EP1281062A1 - Capteur a resonance de plasmon - Google Patents

Capteur a resonance de plasmon

Info

Publication number
EP1281062A1
EP1281062A1 EP01940431A EP01940431A EP1281062A1 EP 1281062 A1 EP1281062 A1 EP 1281062A1 EP 01940431 A EP01940431 A EP 01940431A EP 01940431 A EP01940431 A EP 01940431A EP 1281062 A1 EP1281062 A1 EP 1281062A1
Authority
EP
European Patent Office
Prior art keywords
plasmon resonance
incidence
resonance sensor
plane
sensor according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01940431A
Other languages
German (de)
English (en)
Inventor
Andreas Hofmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BIOSCIENCE VENTURES GROUP AG
Original Assignee
Jandratek GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jandratek GmbH filed Critical Jandratek GmbH
Publication of EP1281062A1 publication Critical patent/EP1281062A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons

Definitions

  • the invention relates to a plasmon resonance sensor for biological, biochemical or chemical tests with a translucent body, in particular glass prism, a reflective metal layer or semiconductor layer applied to a surface of the body with a surface sensitive to molecules to be detected in a sample, which in connection with a cuvette forms a measuring cell, a monochromatic light source, in particular a laser diode, for emitting a diverging light beam or beam path through the translucent body onto the inner surface of the layer and a detector which is assigned to the outgoing beam path reflected by the layer and which is dependent on time and which is sensitive to molecular deposits Surface-changing angle of reflection of the light, at which due to the resonance, an intensity minimum of incident light occurs.
  • a plasmon resonance sensor with a glass prism, a thin gold layer from 40 to 70 nm and a light source in the form of a laser diode is known from US 4,844,613.
  • the phenomenon of surface plasmon resonance is a collective excitation of the electrons on the surface of a layer having free electrons.
  • the resonance frequency of the surface plasmon is very sensitive to the refractive index of the medium that is adjacent to the sensitive surface. This can be used to measure thin layers (refractive index or layer thickness). This effect is used in particular in biosensors to investigate the attachment kinetics of biomolecules to a functionalized metal surface.
  • the resonance condition of the surface plasmons is detected in a time-resolved manner.
  • the surface plasmons of the thin metal layer are excited by light that shines through the glass onto the metal layer at a certain angle or range of angles. The resonance condition is then fulfilled for a certain combination of wavelength and angle of incidence.
  • the intensity of the light reflected on the metal layer is significantly reduced due to the generation of the surface plasmon.
  • either the angle of incidence (at constant wavelength) or the wavelength (at constant angle of incidence) can be scanned and the intensity of the reflected light can be detected.
  • the plasmon resonance sensor described at the outset it is expedient to work with a fixed wavelength and to determine the angle of incidence at which the resonance condition is fulfilled.
  • a laser diode is used which emits an elliptical beam cone.
  • the opening angles are typically 22 ° in one dimension and 9 ° in the other - half of the intensity maximum (FWHM).
  • This beam divergence is used to illuminate the light source with different angles of incidence within a win- ding without any beam shaping optics and without changing the orientation of the light source. to illuminate the range that is considered for the occurrence of the resonance condition.
  • an elongated detector arrangement is provided which records the diverging beam path across its entire dimension in the plane of incidence of light and can thus determine the angle of incidence at which the resonance condition is met at the time of measurement.
  • This known plasmon resonance sensor because it does not require any beam shaping optics and devices for changing the angle of incidence, is comparatively simple and therefore inexpensive to manufacture.
  • light rays with different angles of incidence hit different points of the reflective metal layer, so that high demands must be placed on their homogeneity in order to prevent falsifications of the measurement results. In this sense, however, sufficiently homogeneous metal layers can be applied.
  • the main disadvantage of the known design is therefore seen in the fact that the performance of the plasmon resonance sensor equipped with a single measuring cell, based on the number of tests that can be carried out, is low and that this does not permit simultaneous reference measurements in order to eliminate the influence, for example, of the heating of the reflective metal layer.
  • reference measurements are particularly useful.
  • additional measuring cells must be arranged at a greater distance from one another so that different beam cones do not overlap and thus lead to falsifications. Such a distance would run counter to the desired compact design and also significantly increase the costs for correspondingly large parts.
  • the object of the invention is to create a plasmon resonance sensor which, with a compact and inexpensive design, enables high test performance with error-free results at the same time.
  • this object is achieved according to the invention in that a collimation lens is arranged between the light source and the translucent body, which collimates the incident beam path perpendicular to the plane of incidence, but still leaves it diverging in the plane of incidence.
  • the plasmon resonance sensor according to the invention manages with simple beam shape optics in the form of a cylindrical lens, and therefore requires only a small amount of construction.
  • the original beam divergence for example of a laser diode
  • the targeted parallel alignment of the beam path in the direction perpendicular to the plane of incidence In this direction a narrow beam path is created, which enables a compact juxtaposition of several identical plasmon resonance sensors and, accordingly, of several measuring cells, which leads to a powerful device with the possibility of advantageous reference measurements.
