WO2011096563A1 - パルス電磁波を用いた計測装置及び計測方法 - Google Patents
パルス電磁波を用いた計測装置及び計測方法 Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/16—Measuring radiation intensity
- G01T1/24—Measuring radiation intensity with semiconductor detectors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3581—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation
- G01N21/3586—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation by Terahertz time domain spectroscopy [THz-TDS]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3581—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
Definitions
- the present invention relates to a measuring device and a measuring method using pulsed electromagnetic waves.
- the present invention relates to a measurement apparatus and a measurement method that perform measurement by detecting temporal changes in the electric field strength of pulsed electromagnetic waves.
- Electromagnetic waves having components in a frequency range of 10 GHz to 10 THz, or a wide frequency range including the frequency range are collectively referred to as terahertz light.
- a spectroscopic device and an imaging device in a time domain using pulsed terahertz light have been proposed.
- These devices irradiate various measured samples such as semiconductors and dielectrics with terahertz pulse light and transmit the measured sample or reflect the measured sample, and then change the electric field intensity of the pulsed light over time. And the electric field strength and phase information of each frequency are obtained by Fourier transform. As a result, for example, it is possible to obtain non-destructive physical property data of various measured samples that could not be obtained or was difficult to obtain with a Fourier spectrometer.
- a reference time series waveform is required.
- the reference waveform in the case of the transmission type, a waveform detected when the sample is removed is used, and in the case of the reflection type, a mirror that can be regarded as having a reflectance of 100% is provided instead of the sample, The waveform detected at that time is used.
- the reference waveform is also Fourier transformed to obtain the amplitude intensity and phase information of the electric field for each wavelength.
- Patent Document 1 describes a measurement method using terahertz pulse light in which a sample is limited to a parallel plate.
- the reflected pulse light at the sample incident surface included in the time series waveform of the reflected light is used as a reference signal, and the difference signal obtained by removing the reflected pulse light from the time series waveform of the reflected light is used as a sample signal. How to do it.
- JP 2004-198250 A Japanese Patent No. 4183735
- the conventional apparatus using terahertz pulse light cannot be said to have sufficient detection sensitivity or detection accuracy.
- the measurement apparatus using pulsed electromagnetic waves described in Patent Document 2 it is applied to the field of drug discovery. At this time, it is desired to further improve detection sensitivity and detection accuracy.
- an object of the present invention is to provide a measuring apparatus and a measuring method using pulsed electromagnetic waves that can detect a substance to be detected with high sensitivity and high accuracy.
- a substance detection plate having a semiconductor and an insulator formed on the semiconductor; Means for generating a pulsed electromagnetic wave having an amplitude intensity depending on the amount of a substance to be detected at an irradiation position by irradiating the substance detection plate with a pulse laser beam from the semiconductor side; Detecting means for detecting the amplitude intensity of the pulse electromagnetic wave, From the amplitude intensity, a measuring device using a pulsed electromagnetic wave that measures a change in the state of the solution containing the substance to be detected, A first beam splitter for dividing the pulsed laser beam into two parts; A detection region portion disposed on the insulator and capable of introducing a solution containing a substance to be detected; and A reference region portion that is disposed in the vicinity of the detection region on the insulator and into which a reference solution can be introduced, and The pulse laser beam is divided into two by the first beam splitter, and one of the divided pulse laser beams is irradiated onto the semiconductor corresponding to the detection region, and
- a second beam splitter that divides the pulsed laser light into probe light and pump light; Further comprising time delay means arranged in the optical path of the probe light and capable of delaying the time when the amplitude intensity is detected by the detection means, The pump light is divided into two by the first beam splitter, and one of the divided pump lights is applied to the semiconductor corresponding to the detection region portion, and the other divided pump light is irradiated to the reference region.
- the probe light passes through the time delay means, and irradiates the detection means in synchronization with the incidence of each pulse electromagnetic wave generated by the pump light, It is a measuring device using a pulsed electromagnetic wave that detects the amplitude intensity of each pulsed electromagnetic wave by the pump light incident on the detection means when the probe light is irradiated.
- the time delay means is a measuring device using a pulsed electromagnetic wave that can periodically delay the time when the amplitude intensity is detected by the detection means.
- a second beam splitter that divides the pulsed laser light into probe light and pump light;
- a pulse timing adjusting means arranged in the optical path of the pump light between the first beam splitter and the semiconductor and capable of arbitrarily adjusting the pulse timing of the pump light;
- the pump light is divided into two by the first beam splitter, and one of the divided pump lights is applied to the semiconductor corresponding to the detection region portion, and the other divided pump light is irradiated to the reference region.
- the pulse timing adjusting means adjusts in advance the pulse timing of one of the two pump lights so that the detection timing of the amplitude intensity of each pulse electromagnetic wave detected by the detecting means coincides.
- the probe light irradiates the detection means in synchronization with the incidence of each pulse electromagnetic wave generated by the pump light, It is a measuring device using a pulsed electromagnetic wave that detects the amplitude intensity of each pulsed electromagnetic wave by the pump light incident on the detection means when the probe light is irradiated.
- a substance detection plate having a semiconductor and an insulator formed on the semiconductor; Means for generating a pulsed electromagnetic wave having an amplitude intensity depending on the amount of a substance to be detected at an irradiation position by irradiating the substance detection plate with a pulse laser beam from the semiconductor side; Detecting means for detecting the amplitude intensity of the pulse electromagnetic wave, From the amplitude intensity, a measurement method using a pulsed electromagnetic wave that measures a change in the state of the solution containing the substance to be detected, A splitting step of splitting the pulsed laser light into probe light and pump light; The pump light is divided into two, and one of the divided pump lights is irradiated to the semiconductor corresponding to the detection region part into which the solution containing the substance to be detected can be introduced, and the other divided pump light Irradiating the semiconductor corresponding to the reference region part into which the reference solution can be introduced, condensing each pulse electromagnetic wave generated from the semiconductor corresponding to the detection region part and the reference region part, and An incident step to enter
- a substance detection plate having a semiconductor and an insulator formed on the semiconductor; Means for generating a pulsed electromagnetic wave having an amplitude intensity depending on the amount of a substance to be detected at an irradiation position by irradiating the substance detection plate with a pulse laser beam from the semiconductor side; Detecting means for detecting the amplitude intensity of the pulse electromagnetic wave, From the amplitude intensity, a measurement method using a pulsed electromagnetic wave that measures a change in the state of the solution containing the substance to be detected, A splitting step of splitting the pulsed laser light into probe light and pump light; The pump light is divided into two, and one of the divided pump lights is irradiated to the semiconductor corresponding to the detection region part into which the solution containing the substance to be detected can be introduced, and the other divided pump light Irradiating the semiconductor corresponding to the reference region part into which the reference solution can be introduced, condensing each pulse electromagnetic wave generated from the semiconductor corresponding to the detection region part and the reference region part, and An incident step to enter
- the detection sensitivity and detection accuracy of the measuring device can be improved.
- FIG. 1 shows a first embodiment of a measuring apparatus using pulsed electromagnetic waves according to the present invention.
- the solution concentration distribution measuring device 1 (hereinafter referred to as the measuring device 1) is a measuring device using a pulsed electromagnetic wave 10, and is manufactured on the semiconductor 23, the insulator 22 manufactured on the semiconductor 23, and the insulator 22.
- a substance detection plate 5 (sensing plate) having a substance-sensitive film 21 and a detection region portion that is disposed on the insulator 22 (substance-sensitive film 21) and into which a solution containing the substance to be detected can be introduced.
- a flow path 12 for flowing a solution containing a substance, and a reference region portion 13 (see FIG.
- Place Means for generating a pulsed electromagnetic wave 10 having an amplitude intensity depending on the amount of the substance to be detected at the irradiation position (pulse laser light source 2), and pulse laser light 9 emitted from the pulse laser light source 2
- the substance to be detected is qualitatively or quantitatively measured, and the reaction distribution or concentration of the substance in the solution in the channel 12 It means for obtaining a fabric comprising a (control and analysis unit 8), or the like.
- a substance sensitive film 21 described later constitutes a part of the inner wall surface of the flow channel 12 in the flow channel forming portion 6 (in this embodiment, the bottom portion of the inner wall surface of the flow channel 12). ing.
- the control / analysis device 8 is not particularly limited to a means for obtaining a reaction distribution or concentration distribution of a substance in a solution, and the characteristics of the solution containing the substance to be detected and its change, and the state of the solution It is a means of measuring changes.
- the portion located on the substance detection plate 5 side on the inner wall surface of the flow path 12 is a bottom for convenience.
- E emission is the electric field vector of the electromagnetic wave
- J is the photocurrent density vector
- n is the density of the photoexcited electron / hole pair
- e is the elementary charge amount
- v is the light
- the drift velocity ⁇ of the electron-hole pair accelerated by the electric field E local in the semiconductor at the irradiated position is the charge mobility.
- the amplitude intensity of the generated electromagnetic wave is proportional to the electric field E local in the semiconductor at the position irradiated with light.
- urea is hydrolyzed by reaction, ammonia is generated, and pH is increased.
- FIG. 2 is a schematic diagram of the energy band distribution of the substance detection plate, in which the horizontal axis indicates the position and the vertical axis indicates the energy. Moreover, EC in the figure is a conduction band, and EV is a valence band.
- a depletion layer is formed at the boundary between the insulator 22 and the semiconductor 23. The depletion layer is a region where no carrier exists, and a local electric field E is formed in the depletion layer. Accordingly, an electric field constantly exists in the depletion layer without applying a voltage from the outside. When this depletion layer is irradiated with light to generate electron / hole pairs, electromagnetic waves are generated according to the equation (1).
- the direction and magnitude of the local electric field E may vary depending on the state of the boundary between the insulator 22 and the semiconductor 23 and the characteristics of the semiconductor 23.
- a particularly important point in the principle of electromagnetic wave generation is that a local electric field E is formed.
- the detected substance can be detected without producing an electrode for reading out the signal for each detected substance. be able to.
- FIG. 1 is a schematic diagram of a solution concentration distribution measuring apparatus according to the present embodiment.
- the measuring device 1 of this embodiment includes an irradiation device (optical system), a detection / conversion device 4, and a control / analysis device 8.
- the irradiation apparatus includes a pulsed laser light source 2, a second beam splitter 14, a time delay means 15, an optical chopper 16, a pump light division condensing means (first beam splitter 17 (see FIG. 7), It is mainly composed of the light means 18) and the scanning table 7.
- the irradiation device irradiates the pulsed laser beam 9 (pump light L2) having a predetermined wavelength to the flow path 12 and the reference region 13 which are detection region portions arranged at predetermined positions of the substance detection plate 5.
