JP2009063462A - Optical measuring instrument and particulate analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optical measuring instrument having high measuring precision and high efficiency. <P>SOLUTION: The optical measuring instrument 1 includes at least a substrate 11 to which a flow channel X capable of introducing particulates S is arranged, a light source 12 for irradiating the particulates S with measuring light L12, and a detection part 13 for detecting detection target light L occurring by the irradiation with the measuring light L12 and characterized in that the surface of the flow channel of the substrate 11 is treated so as to emit the detection target light in a predetermined direction by at least either one of the reflection or refraction of the detection target light from the surface of the flow channel. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an optical measurement device and a particle analysis device. More specifically, the present invention relates to a technique for performing optical measurement on a substrate having a flow path into which microparticles can be introduced.

  Since directional light such as laser has the same wavelength and the same phase, when it is focused with a lens, the light can be collected at a small point, and the energy density at the irradiation point is high. Have. Therefore, directional light such as laser is widely used for spectroscopic measurement and the like.

  Laser spectroscopy can be classified into linear laser spectroscopy and nonlinear laser spectroscopy. Linear laser spectroscopy for measuring absorption spectra and excitation spectra is also more sensitive and has higher resolution than spectroscopy using conventional light sources. Non-linear laser spectroscopy enables higher sensitivity and higher resolution spectroscopy. Examples of such include laser-induced fluorescence spectroscopy, laser-Raman spectroscopy, CARS (Coherent anti-Stokes Raman Scattering), polarization spectroscopy, resonance ionization spectroscopy, and photoacoustic spectroscopy. In particular, the one with high time resolution is also called picosecond spectroscopy or femtosecond spectroscopy.

  For example, laser irradiation technology is also used for flow cytometry (Non-Patent Document 1). Flow cytometry is a measurement technique in which cells to be measured are sorted (sorted) while they are alive to analyze cell functions and the like. The cells are poured into the laminar flow and the laser passing through the flow cell is irradiated with a laser. The fluorescence and scattered light generated thereby are measured. In the pulse detection system, fluorescence or scattered light generated when a cell crosses the laser is detected as an electric pulse, and analysis is performed by analyzing a pulse height, a pulse width, a pulse area, and the like. Accordingly, the characteristics of each cell can be analyzed alive by detecting scattered light and fluorescence emitted from each cell.

  Such spectroscopic measurement is performed, for example, on a substrate provided with a flow path. FIG. 6 is a schematic diagram for explaining an example of a conventional optical measurement apparatus. A symbol A in FIG. 6 indicates an optical measuring device. In the optical measuring apparatus A, a flow path X is provided on a substrate A1. And in the flow path X, the microparticle S exists as a sample. For example, the measurement is performed while flowing a liquid or the like as a medium together with the microparticles S in the channel X. The microparticles S are irradiated with the measurement light L2 from the light source A2. Fluorescence, scattered light, and the like generated thereby are detected as detection target lights L3 and L4 by detectors A3 and A4, respectively.

Published by Hiromitsu Nakauchi, “Cellular Engineering Separate Experiment Protocol Series Flow Cytometry Free,” Shujunsha, p12-p13, 2nd Edition, August 31, 2006.

  However, when the measurement is performed in a planar flow path, the detection target light is scattered forward and sideward, so that there is a problem that the light collection efficiency is lowered. Therefore, the main object of the present invention is to provide an optical measuring device with high measurement accuracy and high efficiency.

