WO2022270037A1 - Photometry device and analysis device - Google Patents

Abstract

[Problem] To provide a photometry device that can measure accurate scattered light intensity in a short time. [Solution] This photometry device 5 comprises: a light source 51 that radiates light onto an irradiation area of a cuvette 2 disposed in a photometric position P; a base member 52 opposite the light source 51; and a plurality of first light-receiving elements 53 that are disposed, on the base member 52, within a planar region demarcated by a first radiation direction and a second radiation direction centering around the optical axis of transmitted light output from the cuvette 2 in the photometric position P, and respectively receive scattered light scattered by the cuvette 2 in the photometric position P.

Description

Photometric and analytical equipment

The present invention mainly relates to an analyzer that analyzes a reaction liquid between a specimen and a reagent.

Conventionally, there is known an analyzer that analyzes the components of a specimen by reacting the specimen with a reagent. In this type of analyzer, a plurality of cuvettes containing specimens and reagents are arranged in a circle on a cuvette table, the cuvette table is rotated, and a photometric position between a light source and a spectroscopic detector placed across the cuvette is detected. to pass through the cuvette. At this time, the component of the specimen is analyzed by measuring the absorbance from the amount of light transmitted through the cuvette.

　Depending on the reagents used in the analyzer, there are items that cannot be measured with high sensitivity using only absorbance. Therefore, there is a technique that utilizes the characteristic that light scatters when light is applied to a reagent (for example, Patent Document 1). Patent Document 1 describes a reaction disk (cuvette table) that holds reaction containers (cuvettes) on the circumference and repeats rotation and stop, and a reaction container that is placed at a photometric position and contains a mixture of a sample and a reagent. and a detector (light-receiving element) that detects scattered light or transmitted light from the mixed liquid, the detector is in the moving direction of the reaction vessel due to the rotation of the reaction disk One or more sets are arranged symmetrically at equal angles or equal intervals around the optical axis of the light emitted from the light source in a plane perpendicular to the light source, and the averaged value and/or sum of the light intensity data from each detector is used to calculate the concentration of the substance to be measured in the mixed liquid. That is, in Patent Document 1, scattered light is received by light receiving elements linearly arranged in the vertical direction.

Patent No. 5481402

The intensity of scattered light from particles is much smaller than that of transmitted light. In addition, fluctuations (Brownian motion) occur in the particles due to the thermal motion of water molecules, and this fluctuation causes the distribution of the amount of scattered light to vary greatly depending on the radiation direction. In Patent Document 1, since the light-receiving elements that receive the scattered light are linearly arranged, there is a problem that the intensity of the scattered light cannot be accurately measured by photometry in a short time (for example, 100 us).

The present invention has been made to solve the above problems, and an object of the present invention is to provide a photometric device capable of accurately measuring the intensity of scattered light in a short period of time.

A photometric device according to the present invention includes a light source for irradiating an irradiated area of a cuvette placed at a photometric position, a base member facing the light source, and light emitted from the cuvette at the photometric position on the base member. A plurality of first light-receiving elements arranged in a planar region defined by a first radiation direction and a second radiation direction centering on the optical axis of the transmitted light, and receiving scattered light scattered from the cuvette. and

According to the present invention, it is possible to provide a photometric device that can accurately measure the intensity of scattered light in a short period of time.

It is a top view showing composition of an analysis device concerning one embodiment of the present invention. It is a side view which shows the structure of an optical sensor. 3 is a perspective view showing the detailed configuration of the photometric device; FIG. FIG. 4 is a schematic diagram showing the positional relationship between the cuvette and the base member; 4 is a graph showing the relationship between scattered light intensity (scattered light amount) and particle size. (A) is a perspective view of a filter portion in a first mode, and (B) is a perspective view of a filter portion in a second mode.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, this invention is not limited to the following embodiment.

(Overall configuration of analyzer)
FIG. 1 is a plan view showing a schematic configuration of an analysis device 1 according to one embodiment of the present invention. An analyzer 1 is an apparatus for analyzing a sample (for example, blood, urine, etc.) and a reaction liquid of a reagent, and includes a cuvette table 3 on which rows of cuvettes 2 are arranged in a circle, a driving unit 4, and a photometric device 5. , an optical sensor 6 and an analysis unit 7 .

The cuvette table 3 is formed in an annular shape in plan view, and a plurality of cuvettes 2 are arranged along the annular direction (arc-shaped arrow line in FIG. 1). The cuvette 2 is a container for containing a specimen and a reagent, and has a cubic or rectangular parallelepiped shape with an open top. Inside or around the cuvette table 3, there are provided a sample storage (not shown) that stores sample containers, a reagent store (not shown) that stores reagent containers, and the like. After placing the cuvette 2 on the cuvette table 3, a pipette (not shown) is used to supply the sample and reagent from the sample container and the reagent container to the cuvette 2 .

