JP2003279475A - Surface plasmon resonance sensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a surface plasmon resonance sensor capable of providing a plurality of measurement regions by solving a problem that a conventional surface plasmon resonance sensor has only one measurement region. <P>SOLUTION: This surface plasmon resonance sensor is so structured that a metal thin film is formed on the back face of a prism, a sample solution is directly brought into contact with the surface of the metal thin film, light is entered into the prism in a condition where the light is totally reflected by the interface between the metal thin film and the sample solution, and the state of a substance in the sample solution can be analyzed based on the reflected light. The sensor characteristically includes a continuous sample solution feeding passage bent so as to form at least two measurement regions intercrossing with the surface of the metal thin film formed on the prism. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an improvement of a surface plasmon resonance sensor.

[0002]

2. Description of the Related Art A surface plasmon resonance sensor forms a metal thin film on the back surface of a prism, directly contacts the surface of the metal thin film with a sample solution, and causes the prism to totally reflect at the interface between the metal thin film and the sample solution. Known as a sensor that injects light under certain conditions, detects the refractive index or absorptance of reflected light or transmitted light that is generated by the light detection means, and analyzes the substance state in the sample liquid based on the detection result. There is. When a substance state is analyzed using the surface plasmon resonance sensor described above, usually, a reaction product that specifically reacts with the substance to be analyzed is fixed in advance on the metal thin film, and the substance to be analyzed is contained on the metal thin film. A sample solution is supplied to measure changes in the bending rate and absorption rate associated with the reaction between the substance to be analyzed and the reactant.

[0003]

However, in the above-mentioned conventional surface plasmon resonance sensor, there is only one measurement region in which the substance to be analyzed and the reactant react with each other. Therefore, for example, when the sample liquid contains two kinds of analytes to be measured, first, after measuring a reactant that reacts with one of the analytes with a sensor fixed to a metal thin film, then ,
There is a problem in that the measurement work of the other reaction object, that is, the reaction product that reacts with the measurement object, is performed twice by the sensor fixed to the metal thin film. In this way, being forced to perform the measurement work twice for one sample solution is not limited to the problem of poor work efficiency, and when the amount of sample solution is limited, all analytes can be analyzed. Is a serious problem as it can lead to the serious problem of being unable to measure. Further, for example, in the case of performing a constitutional test using DNA, DN related to constitution is selected from DNA contained in sample liquids such as blood and body fluids of patients.
A single strand of A is generated, and a single strand of DNA of a sample provider whose constitution is known in advance is immobilized on the metal thin film. Then, the D single-stranded DNA in the sample solution is fixed
Whether or not it binds to a single strand of NA is measured as a state change, and if bound, it has the same constitution as the sample provider,
If they do not bind, it is judged that the constitution is different from the constitution of the sample provider. For such tests, the DN of the patient
A sample solution containing a single strand can be used for DN of various sample providers.
Since it has to react with the A single strand, the measurement work has to be performed many times, and the same problem as described above occurs. This problem is not limited to the test using DNA, and is the same in the test using RNA and the test using an antigen-antibody reaction which is an immunological substance. Furthermore, in order to improve the measurement accuracy of the above-mentioned sensor, first the measurement is carried out in the state where the reactant is not fixed, then the measurement is carried out with the reactant fixed, and the two are compared to measure the impurity. Although it is conceivable to correct the error, even in this case, since the work is divided into a plurality of times, the same problem as described above occurs. Furthermore, in order to improve the measurement accuracy of the sensor, it is possible to repeat the same measurement a plurality of times and take the average thereof, but in this case also, since the work is divided into a plurality of times, the same problem as the above problem occurs . An object of the present invention is to solve the problem that the conventional surface plasmon resonance sensor has only one measurement area and to provide a surface plasmon resonance sensor capable of obtaining a plurality of measurement areas.

[0004]

In order to achieve the above object, in the surface plasmon resonance sensor according to the present invention, a metal thin film is formed on the back surface of the prism, and the sample solution is brought into direct contact with the surface of the metal thin film. At the same time, light is incident on the prism under the condition of total reflection at the interface between the metal thin film and the sample liquid, and a surface configured so that the substance state in the sample liquid can be analyzed based on the reflected light. The plasmon resonance sensor is characterized in that it is provided with a continuous sample liquid supply passage which is bent so as to form at least two measurement regions intersecting the surface of the metal thin film formed on the prism.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of a surface plasmon resonance sensor according to the present invention will be described below with reference to an embodiment shown in the accompanying drawings. FIG. 1 is a schematic exploded perspective view of a surface plasmon resonance sensor according to the present invention, and FIG.
3 is a schematic top view of the surface plasmon resonance sensor shown in FIG. 1, and FIG. 3 is a sectional view taken along line AA in FIG. As shown in the drawing, this surface plasmon resonance sensor constitutes a sensor body by stacking two housing plates 1 and 2. Lower housing plate 2
Is provided with a prism 4 having a trapezoidal cross section in the lateral direction with a metal thin film 3 formed on its back surface (see FIGS. 1 and 3). And as shown in FIG. 2 in particular, the housing plate 2
Is formed with a sample liquid supply passage 5 bent in a zigzag pattern so as to intersect the metal thin film 3 of the prism 4 six times. It directly contacts the surface of the metal thin film 3 at the positions P1 to P6 where the metal thin film 3 intersects. Hereinafter, this intersection is referred to as a measurement area. The upper surface of the sample liquid supply passage 5 is closed by stacking and adhering the upper housing plate 1 on the lower housing plate 2 configured as described above.
A sample liquid supply port 6 is formed at a position corresponding to the upstream end of the sample liquid supply passage 5 in the upper housing plate 1, and the sample liquid is supplied from the sample liquid supply port 6 by using, for example, a syringe. It is introduced into the sample liquid supply passage 5.
Reference numerals 10 and 11 in FIG. 3 denote a light source and a photodetector, which supply the sample solution into the sample solution supply passage 5 through the sample solution supply port 6 so that the sample solution covers the entire measurement region P1. When reaching the upper surface of (P6) to (P6), light is incident on the prism 1 from the light source 10 under the condition of being totally reflected at the interface between the metal thin film 2 and the sample solution. As shown by the dotted line in FIG. 3, the incident light repeats total reflection in the prism 4 having a trapezoidal cross section, and the metal thin film 2 in all the measurement regions P1 to P6.
Is totally reflected at the interface between the sample liquid and the sample liquid, and finally comes out of the prism 4 and detected by the photodetector 11.

As described above, in the surface plasmon resonance sensor according to this embodiment, the light emitted from the light source 1 is totally reflected at 6 points, so that 6 kinds of measurement results can be obtained at the same time. Therefore, for example, all the measurement areas P1 to P6
In addition, if the same reactant is fixed, the measurement for one sample liquid can be obtained six times by one measurement, and the measurement accuracy can be improved. Further, for example, if the measurement is performed without fixing the reaction product only to the measurement region P1 on the most upstream side, the measurement can be performed without the reaction product, which is useful for correcting the measurement error due to impurities. Furthermore, for example, if different reactants are fixed in each measurement area,
It is possible to perform measurements on different types of reactants simultaneously.

[0007]

As described above, in the surface plasmon resonance sensor according to the present invention, the metal thin film is formed on the back surface of the prism, the sample solution is brought into direct contact with the surface of the metal thin film, and the metal is attached to the prism. In the surface plasmon resonance sensor configured such that light is incident under the condition of total reflection at the interface between the thin film and the sample liquid, and the state of the substance in the sample liquid can be analyzed based on the reflected light, the prism The measurement area that intersects the surface of the metal thin film formed on
Since a continuous sample solution supply passage bent so as to form at least two locations is provided, if the same reactant is fixed in all measurement regions, multiple measurements can be performed on one sample solution at the same time. In addition, by fixing different reactants in each measurement area, it is possible to measure reactions for different reactants at the same time, and also to secure a measurement area in which the reactants are not fixed. In this case, it is possible to perform the measurement at the same time in the absence of the reaction product.

[Brief description of drawings]

FIG. 1 is a schematic exploded perspective view of a surface plasmon resonance sensor according to the present invention.

FIG. 2 is a schematic top view of the surface plasmon resonance sensor shown in FIG.

3 is a sectional view taken along line AA in FIG.

[Explanation of symbols]

1 Housing plate (upper side) 2 Housing plate (lower side) 3 metal thin film 4 prism 5 Sample liquid supply passage 6 Sample solution supply port 10 light sources 11 Photodetector P1 to P6 measurement area

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yoshisuke Sakai             5-5-1, Nakamachidai, Tsuzuki-ku, Yokohama-shi, Kanagawa             Issue inside Technomedika Co., Ltd. (72) Inventor Takaaki Matsumura             5-5-1, Nakamachidai, Tsuzuki-ku, Yokohama-shi, Kanagawa             Issue inside Technomedika Co., Ltd. (72) Inventor Koji Suzuki             1-1-705 Kokura, Saiwai-ku, Kawasaki-shi, Kanagawa (72) Inventor Kazuyoshi Kurihara             4-1 Idasugiyama-cho, Nakahara-ku, Kawasaki-shi, Kanagawa             305 Claire Maison Oseto F term (reference) 2G057 AA02 AB07 AC01 BA01 GA01                 2G059 AA01 BB04 BB12 CC16 EE02                       FF11 GG10 JJ12 KK01

Claims (4)

[Claims] 1. A metal thin film is formed on the back surface of a prism, a sample solution is brought into direct contact with the surface of the metal thin film, and light is incident on the prism under the condition of total reflection at the interface between the metal thin film and the sample solution. Then, in the surface plasmon resonance sensor configured to be able to analyze the substance state in the sample liquid based on the reflected light, at least the measurement region intersecting the surface of the metal thin film formed on the prism, A surface plasmon resonance sensor comprising a continuous sample liquid supply passage bent so as to be formed at two locations. 2. A surface plasmon resonance sensor characterized in that a reaction product that specifically reacts with a measurement target of a sample liquid is fixed in each measurement region. 3. The surface plasmon resonance sensor according to claim 2, wherein different reactants are fixed in respective measurement areas. 4. The method according to claim 2, further comprising at least one measurement region in which the reactant is not fixed.
The surface plasmon resonance sensor according to.