JP2001305058A - Chemical analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To omit a mechanical movable part so as to improve a measurement throughput and so as to widen a measurement dynamic range without any deterioration of a measurement SN ratio in a chemical array type spectroscopic analyzer. SOLUTION: To an objective lens 310 and a relay lens 241, a spatial light modulation element 240 is arranged in a position conjugate to a well 122 on a chemical array 120, and according to the position and the size of a measurement objective well, the spatial light modulation element 250 is modulated so as to irradiate the well. To the objective lens 310 and a relay lens 420, a spatial light modulation element 430 is arranged in the position conjugate to the well 122, and fluorescence generated from the well is selectively observed by means of a photomultiplier 450.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for detecting a chemical component using a chemical array, and more particularly to providing an optical system for detecting a chemical component in a chemical array and an apparatus therefor.

[0002]

2. Description of the Related Art In the late 1990's, research and development using chemical arrays have been actively conducted for investigating efficacy in pharmaceuticals and determining DNA base sequences. For more information on this chemical array, see (Light-directed, Spatially Addres
sable Parallel Chemical Synthesis), Science, Vol.
251, 767-773 (1991).

As an optical system for detecting a chemical component using this chemical array, PCT WO 92/10587 discloses a so-called confocal system in which a set of a microscopic optical system, an illumination light source and an aperture limiting plate are combined. A microscope is used. For this confocal microscope, the chemical array is scanned in the XY directions to measure the fluorescence from each well.

In Japanese Patent Application Laid-Open No. 11-44647, a well is directly installed on a light source array such as a light emitting diode or a diode laser, and a chemical array is measured without a scanning operation as in PCT WO 92/10587. A method has been proposed.

[0005]

However, in order to reduce the cost of research and development using a chemical array, if the number of wells on the chemical array exceeds 10,000 in 100 rows and 100 columns, the above-described technique will not be used. The decrease in the throughput and the decrease in the measurement accuracy (the ratio between the measurement signal and the noise, hereinafter referred to as the measurement SN) become remarkable.

That is, according to the method described in PCT WO 92/10587, it is necessary to repeatedly move and position the chemical array by the number of wells on the chemical array and perform measurement. In addition, a long positioning time is required for high-precision positioning so that unintended light from an adjacent well is not observed, resulting in a decrease in measurement throughput.

According to the method described in JP-A-11-44647, when a well on a chemical array becomes smaller, a light source array such as a light emitting diode for illuminating the well corresponds to each of the small wells. It becomes difficult to manufacture the light source itself. Further, the size of wells on the chemical array varies, and it is also difficult to accommodate different well sizes for each chemical array.

The present invention has been made to solve the problems of improving the measurement throughput and preventing a decrease in the measurement SN.
It aims to improve the efficiency of R & D by shortening the measurement time, and to provide a wide variety of measurements at a low price by using high-density chemical arrays.

[0009]

In order to solve the above problems, the present invention illuminates a well on a chemical array with measurement light and uses a confocal microscope as an optical system for measuring fluorescence generated thereby. The configuration was used. Then, for the objective lens of the confocal microscope, a spatial light modulator composed of a plurality of elements for modulating the intensity of observation light emitted from the illumination light source is installed at a position conjugate to the well on the chemical array, and the spatial light modulator is The structure is such that the irradiation light is deflected in accordance with the position of the well to be measured on the chemical array and its size when driven.

Further, a spatial light modulator for selectively modulating the intensity of only the fluorescence generated from the well illuminated with the measuring light is provided at a position conjugate with the well of the objective lens of the confocal microscope. In this case, only the light intensity modulated by this was measured.

The intensity modulation by these two spatial light modulators is synchronously processed, and the spatial position of the objective lens of the confocal microscope is selected to be a position conjugate with the well to be measured on the chemical array. .

[0012]

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 shows an entire analysis system according to the present invention. In the figure, the analyzer main body 100
Controlled by the control computer 150a, the measurement result is displayed on the display 150 of the computer 150a.
Will be displayed. The computer 150a has a keyboard 156 and a mouse 155 for setting analysis conditions and the like.
Is provided. On the left side of the analyzer main body 100,
A cooling intake fan 111 for cooling the inside of the analyzer main body 100, an intake filter 110, and an exhaust fan 112 for discharging warm air are provided. On the front side of the analyzer main body 100, a display panel 157 for displaying the operating state and an emergency stop button 160 for urgently stopping the apparatus are provided.