- the configuration of the mirror and the like used to change the direction of the pulse laser beam 9 is not limited to the present embodiment. Considering the arrangement of each component, for example, the number of mirrors may be increased as appropriate. You can change the configuration.
- the irradiation device has means for two-dimensional scanning by irradiating the pulse laser beam 9. That is, the scanning means uses the pulse laser beam while reciprocally moving the substance detection plate 5 and the flow path forming unit 6 on the scanning table 7 (XY automatic stage) on the scanning table 7 using a driving device (not shown). 9 has a function of irradiating the substance detection plate 5 toward the substance detection plate 5.
- the pump light L2 that is the split light of the pulse laser light 9 is irradiated to the semiconductor 23 corresponding to the position of the substance sensitive film 21 that constitutes the bottom of the flow path 12, as shown in FIG. (Irradiated with respect to the flow path 12 positioned on one side surface of the flow path forming portion 6), and is stacked in close contact with the substance detection plate 5 and the substance detection plate 5 by the scanning table 7.
- the semiconductor 23 corresponding to the material sensitive film 21 at the bottom of the flow path 12 is moved to the position where the pump light L 2 is irradiated, and laser light irradiation of the semiconductor 23 is performed.
- the pulse electromagnetic wave 10 is continuously generated from the laser light irradiation position of the semiconductor 23.
- the scanning configuration is not limited to the configuration of the first embodiment, and the pulse laser beam 9 is scanned two-dimensionally on the substance detection plate 5 by a oscillating or rotating mirror (not shown)
- the laser light source 2 may be oscillated or irradiated.
- the plane formed by the path of the pulse laser beam 9 and the pulse electromagnetic wave 10 is substantially horizontal, that is, FIG. 1 is a top view configuration, and this configuration is viewed from the side.
- the pulse laser beam 9 and the pulse electromagnetic wave 10 are arranged so as to form a substantially horizontal plane.
- the pump light L2 obtained by dividing the pulsed laser light 9 is applied to the semiconductor 23 corresponding to one side of the flow path 12 of the flow path forming unit 6 (in this embodiment, the bottom side of the flow path 12). It is configured to do.
- the incident angle of the pump light L2 that is the split light of the pulse laser light 9 to the substance detection plate 5 is an angle at which the wavelength of the pulse laser light 9 is most absorbed by the semiconductor 23 of the substance detection plate 5. preferable. However, depending on the shape and fixing method of each device, it is not necessary to limit to this angle, and there is no particular limitation.
- the pulse laser light source 2 may be a mode-locked titanium sapphire laser or a femtosecond fiber laser capable of generating the pulse laser light 9.
- femtosecond laser light as the pulsed laser light 9
- time-resolved measurement with high time resolution becomes possible, and the reaction of the substance can be observed in real time.
- the maximum optical pulse width that does not affect the semiconductor 23 and the solution can be estimated to be about 10 picoseconds.
- a femtosecond laser even a minute amount of solution can minimize the influence of heating by the laser, and there is an effect that thermal destruction of the sample can be suppressed.
- the second beam splitter 14 is a means for dividing the incident pulse laser beam 9 into the probe beam L1 and the pump beam L2.
- the pump beam L2 is perpendicular to the probe beam L1 that travels straight.
- a half mirror that can be divided is used.
- the time delay means 15 is a means arranged in the optical path of the probe light L1 and capable of periodically delaying the time when the amplitude intensity is detected by the detection / conversion device 4.
- the time delay means 15 includes a movable mirror 15a that can be periodically moved in a predetermined direction by a driving means (not shown), and a stage 15b that holds the movable mirror 15a.
- the time delay unit 15 can reflect the probe light L1 incident on the time delay unit 15 in a direction parallel to and opposite to the incident direction of the probe light L1.
- the time delay means 15 adjusts the optical path length of the probe light L1 by optically delaying the movable mirror 15a by reciprocating the movable mirror 15a in parallel and periodically with respect to the incident direction of the probe light L1.
- the driving means is controlled by the control / analysis device 8. That is, the time delay means 15 periodically detects the probe light L1 provided with a time delay amount at a predetermined time interval by moving the movable mirror 15a for adjusting the optical path length of the probe light L1. 4 (detection element 19 to be described later included in the detection / conversion device 4).
- the optical chopper 16 is disposed in the optical path of the pump light L2, and can chop the pump light L2 at a predetermined frequency.
- the pump beam splitting and condensing means generates the first beam splitter 17 that splits the incident pump beam L2 into two parallel pump beams L2, and 2 generated by the two parallel pump beams L2. It is comprised from the off-axis parabolic mirror which is the condensing means 18 which condenses the two pulse electromagnetic waves 10a and 10b.
- This pump beam splitting and condensing means splits the pump beam L2, which is the pulse laser beam 9, into two parallel beams by dividing the pump beam L2 into two by the first beam splitter 17 (the plate for the beam splitter in the first embodiment).
- the divided pump light L2 is irradiated to the semiconductor 23 corresponding to the flow path 12 which is the detection region portion, and the other divided pump light L2 is irradiated to the semiconductor 23 corresponding to the reference region portion 13. can do.
- the first beam splitter 17, which is a flat plate for a beam splitter is used as in (a) the first embodiment. Examples include a method of separation by internal reflection in a flat plate, (b) a method of separation by a half mirror 36 and a mirror 37 as in a second embodiment described later, and (c) laser scanning by a galvano mirror 38.
- the detection / conversion device 4 includes a detection element 19 serving as detection means and a conversion means.
- the detection / conversion device 4 detects the pulse electromagnetic waves 10a and 10b emitted from the irradiation position of the pulse laser beam 9 (pump light L2) on the semiconductor 23 and collected by the off-axis paraboloidal mirror as the condensing means 18. Thus, it is converted into a time-varying voltage signal corresponding to the time waveform of the electric field amplitude of the pulse electromagnetic wave 10.
- the detection element 19 is, for example, a photoconductive antenna or the like, and is arranged so that the pulse electromagnetic waves 10a and 10b from the irradiation position of the pump light L2 on the substance detection plate 5 can enter, and in synchronization with the incidence of the pulse electromagnetic wave 10, the probe light
- L1 is irradiated to a predetermined position of the detection element 19
- a current proportional to the electric field strength (amplitude strength) of the pulsed electromagnetic waves 10a and 10b incident upon the irradiation is generated.
- the conversion means includes a current amplifier 27 connected to the detection element 19 and a lock-in amplifier 28 connected to the current amplifier 27.
- the lock-in amplifier 28 is connected to the optical chopper 16.
- this conversion means by measuring the current generated in the detection element 19, it is possible to detect the amplitude intensity of the pulsed electromagnetic waves 10a and 10b incident when the probe light L1 is irradiated onto the detection element 19. Further, the frequency components included in the pulse electromagnetic waves 10a and 10b are included in the range from 10 gigahertz to 100 terahertz, whereby the detection / conversion device 4 having a general configuration can be used.
- the pulse electromagnetic wave 10 to be used is preferably a terahertz region rather than a gigahertz region.
- the electromagnetic wave can be easily guided to the detector by an optical technique using a mirror, a lens, or the like.
- the high-frequency region is more so-called light than the terahertz region.
- the control / analysis device 8 detects the presence / absence of the detected substance (qualitative measurement), quantitative measurement of the detected substance, detected substance from the voltage signal converted by the conversion means of the detection / conversion device 4 Is a device that performs an analysis process such as a predetermined analysis using a time-series waveform of a reaction distribution and a concentration distribution, and an amplitude intensity (voltage value) of the pulse electromagnetic wave 10 and a predetermined calculation.
- the control / analysis device 8 is a computer that enables execution of control and analysis described in this specification, and an irradiation device (optical system) via a control signal line (not shown).
- the scanning table 7, the detection / conversion device 4, and the pulse laser light source 2 are also controlled.
- FIG. 3 is a schematic view of the substance detection plate 5.
- the substance detection plate 5 includes a substance sensitive film 21, an insulator 22, a semiconductor 23, and a transparent substrate 24 that form the flow path 12 serving as a detection area part and the bottom part of the reference area part 13. That is, the substance detection plate 5 is formed so as to be in contact with the insulator 22, one end surface of the insulator 22 (left end surface in FIG. 3), a semiconductor 23 having a predetermined thickness, and the semiconductor 23.
- the substance detection plate 5 and the flow path forming unit 6 constitute a measurement plate 20.
- membrane 21 is not required when measuring only the pH of a solution.
- the substance-sensitive film 21 is provided with a film in which an enzyme is immobilized, when a substance to be detected that reacts with the enzyme is present in the solution, the pH changes due to the reaction between the enzyme and the substance to be detected.
- the amplitude intensity of the pulse electromagnetic wave 10 generated from the position where the substance sensitive film 21 exists changes. By detecting this change in amplitude intensity, the substance to be detected can be detected.
- the substance detection plate 5 can detect the distribution by the enzyme reaction.
- the substance-sensitive film 21 is configured by adding an enzyme to the photocrosslinking agent and applying it to the bottom of the flow path 12.
- an enzyme-containing sheet is attached to the bottom of the flow path 12.
- the substance-sensitive membrane 21 is provided with a membrane on which an antigen is immobilized, when a substance to be detected (antibody) that reacts with the antigen is present in the solution, the antigen and the substance to be detected (antibody) are mixed.
- the charge on the surface of the substance sensitive film 21 is changed by the reaction, and the amplitude intensity of the pulse electromagnetic wave 10 generated from the position where the substance sensitive film 21 exists changes.
- the substance (antibody) to be detected can be detected based on the changed amplitude intensity (relative to the frequency).
- the measuring device 1 can be utilized as what is called a biosensor.
- the size (projected area with respect to the semiconductor 23) of the substance sensitive film 21 at the bottom of the flow path 12 is designed corresponding to the irradiation range of the pulse laser beam 9. That is, the size of the material sensitive film 21 is designed so as to be wider than the irradiation range of the pulse laser beam 9 (in the present embodiment, the size of the material sensitive film 21 is about 15 mm ⁇ 15 mm. FIG. 6).
- the size of the substance sensitive film 21 shown is a measurement area).
- the size of the flow path 12 provided on the substance-sensitive film 21 of the present embodiment is about 3 mm in width and about 2 mm in height, and the length of the path is about 18 mm (on the material-sensitive film 21). Channel length).
- the area of the material sensitive film 21 constituting the inner wall surface of the flow channel 12 is preferably at least one-fourth of the surface area of the inner wall surface of the flow channel 12, and is one fourth of the surface area. This is because the area for detecting the reaction distribution may be insufficient when the ratio is less than 1.
