JP3516536B2 - Receiving optical system and particle analyzer equipped with the receiving optical system - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a light-receiving optical system and a particle analyzer including the light-receiving optical system, and more specifically, to a light-receiving optical system used in various optical instruments and provided with a light-receiving lens for receiving target light. System and its light-receiving optical system, a sample containing particle components such as blood cells and various cells is made to flow into the flow cell together with the sheath liquid, and the sample trickle part formed in the flow cell is irradiated with light to scatter from the sample trickle part. The present invention relates to a particle analyzer for measuring the size and properties of particles in a sample by measuring light and fluorescence.

[0002]

2. Description of the Related Art Conventionally, a flow cytometer is widely known as an apparatus for performing particle analysis. Figure 7
The detection part of the conventional general flow cytometer is shown.

In FIG. 7, when a sample containing particle components such as blood cells and various cells is flown as an outer layer in the flow cell 104 (the particle components and the liquid flow in a direction perpendicular to the paper surface), the sample Rivulets are formed.
An irradiation optical system 101 includes an argon laser light source 102 and a condenser lens unit 103. The light emitted from the irradiation optical system 101 is the front flow cell 1
The sample trickle portion 113 formed in 04 is irradiated.

Reference numeral 105 denotes the sample trickle portion 1 of the flow cell 104.
A front light-receiving optical system that receives light emitted forward from 13 is composed of a beam stopper 106, an objective lens unit 107, and a photodiode 108. The beam stopper 106 is for shutting off the direct front light emitted from the argon laser light source 102 and transmitted through the flow cell 104 to the front. Objective lens unit 107
Detects scattered light / fluorescence (forward scattered light / forward fluorescence) emitted forward from the sample trickle portion 113 of the flow cell 104. The photodiode 108 detects forward fluorescence that has passed through the objective lens unit 107.

Reference numeral 109 is a sample trickle portion 1 of the flow cell 104.
13 is a lateral light receiving optical system for receiving light emitted from 13 laterally, which comprises an objective lens unit 110, a sharp cut filter 111, and a photomultiplier 112. The objective lens unit 110 is the flow cell 1
04 scattered light emitted from the sample trickle 113 to the side
Detects fluorescence (side scattered light / side fluorescence). The photomultiplier 112 detects the lateral fluorescence passing through the objective lens unit 110 and the filter 111.

[0006]

In such a flow cytometer, as described above, the objective lens unit 10 occupying a relatively large volume ratio in the front light receiving optical system.
Apart from 7, the beam stopper 106 and its adjusting mechanism (not shown) are arranged at a predetermined distance from the objective lens unit 107, and the volume occupied by the front light receiving optical system is considerably large. .

Such a problem exists not only in a particle analyzer such as a flow cytometer but also in a light receiving optical system in various optical instruments.

The present invention has been made in consideration of such circumstances, and its main purpose is to provide a light receiving optical system which can be downsized and simplified, and a particle analyzer equipped with the light receiving optical system. To provide.

[0009]

According to one aspect of the present invention, a light receiving lens is provided, and an incident surface of the light receiving lens is
A beam stopper for blocking unnecessary incident light is provided, and the beam stopper is one of the incident surfaces of the light receiving lens.
By forming a groove in the area and masking the groove,
A light receiving optical system is provided.

Such a light receiving optical system is applicable to general optical equipment. Here, the light receiving lens receives the target light such as the light emitted from the light source and the light emitted from the portion illuminated by the light source.

In the light receiving optical system according to the present invention, since the beam stopper is provided on the incident surface of the light receiving lens, the light receiving optical system is separately provided.
There is no need to provide a beam stopper or its fine adjustment mechanism. Therefore, unnecessary incident light can be blocked, desired light can be appropriately received, and the optical system can be downsized and simplified. The incident surface of the light receiving lens may be a flat surface or a curved surface.

The beam stopper on the incident surface of the light receiving lens is formed, for example, by using a high precision masking technique in the IC manufacturing process. That is, Cr, Au-Cr,
It is formed by depositing an IC masking material such as Au on the incident surface. Accordingly, the beam stopper can be easily provided with high accuracy.

