、 前記励起光及び前記検出光の光量を測定する光量測定 ステップと、 前記熱レンズ信号の強度を測定する熱レンズ信号強度測定 ステップと、 前記励起光の所定光量と前記測定された励起光の光量との 第 1 の比、 及び剪記検出光の所定光量と前記測定された検出光の光量と の第 2の比を算出する比算出ステップと、 前記測定された熱レンズ信号 の強度、 前記第 1 の比、 及び Z又は前記第 2の比を積算するこ とによ り 前記測定された熱レンズ信号の強度を補正する熱レンズ信号強度検出補 正ステップと を備えるこ と を特徴とする熱レンズ信号補正方法。 1 2. In a thermal lens signal correction method for correcting a thermal lens signal generated by irradiating a liquid sample injected into a groove in a chip with excitation light and detection light, the excitation light and the detection light A light amount measuring step for measuring the light amount of the thermal lens, a thermal lens signal intensity measuring step for measuring the intensity of the thermal lens signal, a first ratio between the predetermined light amount of the excitation light and the measured light amount of the excitation light, and A ratio calculating step of calculating a second ratio between the predetermined light quantity of the pruning detection light and the measured light quantity of the detected light; the intensity of the measured thermal lens signal; the first ratio; and Z or the A thermal lens signal correction method comprising: a thermal lens signal intensity detection correction step of correcting the intensity of the measured thermal lens signal by integrating the second ratio.
PCT/JP2006/307889 2005-04-20 2006-04-07 Thermal lens spectrum analysis system and thermal lens signal correction method WO2006115079A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005122678A JP4145892B2 (en) 2005-04-20 2005-04-20 Thermal lens spectroscopic analysis system and thermal lens signal correction method
JP2005-122678 2005-04-20

Publications (1)

Publication Number Publication Date
WO2006115079A1 true WO2006115079A1 (en) 2006-11-02

Family

ID=37214702

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/307889 WO2006115079A1 (en) 2005-04-20 2006-04-07 Thermal lens spectrum analysis system and thermal lens signal correction method

Country Status (2)

Country Link
JP (1) JP4145892B2 (en)
WO (1) WO2006115079A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8654323B2 (en) 2010-09-27 2014-02-18 Arkray, Inc. Analyzing apparatus
KR101280358B1 (en) 2011-11-28 2013-07-05 대한민국(국가기록원) Character evaluation apparatus of paper recorders materials
RU2659327C2 (en) * 2016-06-16 2018-06-29 Федеральное государственное автономное образовательное учреждение высшего образования "Национальный исследовательский технологический университет "МИСиС" Method of two-beam thermal lens measurements with simultaneous recording of transmission of test sample

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08507367A (en) * 1992-09-18 1996-08-06 フオルシユングスツエントルム カールスルーエ ゲゼルシヤフト ミツト ベシユレンクテル ハフツング Photo thermal sensor
JP2003130826A (en) * 2001-10-22 2003-05-08 Nippon Sheet Glass Co Ltd Method for photothermal spectroscopic analysis, and micro-chemical system
JP2003215034A (en) * 2002-01-29 2003-07-30 Nippon Sheet Glass Co Ltd Thermal lens type analyzer
JP2004257994A (en) * 2003-02-27 2004-09-16 Japan Nuclear Cycle Development Inst States Of Projects Thermal lens absorption spectrophotometer

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08507367A (en) * 1992-09-18 1996-08-06 フオルシユングスツエントルム カールスルーエ ゲゼルシヤフト ミツト ベシユレンクテル ハフツング Photo thermal sensor
JP2003130826A (en) * 2001-10-22 2003-05-08 Nippon Sheet Glass Co Ltd Method for photothermal spectroscopic analysis, and micro-chemical system
JP2003215034A (en) * 2002-01-29 2003-07-30 Nippon Sheet Glass Co Ltd Thermal lens type analyzer
JP2004257994A (en) * 2003-02-27 2004-09-16 Japan Nuclear Cycle Development Inst States Of Projects Thermal lens absorption spectrophotometer

Also Published As

Publication number Publication date
JP2006300721A (en) 2006-11-02
JP4145892B2 (en) 2008-09-03

Similar Documents

Publication Publication Date Title
US11041759B2 (en) Systems and methods for Raman spectroscopy
JP4353529B2 (en) Sensor, sensor device and data transmission processing device
NL2003743C2 (en) Method for detection of an analyte in a fluid sample.
US8077309B2 (en) Chemical analyzer for industrial process control
US7289207B2 (en) Integrated optical biosensor system (IOBS)
US10324034B2 (en) Self-referencing localized plasmon resonance sensing device and system thereof
EP2762858B1 (en) Integrated interferometric optical sensor circuit
JP2007155494A (en) Twin flow cell and concentration measuring system using it
JP5249777B2 (en) Method and apparatus for measuring fluorescence of a sample and use thereof
WO2006115079A1 (en) Thermal lens spectrum analysis system and thermal lens signal correction method
CN209784187U (en) Biosensor and method for measuring the same
JP4517079B2 (en) Slab optical waveguide spectral chemical sensor
Qi et al. Integrated switching circuit for low-noise self-referenced mid-infrared absorption sensing using silicon waveguides
JP4173725B2 (en) Sensors using evanescent waves
Dixit et al. Simultaneous single detector measurement of multiple fluorescent sources
Li et al. Label free optofluidic DNA hybridization detection based on suspended core fiber whispering gallery mode resonator
JP2004020262A (en) Photothermal conversion spectroscopic method and apparatus therefor
Loyez et al. Insulin biotrapping using plasmofluidic optical fiber chips: A benchmark
CN115128735B (en) Optical sensor chip and optical sensing system
JP5772238B2 (en) Microchip for surface plasmon resonance measurement and surface plasmon resonance measurement apparatus
Sanchez et al. Waveguide-enhanced Raman sensors for bioprocess monitoring
JP2004309270A (en) Microchemical system
Bryan et al. A Multiplex “Disposable Photonics” Biosensor Platform and Its Application to Antibody Profiling in Upper Respiratory Disease
CN115308132A (en) Optical rotation biological sensing system and detection method of biological molecule interaction
Grego et al. Tunable wavelength interrogated sensor platform (TWIST) for point-of-care diagnostics of infectious diseases

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU