JPH10170430A - Method and device for measuring surface plasmon - Google Patents

Abstract

PROBLEM TO BE SOLVED: To measure surface plasmon with high precision even with such SPR (surface plasmon resonance) sensor as a photo-detecting sensor of small dynamic range is used. SOLUTION: A light-shielding plate 13 is entirely opened so that the entire of incident surface of a CCD sensor 15 is irradiated with reflection light from a gold thin film 11. Over a wide incidence angle range, intensity of reflection light of excitation light is measured. As a result, a resonance curve of a specified surface plasmon resonance is obtained. Based on the resonance curve, the light-shielding plate 13 is moved so that a reflection light transmits only a narrow region containing pixel number of the CCD sensor 15 corresponding to around minimum value of reflection light quantity. A current supply amount to a light source 1 is so increased as to increase radiation light intensity from the light source 1, thus the light quantity incident on the CCD sensor 15 is increased. Thereby, a plasmon resonance angle curve of large dynamic range is obtained. From the plasmon resonance angle curve, the resonance angle of surface plasmon resonance is accurately obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and an apparatus for measuring surface plasmon.

[0002]

2. Description of the Related Art Conventionally, a sensor using the surface plasmon resonance phenomenon (SPR) has been used as a sensor provided in medical equipment or analytical equipment for measuring an antigen-antibody reaction, or as a gas sensor.
Sensors) are used. The SPR sensor utilizes the phenomenon that the magnitude of the resonance angle changes due to the change in the dielectric constant near the gold thin film on the prism. If the measurement of the antigen-antibody reaction by a medical device equipped with the SPR sensor is taken as an example, the dielectric constant Is correlated with the reaction amount of the antigen-antibody reaction, the reaction amount can be determined from the change in the dielectric constant.

[0003]

The above-mentioned S
The PR sensor irradiates the gold thin film with excitation light from a light source to excite surface plasmon resonance on the gold thin film, and receives reflected light from the gold thin film by a light receiving sensor such as a one-dimensional CCD sensor. Then, a desired measurement operation is performed by detecting a change in a portion (= resonance angle of surface plasmon) where the amount of light received by the light receiving sensor is minimized. One-dimensional C
The CD sensor has the advantages of being relatively inexpensive and having high spatial resolution (= narrow pixel spacing), but has the disadvantage of having a small dynamic range with respect to light intensity.

However, since the change in the resonance angle caused by the change in the dielectric constant is generally very small, a light-receiving sensor having a small dynamic range with respect to the light intensity, such as the one-dimensional CCD sensor, is delicate. It is difficult to detect a change in the resonance angle. Therefore, the SPR sensor having the above configuration is not suitable for measuring the reaction amount of the antigen-antibody reaction, which is a condition of accurate measurement in which a delicate change in resonance angle is sensed.

[0005] Therefore, a method of employing a light receiving sensor having a large dynamic range of light intensity instead of the one-dimensional CCD sensor, and changing the configuration of the SPR sensor to a configuration suitable for obtaining resonance characteristics having a sharp resonance angle. However, none of them was practical in terms of cost and structure.

Accordingly, an object of the present invention is to enable surface plasmons to be measured with high accuracy even when an SPR sensor is configured using a light receiving sensor having a small dynamic range.

[0007]

According to a first aspect of the present invention, there is provided a surface plasmon measuring method in which light from a light source is incident on a plasmon sensor, and the reflected light intensity is detected by a light sensor in a relatively wide reflection angle range. Thus, the step of determining a relatively narrow reflection angle range including the plasmon resonance angle, and masking the optical path so that only the reflected light of the relatively narrow reflection angle range is input to the optical sensor, and the higher intensity reflected light Determining the plasmon resonance angle after adjusting the amount of light from the light source so as to be input to the optical sensor.

According to this configuration, the reflected light is transmitted only to a narrow area corresponding to the vicinity of the minimum value of the reflected light amount, and the excitation light having a high intensity is radiated from the light source intensively at that location. Therefore, the resonance angle of surface plasmon resonance can be accurately obtained.

A surface plasmon measuring device according to a second aspect of the present invention is a device in which light from a light source is made incident on a plasmon sensor and the intensity of reflected light is detected by the optical sensor, thereby limiting the range of reflected light input to the optical sensor. And a mask for
Light amount adjusting means for adjusting the intensity of reflected light input to the optical sensor.