- the flow path width of the flow path 12 is 1/5 or less of the flow path length. When the flow path width is larger than 1/5 of the flow path length, the heat capacity becomes large and rapid heating / cooling is difficult. This is because the utility of performing the reaction using the microchannel is lost.
- a film of an insulator 22 is formed on the semiconductor 23, and the substance sensitive film 21 is formed on the insulator 22 and at a portion corresponding to the bottom of the flow path 12 and the reference region portion 13. Be placed.
- silicon oxide, silicon nitride, or the like is used as the insulator 22.
- the insulator 22 has a thickness of about 270 nanometers, and the semiconductor 23 has a thickness of about 150 nanometers.
- the thickness of the semiconductor 23 is not limited to the pulse laser beam 9 in order to obtain a large amplitude intensity of the pulse electromagnetic wave 10. It is desirable that the size be equal to the light penetration length determined by the wavelength of the light and the type of the semiconductor 23.
- the light penetration length is the reciprocal of the light absorption coefficient for the semiconductor 23.
- the thickness of the semiconductor 23 is about 2 microns, so that the pulse electromagnetic wave 10 can be generated efficiently. Can be made.
- the transparent substrate 24 is necessary when the semiconductor 23, the insulator 22, and the material sensitive film 21 are produced. Further, the transparent substrate 24 is necessary for maintaining the mechanical strength of the substance detection plate 5. In the present embodiment, sapphire is used as the transparent substrate 24. As shown in FIGS. 3 and 4, the semiconductor 23 is disposed on the transparent substrate 24, the insulator 22 is disposed on the semiconductor 23, and the substance sensitive film 21 is disposed on the insulator 22. Is done.
- the pulse laser beam 9 is irradiated from the opposite side of the surface of the substance detection plate 5 on which the substance sensitive film 21 is formed.
- the pulsed laser light 9 (pump light L2) is applied to the semiconductor 23 corresponding to the flow path 12, that is, the surface of the semiconductor 23 immediately below the flow path 12 in FIG. 4 (the lower surface of the semiconductor 23 in FIG. 4).
- a semiconductor film semiconductor 23 formed on an insulator substrate (transparent substrate 24) that transmits the pulse laser beam 9 is used.
- the lead wire 25 is in electrical contact with the semiconductor 23 so that a voltage can be applied to the semiconductor 23 as required. Thereby, the width of the depletion layer in the semiconductor 23 can be controlled.
- a protective film such as silicon nitride on the insulator 22, it is possible to prevent ions in the solution from penetrating into the insulator 22 and making the detection signal unstable. .
- the reference region portion 13 is disposed in the vicinity of the flow channel 12 serving as the detection region portion on the substance sensitive film 21 provided on the insulator 22, and a reference solution can be introduced.
- a plate-shaped flow path forming portion 6 is integrally laminated on the substance detection film 21 in the substance detection plate 5.
- the flow path forming portion 6 has a flow path 12 and a reference area portion 13 that are a crank-shaped detection area portion in a side view, and the flow path 12 and the reference area portion 13 have a square shape in cross section. Yes (see FIG. 7).
- a bottom portion which is a part of the inner wall surface of the flow path 12 is formed by the surface of the substance sensitive film 21. Further, the interface S between the substance sensitive film 21 and the flow path forming part 6 is tightly sealed except for the part of the substance sensitive film 21 that forms the bottom part of the flow path 12 and the reference region part 13.
- the interface between the flow path forming part 6 and the insulator 22 is also sealed in the same manner, and is treated so that the solution does not enter the interface S from the flow path 12 and the reference region part 13. That is, when the solution flows through the channel 12 (reference solution is the reference region 13) or is stored in the channel 12 (reference region 13), the solution is the bottom of the channel 12 (the reference solution is It is configured to come into contact with the surface of the material sensitive film 21 which is the bottom part of the reference region 13.
- the shape of the flow path 12 is not particularly limited to a crank shape, and may be appropriately changed depending on the type of solution reaction.
- the channel shape may be linear, meandering, Y-shaped, or the like. It is also possible to configure the flow path forming unit 6 by providing heating or cooling means in the vicinity of the flow path 12.
- the solution containing the substance to be detected is injected from the solution inlet 32, and the solution which becomes unnecessary after the inspection is discharged from the solution outlet 33.
- the reference electrode 26 which is a means for stabilizing the potential of the solution is interposed at a predetermined position in the middle of the solution supply pipe connected to the solution inlet 32 as shown in FIG.
- the reference electrode 26 has a structure in which a silver / silver chloride electrode is contained in a glass tube sealed with a saturated potassium chloride solution, and is a silver / silver chloride electrode immersed in a saturated potassium chloride solution.
- a voltage source is installed between the reference electrode 26 and the lead wire 25 described above, and a voltage can be applied, which functions as a means for stabilizing the potential of the solution containing the substance to be detected. It is.
- the reference electrode 26 is preliminarily provided in the configuration of the measuring device 1 and is not necessary when the reference region portion 13 is applied. In the measuring device 1, the reference electrode 26 and the lead wire 25 are provided. It is also possible to adopt a configuration without this.
- the control / analysis device 8 causes the pulse laser light source 2 to place the substance detection plate 5 on the opposite side of the semiconductor 23 from the insulator 22 and at a position corresponding to the substance sensitive film 21.
- the pulse laser beam 9 is irradiated.
- the pulse electromagnetic wave 10 generated by the irradiation of the pulse laser beam 9 is detected by the detection / conversion device 4, and the control / analysis device 8 takes in the detection result, and from the amplitude intensity of the pulse electromagnetic wave 10, the substance sensitive film 21 The presence or absence of reaction and the degree of reaction are detected.
- the control / analysis device 8 controls the scanning table 7 to move the measurement plate 20 while continuing to detect the pulse electromagnetic wave 10 on the substance sensitive film 21, and moves the substance sensitive film 21 in the flow path 12.
- the semiconductor 23 corresponding to is irradiated with the pulsed laser light 9.
- the solution concentration distribution measuring apparatus 1 includes means (scanning table 7, pulse laser light source 2) for two-dimensionally scanning and irradiating the pulsed laser light 9, and the pulsed laser light 9 is two-dimensionally provided. Generated by the irradiation of the material-sensitive film 21 (semiconductor 23) continuously irradiated with the pulsed laser light 9 by means of scanning and irradiation (scanning table 7, pulsed laser light source 2).
- the amplitude intensity of the pulse electromagnetic wave 10 can be continuously measured.
- the measuring device 1 in this embodiment includes means (scanning table 7, pulse laser light source 2) for scanning and irradiating the pulse laser light 9 two-dimensionally. There is no need to perform the above, and it is sufficient to determine whether scanning is necessary or not according to the measurement environment.
- control / analysis device 8 measures the substance to be detected qualitatively or quantitatively from the amplitude intensity of the pulse electromagnetic wave 10 to obtain a reaction distribution or concentration distribution of the substance in the solution in the flow path 12. And detecting the presence / absence of a reaction (presence / absence of change in electromagnetic wave amplitude intensity) and the degree of reaction (amount of change in electromagnetic wave amplitude intensity) in the solution based on these. The reaction distribution or concentration distribution is detected and the detected substance is analyzed.
- the measurement method using the pulsed electromagnetic wave according to the present embodiment proceeds according to the flow shown in FIG. 8, and includes a division step S10, an incident step S20, a probe light irradiation step S30, and a time-series waveform generation step S40. , Amplitude intensity acquisition step S50, and difference step S60.
- the substance detection plate 5 is installed at a predetermined position on the scanning table 7, and the irradiation position of the pulse laser beam 9, the flow path 12 and the reference are controlled by the control / analysis device 8.
- the substance detection plate 5 (measurement plate 20) is moved on the scanning table 7 so that the predetermined position (start position) of the substance sensitive film 21 which is the bottom part of the region part 13 coincides.
- the pulse laser light 9 is irradiated from the pulse laser light source 2.
- the dividing step S10 is a step of dividing the pulsed laser light 9 into the probe light L1 and the pump light L2.
- the pulse laser light 9 output from the pulse laser light source 2 in FIG. 1 is converted into two pulse laser lights 9 by the second beam splitter 14 (a half mirror in this embodiment).
- the light is divided into light L1 and pump light L2.
- the incident step S20 divides the pump light L2 into two parts, and the semiconductor 23 corresponding to the flow path 12 which is a detection region part into which the solution containing the substance to be detected can be introduced into the one divided pump light L2. And the other divided pump light L2 is irradiated to the semiconductor 23 corresponding to the reference region part 13 into which the reference solution can be introduced, and the flow path 12 and the reference region part 13 are In this step, each pulse electromagnetic wave 10a, 10b generated from the semiconductor 23 is condensed and made incident on the detection element 19 which is one of the detection means.
- the pump light L ⁇ b> 2 that is one of the pulsed laser lights 9 divided by the beam splitter 14 is allowed to pass through the mirror 29, the optical chopper 16, and the mirror 30, and the pump light L ⁇ b> 2 that has passed through the optical chopper 16. 7 is divided into two by the first beam splitter 17, and one of the divided pump lights L2 is applied to the semiconductor 23 corresponding to the flow path 12 which is the detection region portion. The other divided pump light L2 is applied to the semiconductor 23 corresponding to the reference region portion 13.
- each pulse electromagnetic wave 10a, 10b generated from the semiconductor 23 corresponding to the flow path 12 and the reference region portion 13 which are the irradiation positions of both pump lights L2 is released off-axis as the condensing means 18.
- the object mirror collects light on one end of the detection element 19, and the detection element 19 detects the amplitude intensity of the pulsed electromagnetic waves 10a and 10b generated by the irradiation of the pump light L2.
- the probe light L1 passes through the time delay means 15 and is irradiated to the detection element 19 in synchronization with the incidence of the pulse electromagnetic waves 10a and 10b generated by the pump light L2. It is a process.
- the probe light L1 which is one pulse laser light 9 divided by the beam splitter 14 is transmitted to the detection element 19 through the time delay means 15, the mirror 31, the mirror 34, and the lens 35.
- the edge is irradiated.
- the probe light L ⁇ b> 1 is irradiated in synchronization with each pulse electromagnetic wave 10 a, 10 b generated from the semiconductor 23 corresponding to the flow path 12 and the reference region portion 13 entering the detection element 19.
- the time-series waveform generation step S40 acquires amplitude intensities of the plurality of pulsed electromagnetic waves 10 having different delay times corresponding to the flow path 12 and the reference region portion 13 synchronized with the probe light L1, respectively, 12 and a time-series waveform of the pulse electromagnetic wave 10 corresponding to each of the reference region portion 13 and the reference region portion 13.