On the right side of the analyzer main body 100, a holder 13 for holding one or more chemical arrays 120 at a time is provided.
A holder insertion port 140 for inserting 0 is provided. This right side has an openable door structure so that inspection and the like of the device can be easily performed. The holder insertion port 140 is provided on the right side of the apparatus main body 100 in consideration of cooperation with an unillustrated automatic holder transporter, but mainly inserts the holder manually without using the automatic holder transporter. In this case, it may be installed in front of the apparatus main body 100.

FIG. 2 shows a state in which an outer wall panel is removed to explain the inside of the apparatus main body 100.
Parts and the like that are not particularly required for explaining the gist of the present invention are not shown. In FIG. 2, a substrate 300 mainly mounted with components for operating the chemical array 120 and a substrate 300 mounted with an objective lens 310 under a substrate 200 mainly mounted with components for illumination light.
Is installed. On the substrate 200, a substrate 400 on which observation components are mainly mounted is provided. It is not essential that these hierarchical structures are arranged in this order, and the gist of the present invention does not change as long as the substrate 200 and the substrate 400 are adjacent to each other.

FIG. 3 is a plan view for explaining the devices on the substrate 200 in FIG. 2 and their functions. Light source 210
Is used to excite and emit a fluorescent marker for detecting a substance that is selectively bound to the well 122 on the chemical array 120. Therefore, when the target excitation light emission wavelength is longer than 390 nm, a halogen lamp is mainly used, and when the target excitation light emission wavelength is shorter than 390 nm, a discharge lamp such as a xenon lamp can be used. The light from the light source 210 is shaped into parallel light by the collimator lens 220, and the wavelength for exciting the fluorescent marker is selected by the filter 230. Then, the light is condensed on the spatial light modulator 250 by the relay lens 240.

As the spatial light modulator 250, a Texas Instruments Inc. digital micromirror device (Digital Micromirror) is used.
rorDevice). This device was developed by Larry J. Hornbeck.
igital Light Processing for High-Brightness, High-
Resolution Applications, Electronic Imaging, EI'97
Projection Display III Co-Sponsored by IS & T and SP
As described in IE An Invited Paper 1997, page 4 left side, 16 μm square modulation mirrors are arranged at a 17 μm pitch. The reflection angle of the mirror can be tilted from the neutral position to the elevation and depression angles by 10 degrees and 15 nanoseconds, thereby selecting the spatial position and modulating the intensity. Further, instead of the above-described spatial light modulation element, the same effect can be obtained by controlling the transmission type liquid crystal plate as a spatial light modulation element to be turned on and off, and transmitting or blocking light.

By using these means, it is not necessary to scan the chemical array to measure a plurality of wells on the chemical array, and the measurement throughput can be improved.

Further, by increasing the magnification of the objective lens of the confocal microscope, even if the size of the well on the chemical array is reduced, the measurement can be performed without deteriorating the performance.
Cost performance can be improved by increasing the number of types of measurement for each chemical array.

FIG. 3 shows a case where the spatial light modulator 250 is of a reflection type. The angle at which the relay lens 240 condenses light on the spatial light modulator 250 is uniquely determined depending on the element deflection angle of the spatial light modulator 250. For example, when the light reflected by the spatial light modulator 250 is parallel to the optical axis of the relay lens 241 and the element deflection angle is 10 degrees, the relay lens 240 converts the light to the spatial light modulator 250. The angle at which light is focused upward is 20 degrees. This spatial light modulator 250
The selection of the above element and the control of reflecting the light incident on this element toward the relay lens 241 are performed by the spatial light modulation element control circuit 800. Spatial light modulator control circuit 800
Is a window 151 on the screen of the computer 150a.
A control signal corresponding to the element position on the spatial light modulation element 250 specified by (see FIG. 11) and its modulation state is sent to the spatial light modulation element 250. The spatial light modulator 250 deflects the light to a predetermined deflection angle according to the transmitted signal. The light that is spatially selectively reflected by the spatial light modulator 250 is converted into parallel light by the relay lens 241, and then partially reflected by the half mirror 260, and travels toward the objective lens 310 shown in FIG.