According to this configuration, the range of the reflected light input to the optical sensor by the mask is limited, and the intensity of the reflected light incident toward the limited reflected light range is adjusted by the light amount adjusting means. Therefore, the excitation light of high intensity can be intensively emitted from the light source by increasing the amount of reflected light in the limited reflected light range,
Even an optical sensor having a small dynamic range can detect a subtle change in resonance angle, and can accurately determine the resonance angle of surface plasmon resonance.

In a preferred embodiment according to the second aspect of the present invention, the mask is provided at an arbitrary position in an optical path between the light source and the optical sensor, and a light shielding plate is used for the mask. .

In another embodiment, a liquid crystal shutter array in which the transmission range of reflected light is changed by an electro-optic effect is used as the mask. It is preferable to use a liquid crystal shutter array having a variable light transmittance for each location.

According to this configuration, since the transmission range and the transmittance of the reflected light can be electrically varied, it is not necessary to adjust the intensity of the radiated light from the light source.

Further, as the mask, a mask that limits the reflection angle range of the reflected light to a fixed value or a mask that variably limits the reflection angle range of the reflected light is used.

Further, a light guide plate may be provided in the optical path from the light source to the light sensor to confine and guide the light two-dimensionally.

According to this configuration, the light can be received effectively, so that the measurement accuracy can be improved and the unit and apparatus can be reduced in size because it contributes to space saving.

[0017]

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

FIG. 1 is a block diagram showing a configuration of an optical system of a surface plasmon measuring apparatus according to one embodiment of the present invention.

As shown in the figure, the apparatus has a light source 1 as an optical system, a plurality of lenses 3, 5 having a collimating function and a condensing function, a polarizing plate 7, and a prism 9 having a gold thin film 11. , A light shielding plate 13 and a one-dimensional C as a light receiving sensor
A CD sensor (hereinafter abbreviated as a CCD sensor) 15;

The light source 1 is for exciting surface plasmon resonance on the gold thin film 11 by irradiating the excitation light. In the present embodiment, the light source 1 controls the current supply amount to increase the intensity of the emitted light. A light emitting diode (LED) or a laser diode (LD), which is a light emitting element that can be arbitrarily changed, is used. A predetermined amount of current is supplied to the light source 1 from a driving power supply (both not shown) controlled by a controller via a D / A converter or the like.

The lenses 3 and 5 and the polarizing plate 7 receive the excitation light from the light source 1 and guide it to the prism 9. Prism 9
Excitation light incident through the lenses 3 and 5 and the polarizing plate 7 is received, and is focused on a surface plasmon excitation unit formed on the surface of the prism 9 such as the gold thin film 11. The gold thin film 11 is formed, for example, by depositing gold having a thickness of 50 nm on the surface of the prism 9. Thus, the surface plasmon resonance is excited on the surface of the gold thin film 11 by the excitation light focused on the gold thin film 11.

The light shielding plate 13 is for shielding the incident surface of the CCD sensor 15 on which the reflected light from the gold thin film 11 is incident, and is configured so that the position for shielding the reflected light can be changed arbitrarily. 15 are provided on the incident surface. The light shielding plate 13 is configured to be displaceable from a position where the incident surface of the CCD sensor 15 is fully closed to a position where it is fully opened. As a mechanism for changing the light shielding position by the light shielding plate 13, for example, a mechanism for mechanically sliding the light shielding position, a diaphragm mechanism of a camera, or the like is used.

The CCD sensor 15 receives the reflected light from the gold thin film 11 that enters through the open portion of the light shielding plate 13 and obtains the surface plasmon resonance generated in the gold thin film 11 from the intensity distribution of the received light amount. Detect corners.

FIG. 2 shows a positional relationship between the light shielding plate 13 and the reflected light incident surface of the CCD sensor 15 when the light shielding plate 13 and the CCD sensor 15 are viewed from the prism side according to one embodiment of the present invention. FIG. As is apparent from the figure, the reflected light from the gold thin film 11 enters the reflected light incident surface of the CCD sensor 15 through the gap 13a formed by the light shielding plate 13.