The shape of the beam stopper can be arbitrarily set according to the purpose, such as a linear shape or a planar shape (circular shape, elliptical shape, various polygonal shapes, etc.). Since the shape of the beam stopper can be set arbitrarily, unnecessary light (light from particles when this light receiving optical system is used in a particle analyzer) is not blocked as much as possible, and unnecessary light (this light receiving optical system is used). When used in a particle analyzer, only the forward direct light from the irradiation optical system can be effectively blocked. As a result, the optical signal can be detected with a good S / N ratio.

When forming the beam stopper, it is preferable to form a groove in a part of the incident surface of the light receiving lens and mask it so as to cover the groove part. In this way, a double structure in which light is reflected on both the groove surface and the mask surface, and the incident light is reflected on the mask surface and the groove surface, therefore, for the purpose of blocking unnecessary light, This is because a more suitable beam stopper can be formed.

The light receiving lens may be a conventional objective lens or a rod lens. When the light receiving lens is a rod lens, the size of the lens is generally small, so that the optical system can be further downsized and simplified as compared with the case of an objective lens.

The rod lens is a lens having a cylindrical shape, and the refractive index is distributed so as to continuously change in a parabolic shape from the central axis of the cylinder toward the outer peripheral surface. It is also called a distributed index lens or SELFOC Lens.
When such a rod lens is used, the light incident on one end surface of the rod lens is sine curve (s
ine curve) or helical (helic)
Al) -like optical path is propagated and emitted from the other end face.

As this rod lens, for example, one having a diameter of 1 to 2 mm and a length of 3 to 30 mm is used.

According to another aspect of the present invention, a flow cell capable of forming a trickle of a sample containing a particle component, an irradiation optical system for irradiating a sample trickle portion formed in the flow cell with light, and A front receiving light having a light receiving optical system for receiving light emitted by the irradiation optical system and emitted from the sample trickle portion of the flow cell, and the light receiving optical system having a light receiving lens for receiving the light emitted forward from the sample trickle portion of the flow cell. There is provided a particle analysis device comprising an optical system, wherein the front light-receiving optical system is the one described in any one of claims 1 to 4 .

As the flow cell, a known flow cell that can form a trickle of a sample containing particle components such as blood cells and various cells can be used. With such a flow cell, the sample is made to flow with the sheath liquid as an outer layer to form a sample trickle portion. As the irradiation optical system, for example, a publicly-known system including an argon laser light source and a condenser lens unit can be used. With such an irradiation optical system, the sample trickle portion of the flow cell is irradiated with light.

The light receiving optical system receives the light emitted by the irradiation optical system and emitted from the sample trickle portion of the flow cell, and detects desired scattered light or fluorescence. This light receiving optical system is arranged at a predetermined location according to the purpose of detection. That is, when used as a front light-receiving optical system that receives light emitted forward from the sample trickle portion of the flow cell, it is arranged in front of the sample trickle portion of the flow cell and emits light emitted laterally from the sample trickle portion of the flow cell. When used as a side receiving optical system,
It is arranged laterally of the sample trickle portion of the flow cell, and when used as a front light receiving optical system and a side light receiving optical system, it is arranged in front of and to the side of the sample trickle portion of the flow cell.

The light receiving optical system comprises a front light receiving optical system having a light receiving lens for receiving light emitted forward from the sample trickle portion of the flow cell. What is used as this front light receiving optical system is provided on the incident surface of the light receiving lens.
And, beam stopper der for blocking unwanted incident light
Therefore , (1) the beam stopper is provided by forming a groove in a part of the incident surface of the light receiving lens and further masking the groove , and (2) the beam stopper is the incident surface of the light receiving lens. That are provided in a line on a part of
(3) A beam stopper is provided on a part of the incident surface of the light-receiving lens in a planar shape, (4) The light-receiving lens is a rod lens, and any one of (1) to (3) There are two things.

In the particle analyzer equipped with such a front light receiving optical system, the optical system can be downsized and simplified.

[0023]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below with reference to the drawings. The present invention is not limited to this.