- the time delay unit 15 when the probe light L1 divided by the second beam splitter 14 passes through the time delay unit 15 in the middle of the optical path to the detection element 19, the time delay unit 15
- the probe light L1 is incident and reflected by a movable mirror 15a that is movable in a predetermined direction (in the present embodiment, parallel to the probe light L1). Further, the control / analysis device 8 periodically reciprocates the movable mirror 15a in a predetermined direction at a predetermined frequency, thereby optically delaying the time for the probe light L1 to reach the detection element 19.
- control / analysis device 8 delays the time when the probe light L1 is incident on the detection element 19 while periodically changing the time when the probe light L1 reaches the detection element 19 by the time delay means 15. It is possible to acquire the amplitude intensity of the pulse electromagnetic wave 10 when the probe light L1 is incident in a predetermined time series (see FIG. 9A).
- the control / analyzer 8 generates a time-series waveform of the amplitude intensity based on the amplitude intensity of the detected pulse electromagnetic wave 10.
- the detection element 19 detects the substance.
- the pulse electromagnetic waves 10a and 10b generated from the irradiation position of the pump light L2 on the plate 5 are condensed on the detection element 19, and the probe light L1 is irradiated to a predetermined position of the detection element 19 in synchronization with the incidence of the pulse electromagnetic waves 10a and 10b.
- a current proportional to the electric field strength (amplitude strength) of the pulsed electromagnetic wave 10 incident upon the irradiation is generated.
- the current is converted into a voltage by the current amplifier 27, and then lock-in detection is performed by the lock-in amplifier 28 in synchronization with the chopping of the optical chopper 16. Then, the lock-in detection value is input to the computer 8. That is, it is possible to detect each amplitude intensity of the pulsed electromagnetic waves 10a and 10b that are incident when the probe light L1 is applied to the detection element 19.
- the waveform of the pulse electromagnetic wave 10 (for example, terahertz wave) incident on the detection element 19 is as shown in FIG. 9B, the time that is the time until the probe light L ⁇ b> 1 reaches the detection element 19.
- a discrete signal sequence as indicated by a circle in FIG.
- FIG.9 shows time delay (DELTA) (tau).
- DELTA time delay
- the amplitude intensity acquisition step S50 is a step of acquiring the amplitude intensity at each waveform peak position from the time series waveform corresponding to each of the flow path 12 and the reference region portion 13 generated in the time series waveform generation step S40. is there.
- a predetermined calculation process is performed by the computer 8 from the time-series waveforms w1 and w2 (see FIG. 10) corresponding to the acquired flow path 12 and the reference region portion 13, respectively.
- a peak position of the amplitude intensity in each of the flow path 12 and the reference region portion 13 is obtained.
- the difference step S60 includes the waveform peak position of the flow path 12 (the peak position of the waveform w1 belonging to the detection area portion (flow path 12) located on the left side of FIG. 10) and the waveform peak position of the reference area portion 13 (see FIG. 10 is a step of performing a difference between the amplitude intensities in the peak position of the waveform w2 belonging to the reference region portion 13 located on the right side of FIG.
- the amplitude intensity corresponding to the solution containing the detection target substance introduced into the flow path 12 and the amplitude intensity corresponding to the reference solution introduced into the reference region portion 13 are differentiated. In this way, the characteristics (change in the state of the solution) of the solution containing the substance to be detected are measured.
- a specific measurement example of the substance to be detected is shown below.
- the ammonia concentration change shown in FIG. 11 is that urea solution is stored in the flow path 12, urea is hydrolyzed by the catalytic action of the substance sensitive film 21 containing urease (enzyme), ammonia is generated, and urea concentration in the solution This shows a change that decreases.
- 11A shows the urea concentration change when the measurement method using the pulsed electromagnetic wave 10 according to the present embodiment is not applied to the measurement apparatus 1
- FIG. 11B shows the pulse electromagnetic wave 10 according to the present embodiment in the measurement apparatus 1.
- FIG. 11A shows the urea concentration change when the measurement method using the pulsed electromagnetic wave 10 according to the present embodiment is not applied to the measurement apparatus 1
- FIG. 11B shows the pulse electromagnetic wave 10 according to the present embodiment in the measurement apparatus 1.
- the time variation of the amplitude intensity it is possible to analyze the chemical reaction occurring between the substance to be detected and the sensitive film, the reaction rate of the binding reaction, and the binding constant.
- the time taken from the start of the reaction to the end of the reaction The coupling constant can be obtained from the slope of the graph.
- the measurement plate 20 is moved by the scanning table 7 and continuously irradiated with the pulsed laser light 9, so that the inside of the flow path 12. It is possible to carry out an analysis on the substance to be detected in the entire bottom of the substrate, and it is possible to obtain a large amount of analysis data efficiently in a short time with good workability. Further, since the reaction between the substance to be detected and the substance sensitive film 21 can be directly detected, label-free substance detection can be performed.
- the measuring apparatus 1 using the pulsed electromagnetic wave 10 divides the pulsed laser light 9 into two by the first beam splitter 18 and detects the pumped light L2 which is one of the divided pulsed laser lights. Irradiating the semiconductor 23 corresponding to the region portion and irradiating the semiconductor 23 corresponding to the reference region portion 13 with the probe light L1 which is the other divided pulse laser light 9, the detection region portion and the reference Each pulse electromagnetic wave 10a, 10b generated from the semiconductor 23 corresponding to the region is condensed by the condensing means 18 and detected by one detection element 19.
- the substance detection plate 5 is provided with a detection region portion and a reference region portion, and the position of the substance detection plate 5 is moved to alternately perform laser on each of the detection region portion and the reference region portion.
- the configuration of detecting the pulsed electromagnetic waves 10a and 10b generated by irradiating light was examined. However, in such a configuration, there is no need to move the optical system of the laser and electromagnetic wave, but the solution containing the substance to be detected is stirred, so that the dynamic measurement of the solution cannot be performed and an accurate reaction is performed. Time change cannot be detected. Therefore, the inventor also examined a configuration in which two units of a pulse laser for the detection region and a pulse laser for the reference region were prepared without moving the position of the substance detection plate 5.
- one pulsed laser beam 9 is divided and irradiated to the detection region portion and the reference region portion at the same time, and the pulse electromagnetic waves 10a and 10b respectively generated from the irradiation positions are detected one by a parabolic mirror. It was found that the light was condensed on the means. Further, when detecting the detection region portion and the reference region portion with one detection means, the difference in position is regarded as the difference in detection time (delay time), and the waveforms belonging to the pulse electromagnetic waves 10a and 10b are separated and measured ( Thus, measurement by the device configuration according to the present invention is possible. Thus, according to the measurement device and measurement method using pulsed electromagnetic waves in the present embodiment, the detection sensitivity and detection accuracy of the measurement device can be improved.
- this invention is not limited to the said Example, A various deformation
- FIG. 13 shows a second embodiment of the measuring apparatus using the pulsed electromagnetic wave of the present invention.
- the principle according to the present invention used by the measuring device using the pulsed electromagnetic wave according to the second embodiment is the same as the principle described above.
- the first embodiment is described.
- Members common to the measuring apparatus 1 described in the examples and parts having common functions are denoted by the same reference numerals, and detailed description thereof is omitted.
- the solution concentration distribution measuring device 50 (hereinafter referred to as the measuring device 50) is a measuring device using the pulse electromagnetic wave 10, and is manufactured on the semiconductor 23, the insulator 22 manufactured on the semiconductor 23, and the insulator 22.
- a substance detection plate 5 sensing plate having a substance-sensitive film 21 and a detection region portion that is disposed on the insulator 22 (substance-sensitive film 21) and into which a solution containing the substance to be detected can be introduced.
- a flow path 12 (see FIG. 14) for flowing a solution containing a substance, and a reference region portion 13 which is disposed in the vicinity of the flow path 12 on the insulator 22 (substance sensitive film 21) and into which a reference solution can be introduced. (See FIG.
- a pulse laser beam 9 to the substance detection plate 5 from the semiconductor 23 side opposite to the insulator 22 Irradiating from the pulse laser light source 2 with means (pulse laser light source 2) for generating a pulse electromagnetic wave 10 having an amplitude intensity depending on the amount of the substance to be detected at the irradiation position by irradiating the position corresponding to the path 12
- a second beam splitter 14 that divides the pulsed laser beam 9 into a probe beam L1 and a pump beam L2, and means for two-dimensionally scanning and irradiating the pulsed laser beam 9 (scanning table 7, pulsed laser light source) 2), means for measuring the amplitude intensity of the pulse electromagnetic wave 10 (detection / conversion device 4), and the optical path of the pump light L2 between the first beam splitter 17 and the semiconductor 23 included in the substance detection plate 5
- a pulse timing adjusting means which is a pulse timing adjusting means which can be arbitrarily adjusted to
- control / analyzer 8 for measuring the substance to be detected qualitatively or quantitatively from the amplitude intensity and obtaining the reaction distribution or concentration distribution of the substance in the solution in the flow path 12.
- a substance sensitive film 21 described later constitutes a part of the inner wall surface of the flow channel 12 in the flow channel forming portion 6 (in this embodiment, the bottom portion of the inner wall surface of the flow channel 12). ing. Details of the apparatus configuration will be described below.
- the control / analysis device 8 is not particularly limited to a means for obtaining a reaction distribution or concentration distribution of a substance in a solution, and the characteristics of the solution containing the substance to be detected and its change, and the state of the solution It is a means of measuring changes.
- the “change in the state of the solution” that can be measured by the solution concentration distribution measuring device (the measuring device 1 and the measuring device 50) in the present embodiment includes, for example, a change in the ion concentration of the solution, an antigen antibody in the sample solution Changes in the progress of the reaction (sample solutions include, for example, blood, body fluids, other antigen-containing solutions, etc.), changes in various chemical reaction states in the solution, etc., and changes over time. Is included.
- the portion located on the substance detection plate 5 side on the inner wall surface of the flow path 12 is a bottom for convenience.
- the detection target substance is detected by the apparatus configuration of the measuring apparatus 50 according to the second embodiment shown in FIG.
- FIG. 13 is a schematic diagram of the solution concentration distribution measuring apparatus of the present example.
- the measuring device 50 of this embodiment includes an irradiation device (optical system), a detection / conversion device 4, and a control / analysis device 8.
- the irradiation apparatus includes a pulse laser light source 2, a second beam splitter 14, an optical chopper 16, pump light splitting and condensing means (first beam splitter 17 (see FIG. 14), condensing means 40), It is mainly composed of a pulse timing adjuster 39 and a scanning table 7.