In the above configuration, the excitation light from the light source 1 is focused on the gold thin film 11 on the prism 9 through the lenses 3, 5 and the polarizing plate 7. Surface plasmon resonance is excited on the gold thin film 11 by the excitation light. Here, the excitation light having an angle component for exciting the surface plasmon resonance loses energy due to the excitation of the surface plasmon resonance.
Therefore, the intensity distribution of the reflected light that enters the CCD sensor 15 from the gold thin film 11 through the gap 13a of the light shielding plate 13 is as follows:
The horizontal axis represents the CCD pixel number, and the vertical axis represents the intensity of the reflected light.

In this curve, the point 17 where the amount of light is minimum is the point on the incident surface of the CCD sensor 15 corresponding to the angular component of the excitation light for exciting the surface plasmon resonance described above. 3 is referred to as a resonance angle of surface plasmon resonance, and the curve shown in FIG. 3 is referred to as a resonance curve of surface plasmon resonance.

Next, a method of measuring a surface plasmon resonance curve using the apparatus having the above configuration will be described.

First, the light shielding plate 13 is fully opened and the CCD
Light reflected from the gold thin film 11 is applied to the entire incident surface of the sensor 15. Thus, the reflected light intensity of the excitation light is measured over a wide incident angle range. As a result, FIG.
A surface plasmon resonance resonance curve can be obtained as shown in c

Next, based on the resonance curve obtained as described above, the reflected light is reflected only in a narrow area including the pixel number of the CCD sensor 15 corresponding to the vicinity of the minimum value of the reflected light amount indicated by reference numeral 17 in FIG. The light shielding plate 13 is moved so that the light is transmitted. Then, by controlling the driving power supply by the controller described above, the amount of current supplied to the light source 1 is increased to increase the intensity of the radiated light from the light source 1, and the CCD sensor 15
To increase the amount of light incident on.

FIG. 4 shows the intensity distribution of the reflected light obtained in this manner.

FIG. 4 is a graph in which the minimum value portion of the reflected light shown in FIG. 3 is enlarged in the direction of the vertical axis (Y axis). From this graph, the resonance angle of surface plasmon resonance can be accurately obtained.

By moving the light shielding plate 13 as described above and increasing the intensity of the radiated light from the light source 1, C
By increasing the amount of light incident on the CD sensor 15 to form a sharp resonance curve, a subtle change in the resonance angle can be detected even with the CCD sensor 15 having a small dynamic range, and an SPR sensor with high measurement accuracy can be configured.

As described above, in this embodiment, the range of the angle of incidence of the reflected light from the gold thin film 11 on the CCD sensor 15 is limited and the amount of incident light on the CCD sensor 15 is increased. The same effect as described above can be obtained by limiting the emission angle range of the light emitted from the CCD and increasing the amount of light incident on the CCD sensor 15. Also,
The position of the light shielding plate 13 may be set at an arbitrary position between the light source 1 and the CCD sensor 15. Further, instead of the light shielding plate 13, a light transmittance adjusting device such as a liquid crystal shutter array may be employed as a device capable of limiting the incident angle range to the CCD sensor 15 as the light shielding device.

FIG. 5 is a perspective view showing a liquid crystal shutter array according to a modification of the embodiment of the present invention.

This liquid crystal shutter array comprises a rectangular frame 21 and a plurality of rectangular liquid crystal display units (= pixels) 23 arranged in the frame 21 as shown in the figure. The plurality of pixels 23 function as a light shutter by an electro-optical effect, and the transmission range 25 of the reflected light from the gold thin film 11 can be changed by using the electro-optical effect.

As described above, by adopting the liquid crystal shutter array as the above-mentioned light shielding means, the movable mechanism which is indispensable for the light shielding plate 13 can be eliminated, so that the size and weight of the device can be reduced. In addition, cost can be reduced.

Here, if the liquid crystal shutter array is provided with a function of arbitrarily changing the light transmittance of each pixel 23, the amount of current supplied from the driving power supply to the light source 1 can be controlled to control the light source 1 The same effect as described above can be obtained without changing the intensity of the radiated light from.