The gist of the present invention is the same regardless of whether the half mirror 260 is designed to reflect a part of the light or to selectively reflect a specific wavelength completely without depending on the wavelength of the incident light. The use of the half mirror of the former specification can reduce the cost of the apparatus, and the use of the half mirror of the latter specification has a feature that the ability to observe the fluorescence emitted from the fluorescent marker is further improved.

Next, referring to FIG.
The operation of 0, 430 will be described. FIG. 12 includes a package 600 mainly made of ceramics and connection terminals 610 provided on the side surface for transmitting a modulation signal.
On the upper surface of the package 600, a spatial light modulator 250 or 430 manufactured by a semiconductor process is installed. The total number of the spatial light modulators is 512 to 1280 in the vertical and horizontal directions, and the total number is 260,000 to 1
300,000. FIG. 12B is an enlarged view of a part of the spatial light modulators 250 and 430 of FIG. The light modulating element reflecting surface 620 is used to modulate light in a specific direction.
0 is inclined. Terminals 640 and 650 for controlling this operation are provided at respective light modulating element reflecting surfaces 620.
From the package 600 and connected to a circuit for selecting a row or a column of a modulation element (not shown). FIG.
(3) is an enlarged display of one of the modulation elements shown in FIG. 12 (2).

The light modulation element reflection surface 620 is provided on the torsion bar 660, and the torsion bar 660 is provided.
Tilts or returns to its original position due to the twisting of. Light modulation element reflection surface 6
In order to modulate light by tilting 20, the terminal 640 is set to a higher potential than the terminal 650. At this time, the polarization terminal 621 and the terminal 640 installed on the lower surface of the light modulation element reflection surface 620 are used.
An electrostatic force acts between the dielectric terminal 630 installed above and
The light modulating element reflecting surface 620 is inclined so as to reduce this interval. Conversely, when the terminal 650 is set to a higher potential than the terminal 640, an electrostatic force acts between the dielectric terminal 670 and a polarization terminal (not shown), and the light modulation element reflection surface 620 returns to its original inclination. Note that when the terminal 650 is set to a higher potential than the terminal 640 and the inclination is returned to its original state, the inclination of the light modulation element reflection surface 620 is controlled by a stopper (not shown), and the inclination angle does not become unstable.

FIG. 13 shows the spatial light modulators 250 and 430.
FIG. 4 is a schematic diagram for explaining an operation in the case of a transmission type. This is one in which the portions of the spatial light modulation elements 250 and 430 in the ceramic package 600 in FIG. 12A have a liquid crystal structure, and one of them is enlarged and displayed so as to be able to be compared with the modulation element in FIG. I have. In FIG. 13, two liquid crystals 680 whose polarization directions are perpendicular to each other are shown.
And a liquid crystal 690 are superimposed. In this state, light cannot pass through this modulation element. In order to transmit and modulate light, the terminal 640 is set at a higher potential than the terminal 650 in order to change the polarization direction of the liquid crystal 680.
Then, the polarization directions of the liquid crystal 680 and the liquid crystal 690 are shifted from a right angle, and light can pass through this modulation element.

The choice of the two types of spatial light modulators shown in FIGS. 12 and 13 is that the reflection type in FIG. 12 can increase the light intensity after modulation compared to the transmission type in FIG. Consider the features of little change, capable of modulating strong light, and long life. On the other hand, it is taken into consideration that the transmission type diagram of FIG. 13 can have a smaller installation area, lower operating power, and can be manufactured at lower cost than the reflection type diagram of FIG.

The light shielding plate 242 not shown in FIG.
It is provided so that light not reflected by the spatial light modulation element 250 in the direction of the relay lens 241 does not enter the relay lens 241 again. Although not shown in FIG. 2, the light source 210 is installed in a dedicated small room 280 so that the light emitted from the light source does not disturb the measurement due to stray light, and the filter 230 is provided as a window.
The small room 280 is configured to discharge heat generated by the light source 210 by the exhaust fan 112 to the outside.