First, the present invention provides a substrate on which a flow path capable of introducing microparticles is disposed, a light source that irradiates measurement light to the microparticles, and detection that detects detection target light generated by the irradiation of the measurement light. And an optical measuring device that processes the flow path surface of the substrate so that the detection target light is emitted in a predetermined direction by at least one of reflection and refraction on the flow path surface. By emitting detection target light that may be scattered in a predetermined direction, the detection unit can receive light efficiently. As a result, it is possible to improve the light collection efficiency and to improve the measurement accuracy of the optical measurement while having a simple device structure.
Next, the present invention provides an optical measurement apparatus in which the predetermined direction is coaxial with the incident direction of the measurement light irradiation. By emitting the detection target light in a direction coaxial with the incident direction of the measurement light, not only forward scattered light but also side scattered light can be efficiently condensed.
Subsequently, the present invention provides an optical measurement apparatus in which at least a wavelength selection film that transmits light of a predetermined wavelength is formed in the flow path. By providing a wavelength selection film that transmits light of a predetermined wavelength, it is possible to efficiently collect detection target light to be detected.
In addition, the present invention provides an optical measurement device including at least a region in which the angle of the flow channel surface with respect to the cross-sectional view of the flow channel and the incident direction of the measurement light is approximately 45 degrees. Thereby, the light scattered to the side of the fine particles can be efficiently reflected and emitted in a predetermined direction.
Furthermore, by making the substrate have a structure in which the flow path layer is laminated on the support layer, it is possible to prevent the substrate from warping or deformation.
The present invention also provides an optical measurement apparatus in which a flow path is also disposed in the support layer. By providing a channel in the support layer, optical measurement can be performed on both sides of the substrate.

  ADVANTAGE OF THE INVENTION According to this invention, it can be set as the optical measuring apparatus which can perform a highly efficient optical measurement on a board | substrate with a high measurement precision.

  DESCRIPTION OF EXEMPLARY EMBODIMENTS Hereinafter, preferred embodiments of an optical measurement device and a particle analysis device according to the invention will be described with reference to the accompanying drawings. Each embodiment shown in the accompanying drawings is an exemplification of the present invention, and the scope of the present invention is not interpreted narrowly.

  FIG. 1 is a schematic side view of a first embodiment of an optical measuring device according to the present invention.

  Reference numeral 1 in FIG. 1 indicates an optical measuring device 1. The optical measurement apparatus 1 includes a substrate 11, a light source 12, and a detection unit 13. Hereinafter, the symbol S indicates the fine particles to be irradiated.

  Optical measurement is performed by irradiating the microparticle S with the measurement light L12 from the light source 12 and detecting the detection target lights L131, L132, and L133 obtained by the detection unit 13 (see reference numerals 131, 132, and 133). Is what you do.

  The type of light to be detected is not limited, and the necessary light can be appropriately selected in consideration of the type of microparticles S, measurement conditions, and the like. Examples of the detection target light include fluorescence and scattered light emitted from the microparticles S. The detection target light is detected by, for example, labeling the microparticles S with a specific fluorescent material in advance and irradiating the excitation light from the light source 12 as the measurement light L12. The fluorescence emitted by this is detected as detection target light.

  When a fluorescent dye is used, for example, the measurement light L12 can be directional light, and a fluorescent dye corresponding to this wavelength (for example, the wavelength of the laser) can be used.

  For example, in the case of an Ar ion laser (488 nm), fluorescent dyes such as FITC (fluorescein isothiocyanate), PE (phycoerythrin), and PerCP (peridinin chlorophyll protein) can be used. In the case of a He—Ne laser (633 nm), a fluorescent dye such as APC (allophycocyanin) or APC-Cy7 can be used. In the case of a die laser (598 nm), a fluorescent dye such as TR (Texas Red) can be used. In the case of a Cr laser (407 nm) laser or a semiconductor laser, a fluorescent dye such as Cascade Blue can be used.

  The detection target light may be detected by detecting scattered light from the microparticles S without performing labeling or the like. For example, the scattered light generated by irradiating the microparticle S with the measurement light L22 may be detected. Also in this case, for example, by using the light L22 as directional light, more accurate position information can be detected. Examples of the scattered light include forward scattered light (see reference L131) and side scattered light (see reference L132 and L133).

  In the present invention, the detection target lights L131, L132, and L133 are reflected or interfered by the reflection films 1111, 1111, and 1111 provided on the flow path surface of the flow path layer 11. Thus, by making it radiate | emit in a predetermined direction, detection object light can be condensed efficiently and this can be detected by the detection part 13. FIG. In particular, the detection accuracy of the detectors 131, 132, and 133 can be improved by emitting the detection target lights L131, L132, and L133 toward the installation directions of the corresponding detectors 131, 132, and 133, respectively. .

  As for the structure of the substrate 11, it is more preferable that the substrate 11 has a region in which the angle of the channel surface with respect to the sectional view of the channel X and the incident direction of the measurement light L12 is approximately 45 degrees (see FIG. 1). ). Thereby, the side scattered light, fluorescence, etc. which come out from the side of the microparticle S can be efficiently reflected and emitted in a predetermined direction (see, for example, the detection target lights L132 and L133). Therefore, it can be set as the outstanding light condensing efficiency.

