NL1022916C2 - Device is for investigating a thin layer structure on a surface by making use of superficial plasmon resonance - Google Patents

Device is for investigating a thin layer structure on a surface by making use of superficial plasmon resonance Download PDF

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Publication number
NL1022916C2
NL1022916C2 NL1022916A NL1022916A NL1022916C2 NL 1022916 C2 NL1022916 C2 NL 1022916C2 NL 1022916 A NL1022916 A NL 1022916A NL 1022916 A NL1022916 A NL 1022916A NL 1022916 C2 NL1022916 C2 NL 1022916C2
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Netherlands
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comprises
characterized
surface
device
detector
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NL1022916A
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Dutch (nl)
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Gerardus Henricus Mari Engbers
Lucas Marinus Hendr Groenewoud
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Ssens B V
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55Specular reflectivity
    • G01N21/552Attenuated total reflection
    • G01N21/553Attenuated total reflection and using surface plasmons
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/10Scanning
    • G01N2201/105Purely optical scan
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/10Scanning
    • G01N2201/108Miscellaneous
    • G01N2201/1087Focussed scan beam, e.g. laser
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/12Circuits of general importance; Signal processing
    • G01N2201/121Correction signals
    • G01N2201/1211Correction signals for temperature

Abstract

The device (1) is for investigating a thin layer structure (2) on the surface (3) by making use of superficial plasmon resonance and comprises a detector (5) for receiving light reflected from the surface and an assembly (4) for conducting light to the surface and for conducting light from the surface to the detector. The assembly incorporates a movable mirror (41). The device also includes first units for regulating the position of the movable mirror following a galvanometric first principle. The detector is two-dimensional preferably a picture sensor of a digital camera. Second devices are incorporated for controlling the detector and are suitable for receiving information concerning the position of the movable mirror.

Description

Apparatus and method for investigating a thin layer structure using H of surface plasmon resonance and apparatus and method for controlling temperature The invention relates to an apparatus for investigating a thin layer structure on a surface using surface plasmon resonance which device comprises.

- a detector for receiving light reflected from the surface, and I - an assembly for guiding light to the surface and for guiding H 10 light reflected on the surface to the detector, which assembly comprises a movable I mirror.

The invention further relates to a method for examining a thin layer buildup on a surface using surface plasmon resonance, which method comprises guiding light to the surface by means of an assembly comprising a movable mirror and guiding light to the surface and surface reflected light to a detector.

The invention further relates to a device and a method for controlling temperature.

Research and analysis techniques are known based on the physical phenomenon of surface plasmon resonance, also known as surface plasmon resonance or SPR.

SPR can occur at an interface, whereby the amount of light reflected at the interface I can strongly decrease at a certain angle of incidence. SPR techniques are used in the investigation of thin layer structures on a surface, and in particular in (bio) chemical determinations and the study of macromolecular interactions on a surface, see for example WO 98/34098, WO 01/692099 and WO 01 / 01/79817.

In principle, there are three measuring methods: (i) measuring the intensity of light reflected at the interface as a function of the angle of incidence, (ii) measuring (with a constant angle of incidence) the (change of) intensity of the reflected light on a flank 30 of an SPR dip, and (iii) measuring (at a constant angle of incidence) the intensity of the reflected light as a function of the wavelength of the light.

Zero-dimensional measurements can be made, that is, only a single spot or spot is investigated. In addition, one-dimensionally or two-dimensionally measured can be 1 9199 91 ft 2, whereby a number of spots in a row or a plane with spots can be studied, respectively.

There is a great need for systems with which many spots can be examined simultaneously or within a short time. People want to be able to measure quickly and preferably process the data "real-time". In this way the kinetics of interactions can also be studied. Keywords are "many", "fast" and "accurate". That is, many spots, and much data that can be retrieved and processed quickly, with great demands being made on the accuracy of the angle of incidence to be set and measured, and on the location and time resolution.

It is important to be able to precisely control and determine the temperature of the thin layer of superstructure to be investigated since SPR is very temperature sensitive.

There is therefore a need for a system for analysis and research based on SPR, in particular for (bio) chemical determinations and the study of interactions on a surface, with which a larger number of spots can be faster and more accurately compared to known systems. be investigated and studied. There is also a need for a system for precisely controlling and determining temperature. The object of the present invention is to provide such systems.

To this end, the invention provides a device of the type mentioned in the preamble, wherein the device also comprises first means for controlling the position of the movable mirror according to a galvanometric principle.