FIG. 4 is a plan view for explaining the devices on the substrate 300 in FIG. 2 and their functions. Substrate 200
The light reflected by the half lens 260
The light passes through 70 and enters the objective lens 310. The incident light focuses on a combined lens of the objective lens 310 and the relay lens 241 at a position conjugate with the element on the spatial light modulator 250. This focus is on the plane of the chemical array 120 where the wells 122 (see FIG. 6) lie.

The actuator controller 350 drives and controls the actuator 320 to drive the arm 360 that supports the holder 130 that holds one or more chemical arrays 120 at a time. That is, the actuator control unit 3
Based on the 50 command signals, the chemical array 120 to be measured is positioned so as to be sequentially below the objective lens. Fluorescence excited and emitted by illuminating the well 122 is condensed by the objective lens 310 again, and
Go through 70.

The light illuminating the well 122 is
The direction is bent by 90 degrees by a total reflection mirror (not shown) installed thereunder, and the direction is eliminated by an extinction device 340 located therebelow, so that scattered light caused by this light does not enter the objective lens 310 again. I have.

FIG. 5 is a plan view for explaining the devices on the substrate 400 in FIG. 2 and their functions. The light transmitted through the half mirror 260 and further transmitted through the opening 460 is bent by the total reflection mirror 410 toward the upper surface of the substrate 400. This light is collected on the surface of the spatial light modulator 430 by the relay lens 420. The spatial light modulator 430 is provided at a position conjugate to the well 122 on the chemical array 120 with respect to the combined lens of the objective lens 420 and the relay lens 420. The spatial light modulation element 430 is deflected to a predetermined deflection angle based on a signal from the spatial light modulation element control circuit 800, similarly to the spatial light modulation element 250 that deflects light from the light source in FIG. The light spatially reflected by the spatial light modulator 430 is condensed by a lens 425, and after a specific wavelength is selected by a rotary filter 442, the light is incident on a photomultiplier 450 and its intensity is measured. You.

The rotary filter 442 is connected to the well 12
A plurality of types of narrow band transmission filters are arranged on a disk so as to select a wavelength at which the amount of the fluorescent marker and the emission intensity change linearly from the fluorescent light emitted from the second fluorescent marker. . Then, a rotary filter that transmits a target wavelength is selected by the rotary filter control device 443. Immediately before this, the light incident on the photomultiplier 450 is
The dark current that is intermittently interrupted at 0 and is present in the photomultiplier 450 is measured, and the previous light intensity is corrected. The timing at which the rotary shutter 440 blocks light is controlled by the rotary shutter control device 441.

A light-shielding plate 422 not shown in FIG.
Is installed so that light not reflected by the spatial light modulation element 430 in the direction of the lens 425 does not enter the lens 425 again. The ventilation hole 470 is provided for the intake fan 1
After the cooling air introduced by 11 cools the photomultiplier 450, it passes through this hole to cool the inside of the small room 280 in which the light source 210 is installed. The photomultiplier 450 may be forcibly cooled using an electronic cooling element or the like in order to improve its light receiving sensitivity and stabilize it. Therefore, it is provided to make effective use of the cool air. Although not shown in FIG. 2, the photomultiplier 450 is installed in a dedicated small room so that stray light does not enter and an error occurs in a measurement result.

FIG. 6 shows a chemical array 120.
The well substrate 121 is preferably made of a transparent material. In particular, the well substrate 121 is made of a material that does not reflect light near the wavelength of the fluorescence generated from the well 122 or has an antireflection treatment. The handling hole 123 is for connecting the arm 360 of the actuator 320. Activate arm 360 and run chemical array 1
Positioning 20 is performed. The well 122 is a well substrate 1
21 is spotted in an arbitrary arrangement pattern, and an alignment mark 124 is drawn to recognize the spotted position. The alignment mark 124 is on the same surface as the well 122, and is a rectangular reflection mark that is long in a direction perpendicular to the direction in which the chemical array 120 is held by the holder 130 and inserted into the apparatus main body 100.