- the irradiation device irradiates the pulsed laser beam 9 (pump light L2) having a predetermined wavelength to the flow path 12 and the reference region 13 which are detection region portions arranged at predetermined positions of the substance detection plate 5.
- the configuration of the mirror and the like used to change the direction of the pulse laser beam 9 is not limited to the present embodiment.
- the irradiation apparatus (optical system) can also be configured to have time delay means 15 in the optical path of the probe light L1.
- the time delay means 15 can be used during periodic calibration of the measuring device.
- the configuration of the measuring device 50 that does not have the time delay means 15 is shown.
- the irradiation device has means for two-dimensional scanning by irradiating the pulse laser beam 9. That is, the scanning means uses the pulse laser beam while reciprocally moving the substance detection plate 5 and the flow path forming unit 6 on the scanning table 7 (XY automatic stage) on the scanning table 7 using a driving device (not shown). 9 has a function of irradiating the substance detection plate 5 toward the substance detection plate 5.
- the pump light L2 that is the split light of the pulse laser light 9 is irradiated to the semiconductor 23 corresponding to the position of the substance sensitive film 21 that constitutes the bottom of the flow path 12, as shown in FIG. (Irradiated with respect to the flow path 12 positioned on one side surface of the flow path forming portion 6), and is stacked in close contact with the substance detection plate 5 and the substance detection plate 5 by the scanning table 7.
- the semiconductor 23 corresponding to the material sensitive film 21 at the bottom of the flow path 12 is moved to the position where the pump light L 2 is irradiated, and laser light irradiation of the semiconductor 23 is performed.
- the pulse electromagnetic wave 10 is continuously generated from the laser light irradiation position of the semiconductor 23.
- the scanning configuration is not limited to the configuration of the second embodiment, and the pulse laser beam 9 is scanned two-dimensionally on the substance detection plate 5 by a oscillating or rotating mirror (not shown) or the pulse
- the laser light source 2 may be oscillated or irradiated.
- the plane formed by the path of the pulse laser beam 9 and the pulse electromagnetic wave 10 is a substantially horizontal plane, that is, FIG. 13 is a top view configuration, and this configuration is viewed from the side.
- the pulse laser beam 9 and the pulse electromagnetic wave 10 are arranged so as to form a substantially horizontal plane.
- the pump light L2 obtained by dividing the pulsed laser light 9 is applied to the semiconductor 23 corresponding to one side of the flow path 12 of the flow path forming unit 6 (in this embodiment, the bottom side of the flow path 12). It is configured to do.
- the incident angle of the pump light L2 that is the split light of the pulse laser light 9 to the substance detection plate 5 is an angle at which the wavelength of the pulse laser light 9 is most absorbed by the semiconductor 23 of the substance detection plate 5. preferable. However, depending on the shape and fixing method of each device, it is not necessary to limit to this angle, and there is no particular limitation. *
- the second beam splitter 14 is a means for dividing the incident pulse laser beam 9 into the probe beam L1 and the pump beam L2.
- the pump beam L2 is perpendicular to the probe beam L1 that travels straight. A half mirror that can be divided is used. *
- the optical chopper 16 is disposed in the optical path of the pump light L2 (in this embodiment, the optical path between the mirror 29 and the first beam splitter 17), and can chop the pump light L2 at a predetermined frequency. It is. *
- the pump beam splitting and condensing means generates the first beam splitter 17 that splits the incident pump beam L2 into two parallel pump beams L2, and 2 generated by the two parallel pump beams L2. It is comprised from the off-axis parabolic mirror which is the condensing means 40 which condenses the two electromagnetic waves 10a and 10b.
- the first beam splitter 17 according to this embodiment is a parallel plate mirror type beam splitter shown in FIG. 12B, and the straight traveling pump light L2 is divided into two parallel pump lights L2. Is possible.
- the pump beam splitting and condensing means splits the pump beam L2 that is the pulse laser beam 9 into two parallel beams by the first beam splitter 17, and the one split pump beam L2 is detected.
- the pulse timing adjuster 39 is arranged in the optical path of the pump light L2 shown on the upper side of the two pump lights L2. Note that the optical path of the pump light L2 in which the pulse timing adjuster 39 is arranged is arranged on the optical path of one of the pump lights L2 of the pump light L2 which is parallel light divided into two by the beam splitter 17. That's fine.
- the detection / conversion device 4 includes a detection element 19 as detection means and conversion means described later.
- the detection / conversion device 4 detects the pulse electromagnetic waves 10a and 10b emitted from the irradiation position of the pulse laser beam 9 (pump light L2) on the semiconductor 23 and collected by an off-axis parabolic mirror which is a condensing means 40. Thus, it is converted into a time-varying voltage signal corresponding to the time waveform of the electric field amplitude of the pulse electromagnetic wave 10.
- a photoconductive antenna or the like can be applied to the detection element 19, and the pulse electromagnetic waves 10 a and 10 b from the irradiation position of the pump light L ⁇ b> 2 on the substance detection plate 5 are arranged to be incident thereon, and synchronized with the incidence of the pulse electromagnetic wave 10.
- the probe light L1 is irradiated to a predetermined position of the detection element 19, a current proportional to the electric field strength (amplitude strength) of the pulse electromagnetic waves 10a and 10b incident upon the irradiation is generated.
- the conversion means includes a current amplifier 27 connected to the detection element 19 and a lock-in amplifier 28 connected to the current amplifier 27.
- the lock-in amplifier 28 is connected to the optical chopper 16.
- this conversion means by measuring the current generated in the detection element 19, it is possible to detect the amplitude intensity of the pulsed electromagnetic waves 10a and 10b incident when the probe light L1 is irradiated onto the detection element 19. Further, the frequency components included in the pulse electromagnetic waves 10a and 10b are included in the range from 10 gigahertz to 100 terahertz, whereby the detection / conversion device 4 having a general configuration can be used.
- the control / analysis device 8 detects the presence / absence of the detected substance (qualitative measurement), quantitative measurement of the detected substance, detected substance from the voltage signal converted by the conversion means of the detection / conversion device 4 Is a device that performs an analysis process such as a predetermined analysis using a time-series waveform of a reaction distribution and a concentration distribution, and an amplitude intensity (voltage value) of the pulse electromagnetic wave 10 and a predetermined calculation.
- the control / analysis device 8 is a computer that enables execution of control and analysis described in this specification, and an irradiation device (optical system) via a control signal line (not shown).
- the scanning table 7, the detection / conversion device 4, and the pulse laser light source 2 are also controlled. *
- the control / analysis device 8 causes the pulse laser light source 2 to place the substance detection plate 5 on the opposite side of the semiconductor 23 from the insulator 22 and at a position corresponding to the substance sensitive film 21.
- the pulse laser beam 9 is irradiated.
- the pulse electromagnetic wave 10 generated by the irradiation of the pulse laser beam 9 is detected by the detection / conversion device 4, and the control / analysis device 8 takes in the detection result, and from the amplitude intensity of the pulse electromagnetic wave 10, the substance sensitive film 21 The presence or absence of reaction and the degree of reaction are detected.
- the control / analysis device 8 controls the scanning table 7 to move the measurement plate 20 while continuing to detect the pulse electromagnetic wave 10 on the substance sensitive film 21, and moves the substance sensitive film 21 in the flow path 12.
- the semiconductor 23 corresponding to is irradiated with the pulsed laser light 9.
- the measuring device 50 includes means (scanning table 7, pulse laser light source 2) for two-dimensionally scanning and irradiating the pulse laser light 9 and scanning the pulse laser light 9 two-dimensionally.
- the pulsed laser light 9 is continuously irradiated onto the substance sensitive film 21 (semiconductor 23) by means of irradiation (scanning table 7, pulsed laser light source 2), and the pulse electromagnetic wave 10 generated by the irradiation. Can be measured continuously.
- the measuring device 50 in this embodiment includes means for two-dimensionally scanning and irradiating the pulsed laser light 9 (scanning table 7, pulsed laser light source 2). There is no need to perform the above, and the necessity of scanning may be determined according to the measurement environment, and the irradiation means (scanning table 7, pulse laser light source 2) may be used as appropriate.
- control / analysis device 8 measures the substance to be detected qualitatively or quantitatively from the amplitude intensity of the pulse electromagnetic wave 10 to obtain a reaction distribution or concentration distribution of the substance in the solution in the flow path 12. And detecting the presence / absence of a reaction (presence / absence of change in electromagnetic wave amplitude intensity) and the degree of reaction (amount of change in electromagnetic wave amplitude intensity) in the solution based on these. The reaction distribution or concentration distribution is detected and the detected substance is analyzed.
- the measurement method using pulsed electromagnetic waves includes a dividing step S100, an incident step S200, a pulse timing adjustment step S300, a probe light irradiation step S400, and an amplitude intensity detection step S500. And having.
- the substance detection plate 5 is installed at a predetermined position on the scanning table 7, and the irradiation position of the pulse laser beam 9, the flow path 12 and the reference are controlled by the control / analysis device 8.
- the substance detection plate 5 (measurement plate 20) is moved on the scanning table 7 so that the predetermined position (start position) of the substance sensitive film 21 which is the bottom part of the region part 13 coincides.
- the pulse laser light 9 is irradiated from the pulse laser light source 2.
- the dividing step S100 is a step of dividing the pulsed laser light 9 into the probe light L1 and the pump light L2.
- the pulse laser light 9 output from the pulse laser light source 2 is converted into two pulse laser lights 9 by the second beam splitter 14 (a half mirror in this embodiment).
- the light is divided into light L1 and pump light L2.
- the pump light L2 is divided into two, one of the divided pump lights L2 is adjusted to a predetermined pulse timing by a pulse timing adjuster 39, and a solution containing the substance to be detected can be introduced.
- the semiconductor 23 corresponding to the flow path 12 which is a certain detection region is irradiated to the semiconductor 23 corresponding to the reference region 13 into which the reference solution can be introduced with the other divided pump light L2.
- the pulse electromagnetic waves 10a and 10b generated from the semiconductor 23 corresponding to the flow path 12 and the reference region 13 are collected and incident on the detection element 19 which is one of the detection means.
- the pump light L2 which is one of the pulse laser beams 9 divided by the beam splitter 14 is passed through the mirror 29 and the optical chopper 16.
- the pump light L2 that has passed through the optical chopper 16 is divided into two by the first beam splitter 17 as shown in FIGS. Then, it is adjusted to a predetermined pulse timing by passing through a pulse timing adjuster 39, and the semiconductor 23 corresponding to the flow path 12 which is the detection region portion is irradiated with the other divided pump light L2 The semiconductor 23 corresponding to the reference region portion 13 is irradiated.