It is to be noted that the term "light" includes all electromagnetic phenomena and therefore does not exclude frequencies outside the visible range. With a galvanometer the position of the movable mirror can be adjusted very H accurately and quickly. Thus, H depending on the configuration of the assembly and the measuring method, the angle of incidence on H the surface can be set very precisely and quickly and / or the surface can be scanned very accurately and H quickly. Moreover, a galvanometer of the "closed-loop" type H 30 can transmit information about the position of the movable mirror, for example to the detector or the control of the device.

^^ B

In a preferred embodiment of a device according to the invention, the detector is two-dimensional, for example an image sensor of a digital camera.

A relevant part of the surface can thus be imaged with an in principle unlimited number of spots. The number of spots 5 to be measured and investigated simultaneously or in a short time is therefore in principle unlimited. In addition, when using a digital camera, the data can be retrieved and processed with an in principle unlimited speed and in principle unlimited H location and time resolution, image by image and pixel by pixel, using digital imaging techniques. All this is of course dependent on the speed of the camera and the capacity of the equipment used to process the data.

B The device preferably also comprises second means for controlling the detector B, which second means are suitable for receiving information regarding the B position of the movable mirror.

Thus, the data recording of the detector may be directly or indirectly related to the position I of the movable mirror. This offers all kinds of advantages and possibilities that will be clear to a person introduced in the field.

Preferably, the assembly also comprises an optical element, at least partially substantially spherical, preferably a hemispherical prism.

I A hemispherical prism, in combination with the correct other optical components, gives a good image quality, better than with the use of conventional flat prisms and I cylindrical optics.

Preferably, the assembly also comprises a, preferably hinged, for instance diamond-shaped or triangular, structure for mutually adjusting and adjusting the positions of two or more parts of the assembly, mutually and relative to the surface.

With such a construction, the angle of incidence of the light can be varied and adjusted, whereby at least a part of the components of the assembly are adjusted simultaneously. This way, the entire optic can remain aligned and in focus, and individual, often laborious and time-consuming, individual alignment and focusing of individual or groups of components is not necessary.

Preferably the device also comprises a light source which light source can produce incoherent light.

An incoherent light source can be advantageous in certain cases because annoying interference phenomena, such as common with the use of a coherent light source as a laser, will generally not occur.

The assembly can also comprise a wavelength-dependent filter.

I For example, a stable, incoherent white light source can be used as the light source.

The wavelength of the transmitted light can then be selected as desired, for example a larger wavelength if the SPR angle is to be accurately determined, or several wavelengths for accurately calculating the optical thickness of the thin layer structure. As a rule of thumb, an optimum wavelength of twice the thickness of the layer to be measured applies.

The assembly can also comprise a polarization-dependent filter.

With polarized light you can measure more accurately and the SPR angle can be determined with greater precision. And polarization-dependent measurement can provide information about the orientation of molecules in the thin layer structure.

The assembly can herein comprise at least one optical element, which optical element is provided with an anti-reflection layer.

The anti-reflection layer increases the image quality, which benefits the accuracy and resolution of the measurement.

The detector is herein preferably positioned such that the angle between light incident on the detector and the plane of the detector is less than 65 °, preferably substantially equal to the angle between the surface and the light reflected on the surface.

A small angle is desirable in a preferred embodiment of a device according to the invention with a two-dimensional detector in order to obtain a good and sharp image of the dimensioned H surface with a good location resolution.

H The detector is herein preferably of the (micro) lensless type.

Such a detector can also properly detect light incident on the detector at a small angle, which detectors provided with micro-lenses cannot or cannot do well.

In addition, the device can also comprise third means for controlling the temperature of at least a part of the thin-layer structure, which third means comprise at least two

Peltier elements and at least two temperature sensors.

I SPR is often very temperature sensitive. With several Peltier elements and temperature sensors, the temperature at the relevant part of the surface can be accurately and quickly controlled. This will become clearer in the 10 explanation that follows.

The invention also provides a method of the type mentioned in the preamble, wherein the position of the movable mirror is controlled by first means according to a galvanometric principle.

The position of the movable mirror can thus be adjusted very accurately and quickly, and information about the position of the movable mirror can also be passed on, for example, to the detector or the control of the device.

In a preferred embodiment of a method according to the invention, the method also comprises recording an image by means of a two-dimensional detector, for example I an image sensor of a digital camera.