FIGS. 7 and 8 show changes in the light intensity observed by the photomultiplier 450 when the alignment mark 124 is used for positioning the chemical array 120. FIG. At the time of alignment, light is irradiated only on the alignment mark 124 by selective modulation processing of the illumination spatial light modulation element 250. In this state, the position in the direction perpendicular to the surface of the chemical array 120 (the so-called focal position) and the photomultiplier 450
The change in the light intensity observed at is as shown in FIG. The positioning of the chemical array 120 in the vertical direction is realized by operating the actuator 320 in the vertical direction (z direction in FIG. 6) so that the light intensity reaches a peak. Similarly, the direction parallel to the surface of the chemical array 120 (holder 130
The change in the light intensity observed by the photomultiplier 450 with respect to the position (insertion direction) is as shown in FIG. Therefore,
The positioning of the chemical array 120 in the parallel direction is as follows.
This is realized by operating the actuator 320 in the insertion direction (x direction in FIG. 6) so that the light intensity reaches a peak.

FIG. 9 shows spatial light modulators 250 and 430,
FIG. 3 schematically shows the size of the chemical array 120 and the interval between them. Chemical array 1 from objective lens 310
20 is L310, the maximum outer width of the chemical array 120 is W120, the pitch of the well 122 is Wp120,
The distance from the relay lens 241 to the spatial light modulator 250 is L241, and the minimum outer width of the spatial light modulator 250 is W
250, element pitch Wp250, relay lens 420
Let L430 be the distance from to the spatial light modulator 430, the minimum outer width of the spatial light modulator 430 be W430, and the element pitch be Wp430. In FIG. 9, in order to perform measurement without mechanical scanning, it is necessary that W120 ≦ L310 ÷ L241 × W250 (1) and W120 ≦ L310 ÷ L420 × W430 (2). Further, regarding illumination of the well 122 by the spatial light modulation element 250, it is necessary to satisfy Wp120 = n × m × Wp250 (3) in order to apply illumination light only to the target well. However, n is an integer of 1 or more, and this value can be more efficiently illuminated as the number of illumination elements around the well is larger.

M is the illumination magnification, which is approximately m = L310 ÷ L241 (4). Since n is an integer, in order to satisfy the condition (3), the value of m takes a specific value such that m = Wp120) (n × Wp250) (5). Therefore, from the expression (4) and the condition (5), the value of L241, that is, the spatial light modulator 2 is set so that L241 = L310 ÷ Wp120 × (n × Wp250) (6)
Adjust the distance up to 50. By the way, since L241 is approximately equal to the focal length of the relay lens 241, a variable focal length lens such as a zoom lens is applied as the relay lens 241. Spatial light modulation element 430
The condition for spatially selecting the light from the well 122 by the above is not particularly limited as long as the condition (3) is already satisfied.

However, when the thickness of the well 122 is large, a higher definition is required to select only the desired fluorescence.
(Wp430 is small) is preferably adopted.

FIG. 10 shows well 1 on chemical array 120.
22 shows light patterns 2501 to 2509 from the spatial light modulation element 250 illuminating 22. In FIG. 10, the equation
In the case of n = 3 in (3), it is assumed that the illumination magnification m has already been determined. Assuming that the element of the spatial light modulation element 250 facing the well 122 to be illuminated is W250 (i, j) (2501 in FIG. 10), W250 (i−1) centered on W250 (i, j) (2501). j-1) (from 2505) to W2
Spatial modulation is performed on a total of 9 pieces up to 50 (i + 1, j + 1) (2509) to illuminate the well 122 to be illuminated. As a result, all of the fluorescence excited in the well is generated from the target well (122 in FIG. 10), and the measurement S
N does not decrease. Thus, when n is an odd number, W250 (i- (n-1) / 2, j- (n-1) / 2) to W250 (i
+ (n-1) / 2 , j + (n-1) / 2) performs spatial modulation on ^two n of, if n is an even number, W250 (i- (n-2 ) / 2, j- (n-2) / 2) to W
If spatial modulation is performed on (n-1) ² pieces of 250 (i + (n-2) / 2, j + (n-2) / 2), the measured SN does not decrease.