The drive unit 4 is a member that rotates the row of cuvettes 2 in an annular direction. In this embodiment, the driving section 4 comprises a driving gear 41 and a driven gear 42 connected to the cuvette table 3 . The driving gear 41 is attached to a stepping motor (not shown), and by driving the stepping motor to rotate the driving gear 41 , the cuvette table 3 can be rotated via the driven gear 42 . The mechanism for rotating the cuvette table 3 is not limited to this. For example, a pulley may be attached to the center shaft of the cuvette table 3 and driven by a timing belt.

The photometry device 5 is a member that irradiates light onto each cuvette 2 passing through the photometry position P while the row of cuvettes 2 rotates, and measures the emitted light from the irradiated region of the cuvette 2 at the photometry position P. . FIG. 1 shows a light source 51 , a base member 52 and a first light receiving element 53 as members constituting the photometric device 5 . A more detailed configuration of the photometric device 5 will be described later.

The cuvette table 3 is provided with slits 31 arranged corresponding to each cuvette 2 . The number of slits 31 is the same as the number of cuvettes 2 , and the slits 31 are arranged in an annular direction on the outer peripheral edge of the cuvette table 3 .

The optical sensor 6 is a member that detects the slit 31 . As shown in FIG. 2, the optical sensor 6 has a U-shape and includes a light source 61 and a light receiving element 62 facing each other with the outer peripheral edge of the cuvette table 3 interposed therebetween. The emitted light from the light source 61 reaches the light receiving element 62 only while the slit 31 is passing between the light source 61 and the light receiving element 62, and the voltage signal photoelectrically converted by the light receiving element 62 is output to the analysis unit 7. be done.

Which slit 31 each cuvette 2 corresponds to can be grasped by a known method. In this embodiment, in the initialization operation, the origin detection dog (not shown) that rotates together with the cuvette table 3 is detected by the origin sensor (not shown) installed on the fixed side, thereby executing the origin search. be done. After that, when the cuvette table 3 is rotated again, it is possible to monitor which cuvette 2 is passing through the photometric position P or the vicinity of the photometric device 5 by counting the number of slits 31 passing through the optical sensor 6 . can.

(Configuration of photometric device)
FIG. 3 is a perspective view showing the detailed configuration of the photometric device 5. As shown in FIG. The photometric device 5 mainly includes a light source 51 , a base member 52 , a plurality of first light receiving elements 53 , a mirror 54 , a spectral mirror 55 , a plurality of second light receiving elements 56 and a filter section 57 . ing.

The light source 51 irradiates the irradiated area of each cuvette 2 placed at the photometric position P with light. The light incident on the irradiated region of the cuvette 2 passes through the interior of the cuvette 2 and exits from the irradiated region of the cuvette 2 (more precisely, the back surface of the irradiated region). As the light source 51, for example, a halogen lamp that emits light of multiple wavelengths (for example, 380 nm to 800 nm) in a predetermined wavelength band can be used.

The base member 52 is an annular flat plate facing the light source 51 . The base member 52 has a circular opening 52a in its center, and transmitted light emitted from the cuvette 2 passes through the opening 52a.

As shown in FIG. 4, the first light receiving element 53 is arranged on the side facing the photometry position P with respect to the base member 52 . Specifically, the first light receiving element 53 is arranged on the base member 52 in a first radiation direction D1 and a second radiation direction D2 centered on the optical axis La of the transmitted light emitted from the cuvette 2 at the photometry position P. and receive scattered light scattered from the cuvette 2 at the photometric position P, respectively. The planar region where the first light receiving element 53 is arranged is an annular region surrounding the optical axis La on the base member 52, and is based on the scattering range due to fluctuation of particles in the reaction liquid of the cuvette 2. . In the present embodiment, the first light receiving elements 53 are planarly arranged in an annular region.