I For example, an in principle unlimited number of spots can be measured and imaged simultaneously or in a short time, and digital imaging techniques can be used for processing the data, with all the associated benefits.

25

The method preferably also comprises of controlling the detector by means of second means, wherein information regarding the position of the movable mirror is passed on to the second means.

The detector can thus be directly or indirectly controlled with the position of the mirror as a parameter. The advantages thereof will be clear to a person introduced in the field.

t ö z 2 9 1 8 6

Preferably, the method also comprises guiding light by means of an optical element, at least partially substantially spherical, preferably a hemispherical prism.

The use of spherical optics offers advantages over conventional cylindrical optics, in particular the image quality appears to be better.

5

The method preferably also comprises, mutually and relative to the surface, coordinated modification and adjustment of two or more parts of the assembly and a second part of the assembly by means of a, preferably hinged, for example diamond-shaped or triangular, construction.

Thus, the entire optic can be adjusted in a single movement, aligned and in focus, without any, laborious and time-consuming, individual alignment and focusing of individual or groups of components.

Preferably the method also comprises the use of incoherent light.

In this way, annoying interference phenomena, such as are common with the use of a coherent light source as a laser, can be prevented.

In addition, the method may also comprise the wavelength-dependent filtering of light.

The wavelength of the transmitted light can be chosen as desired, for example a larger wavelength so that the SPR angle can be accurately determined, or several wavelengths so that the optical thickness of the thin layer structure can be accurately calculated. In addition, a stable, incoherent white light source can then be used.

In addition, the method may also comprise polarization-dependent filtering of light.

H In this way, measurement can be more accurate and the SPR angle can be determined with greater precision.

In addition, the method may also comprise the use of at least one optical element, which optical element is provided with an anti-reflection layer.

Werken Η Working with optical elements with an anti-reflection layer results in an increase in image quality, which benefits the accuracy and resolution of the measurement.

In addition, the method may also include dropping light onto the detector at an angle of less than 65 °, preferably an angle that is substantially equal to the angle between the surface and the light reflected at the surface.

I This way a good and sharp image with a good location resolution can be obtained. This will become clearer in the following explanation with reference to the figure.

Preferably, use is made here of a detector of the (micro) lensless type.

In this way, light that falls on the detector at a small angle can also be properly registered, which is impossible or impossible with the use of micro-lensed detectors.

The method may also comprise controlling the temperature of at least a part of the thin layer structure by means of third means, which third means comprise at least two Peltier elements and at least two temperature sensors.

Thus, the temperature at the location of the relevant part of the surface can be accurately adjusted

I and can be regulated quickly, which benefits measuring accuracy since SPR

I is often very temperature sensitive.

20

The invention further provides a device for controlling temperature wherein the device comprises at least two Peltier elements and at least two temperature sensors, and a method for controlling temperature using at least two Peltier elements and at least two temperature sensors.

25 The Peltier elements can be controlled based on temperature measurements at multiple locations. If there is a big difference between the desired and the actual temperature at a certain location, the elements can cool or heat together to achieve the desired temperature quickly. Thereafter, for example, a Peltier element can cool and properly heat another so that a continuous heat flow is achieved at a certain location. This makes it possible to control the temperature at that location very precisely.

1022916 The invention is explained in more detail below. To that end: I-figure 1a schematically shows a first part of a preferred embodiment of a device according to the invention, and I-figure 1b schematically shows a second part of a preferred embodiment of a device according to the invention.

Figure 1 shows an SPR instrument (1) according to the invention, the optical part of which I is schematically shown in Figure 1a. Light from a white light source (6) is guided via an optical fiber (7) to a first lens (46). The use of an optical fiber gives the instrument (1) flexibility, and is co-determining among other things for the spot size. The light is collimated by means of the first lens (46) and subsequently polarized and colored by means of a polarizing filter (44) and a color filter (43). The color filter (43) can be selected as desired, which increases the flexibility of the instrument (1)

further increased. For example, a larger wavelength can be chosen so that the SPR

The angle can be accurately determined, or multiple wavelengths so that the optical thickness of the thin layer structure (2) to be examined can be accurately calculated. Optionally, the combination of white light source (6) and color filter (43) can be replaced by a laser light source with a desired specific wavelength.