[0024]

[Embodiment 1] FIG. 1 shows a detection unit in a flow cytometer as a particle analyzer according to Embodiment 1 of the present invention. In FIG. 1, 1 is an irradiation optical system, which comprises an argon laser light source 2 and a condenser lens unit 3. The light emitted from the irradiation optical system 1 is applied to the front flow cell 4. A sample trickle portion 15 is formed in the flow cell 4 when a sample containing a particle component such as blood cells and various cells flows as a sheath liquid (the particle component and the liquid flow in a direction perpendicular to the paper surface).

Reference numeral 5 denotes a front light-receiving optical system for receiving light emitted forward from the sample trickle portion 15 of the flow cell 4, which comprises a rod lens unit 26 and a photodiode 8. The rod lens unit 26 detects scattered light / fluorescence (forward scattered light / forward fluorescence) emitted forward from the sample trickle portion 15 of the flow cell 4. Photodiode 8
Detects forward fluorescence passing through the rod lens unit 26.

Reference numeral 9 denotes a lateral light receiving optical system for receiving light emitted laterally from the sample trickle portion 15 of the flow cell 4, which comprises a rod lens unit 13, a sharp cut filter 11 as a wavelength selection filter, and a photo. And a multiplier 12. The rod lens unit 13 detects scattered light / fluorescence (side scattered light / side fluorescence) emitted laterally from the sample trickle portion 15 of the flow cell 4. The photomultiplier 12 detects the lateral fluorescence passing through the rod lens unit 13 and the filter 11.

FIG. 2 shows each rod lens unit 26/13.
FIG. Each rod lens unit 26 ・ 13
Are rod lenses 26a and 13a as light receiving lenses.
And a cylindrical member 26 in which parts of the rod lenses 26a and 13a are inserted and adhered and held by glass solder.
It consists of b and 13b. Rod lens 26a ・ 1
3a is formed of rod lens material 6a obtained by subjecting SML H18 manufactured by Nippon Sheet Glass Co., Ltd. to a predetermined polishing process. The rod lens material 6a has a diameter of 1.8 mm,
It has a cylindrical shape with a length of 10.0 mm, and one end surface (end surface nearer to the flow cell) which is the incident surface thereof is flat.

As shown in FIG. 3, the rod lens 26a in the front light receiving optical system comprises a rod lens material 6a and a beam stopper 16 provided on the incident surface of the rod lens material 6a. The beam stopper 16 has a width of 100 to 20 that crosses the center of the incident surface of the rod lens material 6a.
It has a linear shape of 0 μm, and blocks front direct light emitted from the argon laser light source 2 and transmitted to the front of the flow cell 4.

The beam stopper 16 is formed by using a high precision masking technique in the IC manufacturing process. That is, it is formed by vapor-depositing an IC masking material such as Cr, Au-Cr, or Au on the incident surface of the rod lens 6a.

The beam stopper 16 can be used for general light receiving lenses other than the rod lens, but in order to form the beam stopper 16 with high accuracy, it is necessary that the outer dimensions of the light receiving lens have good accuracy in the manufacturing process. . From this point, it can be said that the rod lens is excellent as the lens forming the beam stopper 16.

Next, FIG. 8 shows a scattergram obtained when the reticulocyte preparation particles (Let Check: manufactured by Toa Medical Electronics Co., Ltd.) were measured by adjusting the apparatus. Regarding the distribution form of scattergram and the counting result, RET # (reticulocyte count) and RET% (reticulocyte ratio), the conventional device and the device according to the example of the present invention were compared. As a result, it was found that there is no problem in the device according to the first embodiment, and the conventional objective lens can be replaced with the rod lens.

[0032]

Second Embodiment The shape of the beam stopper can be set arbitrarily. The beam stopper 16 in the rod lens 26a of FIG. 3 is linear here with a width of 100 to 200 μm, but can have a width of several tens of μm to several hundreds of μm depending on the purpose, and is shown in FIG. Like the beam stopper 17 of the rod lens 36a, the rod lens material 6a may be formed in a planar shape (circular, elliptical, various polygonal shapes, etc.) at the center of the incident surface. In addition, rod lens material 6
The incident surface of a may be a flat surface or a curved surface.