- the light is condensed on one end of the detection element 19 by the object mirror and is incident on one detection element 19.
- the pulse timing adjuster 39 is configured to pass the pump light L2 irradiated to the semiconductor 23 corresponding to the flow path 12 that is the detection region portion, but is not particularly limited.
- the pulse timing adjuster 39 may be configured to pass the pump light L ⁇ b> 2 irradiated to the semiconductor 23 corresponding to the reference region portion 13. That is, the pulse timing adjuster 39 may be configured to pass either one of the two pump lights L2 divided by the beam splitter 17.
- the pulse of one pump light L2 of the two pump lights L2 is set so that the detection timings of the amplitude intensities of the respective pulse electromagnetic waves 10a and 10b detected by the detection element 19 coincide with each other. This is a step of adjusting the timing in advance.
- One pump light L2 of the two pump lights L2 (in this embodiment, the pump light L2 applied to the semiconductor 23 corresponding to the flow path 12) so that the detection timings of the amplitude intensities of the electromagnetic waves 10a and 10b coincide. ) Is adjusted in advance.
- the pulse timing adjustment is performed in the middle of the optical path where one of the pump lights L2 divided into two parallel lights by the first beam splitter 17 reaches the semiconductor 23 of the substance detection plate 5.
- the pump light L2 is incident on the adjusting mirror 39a arranged to be adjustable in a predetermined direction (in the present embodiment, a direction orthogonal to the probe light L2) in the pulse timing adjuster 39,
- the incident pump light L2 is reflected by the adjusting mirror 39a.
- the optical path length of one probe light L1 is adjusted by fixing the adjustment mirror 39 included in the pulse timing adjuster 39 at a predetermined position. Can do.
- the pulse electromagnetic wave 10a generated from the semiconductor 23 corresponding to one probe light L1 and the pulse electromagnetic wave 10b corresponding to the other probe light L2 are incident on the detection element 19 at different timings.
- the optical path length in advance by moving the adjusting mirror 39a of the adjuster 39, the time when the pulse electromagnetic wave 10a reaches the detection element 19 (optical time timing) and the pulse electromagnetic wave 10b reach the detection element 19 Time (optical time timing) can be matched.
- the pulse timing so that the detection timings coincide with each other, the amplitude intensities of the two pulse electromagnetic waves 10a and 10b are detected by the detection element 19 at the same detection timing.
- the pulse timing adjustment step S300 is not necessarily executed as a subsequent step of the incident step S200.
- the pulse timing adjustment step S300 may be performed in other steps such as when the measurement person or the control / analysis device 8 monitors the measurement preparation stage before the measurement using the measurement device 50 or the measurement result obtained by the measurement device 50. Regardless of the method, it may be executed as needed.
- Probe light irradiation step S400 is a step of irradiating the detection element 19 with the probe light L1 in synchronization with the incidence of the respective pulsed electromagnetic waves 10a and 10b generated by the pump light L2.
- the probe light L ⁇ b> 1 that is one pulse laser light 9 divided by the beam splitter 14 is irradiated to the other end of the detection element 19 through the mirror 31, the mirror 34, and the lens 35.
- the probe light L1 is irradiated in synchronization with each pulse electromagnetic wave 10a, 10b generated from the semiconductor 23 corresponding to the flow path 12 and the reference region portion 13 entering the detection element 19. .
- the amplitude intensity detection step S500 the amplitude intensity of each of the pulse electromagnetic waves 10a and 10b by the pump light L2 incident on the detection element 19 when the detection element 19 is irradiated with the probe light L1 in the probe light irradiation step S400 is detected. It is a process.
- the control / analysis device 8 detects the amplitude intensity of the pulsed electromagnetic waves 10a and 10b.
- the detection element 19 is generated from the irradiation position of the pump light L2 on the substance detection plate 5.
- the pulse electromagnetic waves 10a and 10b are condensed on the detection element 19, and the probe light L1 is irradiated to a predetermined position of the detection element 19 in synchronization with the incidence of the pulse electromagnetic waves 10a and 10b, the pulse electromagnetic wave 10 incident upon the irradiation A current proportional to the electric field strength (amplitude strength) is generated.
- the current is converted into a voltage by the current amplifier 27, and then lock-in detection is performed by the lock-in amplifier 28 in synchronization with the chopping of the optical chopper 16. Then, the lock-in detection value is input to the computer 8. That is, it is possible to detect each amplitude intensity of the pulsed electromagnetic waves 10a and 10b that are incident when the probe light L1 is applied to the detection element 19. In particular, in the present embodiment, since the detection timings of the amplitudes of the pulse electromagnetic waves 10a and 10b are matched in the pulse timing adjustment step S300, the amplitude intensities of the pulse electromagnetic waves 10a and 10b are detected in a superimposed state.
- the control / analysis apparatus 8 can acquire a time-series waveform in which the pulse electromagnetic waves 10a and 10b are superimposed as shown in FIG.
- the vertical axis represents the terahertz wave amplitude
- the horizontal axis represents time.
- the waveform on the left broken line is the waveform w3 belonging to the detection region portion (flow channel 12)
- the waveform on the right dotted line is the waveform w4 belonging to the reference region portion 13 and is indicated by a thick line.
- the waveform is a waveform w5 obtained by superimposing the waveform w3 and the waveform w4. As shown in FIG.
- the pulse timing adjuster 39 adjusts the pulse timing of one pump light L2, and the detection timing at which the pulse electromagnetic wave 10a by the one pump light L2 is detected by the detection element 19 and the other pump light.
- the amplitude intensities of the pulse electromagnetic waves 10a and 10b can be acquired at the same detection timing.
- the detection timing adjusted by the pulse timing adjuster 39 is a timing used for canceling the waveform w4 from the waveform w3 as shown in FIG.
- the amplitude intensity of the pulse electromagnetic wave 10a and the amplitude intensity of the pulse electromagnetic wave 10b are simultaneously detected by the detection element 19, so that the amplitude of the pulse electromagnetic wave 10a generated by the irradiation of one pump light L2 is detected.
- the amplitude intensity of the pulse electromagnetic wave 10b is subtracted from the amplitude intensity of the pulse electromagnetic wave 10a.
- the measuring device 50 measures the characteristics of the solution containing the substance to be detected (changes in the state of the solution).
- the measurement method using the pulse electromagnetic wave 10 When the measurement method using the pulse electromagnetic wave 10 is not applied to the measurement apparatus 50 according to the second embodiment, for example, the amplitude intensity is measured without removing noise due to shaking of the solution or the like.
- the measurement method using the pulse electromagnetic wave 10 when the measurement method using the pulse electromagnetic wave 10 is applied to the measurement apparatus 50 according to the second embodiment, it is possible to cancel the noise derived from the solution. In this way, by applying the measurement method using the pulsed electromagnetic wave to the measurement apparatus 50 according to the second embodiment, noise derived from the solution is canceled and detection sensitivity and detection accuracy are dramatically improved. Can do. *
- the detection sensitivity and detection accuracy of the measuring device can be improved.
- an apparatus for detecting an interaction reaction (antigen-antibody, enzyme reaction, allergic reaction, etc.) between biological substances with high throughput.
- an interaction reaction antigen-antibody, enzyme reaction, allergic reaction, etc.
- it can be widely used in fields such as clinical testing, tailor-made medicine, medical research, drug development, environmental pollutant evaluation, food safety management, and agricultural chemical testing.