The collimated polarized and colored light is guided via a movable mirror (41) to a second lens (47). The movable mirror (41) is mounted on a galvanometer (not shown) and can rotate through an angle of about 20 °. The position of H the movable mirror (41) can thus be adjusted with great precision and speed. A focal point of the second lens (47) coincides with a focal point of a hemispherical prism (42). The combination of second lens (47) and hemispherical prism (42) directs the H light beam onto (a portion of) the flat side of the prism (42) which flat surface forms a surface (3) on which the thin layer to be examined builds up ( 2) rest. The light reflected on the surface (3) is guided through a third lens (48) with the same characteristics as the second lens (47) to a detector (5) where the surface (3), 30 or at least a part thereof is pictured.

The detector (5) is formed by an image sensor of a digital camera that is directly or indirectly controlled by the galvanometer. For example, the digital camera can be indirectly H triggered by a computer based on data about the position of the movable mirror (41). For example, suppose the mirror takes less than 5 msec to reach a certain position, then the camera can be instructed to take an image 5 msec after the mirror has been instructed to go to a certain 5 position. Or the control of the movable mirror (41) can, for example, be directly linked to the triggering of the camera. For example, the images to be recorded by the camera can be related to the position of the movable mirror (41) and thus with a certain angle of incidence of the light on the surface (3) or with a certain position on the surface (3).

10

The image sensor (5), unlike conventional CCD image sensors, is not provided with I micro lenses. Conventional micro-lens-equipped CCD image sensors detect little or no light incident at an angle of less than about 65 °. With the image sensor (5) without microlenses, the light incident on the image sensor at a small angle can nevertheless be properly registered, and thus a good, sharp, undistorted image of the dimensioned surface (3) can be formed. Other types of image sensors without microlenses, such as CMOS and CID, are also suitable in principle, but for many applications I do not (yet) suffice with regard to dynamic range, resolution or "frame rate" and so on.

In the given example, the angle between the reflected beam and the surface (3) is equal to the angle between the beam incident on the image sensor (5) and the plane of the image sensor (5). Thus, an undistorted image of (a part of) the surface (3) with a good location resolution can be formed on the image sensor (5). This is of great importance, for example, to be able to properly image a surface of multiple spots.

The assembly of optical components (41-48) is mounted on a mechanical diamond-shaped hinged construction (7) schematically shown in Figure 1b. In this way, the entire optic can be adjusted in a single movement, aligned and in focus, without one, laborious and time-consuming, individual alignment and focusing of individual or groups of components (41-48). An alternative is, for example, a hinged triangular construction whose length of the base can be varied.

The temperature of the thin layer structure (2) to be investigated is controlled in the given exemplary embodiment by means of two Peltier elements (not shown) and three 1022916 I 10 I temperature sensors (not shown). The Peltier elements are placed on either side of the thin layer of superstructure (2). A temperature sensor I is positioned close to each Peltier element. The third temperature sensor is arranged as close as possible to the surface to be measured (3). If the temperature measured by the third sensor deviates much from the desired temperature of the thin layer of superstructure (2), both Peltier I elements can together provide heating or cooling so that the desired temperature I can be reached quickly. The one Peltier element can then heat and the other cool I so that a continuous heat flow is achieved at the location of the thin layer of superstructure (2). It appears that in this way, in which the Peltier elements are controlled on the basis of the temperatures measured by the temperature sensors, the temperature of the thin layer structure (2) can be regulated quickly and very precisely.

Such a temperature control system is of course also suitable for other applications where very precise temperature control is desired or required.

It will be clear to a person skilled in the relevant field that the invention is by no means limited to the exemplary embodiment described and that many variations and combinations are still possible within the scope of the invention.

Claims (26)