The first radiation direction D1 is the direction from the photometry position P to the inner edge of the base member 52 (the edge of the opening 52a), and the second radiation direction D2 is the direction from the photometry position P to the outer edge of the base member 52. be. Although the photometry position P is indicated by a dot in FIG. 4, it is not particularly limited as long as it is within the reaction liquid inside the cuvette 2 on the optical axis La. The first radiation direction D1 may be a direction from the photometry position P toward the outside of the inner edge of the base member 52, and the second radiation direction D2 may be a direction from the photometry position P toward the inside of the outer edge of the base member 52. may be

Part of the light passing through the inside of the cuvette 2 is scattered by the particles of the reaction liquid and emitted from the cuvette 2 as scattered light. This scattering is called Rayleigh scattering, and the intensity of the scattered light is obtained by the following formula.
I(θ)=(I ₀ π ⁴ d ⁶ /8R ² λ ⁴ )*(m ² −1/m ² +1)*(1+cos ² θ)
I(θ): Scattered light intensity θ: Scattering angle I ₀ : Incident light intensity d: Particle size R: Distance from scattering particle m: Refractive index of solvent λ: Wavelength θ: Scattering angle for incident light

Thus, the scattered light intensity I(θ) is inversely proportional to the scattering angle θ. The scattering angle θ is the angle between the direction of emission of the scattered light and the optical axis La.

FIG. 5 is a graph showing the relationship between scattered light intensity (scattered light amount) and particle size. It can be seen that the scattered light intensity increases mainly when the scattering angle is 20° to 30°. Therefore, in this embodiment, as shown in FIG. 4, the angle θ1 formed between the first radiation direction D1 and the optical axis La is set to 20°, and the angle θ2 formed between the second radiation direction D2 and the optical axis La is set to 30°. ° is set. That is, the angle between the straight line connecting the first light receiving element 53 and the photometry position P and the optical axis La is 20° to 30°, and most of the scattered light emitted from the cuvette 2 is incident on Each first light-receiving element 53 photoelectrically converts the scattered light and outputs a voltage signal having an intensity corresponding to the amount of light to the analysis unit 7 . The analysis unit 7 calculates the total value of the voltage signals from the respective first light receiving elements 53 as the intensity of the scattered light.

As described in [Problems to be Solved by the Invention], the distribution of the amount of scattered light varies greatly depending on the radiation direction due to Brownian motion of particles. That is, scattered light is not emitted uniformly in a radial pattern. On the other hand, in this embodiment, since the plurality of first light receiving elements 53 are arranged in a plane, even if the amount of scattered light varies locally, the entire area where the first light receiving elements 53 are arranged is almost constant. Therefore, the scattered light intensity can be accurately measured in a short time by correcting variations in the amount of scattered light.

It should be noted that the values of the angles θ1 and θ2 are not limited to the above values, and can be changed as appropriate according to the particle size of the particles. In this embodiment, the base member 52 is movable along the optical axis La by a drive mechanism (not shown), and by moving the base member 52, the angles θ1 and θ2 can be adjusted.

The transmitted light that has passed through the opening 52a is incident on the spectroscopic mirror 55 via the mirror 54, and the spectroscopic mirror 55 disperses the incident light by wavelength band and reflects it to the second light receiving element 56. Each of the second light receiving elements 56 photoelectrically converts the transmitted light in different wavelength bands, and outputs a voltage signal having an intensity corresponding to the amount of light to the analysis section 7 .

Note that the second light receiving element 56 may be provided near the center of the base member 52 without providing the opening 52a in the base member 52 . However, disposing the second light receiving element 56 on the opposite side of the base member 52 to the photometric position P as in the present embodiment facilitates the installation of an optical system that disperses the transmitted light.

As shown in FIG. 3, the filter section 57 is connected to a rotating shaft 58a rotated by a motor 58. As shown in FIGS. 6A and 6B, the filter section 57 includes a cylindrical section 573 and single-wavelength filters 574 provided inside both ends of the cylindrical section 573 . Two circular passage holes 57a are formed in opposing side surfaces of the cylindrical portion 573 in the middle portion in the longitudinal direction. The central axis of the cylindrical portion 573, the line connecting the centers of the two through holes 57a, and the longitudinal direction of the rotating shaft 58a are orthogonal to each other.

In the first mode, as shown in FIG. 6(A), the filter part 57 is oriented so that the central axis of the cylindrical part 573 coincides with the emission direction of the light L1 from the light source 51 . At this time, the multi-wavelength light L1 passes through the single-wavelength filter 574, and the single-wavelength filter 574 passes the single-wavelength (for example, 700 nm) light L2. The light L2 is scattered at the photometry position P, emitted from each cuvette 2, and received by the first light receiving element 53. FIG.

In the second mode, as shown in FIG. 6(B), the filter part 57 is oriented so that the line connecting the centers of the two passage holes 57a coincides with the emission direction of the light L1. At this time, the multi-wavelength light L1 in the predetermined wavelength band passes through the passage hole 57a as it is. The light L1 passes through the photometric position P, is emitted from each cuvette 2, and is received by the second light receiving element 56. FIG.