For example, in the above-mentioned liquid crystal shutter array, the light transmittance of all the pixels 23 constituting the display section is set as follows.
It is set to be variable for each pixel 23. In this case, the light transmittance of each pixel 23 is set to 100% or 0%.
May be switched to any one of the two stages, or may be switched to any one of 100%, 50%, and 0%. Furthermore, 100%, 66%, 33%,
Four-stage switching for switching to 0% or more stages may be performed.

Here, the light transmittance of each pixel 23 is set to 3
The case where the stages are switched will be described. For example, first, the light transmittance of all the pixels 23 is set to 50%, and the reflected light intensity is measured for the total reflection angle of the excitation light to obtain a resonance curve as shown in FIG. Next, with respect to each pixel 23 corresponding to a range excluding the vicinity of the resonance angle in the resonance curve, the light transmittance thereof is changed to 0% to block light, and conversely, the pixels 23 correspond to a range near the resonance angle. For each pixel 23, the transmittance is increased by changing the transmittance of the pixel 23 to 100%. Thus, the area outside the vicinity of the resonance angle is masked by the light-shielding plate 13 as described above, and the area within the range is similar to the resonance curve of FIG. A resonance curve can be obtained

In the present modified example, the example in which the transmission range is changed by using the liquid crystal shutter array and the light transmittance of each pixel 23 is changed has been described.
Any device other than the above-described liquid crystal shutter array may be used as long as it can change the transmission range of the reflected light incident on the CD sensor 15 and adjust the light transmittance.

Whether the prism 9 for guiding the radiated light from the light source 1 to the gold thin film 11 is a light guide plate, or a light guide plate for guiding the reflected light from the gold thin film 11 to the CCD sensor 15 is provided. A light guide plate may be provided between the light source 1 and the gold thin film 11 and between the gold thin film 11 and the CCD sensor 15 to confine the emitted light and / or the reflected light in two dimensions. As a result, the loss of the reflected light from the gold thin film 11 incident on the CCD sensor 15 is reduced, and the measurement accuracy of the resonance angle is improved. With such a configuration, space can be saved, so that units and devices can be reduced in size. Furthermore, even when a light emitting element having a low intensity of radiated light is used as the light source 1, light loss is small. A sensor can be configured.

Even if another light receiving element such as a photodiode array is used in addition to the above-described CCD sensor 15 as the light receiving sensor, the high accuracy S
A PR sensor can be configured.

[0043]

FIG. 6 (a) shows a C according to an embodiment of the present invention.
This is comparison data by light emission amount of the received light intensity distribution in the CD sensor 15, and this data is obtained by changing the range of the incident surface of the CCD sensor 15 which is not masked by the light shielding means. From this data, it is possible to confirm the operational effects of the light shielding means such as the light shielding plate 13 in the device according to the embodiment of the present invention.

In FIG. 6A, the horizontal axis represents the pixel number of the CCD sensor 15, and the vertical axis represents the light receiving intensity. When the area not masked by the light-shielding tape 35 is wide, the resonance curve 31 is set with the light emission amount constant as "no mask", and when the area not masked by the light-shielding tape 35 is narrow, the light emission amount is determined as "with mask". And a resonance curve 83 was obtained.

The process of the above experiment will be described in more detail.
First, as shown in FIG. 6B, an area that is not masked by the light-shielding tape 35 is provided 7.3 mm near the left side, including the central part of the CCD sensor 15. And light source 1
The current supply to the LED used as the LED is maintained at 7 mA by the controller, and the unmasked CCD is used.
The reflected light is made incident on the entire incident surface of the sensor 15,
The light receiving intensity for each pixel number was measured to obtain a resonance curve 31. Next, the mask (light-shielding tape 3
5) is moved to the center of the CCD sensor 15 and
The area of the CD sensor 15 that is not masked by the light-shielding tape 35 is reduced to 1.3 mm. Then, the amount of current supplied to the LED is increased to 19 mA so that the reflected light is made incident on the entire non-masked incident surface of the CCD sensor 15, and the light receiving intensity for each pixel number is measured to obtain the resonance curve 33. I got

That is, the reflected light intensity is measured by the CCD sensor 15 over a wide range of reflection angles without using a mask, and a narrow reflection angle range including a plasmon resonance angle is determined from the resonance curve 31, and the narrow reflection angle range is determined. Only reflected light in the reflection angle range is C
The optical path is masked by a light-shielding tape 35 so as to be incident on the CD sensor 15, the amount of light is increased, and a resonance curve 33 is taken to measure the plasmon resonance angle in detail.