  1. An apparatus (1) for examining a thin layer structure (2) on a surface (3) using surface plasmon resonance, which apparatus (1) comprises: 5. a detector (5) for receiving at the surface (3) reflected light, and - an assembly (4) for guiding light to the surface (3) and for guiding light reflected on the surface (3) to the detector (5), which assembly (4) is a movable mirror (41), wherein the device (1) also comprises first means for controlling the position of the movable mirror (41) according to a galvanometric principle.
  2. Device (1) according to claim 1, characterized in that the detector (5) is two-dimensional, for example an image sensor of a digital camera.
  3. Device (1) according to claim 1 or 2, characterized in that the device (1) also comprises second means for controlling the detector (5), which second means are suitable for receiving information regarding the position of the movable mirror (41).
  4. Device (1) according to one of claims 1 to 3, characterized in that the assembly (4) also comprises an optical element (42), which is at least partly substantially spherical, preferably a hemispherical prism.
  5. Device (1) according to one of claims 1 to 4, characterized in that the assembly (4) also comprises a structure (7), preferably hinged, for example diamond-shaped or triangular, for mutually and with respect to the surface (3), tuned modification and adjustment of the positions of two or more parts (71-73) of the assembly 25 (4).
  6. Device (1) according to one of claims 1 to 5, characterized in that the device (1) also comprises a light source (6) which light source (6) can produce incoherent light.
  7. Device (1) according to one of claims 1 to 6, characterized in that the assembly (4) also comprises a wavelength-dependent filter (43).
  8. Device (1) according to one of claims 1 to 7, characterized in that the assembly (4) also comprises a polarization-dependent filter (44). 1 022 9: 12
  9. Device (1) according to one of claims 1 to 8, characterized in that the assembly (4) comprises at least one optical element (42-48), which optical element (42-48) is provided with an anti-reflection low.
  10. Device (1) according to one of claims 1 to 9, characterized in that the detector (5) is positioned such that the angle between light incident on the detector (5) and the plane of the detector (5) ) is less than 65 °, preferably substantially equal to the angle between the surface (3) and the light reflected on the surface (3).
  11. Device (1) according to one of claims 1 to 10, characterized in that the detector (5) is of the (micro) lensless type. I 10
  12. Device (1) according to one of claims 1 to 11, characterized in that the device (1) also comprises third means for controlling the temperature of at least a part of the thin layer structure (2) which third means comprise at least two Peltier elements I and at least two temperature sensors.
  13. 13. Method for examining a thin layer structure (2) on a surface (3) using surface plasmon resonance which method comprises guiding light I by means of an assembly (4) comprising a movable mirror (41) to the surface (3) and guiding light reflected from the surface (3) to a detector (5), the position of the movable mirror (41) being controlled by first means according to a galvanometric principle.
  14. A method according to claim 13, characterized in that the method also comprises recording an image by means of a two-dimensional detector (5), for example an I image sensor of a digital camera.
  15. 15. Method as claimed in claim 13 or 14, characterized in that the method also comprises of controlling the detector (5) by means of second means whereby information regarding the position of the movable mirror (41) is passed on to the second means .
  16. A method according to any one of claims 13-15, characterized in that the method also comprises guiding light by means of an at least partially substantially spherical optical element (42), preferably a hemispherical prism.
  17. A method according to any one of claims 13-16, characterized in that the method also comprises adjusting and adjusting the positions of two or more parts (71-73), mutually and relative to the surface (3) of the assembly (4) by means of a preferably hinged, for example diamond-shaped or triangular, structure (7).
  18. A method according to any one of claims 13-17, characterized in that the method also comprises the use of incoherent light.
  19. A method according to any one of claims 13-18, characterized in that the method also comprises filtering light depending on wavelength.
  20. A method according to any one of claims 13-19, characterized in that the method also comprises polarization-dependent filtering of light.
  21. A method according to any one of claims 13-20, characterized in that the method also comprises the use of at least one optical element (42-48), which optical element (42-48) is provided with an anti-reflection layer.
  22. A method according to any one of claims 13-21, characterized in that the method also comprises dropping light on the detector (5) at an angle of less than 65 °, preferably an angle which is substantially equal to the angle between the surface (3) and the light reflected on the surface (3).
  23. 23. A method according to any one of claims 13-22, characterized in that use is made of a detector (5) of the (micro) lensless type.
  24. A method according to any one of claims 13-23, characterized in that the method also comprises controlling the temperature of at least a part of the thin layer structure (2) by third means, said third means comprising at least two Peltier elements and at least two temperature sensors.
  25. 25. A temperature control device wherein the device comprises at least two Peltier elements and at least two temperature sensors.
  26. 26. A method for controlling temperature using at least two Peltier elements and at least two temperature sensors. 25 1 022 9 1 6
NL1022916A 2003-03-13 2003-03-13 Device is for investigating a thin layer structure on a surface by making use of superficial plasmon resonance NL1022916C2 (en)

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Publication number Priority date Publication date Assignee Title
NL2005902C2 (en) * 2010-11-25 2012-05-29 Ibis Technologies B V Method and apparatus for surface plasmon resonance angle scanning.

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL2005902C2 (en) * 2010-11-25 2012-05-29 Ibis Technologies B V Method and apparatus for surface plasmon resonance angle scanning.
WO2012070942A1 (en) 2010-11-25 2012-05-31 Ibis Technologies B.V. Method and apparatus for surface plasmon resonance angle scanning

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