  Therefore, according to the present invention, the measurement accuracy can be improved while having a simple device structure. The predetermined direction can be appropriately adjusted in consideration of the apparatus structure and the like, but is preferably coaxial with the measurement light L12. Furthermore, it is desirable that the incident direction of the measurement light L12 is a direction facing substantially perpendicular to the surface of the flow path. Thereby, the side scattered light etc. which are scattered in the four circumferences can be condensed efficiently.

  Hereinafter, each configuration of the optical measuring device 1 will be described in more detail.

  The substrate 11 has a structure including a flow path X into which the fine particles S can be introduced. The flow path X is formed by laminating the flow path layer 111 and the flow path protection layer 112. The flow path surface of the flow path layer 111 is formed by a reflective film 1111. In FIG. 1, the structure in the flow path X is simplified, but the microparticles S can move in the flow path X by flowing a medium in the flow path X. FIG. 1 shows a state in which the microparticles S are moving in the direction perpendicular to the paper surface, and is a state in which the channel width of the channel X is viewed from the front.

  In the present invention, the type of fine particles S present in the flow path X is not limited. For example, the microparticle S may be a microstructure such as various living cells or beads. Moreover, the medium in the flow path X should just be a fluid, and various solutions, gas, etc. can be used for it. A suitable medium can be selected in consideration of the fine particles S, irradiation conditions, and the like.

  The flow path surface of the flow path layer 111 may be processed so that the detection target lights L131, L132, and L133 can be reflected or refracted by the flow path surface, and the processing method is not limited. Absent. As a processing method, for example, a reflective film 1111 may be provided on a predetermined surface or a plurality of surfaces of the flow path surface.

  Moreover, you may provide the interference film which can strengthen reflected light intensity on the flow-path surface. As a result, the light intensities of the detection target lights L131, L132, and L133 can be amplified, which is desirable because the measurement accuracy can be further improved. Although what is used as such an interference film is not limited, for example, a dielectric multilayer film filter (interference film filter) using multilayer film interference and the like can be mentioned. Further, by performing surface treatment using thin film interference on the flow path surface, the flow path surface can be designed to have an arbitrary transmittance or reflectance.

  More preferably, it is desirable to provide a wavelength selection film that transmits light of a predetermined wavelength. In particular, it is desirable to form the wavelength selection film so as to face substantially perpendicular to the incident direction of the measurement light L12 on the channel surface. An example of this will be described later.

  The type of the light source 12 is not particularly limited, but is preferably a directional light source such as a laser or an LED (Light Emission Diode). When a laser is used as the measurement light L12, examples of the medium include a semiconductor laser, a liquid laser, a gas laser, and a solid laser.

Examples of semiconductor lasers include GaAs lasers and InGaAsP lasers. Examples of the gas laser include He—Ne laser (red), Ar laser (visible, blue, or green), CO ₂ laser (infrared), and excimer laser (purple, etc.). Examples of the liquid laser include a dye laser. Examples of the solid laser include a ruby laser, a YAG laser, and a glass laser. Further, a DPSS (diode-excited solid state laser) that excites and oscillates a solid medium such as Nd: YAG with a laser diode (LD) can also be used.

  Although not shown, a scanning unit for the measurement light L12 can be separately provided. The optical measurement apparatus 1 according to the present invention includes a light source 12 that emits measurement light L12 that is an irradiation spot smaller than the flow path width of the flow path X, and scanning means that scans the measurement light L12 in the flow path width direction. Furthermore, it is desirable to provide an optical measuring device provided. Thereby, sufficient and accurate light irradiation can be performed on the fine particles S. Therefore, not only the light condensing efficiency after irradiation but also an optical measuring device excellent in irradiation efficiency during irradiation can be obtained. Thereby, a measurement result with higher accuracy can be obtained. It is particularly suitable when the measurement light L12 is directional light such as a laser.