Thus, by switching between the first mode and the second mode, both the transmitted light and the scattered light of the reaction liquid can be photometrically measured.

(Additional notes)
The present invention is not limited to the above embodiments, and can be modified in various ways within the scope of the claims. Forms obtained by appropriately combining technical means disclosed in the embodiments are also techniques of the present invention. included in the scope.

For example, in the above-described embodiment, the first light receiving element 53 is arranged in a ring-shaped region on the base member 52 in a planar manner, but the arrangement is not limited to a circular ring as long as it is arranged in a planar manner. For example, the first light receiving elements 53 can be arranged in a rectangular frame shape or an arc shape. Further, the planar region in which the first light receiving element 53 is arranged may be a discontinuous surface.

Further, although the photometric device 5 according to the above-described embodiment can measure both the transmitted light and the scattered light of the reaction liquid, it may be possible to measure only the scattered light. In this case, as the light source 51, a light source that emits light of a single wavelength, such as a semiconductor laser, can be used, and the filter section 57 need not be provided.

3, the photometric device 5 according to the above-described embodiment has the base member 52 disposed on the opposite side of the photometric position P from the light source 51 (that is, disposed between the photometric position P and the mirror 54). ), and the plurality of first light receiving elements 53 are arranged on the side facing the photometric position P with respect to the base member 52 , but the present invention is not limited to this. The base member 52 may be arranged between the photometry position P and the light source 51 (or the filter section 57), and the plurality of first light receiving elements 53 may be arranged on the side facing the photometry position P with respect to the base member 52. .

1 Analysis device 2 Cuvette 3 Cuvette table 31 Slit 4 Drive unit 41 Drive gear 42 Driven gear 5 Photometry device 51 Light source 52 Base member 52a Opening 53 First light receiving element 54 Mirror 55 Spectral mirror 56 Second light receiving element 57 Filter section 573 Cylindrical Part 574 Single-wavelength filter 57a Passing hole 58 Motor 58a Rotating shaft 6 Optical sensor 61 Light source 62 Light receiving element 7 Analysis part D1 First radiation direction D2 Second radiation direction La Optical axis P Photometry position

Claims (12)

a light source that irradiates light onto the irradiated area of the cuvette placed at the photometric position;
a base member facing the light source;
Disposed on the base member in a planar region defined by a first radiation direction and a second radiation direction around the optical axis of the transmitted light emitted from the cuvette at the photometry position, and scattered from the cuvette a plurality of first light-receiving elements that respectively receive scattered light;
A photometric device with The photometric device according to claim 1, wherein the planar area is an annular area surrounding the optical axis on the base member. The measurement device according to claim 1 or claim 2, wherein the planar region is a region based on a scattering range due to fluctuations of particles in the reaction liquid of the cuvette. The photometric device according to any one of claims 1 to 3, further comprising a second light receiving element that receives the transmitted light. The base member has an opening through which the transmitted light passes,
5. The photometric device according to claim 4, wherein said second light receiving element is arranged on the opposite side of said photometric position with respect to said base member. The base member is arranged between the photometric position and the light source,
6. The photometric device according to claim 5, wherein said plurality of first light receiving elements are arranged on a side facing said photometric position with respect to said base member. an angle between the first radiation direction and the optical axis is smaller than an angle between the second radiation direction and the optical axis;
an angle formed by the first radiation direction and the optical axis is 20° or more;
7. The photometric device according to claim 1, wherein an angle formed by said second radiation direction and said optical axis is 30[deg.] or less. The light source emits light of a single wavelength,
8. The photometric device according to claim 1, wherein the plurality of first light receiving elements receive the light of the single wavelength scattered at the photometric position and emitted from the cuvette. The light source emits light of multiple wavelengths,
7. The photometric device according to claim 5, wherein said second light receiving element receives said multi-wavelength light transmitted through said photometric position and emitted from said cuvette. The light source emits light of multiple wavelengths,
A filter unit having a first mode for passing the multi-wavelength light through a single-wavelength filter and a second mode for passing the multi-wavelength light as it is, is arranged between the light source and the photometry position, 10. The photometric device according to any one of claims 1 to 9. The photometric device according to any one of claims 1 to 10, further comprising a driving mechanism for moving the base member along the optical axis. a photometric device according to any one of claims 1 to 11;
a cuvette table on which the rows of cuvettes are arranged in a circle;
a driving unit that rotates the rows of cuvettes in a circular direction to pass each cuvette to the photometric position;
an analysis unit that analyzes the contents of the cuvette based on the photometric data of the photometric device;
analyzer with

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