[0033]

[Third Embodiment] FIG. 5 shows a case where the beam stopper 16 is formed.
Like the rod lens 46a shown in FIG. 3, it is preferable that a part of the incident surface of the rod lens material 6a is cut into a linear groove 18 having a V-shaped cross section and masked so as to cover the groove 18 portion. This is because it is possible to form an ideal double structure in which light is reflected by the masking portion, but even if a minute amount of light passes through the masking portion, it is reflected by the groove 18. is there.

The manufacturing process at that time will be illustrated. First, rod lens material 6a (diameter 1.8 mm, length 1
It has a cylindrical shape of 0.0 mm, and one end surface which is the incident surface thereof is made flat).
Ultrasonic processing is performed to form the linear groove 18 having a character shape. Then, a photoresist is applied to the entire incident surface. A mask pattern in which a desired beam stopper shape is patterned is arranged thereon, and ultraviolet rays are exposed to cure and fix the photoresist film in the exposed portion. Then, the unexposed photoresist portion (the portion which becomes the beam stopper 16) is removed by an organic solvent. Then, Cr is vapor-deposited. Then, the remaining photoresist is removed with a chemical such as sulfuric acid + hydrogen peroxide solution. Finally, the AR coat 19 is applied to the entire incident surface.

Rod lens 4 manufactured in this way
11 shows a case where forward scattered light from latex particles having a diameter of 7 μm is measured by a flow cytometer using 6a instead of the rod lens 26a of FIG. 1 and a conventional flow cytometer shown in FIG. (Conventional) and FIG. 12 (Example 3) will be described. As is clear by comparing the two, the third embodiment of the present invention is detected as a signal having a magnitude about 1.5 times that of the conventional signal.

[0036]

[Embodiment 4] In the detection part of the conventional flow cytometer, as shown in FIG. 7, the lens unit 110 and the filter 111 are separately used, but the flow cytometer according to the embodiment 4 of the present invention. In the detection section in (1), both are integrally configured to achieve downsizing and simplification. Integral here means that the lens and the filter can be handled as one part by coating the lens surface with the filter material, adhering the lens and the filter material, or configuring the lens itself with the filter material. Is to

An example thereof is shown in FIG. Rod lens 20
Is composed of a cylindrical rod lens body 20a and a cylindrical colored glass 20b as a wavelength selection filter. The exit surface (right end surface) of the rod lens body 20a and one end surface (left end surface) of the colored glass 20b are optically bonded. Further, the incident surface (left end surface) of the rod lens body 20a is coated with a filter material to form an interference film 20c as a wavelength selection filter. Also,
The AR coating 2 is provided on the emission surface (right end surface) of the colored glass 20b.
0d is applied.

The rod lens 20 shown in FIG. 6 was used in place of the rod lens unit 13 and the filter 11 used in the lateral light receiving optical system 9 of the detector in the flow cytometer shown in FIG. And let check was measured like the above. Then, the same result as the above was obtained, and it was confirmed that there was no problem.

As described above, it is preferable that the rod lens 20 itself has a filter function. The technical idea of providing the light receiving lens with a filter can be applied not only to the lenses other than the rod lens but also to the irradiation optical system as well as the light receiving optical system.

In the light receiving optical system according to the first aspect of the present invention, since the beam stopper for blocking unnecessary incident light is provided on the incident surface of the light receiving lens, the beam stopper and the beam stopper are separately provided. There is no need to provide a fine adjustment mechanism. Therefore, it is possible to preferably receive the intended light other than the direct light, and it is possible to reduce the size and simplification of the optical system. In addition, the beam stopper is
A groove is formed on a part of the entrance surface of the lens
The groove surface and the mass
The double structure that reflects light on both the
Incident light is reflected on the mask surface and the groove surface.
Therefore, a more comfortable beam stopper can be obtained.

According to the second aspect of the light receiving optical system of the present invention, the beam stopper is provided on a part of the incident surface of the light receiving lens.
Since it is provided linearly, a linear beam stopper is required.
In the light receiving optical system, it is possible to easily obtain high accuracy of the beam stopper.