  By irradiating the measurement light L12 while scanning in the flow path width direction, a plurality of irradiation spots can be created across the width direction of the flow path X. As a result, it is possible to reliably and sufficiently irradiate the fine particles S moving in the flow path X. When the microparticles S move in the channel X, the position of the microparticles S in the channel X changes. In particular, when the size of the microparticle S is considerably smaller than the channel width of the channel X, the microparticle S moves in the channel X with a certain degree of freedom. For this reason, large irradiation unevenness, irradiation position shift, focus position shift, and the like may occur. This is a cause of a decrease in the irradiation efficiency of the measurement light L12.

  In this regard, the beam spot diameter is increased or the irradiation time is increased. However, there are restrictions on the light source such as the output power of the light source must be increased in order to increase the energy density of the beam spot and the irradiation time is limited. On the other hand, in the present invention, the measurement light L12 having a small beam spot diameter is irradiated while scanning in the channel width direction. Thereby, the light beam can be reliably and sufficiently irradiated with light without enlarging the beam spot diameter and without irradiating for a long time.

  In this case, it is desirable to perform the surface treatment on the surface of the flow path of the substrate 11 in consideration of the scanning angle and scanning speed of the measuring light L12. For example, in consideration of the incident angle range of the measurement light L12, a reflection film or an interference film may be provided so that the detection target lights L131, 132, 133 and the like are emitted in a predetermined emission direction.

  The scanning conditions are not particularly limited, but it is desirable to irradiate with light satisfying the following formula (1). By scanning under such conditions, the fine particles S cross the scanning spot one or more times within the time when the scanning spot passes through the channel width of the channel X. As a result, the fine particles S present in the flow channel X can always be detected by the scanning spot.

  The scanning means is not particularly limited, but it is preferable to scan the measurement light L12 with a galvanometer mirror, an electro-optical element, a polygon mirror, a MEMS element, or the like. In particular, since the electro-optic element has no movable part, it is preferable in terms of high stability and reliability. A plurality of these scanning means may be used.

  Further, although not shown, an irradiation control means for performing irradiation control of the measurement light L12 based on position information of the microparticles S in the flow path X may be further provided. Specifically, the position information of the microparticles S in the flow path X is obtained by irradiating a separate light source and light for obtaining the position information of the microparticles S from the light source, and based on this position information. It is desirable that the optical control device further includes an irradiation control means for controlling the irradiation of the light source 12.

  Separately, the position information (for example, the moving speed, the existing position in the flow path X, etc.) of the microparticles S in the flow path X is obtained, and the light irradiation is controlled based on this information, thereby measuring light more accurately. The fine particles S can be irradiated with L12. This position information refers to information relating to the moving speed of the microparticles S existing in the flow channel X, the three-dimensional location, etc., and includes all information related to the vector of the microparticles S in the flow channel X. To do.

  For example, a light irradiation spot for obtaining position information is provided in the flow path X at a position different from the irradiation spot of the measurement light L12. Then, fluorescence or scattered light obtained by irradiating the microparticles S with this light is detected. This detection result can be obtained as position information of the microparticles S.

  Then, this position information is fed back to the optical system of the light source 12 as a trigger timing of light irradiation of the light source 12 or the like. Thereby, the measurement light L12 can be irradiated to a desired irradiation position at an appropriate irradiation timing. Of course, the measurement light L12 emitted from the light source 12 may also be used for obtaining the positional information of the microparticles S and the like.

  In the detection unit 13, the measurement data of the detected light to be detected is converted into a digital signal by an analog-digital converter (ADC) or the like, and this signal is arithmetically processed by a computer, whereby the fine particles S can be measured.

  As the detection unit 13, detectors 131, 132, 133 corresponding to the emission direction of the detection target light can be provided. The number of light to be collected does not need to be three, and the number of detectors is not limited to three. In the present invention, since the detection target lights are emitted in a predetermined direction, the detection target lights L131, L132, and L133 can be condensed into one by a condenser lens or the like. This can also reduce the number of detectors. A detector that detects forward scattered light, a detector that detects side scattered light, and a detector that detects fluorescence can also be provided.

  The optical measurement apparatus according to the present invention can measure fine particles on a substrate on which a flow path is disposed, and furthermore, the substrate can be removed from the apparatus main body, so that the substrate can be disposable. For this reason, it is possible to suppress the contamination of the object to be measured in the repeated use of the substrate, and it is possible to increase the purity of the cell or to suppress the contamination when handling living cells or the like.