FIG. 11 schematically shows the control by the control computer 150 and the display of the measurement results.
In the window 151 on the screen, the state of modulation of the spatial light modulator 250 is displayed. The modulation position can be changed with the scroll bars 1511 and 1512, and the modulation element can be arbitrarily changed by clicking the target element display with the mouse. A window 152 on the screen has a spatial light modulator 43
The state of modulation of 0 is displayed, and the display contents and the method of operation are the same as those of the window 151. The window 153 displays the measured fluorescence intensity and wavelength. Here, the measurement results of other fluorescence wavelengths can also be displayed in an overlapping manner. In the window 154, a schematic diagram of the chemical array 120 is displayed, and the measurement result display points for the corresponding wells are displayed in different colors. The data can be converted and transferred for further analysis by another computer.

The measurement using the analyzer according to the present invention is performed as follows. That is, the chemical array 120 is
One or more are held at 0. The holder 130 is inserted into the holder insertion port 140. Apparatus body 10 that recognizes that holder 130 has been inserted into holder insertion port 140
0 causes the arm 360 to move the first chemical array 120 just below the objective lens 310 at the same time as the actuator 320 retracts it. And Chemical Array 1
For the alignment of 20 with the measurement optical system, the modulation state of the spatial light modulator 250 is modulated according to the alignment mark 124 on the chemical array 120 so that the light intensity observed by the photomultiplier 450 takes the maximum value. Fine adjustment in the x direction and z direction is performed. Thereafter, the spatial light modulator 250 is modulated according to the illumination magnification, the number of illumination elements, and the well alignment on the chemical array 120.

Then, of the fluorescence generated from the well,
A rotary filter is selected so as to observe a specific wavelength, and the light intensity incident on the photomultiplier 450 is measured. At this time, when the thickness of the well to be measured is large, the spatial light modulation element 430 performs intensity modulation so as to select only light from the well. However, the plurality of elements of the spatial light modulator 430 are not simultaneously modulated, and the individual elements are successively modulated in time series. After measuring the light intensity incident on the photomultiplier 450, while moving to another well measurement,
The rotary shutter 440 is closed so that light does not enter the photomultiplier 450, the dark current value of the photomultiplier 450 is measured, and the light intensity value from the previous well is corrected. The measurement result is sent to the control computer 150, and the recording and display are performed together with the wavelength of the illumination light.

According to the embodiment described above, the following effects can be obtained. That is, the chemical array can be measured without mechanical scanning by operating the modulation state of the spatial light modulator 250 so as to adapt to the arrangement of the wells 122 on the chemical array 120. Therefore, the measurement throughput can be improved. Spatial light modulator 2
The fifty modulation states are transferred to the wells 122 on the chemical array 120.
By operating to adapt to the shape of the above, only the fluorescence from the target well can be measured. At this time, since no fluorescence is generated from the adjacent well, the measurement S
N is not reduced.

The effect of the above (2) is further improved by the chemical array 12
The shape of the well 122 on 0 is substantially independent of the quantity and shape, such as one on the entire surface of the chemical array 120, two or more, and square or round. Therefore, if this degree of freedom is used, the dynamic range of measurement can be dramatically improved. By manipulating the modulation state of the spatial light modulation element 430, measurement can be performed utilizing the above effects even when the well has a thickness.

Further, when performing a more detailed measurement by narrowing the corresponding measurement range of the chemical array 120, the spatial modulation element 250 uses all of the elements to form the chemical array 120.
By illuminating all of the wells at once and the spatial light modulator 430 introducing all light into the photomultiplier 450 with all of the elements, the chemical array 120
It is possible to quickly determine whether or not there is a well that emits fluorescence, thereby improving the measurement throughput.

When a reflection type element is used as the spatial light modulation elements 250 and 430, it is expected that light leaking from between the elements of the spatial light modulation element 250 on the illumination light side will become stray light and lower the measurement SN. You. However, in this embodiment, since the light incident on the photomultiplier 450 is further spatially modulated by the spatial light modulator 430, the measured SN is not reduced. Therefore, a spatial light modulator having an aperture ratio of 100% or less can be used, and the cost of the device can be reduced.