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Abstract
Description
半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を備え、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測装置であって、
前記パルスレーザー光を2分割する第1ビームスプリッタと、
前記絶縁体上に配置され、被検出物質を含む溶液が導入可能である検出領域部と、
前記絶縁体上の前記検出領域近傍に配置され、参照溶液が導入可能である参照領域部と、を備え、
前記パルスレーザー光を、前記第1ビームスプリッタにより2分割し、分割された一方のパルスレーザー光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方のパルスレーザー光を前記参照領域に対応する前記半導体に照射し、前記検出領域及び前記参照領域に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段により検出するパルス電磁波を用いた計測装置であ
る。
前記パルスレーザー光をプローブ光とポンプ光とに2分割する第2ビームスプリッタと、
前記プローブ光の光路に配置され、前記検出手段にて前記振幅強度が検出される時間を遅延可能である時間遅延手段と、をさらに備え、
前記ポンプ光は、前記第1ビームスプリッタにより2分割され、分割された一方の前記ポンプ光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を前記参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段に入射し、
前記プローブ光は、前記時間遅延手段を通過し、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射し、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出するパルス電磁波を用いた計測装置である。
前記時間遅延手段は、前記検出手段にて前記振幅強度が検出される時間を周期的に時間
遅延可能であるパルス電磁波を用いた計測装置である。
前記パルスレーザー光をプローブ光とポンプ光とに2分割する第2ビームスプリッタと、
前記第1ビームスプリッタと前記半導体との間における前記ポンプ光の光路に配置され、前記ポンプ光のパルスタイミングを任意に調整可能であるパルスタイミング調整手段と、をさらに備え、
前記ポンプ光は、前記第1ビームスプリッタにより2分割され、分割された一方の前記ポンプ光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を前記参照領域部に対応する前記半導体に照射し、かつ前記一方又は他方のポンプ光のうちどちらか一方を前記パルスタイミング調整手段を通過させ、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段に入射し、
前記パルスタイミング調整手段は、前記検出手段にて検出される前記各々のパルス電磁波の振幅強度の検出タイミングが一致するように、前記両方のポンプ光のうち一方のポンプ光のパルスタイミングが予め調整され、
前記プローブ光は、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射し、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出するパルス電磁波を用いた計測装置である。
半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を用いて、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測方法であって、
前記パルスレーザー光をプローブ光とポンプ光とに2分割する分割工程と、
前記ポンプ光を2分割し、分割された一方の前記ポンプ光を前記被検出物質を含む溶液が導入可能である検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を参照溶液が導入可能である参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光して、ひとつの前記検出手段に入射する入射工程と、
前記プローブ光を、所定の周期にて時間遅延させながら、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射する工程と、
前記プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出することで、前記検出領域部及び前記参照領域部のそれぞれにおける遅延時間の異なる複数の前記パルス電磁波の振幅強度を取得して、前記検出領域及び前記参照領域のそれぞれにおける前記パルス電磁波の時系列波形を生成する時系列波形生成工程と、
前記時系列波形生成工程で生成された前記検出領域及び前記参照領域のそれぞれにおける前記パルス電磁波の時系列波形から各々の波形ピーク位置における振幅強度を取得する振幅強度取得工程と、
前記検出領域の波形ピーク位置と前記参照領域の波形ピーク位置における各振幅強度の差分を行う差分工程と、を有するパルス電磁波を用いた計測方法である。
半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を用いて、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測方法であって、
前記パルスレーザー光をプローブ光とポンプ光とに2分割する分割工程と、
前記ポンプ光を2分割し、分割された一方の前記ポンプ光を前記被検出物質を含む溶液が導入可能である検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を参照溶液が導入可能である参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光して、ひとつの前記検出手段に入射する入射工程と、
前記検出手段にて検出される前記各々のパルス電磁波の振幅強度の検出タイミングが一致するように前記両方のポンプ光のうち一方のポンプ光のパルスタイミングを予め調整するパルスタイミング調整工程と、
前記プローブ光を、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射する工程と、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出する工程と、を有するパルス電磁波を用いた計測方法である。
2 パルスレーザー光源
4 検出・変換装置
5 物質検出プレート
9 パルスレーザー光
10 パルス電磁波
12 流路(検出領域部)
13 参照領域部
14 第2ビームスプリッタ
15 時間遅延手段
17 第1ビームスプリッタ
18、40 集光手段
22 絶縁体
23 半導体
溶液濃度分布計測装置1(以下、計測装置1という)は、パルス電磁波10を用いた計測装置であり、半導体23と当該半導体23上に作製される絶縁体22と当該絶縁体22上に作製される物質感応膜21とを有する物質検出プレート5(センシングプレート)と、前記絶縁体22(物質感応膜21)上に配置され、被検出物質を含む溶液が導入可能な検出領域部である被検出物質を含む溶液を流すための流路12と、前記絶縁体22(物質感応膜21)上の前記流路12近傍に配置され、参照溶液が導入可能である参照領域部13(図7参照)と、溶液の電位を安定させる手段(後述する参照電極26)と、前記物質検出プレート5にパルスレーザー光9を前記絶縁体22の反対側である前記半導体23側から前記流路12に対応する位置に照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波10を発生させる手段(パルスレーザー光源2)と、前記パルスレーザー光源2から照射されたパルスレーザー光9をプローブ光L1とポンプ光L2とに2分割する第2ビームスプリッタ14と、前記パルスレーザー光9を2次元的に走査して照射する手段(走査台7、パルスレーザー光源2)と、前記パルス電磁波10の振幅強度を計測する手段(検出・変換装置4)と、前記プローブ光L1の光路に配置され、前記検出・変換装置4にて前記振幅強度が検出される時間を周期的に遅延可能である時間遅延手段15と、前記振幅強度より、被検出物質を定性的もしくは定量的に計測して前記流路12内の溶液中の物質の反応分布もしくは濃度分布を得る手段(制御・解析装置8)等を備える。また、本実施例においては、後述する物質感応膜21が、前記流路形成部6内の流路12の内壁面の一部(本実施例では、流路12内壁面の底部)を構成している。以下、本発明に係る原理、及び、装置構成の詳細について説明する。
なお、前記制御・解析装置8は、特に溶液中の物質の反応分布もしくは濃度分布を得る手段に限定するものではなく、前記被検出物質を含む溶液の特性及びその変化、並びに、溶液の状態の変化を計測する手段である。
また、本実施例においては前記流路12の内壁面において、物質検出プレート5側に位置する部分を便宜上底部とする。
図1は、本実施例の溶液濃度分布計測装置の概略図である。この図に示すように、本実施例の計測装置1は、照射装置(光学系)、検出・変換装置4、及び制御・解析装置8を備える。
なお、パルスレーザー光9の方向を変更するために使用した鏡等の構成は、本実施形態に限定するものではなく、各構成部品の配置を考慮して、例えば更に鏡の数を増やす等適宜構成を変更してもかまわない。
また、このパルスレーザー光9の波長は、300ナノメートル(300nm=0.3μm)以上、2ミクロン(2μm)以下の範囲に含まれるものであり、時間平均のエネルギーが0.1mW以上、10W以下であり、パルス幅が1フェムト秒(1fs=0.001ps)以上、10ピコ秒(10ps)以下であるのがよい。
すなわち、電磁波の励起に際しては、光源として時間の幅の小さなパルスレーザー光9を用いることにより、半導体23及び溶液に大きな影響を及ぼさない状態で、電磁波の励起ができる。また、特にパルスレーザー光9としてフェムト秒レーザー光を使用することで、高い時間分解能による時間分解計測が可能となり、物質の反応をリアルタイムで観測可能となる。なお、半導体23及び溶液に熱的影響を及ぼさない最大光パルス幅は、約10ピコ秒と見積ることができる。また、フェムト秒レーザーを使用することで、微小量の溶液であっても、レーザーによる加熱の影響を最小限に抑えることができ、試料の熱破壊を抑制できるという効果がある。
すなわち、時間遅延手段15は、前記プローブ光L1の光路長を調整するための可動鏡15aを周期的に移動させることで所定時間間隔の時間遅延量を付与したプローブ光L1を前記検出・変換装置4(検出・変換装置4が有する後述する検出素子19)に入射することができる。
なお、前記第1ビームスプリッタ17の例としては、図12に示すレーザー光の分離方法のように、(a)第1実施例の如く、ビームスプリッタ用平板である第1ビームスプリッタ17を用いて平板内での内部反射により分離する方法、(b)後述する第2実施例の如く、ハーフミラー36と鏡37により分離する方法、(c)ガルバノミラー38によるレーザースキャン等が挙げられる。
なお、流路12の形状としては特にクランク状に限定するものではなく、溶液反応の種類等により適宜変更してもかまわない。例えば、流路形状としては直線状、蛇行状、Y字状等などがあげられる。
また、流路12の近傍に加熱もしくは冷却手段を設けて流路形成部6を構成することも可能である。
なお、上記参照電極26は、計測装置1の構成上予備的に設けたものであり、参照領域部13を適用する場合は不要であり、計測装置1においては参照電極26及びリード線25を設けない構成とすることも可能である。
なお、本実施例における計測装置1は、前記パルスレーザー光9を2次元的に走査して照射する手段(走査台7、パルスレーザー光源2)を備えているが、計測を行う際に必ず走査を行う必要はなく、計測環境に応じて走査の要不要を判断し適宜使用すればよい。
こうして、前記被検出物質を含む溶液の特性(溶液の状態の変化)を計測する。以下に、具体的な被検出物質の計測例を示す。
図11に示すアンモニア濃度変化は、尿素溶液を流路12に貯留し、ウレアーゼ(酵素)を含む物質感応膜21の触媒作用により、尿素が加水分解され、アンモニアが発生し、溶液中の尿素濃度が減少する変化を示したものである。
図11における(a)は計測装置1において本実施形態に係るパルス電磁波10を用いた計測方法を適用しない場合の尿素濃度変化、(b)は計測装置1においてに本実施形態に係るパルス電磁波10を用いた計測方法を適用した場合の尿素濃度変化である。
図11の(a)と(b)を比較すると、本実施形態に係るパルス電磁波10を用いた計測方法を適用しない場合(図11(a))は、溶液の揺れ等によるノイズがのっているために尿素濃度変化と振幅強度との関係にばらつきが生じている。一方、本実施形態に係るパルス電磁波10を用いた計測方法を適用した場合(図11(b))は、前記差分工程S60により溶液由来のノイズがキャンセルされるため、尿素濃度変化と振幅強度との関係がほぼ比例的に変化(濃度減少に伴って振幅強度が減少)していることがわかる。このように、本実施形態に係る計測装置1に上記パルス電磁波を用いた計測方法を適用することにより、溶液に由来するノイズをキャンセルして、飛躍的に検出感度及び検出精度を向上することができる。
なお、第2実施例に係るパルス電磁波を用いた計測装置が用いる本発明に係る原理は、上述した原理と同じであり、第2実施例に係るパルス電磁波を用いた計測装置において、第1実施例で説明した計測装置1と共通の部材や共通の機能を有する部分については、同じ符号で示し、その詳細な説明を省略する。
なお、前記制御・解析装置8は、特に溶液中の物質の反応分布もしくは濃度分布を得る手段に限定するものではなく、前記被検出物質を含む溶液の特性及びその変化、並びに、溶液の状態の変化を計測する手段である。また、本実施形態における溶液濃度分布計測装置(計測装置1及び計測装置50)により計測可能である「溶液の状態の変化」とは、例えば、溶液のイオン濃度の変化、試料溶液中の抗原抗体反応の進行状態変化(試料溶液としては、例えば、血液、体液、その他の抗原を含む溶液等)、溶液中における種々の化学反応状態の変化、等が挙げられるとともに、これらの時間経過毎の変化を含むものである。
また、本実施例においては前記流路12の内壁面において、物質検出プレート5側に位置する部分を便宜上底部とする。
なお、パルスレーザー光9の方向を変更するために使用した鏡等の構成は、本実施形態に限定するものではなく、各構成部品の配置を考慮して、例えば更に鏡の数を増やす等適宜構成を変更してもかまわない。
なお、照射装置(光学系)は、図15に示すように、プローブ光L1の光路に時間遅延手段15を有した構成とすることも可能である。時間遅延手段15を設けた場合、時間遅延手段15は定期的な計測装置の校正時に使用することができる。第2実施例においては、時間遅延手段15を有しない計測装置50の構成を示す。
また、前記第1ビームスプリッタ17により分割された2つの平行光であるポンプ光L2が前記半導体23に照射するまでの2つのポンプ光L2の光路のうち、一方のポンプ光L2の光路(図13では、2つのポンプ光L2のうち上側に示すポンプ光L2の光路)にパルスタイミング調整器39が配置されている。