  FIG. 2 is a schematic side view of the second embodiment of the optical measuring device according to the present invention.

  Reference numeral 2 in FIG. 2 indicates an optical measuring device. The optical measuring device 2 is characterized in that at least a wavelength selection film that transmits light of a specific wavelength is formed on the surface of the flow path. In the following, description of points in common with the first embodiment will be omitted, and differences will be mainly described.

  The optical measurement apparatus 2 irradiates the measurement light L22 from the light source 22 to the fine particles S existing in the flow path X of the substrate 21. The detection target lights L231, L232, and L233 thus obtained are detected by the detectors 231, 232, and 233 of the detector 23, respectively. Reflective films 2111 and 2111 and a wavelength selection film 2112 are formed on the flow path surface of the substrate 21.

  The substrate 21 includes a flow path layer 211 and a flow path protection layer 212. Then, by providing the wavelength selection film 2112 that transmits light of a predetermined wavelength on the surface of the flow path, the measurement light L22 that does not need to be detected can be transmitted as it is. As a result, the measurement light L22 can be prevented from entering the detection target lights L231, L232, and L233. In particular, it is preferable when detecting forward scattered light (see reference numeral L231) because the measurement accuracy can be further improved. Therefore, the wavelength selection film 2112 is desirably formed so as to face substantially perpendicular to the direction in which the measurement light L22 is incident on the flow path surface (see FIG. 2).

  Although the kind of wavelength selection film | membrane is not limited, For example, optical interference films, such as a silicon nitride, aluminum nitride, a silicon oxide, can be used. More preferably, from the viewpoint of preventing corrosion of the optical interference film by a fluid, it is desirable to use a multilayer structure of these optical interference films, a multilayer structure in which corrosion prevention films are laminated, or the like.

  FIG. 3 is a schematic side view of a third embodiment of the optical measurement apparatus according to the present invention.

  The code | symbol 3 of FIG. 3 has shown the optical measuring apparatus. The optical measuring device 3 is characterized in that the shape of the flow path surface is formed into a curved surface. In the following, common points with the above-described embodiments will be omitted, and differences will be mainly described. Note that FIG. 3 shows only the flow channel structure, and the configuration of the entire apparatus is omitted.

  The optical measuring device 3 irradiates the measurement light L32 to the fine particles S existing in the flow path X of the substrate 31. The detection target light L331, L332, L333, L334, and L335 thus obtained are detected. The substrate 31 includes a flow path layer 311 and a flow path protection layer 312. A reflective film 3111 is formed on the flow path surface of the flow path layer 311, and the shape thereof is a curved surface.

  As described above, the shape of the flow path surface of the flow path X is not limited, but it is more preferable that the shape is a curved surface. It is preferable in that at least the light to be detected such as side scattered light and fluorescence emitted from the microparticles S can be collected and emitted in a predetermined direction. The shape of the curved surface is preferably a parabolic shape so that light condensed by the curved surface structure can be efficiently incident on a detection unit (not shown) using a detection optical lens or the like.

  Although not shown, the detection target light L331, L332, L333, L334, and L335 may be collected by using a condensing lens and then detected by a detection unit (not shown).

  FIG. 4 is a schematic side view of the fourth embodiment of the optical measurement apparatus according to the present invention.

  Reference numeral 4 in FIG. 4 indicates an optical measuring device. The optical measuring device 4 is characterized in that a substrate on which two flow path layers are bonded is used. In the following, common points with the above-described embodiments will be omitted, and differences will be mainly described.

  The optical measuring device 4 includes a substrate 41, and a flow path X is formed on the substrate 41 by laminating a flow path layer 411 and a flow path protection layer 412. And each flow path layer 411,411 is bonded together through the bonding layer 413. FIG. Thereby, it can measure on both surfaces (front and back) of the substrate 41, respectively.

  The optical measurement performed in the flow path X of each flow path layer 411 will be described. The measurement light L42 is irradiated from the light source 42 to the microparticles S present in the flow path X. The detection unit 43 detects the detection target lights L431, L432, and L433 thus obtained. The detection unit 43 includes detectors 431, 432, and 433 corresponding to each detection target light.