Scanning by the spatial light modulators 250 and 430 consumes less power than mechanical scanning, so that running costs can be reduced. The scanning by the spatial light modulators 250 and 430 has a smaller mass of the movable part than the mechanical scanning, so that noise during operation is reduced. Furthermore, the size of the apparatus can be reduced, which is resistant to disturbances such as vibrations during operation.

[0047]

As described above, by adopting the configuration of the analyzer of the present invention, it is possible to realize an apparatus which can improve the measurement throughput and prevent the decrease of the measurement SN, can shorten the measurement time, and can provide a small and inexpensive apparatus.

[Brief description of the drawings]

FIG. 1 is a perspective view of an embodiment of an exposure apparatus according to the present invention.

FIG. 2 is a perspective view illustrating an embodiment of an exposure apparatus according to the present invention.

FIG. 3 is a perspective view illustrating an embodiment of an exposure apparatus according to the present invention.

FIG. 4 is a perspective view illustrating an embodiment of an exposure apparatus according to the present invention.

FIG. 5 is a perspective view for explaining an embodiment of an exposure apparatus according to the present invention.

FIG. 6 is a perspective view illustrating an embodiment of an exposure apparatus according to the present invention.

FIG. 7 is a graph for explaining positioning of a chemical array according to the present invention.

FIG. 8 is a graph for explaining positioning of a chemical array according to the present invention.

FIG. 9 is a perspective view for explaining an embodiment of an exposure apparatus according to the present invention.

FIG. 10 is a perspective view illustrating an embodiment of an exposure apparatus according to the present invention.

FIG. 11 is a perspective view of an embodiment of an exposure apparatus according to the present invention.

FIG. 12 is a diagram illustrating the configuration and operation of a reflective spatial light modulator.

FIG. 13 is a configuration diagram of a transmission type spatial light modulation element.

[Explanation of symbols]

Reference Signs List 100 apparatus main body, 110 intake filter, 111 intake fan, 112 exhaust fan, 150 control computer, 340 extinction device, 350 actuator control circuit, 800 spatial light modulation element control circuit, 410 total reflection mirror.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) G01N 33/53 G01N 33/53 M 33/566 33/566 F term (reference) 2G042 AA01 BD12 BD20 CB03 DA08 FA11 FB05 HA07 2G043 BA16 EA01 GA06 GA08 GB07 GB18 GB21 HA06 HA07 HA09 HA11 HA15 JA02 JA03 LA02 MA01 MA04 2G045 AA35 DA12 DA13 DA14 FA11 FA13 FA14 FB07 FB12 GC15 HA02 HA09 2H052 AA08 AA09 AC15 AC27 AC28 AD19 AD34 AF34

Claims (6)

[Claims] An apparatus for measuring a biological sample mixed with a specific reagent that emits fluorescence by irradiating light from a light source to a well of a chemical array formed on a transparent substrate, wherein the well is irradiated with illumination light. A spatial light modulation element comprising a plurality of elements for spatially selecting light from a light source at a position conjugate with the well of the optical system is installed, and the light or light from the well to drive the spatial light modulation element and irradiate the well A chemical analyzer characterized by illuminating a plurality of wells singly or simultaneously by selectively modulating reflected light and observing the intensity of fluorescence generated from the wells. 2. The chemical analyzer according to claim 1, wherein said spatial light modulator is an element utilizing surface reflection. 3. The chemical analyzer according to claim 1, wherein said spatial light modulator is an element that transmits or blocks light. 4. A chemical analyzer for measuring a sample component using a chemical array in which a well in which a specific reagent that emits fluorescence is reacted with a biological sample is formed on a transparent substrate, wherein the fluorescence generated from the well is detected. An optical system to observe, and a spatial light modulation element that spatially selects light from the well is installed at a position conjugate to the well in the optical system, and the spatial light modulation element is selectively modulated. A chemical analyzer characterized by observing the light intensity of fluorescent light generated from a plurality of wells singly or simultaneously. 5. The chemical analyzer according to claim 4, wherein the element for spatially selecting the light from the light source is an element utilizing the reflection of the surface. 6. The chemical analyzer according to claim 4, wherein the element for spatially selecting the light from the light source is an element utilizing transmission or blocking of the light.