According to the third aspect of the light receiving optical system of the present invention, the beam stopper is provided on a part of the incident surface of the light receiving lens.
Since is provided a planar, in the required light receiving optical system of the planar beam stopper, the precision of the beam stopper
Can be easily obtained .

According to the light receiving optical system of the fourth aspect of the present invention, the light receiving lens is a rod lens.
To the effect obtained by the light receiving optical system described in any one of
In addition to the result, compare when the light receiving lens is an objective lens
Then, the size of the lens generally becomes smaller,
The optical system can be downsized and simplified .

According to the particle analyzer of the fifth aspect of the present invention, the light receiving optical system is arranged in front of the sample trickle portion of the flow cell.
Front light receiving having a light receiving lens for receiving light emitted toward one side
An optical system is provided, and the front light-receiving optical system comprises:
To any one of 4 to 4,
It is possible to reduce the size and simplification of the system and hence the particle analyzer .

[0045]

[0046]

[Brief description of drawings]

FIG. 1 is a schematic configuration explanatory view showing a detection unit of a flow cytometer according to a first embodiment of the present invention.

FIG. 2 is an enlarged configuration explanatory view showing a rod lens unit of a front light receiving optical system in the detection unit of the flow cytometer of FIG.

FIG. 3 is an enlarged perspective view showing a rod lens in the rod lens unit of FIG.

FIG. 4 is an enlarged perspective view showing a rod lens of the front light receiving optical system in the detection unit of the flow cytometer according to the second embodiment of the present invention.

FIG. 5 is an enlarged vertical cross-sectional view showing a rod lens of a front light receiving optical system in the detection unit of the flow cytometer according to the third embodiment of the present invention.

FIG. 6 is an enlarged side view showing a rod lens of a front light receiving optical system in a detection unit of a flow cytometer according to a fourth embodiment of the present invention.

FIG. 7 is a schematic configuration explanatory view showing a detection unit of a conventional flow cytometer.

FIG. 8 is an explanatory diagram showing a scattergram of a rod lens used in the detection unit of the flow cytometer according to the first embodiment of the present invention.

FIG. 9 is an explanatory diagram showing an output when forward scattered light is detected by a beam stopper and an objective lens unit, which are used in a detection unit of a conventional flow cytometer.

FIG. 10 is an explanatory diagram showing an output when forward scattered light is detected by a rod lens with a beam stopper used in the detection unit of the flow cytometer according to the third embodiment of the present invention.

[Explanation of symbols]

1 Irradiation optical system 4 flow cell 5 Front light receiving optical system 13 Rod lens unit 13a Rod lens (light receiving lens) 13b cylindrical member 15 Sample trickle 16 Beam stopper 17 Beam stopper 20 Rod lens (light receiving lens) 26 Rod lens unit 26a Rod lens (light receiving lens) 26b Cylindrical member 36a Rod lens (light receiving lens) 46a Rod lens (light receiving lens)

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Claims (5)

(57) [Claims] [Claim 1 further comprising a light receiving lens, the incident surface of the light receiving lens, made by beam stopper for blocking unwanted incident light is provided, the beam stopper
Forms a groove on a part of the incident surface of the light receiving lens and
A light-receiving optical system provided by masking the groove . 2. The light receiving optical system according to claim 1 , wherein the beam stopper is linearly provided on a part of the incident surface of the light receiving lens. 3. The light receiving optical system according to claim 1 , wherein the beam stopper is provided in a planar shape on a part of the incident surface of the light receiving lens. 4. A light receiving lens, light receiving optical system according to any one of claims 1 to 3 is a rod lens. 5. A flow cell capable of forming a trickle of a sample containing a particle component, an irradiation optical system for irradiating a sample trickle portion formed in this flow cell with light, and a flow cell of the flow cell irradiated by this irradiation optical system. A light-receiving optical system for receiving light emitted from the sample trickle portion, wherein the light-receiving optical system includes a front light-receiving optical system having a light-receiving lens for receiving light emitted forward from the sample trickle portion of the flow cell, The front light receiving optical system is the one described in any one of claims 1 to 4 .