  If it is a board | substrate etc. which consist only of the flow path layer 411, it may deform | transform by the influence of temperature, humidity, etc. As a result, the focal position of light irradiation may change. In such a case, separate optical alignment is required. Or the frequency | count which can be used for a measurement may be limited.

  On the other hand, at least according to the present invention, at least one of the flow path layers 411 can be supported by the one flow path layer 411 via the bonding layer 413. That is, the flow path layers 411 and 411 can support each other. As a result, the warping phenomenon as described above can be prevented.

  And in this invention, it is not limited to the board | substrate structure which bonds the two flow-path layers 411,411. For example, a substrate structure in which at least one flow path layer 411 is stacked on a simple support layer may be employed. That is, one flow path layer 411 shown in FIG. 4 can be used as a dummy layer. In this case, in the support layer (dummy layer), processing conditions performed on the substrate 41, fine particle information (for example, a cell name, a compound name, etc.), and the like can be written.

  In the case of scattered light detection or fluorescence detection by the conventional transmission method, measurement light can be irradiated only from one direction of the substrate. On the other hand, according to the present invention, the detection target lights L431, L432, and L433 are emitted or reflected in a predetermined direction (preferably, coaxially with the measurement light L42) by reflecting or refracting the detection target light L431, L432, or L433. it can. Thereby, measurement on both surfaces of the substrate 41 is possible. As a result, the analysis processing speed of the microparticles S present in the flow path X can be improved, and deformation and warping due to temperature, humidity, and the like can be prevented.

  The material of the flow path layer 411 is not limited, and for example, polycarbonate, various plastics, or the like can be used. In particular, when used as a support layer, a silicon substrate, a glass substrate, or the like can be used as the material having a high effect of preventing warping. Further, the flow path layers 411 and 411 can be joined by pressure bonding or thermocompression bonding, and for example, a thermosetting resin or a UV curable resin can be used for the bonding layer 413.

  The material of the flow path protection layer 412 is not limited, and for example, polycarbonate, various plastics, or the like can be used. Further, the flow path protective layer 412 can also be used as a sealable sealing layer. By providing such a channel protective layer 412, the microparticles S can be efficiently introduced into the channel X.

  Further, the thickness of the flow path layer 411, the flow path protection layer 412, and the bonding layer 413 is not limited, but it is preferable that the thicknesses are preferably substantially the same, thereby deforming due to temperature and humidity. This is preferable in that it can be canceled out.

  FIG. 5 is a conceptual diagram of a fifth embodiment of the optical measuring device according to the present invention.

  Reference numeral 5 in FIG. 5 denotes an optical measuring device. The optical measurement device 5 includes a substrate 51, a light source 52, a detection unit 53, reflection mirrors 54, 55, 56, and a condenser lens 57. In the following, common points with the above-described embodiments will be omitted, and differences will be mainly described. In FIG. 5, the structure of the substrate 51, the fine particles in the flow path, and the like are shown in a simplified manner, and of course, it can be designed to have various structures of the substrate described so far.

  The measurement light L52 is irradiated from the light source 52, is condensed by the objective lens 57 through the reflection mirror 54, and is irradiated to the fine particles in the flow path of the substrate 51. Then, the detection target lights L531 and L532 generated thereby are emitted in the coaxial direction with the measurement light L52, and detected by the detection unit 53 via the reflection mirrors 55 and 56. In the detector 53, the detector 531 detects the detection target light L531 and the detector 532 detects the detection target light L532.

  As described above, in the present invention, since the detection target light to be detected is not transmitted but reflected in a predetermined direction, the detectors 531 and 532 of the detection unit 53 can be installed together. This is desirable in that the device configuration can be simplified. It is desirable that the incident optical path and the outgoing optical path are the same optical path.

  The optical measuring device according to the present invention can be applied to various technical fields, for example, measuring devices using directional light including particle size distribution measurement, fluid image analysis, three-dimensional measurement, laser microscope, and the like.・ Applicable to analysis equipment. Among these, it can be suitably used for a fine particle analyzer that irradiates fine particles present in a flow path.

  Examples of the particle analyzer include analyzers such as a flow cytometer and a bead assay (flow bead assay). That is, the minute particles are sorted by irradiating the minute particles with light and detecting the detection target light such as fluorescence and scattered light.