Here, the two resonance curves 31, 33
Comparing the difference in the width of the received light intensity in the 100 pixel range near the resonance angle where the received light intensity has the lowest value, "no mask"
In the case of the resonance curve at the time of, the width of the received light intensity is S1 =
In the case of the resonance curve 33 with about 30 and “with mask”, the width of the received light intensity was about S2 = 100. From this experimental result, it has been clarified that the dynamic range of the resonance curve 33 is more than three times as large as that of the resonance curve 31, and that the plasmon resonance angle can be measured with high accuracy.

The contents described above relate to one embodiment of the present invention, and do not mean that the present invention is limited to only the contents described above.

[0049]

As described above, according to the present invention,
SPR using light sensor with small dynamic range
Even if a sensor is configured, surface plasmons can be measured with high accuracy.

[Brief description of the drawings]

FIG. 1 is a block diagram showing a configuration of an optical system of a surface plasmon measuring device according to an embodiment of the present invention.

FIG. 2 is a diagram showing a positional relationship between a light shielding plate and a reflected light incident surface of a CCD sensor according to one embodiment.

FIG. 3 is a diagram showing an intensity distribution of reflected light incident on a CCD sensor.

FIG. 4 is a graph obtained by enlarging a minimum value portion of the reflected light in FIG. 3 in a vertical axis direction.

FIG. 5 is a perspective view of a liquid crystal shutter array according to a modification of the embodiment.

FIG. 6 is an explanatory diagram showing the contents of an experiment using the measuring device according to one embodiment and the results thereof.

[Explanation of symbols]

 REFERENCE SIGNS LIST 1 light source 3, 5 lens 7 polarizing plate 9 prism 11 gold thin film 13 light shielding plate 15 one-dimensional CCD sensor 17 place where reflected light quantity is minimum 21 frame of liquid crystal shutter array 23 liquid crystal display unit (= vicel) 25 transmission range of reflected light 31, 33 Resonance curve 35 Light shielding tape

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[Procedure amendment]

[Submission date] February 27, 1997

[Procedure amendment 1]

[Document name to be amended] Drawing

[Correction target item name] All figures

[Correction method] Change

[Correction contents]

FIG.

FIG. 2

FIG. 5

FIG. 3

FIG. 4

FIG. 6

Claims (9)

[Claims] 1. A step of irradiating a plasmon sensor with light from a light source and detecting a reflected light intensity in a relatively wide reflection angle range by the optical sensor to determine a relatively narrow reflection angle range including a plasmon resonance angle. And masking the optical path so that only the reflected light in the relatively narrow reflection angle range is input to the optical sensor, and adjusting the amount of light from the light source so that the reflected light having higher intensity is input to the optical sensor, and then adjusting the plasmon resonance. Determining a corner; and a surface plasmon measuring method. 2. A surface plasmon measuring device for causing light from a light source to enter a plasmon sensor and detecting the intensity of reflected light by the optical sensor, wherein: a mask for limiting a range of reflected light input to the optical sensor; A surface plasmon measuring device, comprising: a light amount adjusting means for adjusting the intensity of reflected light to be input. 3. The surface plasmon measurement device according to claim 2, wherein the mask is provided at an arbitrary position in an optical path between the light source and the optical sensor. 4. The surface plasmon measuring device according to claim 2, wherein said mask is a light shielding plate. 5. The surface plasmon measurement device according to claim 2, wherein the mask is a liquid crystal shutter array whose transmission range of reflected light is variable by an electro-optic effect. 6. The surface plasmon measurement device according to claim 5, wherein the liquid crystal shutter array has a variable transmittance for each location. 7. The surface plasmon measurement device according to claim 2, wherein the mask limits a reflection angle range of the reflected light to a constant value. 8. The surface plasmon measuring device according to claim 2, wherein the mask variably limits a reflection angle range of the reflected light. 9. The surface plasmon measurement device according to claim 2, further comprising: a light guide plate for guiding light by confining light two-dimensionally in an optical path from the light source to the light receiving sensor.