なお、パルスタイミング調整器39を配置するポンプ光L2の光路は、ビームスプリッター17により2つに分割された平行光であるポンプ光L2のうち、どちらか一方のポンプ光L2の光路上に配置すればよい。
なお、本実施例における計測装置50は、前記パルスレーザー光9を2次元的に走査して照射する手段(走査台7、パルスレーザー光源2)を備えているが、計測を行う際に必ず走査を行う必要はなく、計測環境に応じて走査の要不要を判断し、前記照射する手段(走査台7、パルスレーザー光源2)を適宜使用すればよい。
なお、本実施例では、パルスタイミング調整器39に、検出領域部である流路12に対応する半導体23に照射されるポンプ光L2を通過させる構成としているが、特に限定するものではない。例えば、パルスタイミング調整器39に、参照領域部13に対応する半導体23に照射されるポンプ光L2を通過させる構成としてもかまわない。つまり、パルスタイミング調整器39に、ビームスプリッタ17により分割された2つのポンプ光L2のうちどちらか一方のポンプ光L2を通過させる構成とすればよい。
なお、パルスタイミング調整工程S300は、入射工程S200の後工程として必ずしも実行する必要はない。例えば、パルスタイミング調整工程S300は、計測装置50を用いて計測を行う前の計測準備段階や計測装置50による計測結果を計測者や制御・解析装置8がモニターしている時など、他の工程に関係なく、必要に応じて適宜実行してもかまわない。
Claims (6)
- 半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を備え、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測装置であって、
前記パルスレーザー光を2分割する第1ビームスプリッタと、
前記絶縁体上に配置され、被検出物質を含む溶液が導入可能である検出領域部と、
前記絶縁体上の前記検出領域近傍に配置され、参照溶液が導入可能である参照領域部と、を備え、
前記パルスレーザー光を、前記第1ビームスプリッタにより2分割し、分割された一方のパルスレーザー光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方のパルスレーザー光を前記参照領域に対応する前記半導体に照射し、前記検出領域及び前記参照領域に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段により検出することを特徴とするパルス電磁波を用いた計測装置。 - 前記パルスレーザー光をプローブ光とポンプ光とに2分割する第2ビームスプリッタと、
前記プローブ光の光路に配置され、前記検出手段にて前記振幅強度が検出される時間を遅延可能である時間遅延手段と、をさらに備え、
前記ポンプ光は、前記第1ビームスプリッタにより2分割され、分割された一方の前記ポンプ光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を前記参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段に入射し、
前記プローブ光は、前記時間遅延手段を通過し、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射し、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出することを特徴とする請求項1に記載のパルス電磁波を用いた計測装置。 - 前記時間遅延手段は、前記検出手段にて前記振幅強度が検出される時間を周期的に時間遅延可能であることを特徴とする請求項2に記載のパルス電磁波を用いた計測装置。
- 前記パルスレーザー光をプローブ光とポンプ光とに2分割する第2ビームスプリッタと、
前記第1ビームスプリッタと前記半導体との間における前記ポンプ光の光路に配置され、前記ポンプ光のパルスタイミングを任意に調整可能であるパルスタイミング調整手段と、をさらに備え、
前記ポンプ光は、前記第1ビームスプリッタにより2分割され、分割された一方の前記ポンプ光を前記検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を前記参照領域部に対応する前記半導体に照射し、かつ前記一方又は他方のポンプ光のうちどちらか一方を前記パルスタイミング調整手段を通過させ、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光手段により集光して、ひとつの前記検出手段に入射し、
前記パルスタイミング調整手段は、前記検出手段にて検出される前記各々のパルス電磁波の振幅強度の検出タイミングが一致するように、前記両方のポンプ光のうち一方のポンプ光のパルスタイミングが予め調整され、
前記プローブ光は、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射し、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出することを特徴とする請求項1に記載のパルス電磁波を用いた計測装置。 - 半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を用いて、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測方法であって、
前記パルスレーザー光をプローブ光とポンプ光とに2分割する分割工程と、
前記ポンプ光を2分割し、分割された一方の前記ポンプ光を前記被検出物質を含む溶液が導入可能である検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を参照溶液が導入可能である参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光して、ひとつの前記検出手段に入射する入射工程と、
前記プローブ光を、所定の周期にて時間遅延させながら、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射する工程と、
前記プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出することで、前記検出領域部及び前記参照領域部のそれぞれにおける遅延時間の異なる複数の前記パルス電磁波の振幅強度を取得して、前記検出領域及び前記参照領域のそれぞれにおける前記パルス電磁波の時系列波形を生成する時系列波形生成工程と、
前記時系列波形生成工程で生成された前記検出領域及び前記参照領域のそれぞれにおける前記パルス電磁波の時系列波形から各々の波形ピーク位置における振幅強度を取得する振幅強度取得工程と、
前記検出領域の波形ピーク位置と前記参照領域の波形ピーク位置における各振幅強度の差分を行う差分工程と、を有することを特徴とするパルス電磁波を用いた計測方法。 - 半導体と当該半導体上に作製される絶縁体とを有する物質検出プレートと、
前記物質検出プレートにパルスレーザー光を前記半導体側から照射することで、照射位置における被検出物質の量に依存する振幅強度を持ったパルス電磁波を発生させる手段と、
前記パルス電磁波の振幅強度を検出する検出手段と、を用いて、
前記振幅強度より、前記被検出物質を含む溶液の状態の変化を計測するパルス電磁波を用いた計測方法であって、
前記パルスレーザー光をプローブ光とポンプ光とに2分割する分割工程と、
前記ポンプ光を2分割し、分割された一方の前記ポンプ光を前記被検出物質を含む溶液が導入可能である検出領域部に対応する前記半導体に照射するとともに、分割された他方の前記ポンプ光を参照溶液が導入可能である参照領域部に対応する前記半導体に照射し、前記検出領域部及び前記参照領域部に対応する前記半導体から発生する各々のパルス電磁波を集光して、ひとつの前記検出手段に入射する入射工程と、
前記検出手段にて検出される前記各々のパルス電磁波の振幅強度の検出タイミングが一致するように前記両方のポンプ光のうち一方のポンプ光のパルスタイミングを予め調整するパルスタイミング調整工程と、
前記プローブ光を、前記ポンプ光により発生した前記各々のパルス電磁波の入射と同期させて前記検出手段に照射する工程と、
当該プローブ光の照射時に前記検出手段に入射した前記ポンプ光による前記各々のパルス電磁波の振幅強度を検出する工程と、を有することを特徴とするパルス電磁波を用いた計測方法。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2013161860A1 (ja) * | 2012-04-24 | 2013-10-31 | 国立大学法人岡山大学 | 半導体非破壊検査装置及び半導体非破壊検査方法 |
JP2014167443A (ja) * | 2013-02-28 | 2014-09-11 | Dainippon Screen Mfg Co Ltd | 検査装置および検査方法 |
JP6266719B1 (ja) * | 2016-08-31 | 2018-01-24 | フェムトディプロイメンツ株式会社 | テラヘルツ時間領域分光装置 |
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Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007064700A (ja) * | 2005-08-30 | 2007-03-15 | Canon Inc | センシング装置 |
JP2007078621A (ja) * | 2005-09-16 | 2007-03-29 | Canon Inc | センシング装置 |
JP2008170353A (ja) * | 2007-01-12 | 2008-07-24 | Okayama Univ | 物質検出装置、物質検出、物質検出プレート、及び、測定セル |
JP2008277565A (ja) * | 2007-04-27 | 2008-11-13 | Matsushita Electric Ind Co Ltd | テラヘルツ波発生装置 |
JP4183735B1 (ja) * | 2007-10-15 | 2008-11-19 | 国立大学法人 岡山大学 | 物質分布計測装置 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07100753B2 (ja) | 1990-11-19 | 1995-11-01 | 昭島化学工業株式会社 | 熱安定化された塩素含有樹脂組成物 |
JP2004198250A (ja) | 2002-12-18 | 2004-07-15 | Tochigi Nikon Corp | 時間分解反射測定方法およびテラヘルツ時間分解反射測定装置 |
GB2411093B (en) * | 2004-02-13 | 2007-10-24 | Teraview Ltd | Terahertz imaging system |
JP4910223B2 (ja) * | 2005-12-27 | 2012-04-04 | レンセラール ポリテクニック インスティチュート | テラヘルツ放射線を検出する光学技術を利用して離れたところにある物体を分析する方法 |
-
2011
- 2011-02-07 JP JP2011552854A patent/JP5807957B2/ja active Active
- 2011-02-07 WO PCT/JP2011/052529 patent/WO2011096563A1/ja active Application Filing
- 2011-02-07 US US13/577,604 patent/US8710440B2/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007064700A (ja) * | 2005-08-30 | 2007-03-15 | Canon Inc | センシング装置 |
JP2007078621A (ja) * | 2005-09-16 | 2007-03-29 | Canon Inc | センシング装置 |
JP2008170353A (ja) * | 2007-01-12 | 2008-07-24 | Okayama Univ | 物質検出装置、物質検出、物質検出プレート、及び、測定セル |
JP2008277565A (ja) * | 2007-04-27 | 2008-11-13 | Matsushita Electric Ind Co Ltd | テラヘルツ波発生装置 |
JP4183735B1 (ja) * | 2007-10-15 | 2008-11-19 | 国立大学法人 岡山大学 | 物質分布計測装置 |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013170899A (ja) * | 2012-02-20 | 2013-09-02 | Canon Inc | 測定装置及び測定方法、トモグラフィー装置 |
WO2013161860A1 (ja) * | 2012-04-24 | 2013-10-31 | 国立大学法人岡山大学 | 半導体非破壊検査装置及び半導体非破壊検査方法 |
JPWO2013161860A1 (ja) * | 2012-04-24 | 2015-12-24 | 国立大学法人 岡山大学 | 半導体非破壊検査装置及び半導体非破壊検査方法 |
JP2014167443A (ja) * | 2013-02-28 | 2014-09-11 | Dainippon Screen Mfg Co Ltd | 検査装置および検査方法 |
JP6266719B1 (ja) * | 2016-08-31 | 2018-01-24 | フェムトディプロイメンツ株式会社 | テラヘルツ時間領域分光装置 |
JP2018036121A (ja) * | 2016-08-31 | 2018-03-08 | フェムトディプロイメンツ株式会社 | テラヘルツ時間領域分光装置 |
WO2018042938A1 (ja) * | 2016-08-31 | 2018-03-08 | フェムトディプロイメンツ株式会社 | テラヘルツ時間領域分光装置 |
US10352849B2 (en) | 2016-08-31 | 2019-07-16 | Femto Deployments Inc. | Terahertz time domain spectroscopic apparatus |
CN109187419A (zh) * | 2018-08-28 | 2019-01-11 | 清华大学深圳研究生院 | 支柱绝缘子孔泡检测方法及装置、终端、存储介质 |
CN109187419B (zh) * | 2018-08-28 | 2021-04-06 | 清华大学深圳研究生院 | 支柱绝缘子孔泡检测方法及装置、终端、存储介质 |
CN113899923A (zh) * | 2021-10-18 | 2022-01-07 | 中国人民解放军军事科学院国防工程研究院工程防护研究所 | 一种hemp辐射场与注入能量同步加载试验环境模拟***及方法 |
CN113899923B (zh) * | 2021-10-18 | 2024-02-23 | 中国人民解放军军事科学院国防工程研究院工程防护研究所 | 一种hemp辐射场与注入能量同步加载试验环境模拟***及方法 |
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US20120305774A1 (en) | 2012-12-06 |
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