  Flow cytometry is intended only for measuring the size, structure, etc. of microparticles, or used as a configuration so that desired microparticles can be sorted based on the measured size, structure, etc. There is. Among these, a cell sorter can be used particularly for sorting cells.

  When sorting fine particles, the optical measuring device of the present invention can be used for an optical detection mechanism. In other words, since it is possible to irradiate light at an accurate position with respect to microparticles (biological cells, etc.) existing in the flow path, it is possible to sort accurately and efficiently even stem cells, etc. that are present in a very small amount in biological cells. it can.

  Alternatively, also when used as a microreactor that performs a predetermined chemical reaction in the flow path X, the optical measurement device of the present invention can be used as an optical detection mechanism. It is used for applications in which some kind of reaction proceeds in the flow path X, the subsequent reaction product (microparticles S) is irradiated with directional light for spectroscopic detection, and sorting is performed according to the result. be able to.

  Accordingly, the particle analyzing apparatus including the optical measuring apparatus described so far can be used. Further, a processing unit that processes the microparticles S existing in the flow path, a processing unit that performs a predetermined process, a predetermined standard, and the like. According to the above, it is possible to separately provide a separation unit that performs separation.

  Specifically, the processing unit includes a unit that performs an operation to apply some hand to the microparticles S, and examples include a unit that performs laser processing, surface processing, and the like. The processing unit includes a unit that performs some processing on the fine particles S, and examples include a unit that performs chemical processing, physical processing, activation processing, heating processing, cleaning processing, and the like. Examples of the sorting unit include one that sorts and separates the microparticles S based on some standard, and further sorts (sorts) the fine particles.

  Thus, based on the reaction result and position information of the microparticles S obtained by light irradiation, processing, processing, sorting, and the like can be performed separately. Since the light collection efficiency of the detection target light or the like generated by the light irradiation of the present invention is excellent, more accurate light detection (spectroscopic measurement or the like) is possible. That is, in the present invention, not only the processing unit, the processing unit, and the sorting unit are simply combined with the optical measurement device, but also the detection result by light irradiation can be fed back to these operations. Thereby, it is possible to accurately and efficiently perform processing, processing, and sorting on the microparticles S separately performed.

  According to the optical measurement apparatus and the particle analysis apparatus according to the present invention, since optical measurement with high measurement accuracy is possible, it can be applied not only to the biotechnology field but also to a wide range of fields including various optical measurement instruments and analysis instruments. .

1 is a schematic side view of a first embodiment of an optical measuring device according to the present invention. It is a side schematic diagram of a 2nd embodiment of an optical measuring device concerning the present invention. It is a side schematic diagram of a 3rd embodiment of an optical measuring device concerning the present invention. It is a side schematic diagram of a 4th embodiment of an optical measuring device concerning the present invention. It is the schematic of 5th Embodiment of the optical measuring device which concerns on this invention. It is the schematic for demonstrating an example of the conventional optical measuring device.

Explanation of symbols

1, 2, 3, 4, 5 Optical measuring device 11, 21, 31, 41, 51 Substrate 12, 22, 42, 52 Light source 13, 23, 43, 53 Detector X Channel S Microparticle

Claims (7)

A substrate provided with a flow path capable of introducing microparticles;
A light source for irradiating the microparticles with measurement light;
A detection unit for detecting detection target light generated by irradiation of the measurement light;
Comprising at least
An optical measurement apparatus in which the flow path surface of the substrate is processed so that the detection target light is emitted in a predetermined direction by at least one of reflection and refraction on the flow path surface.   The optical measurement apparatus according to claim 1, wherein the predetermined direction is a direction coaxial with an incident direction of the measurement light irradiation.   The optical measurement apparatus according to claim 1, wherein at least a wavelength selection film that transmits light of a predetermined wavelength is formed in the flow path.   The optical measurement apparatus according to claim 1, further comprising at least a region in which an angle of the flow channel surface with respect to a cross-sectional view of the flow channel and an incident direction of the measurement light is approximately 45 degrees.   The optical measurement apparatus according to claim 1, wherein the substrate has a structure in which a flow path layer is laminated on a support layer.   The optical measuring device according to claim 5, wherein a flow path is also disposed in the support layer.   A fine particle analyzer comprising the optical measuring device according to claim 1.