  • Figure 1 is a side view of a plasmon resonance sensor
  • Figure 2 is a top view of a plasmon resonance sensor with four measuring cells
  • FIG. 3 shows a plasmon resonance sensor similar to the embodiment according to FIG. 2, but in which each measuring cell is assigned its own light source;
  • Figure 4 shows a further modification compared to the embodiment of Figure 3, according to which each measuring cell and light source is assigned its own collimation optics.
  • a translucent body 1 in the form of a glass prism with a triangular cross-sectional shape is provided.
  • This prism has a light incident side 2, a light incident side 3 and a horizontally oriented upper reflection side 4.
  • On this reflection side 4 is a reflective measurement tall Mrs 5 applied, which consists for example of gold in a thickness of 50 nm.
  • a sensitive coating 6 is also applied to the metal layer 5, as is indicated schematically.
  • This sensitive coating is matched, for example, to the biomolecules to be detected in the sample to be examined, so that the biomolecules in question attach to the sensitive coating.
  • Such coatings and their regeneration for example by means of a hydrochloric acid solution, are familiar to the person skilled in the art.
  • a monochromatic light source 7 in the form of a laser diode is assigned to the light incidence side 2, and in a corresponding manner the detector 3 is at a distance from the light exit side 3 of the prism 1.
  • a divergent beam path 9 is generated by the laser diode 7, which is reflected on the metal layer 5 and is directed onto the detector 8.
  • the beam path 9 is divided into an incident beam path 10 in front and an outgoing beam path 11 behind the metal layer 5, the plane of incidence 12 (FIG. 2) running parallel to the plane of the drawing in FIG. 1.
  • collimation optics 13 are arranged in the form of a cylindrical lens, which is arranged inclined in the plane of incidence 12 in accordance with the incident beam path.
  • This cylindrical lens 13 brings about collimation or parallel alignment of the light beams only in a direction perpendicular to the plane of incidence 12 (FIG. 2), while the beam divergence is retained in the plane of incidence, as shown in FIG. 1.
  • the beam path 9 runs through the prism 1 within a comparatively narrow area with a small dimension perpendicular to the plane of incidence 12.
  • the occurring plasmon resonance on which the test method carried out with the plasmon resonance sensor according to the invention is based, is indicated schematically in FIG. 1.
  • the divergence of the beam path 9 in the plane of incidence 12 is sufficiently large to cover the range of angles of incidence within which the resonance phenomenon occurs.
  • the reso- Specifically leading angles of incidence change as a result of the attachment of molecules from the sample to be examined to the sensitive coating 6.
  • the incident light beam is noticeably weakened at the respectively resonant angle of incidence, and this angle of incidence is determined by the detector 8 in a time-resolved manner.
  • a laser diode 15, a cylindrical lens 16 and a prism 17 are provided in accordance with the description of FIG. 1, which likewise has a triangular cross section and extends perpendicular to the plane of incidence 12 of the light, four measuring cells 18 on the prism 17, 19, 20 and 21 are formed, on each of which the metal layer 5 and the sensitive coating 6 are present.
  • Each measuring point is assigned its own detector 22, 23, 24 or 25.
  • the incident beam path 10 corresponds to the description with reference to FIG. 1. Accordingly, there is divergence between the laser diode 15 and the cylindrical lens 16 both in the plane of incidence 12 and perpendicular to it, while behind the cylindrical lens 16 there is only divergence in the plane of incidence 12 and perpendicular to the Plane of incidence there is a parallel beam path.
  • the various measuring cells 18 to 21 and the associated detectors 22 to 25 are not only spaced apart from one another, but in particular are radially decoupled from one another, as illustrated by the outgoing beam paths 26, 27, 28 and 29, and this even with a small distance between the measuring cells 18 to 21 and accordingly between the detectors 22 to 25 and despite the intended divergence in the emerging beam paths 26 to 29, which is only present in the direction of the plane of incidence 12.
  • a compact arrangement with four measuring cells 18 to 21 with only one laser diode 15, a cylindrical lens 16 and a prism 17 can thus be achieved.
  • the four measuring cells 18 to 21 four samples can be examined simultaneously, or three samples in connection with a reference measurement based on a known reference sample.
  • the increase in performance by additional measuring cells is particularly valuable because the individual measurements can be comparatively time-consuming, depending on the samples to be examined or the molecules to be detected.
  • the duration of the examination or measurement in particular in the case of biological or biochemical tests, can be up to one hour.
  • FIGS. 3 and 4 also provide a common prism 17 with four measuring cells and detectors assigned to them.
  • the differences relate to the beam path in each case, without however changing the beam divergence in the plane of incidence and the collimation in the direction perpendicular to the plane of incidence.
  • the measuring cells 30 to 33 are assigned their own laser diodes 34 to 37. Nevertheless, a common cylindrical lens 38 can be used, which collimates the four differently directed beam paths 39 to 42. Corresponding to the fan-shaped beam paths 39 to 45, the arrangement of the detectors 43 to 46 is spread out in a somewhat more space-consuming manner.
  • each of the laser diodes 51 to 54 assigned to a measuring cell 47 to 50 is assigned its own cylindrical lens 55 to 58.
  • the individual beam paths 59 to 62 run parallel to one another until they strike the detectors 63 to 66 assigned to the measuring cells 47 to 50.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un capteur à résonance de plasmon dans lequel une optique de collimation (13), se présentant sous la forme d'une lentille cylindrique, est montée entre la diode laser (7) et le prisme (1) pourvu de la couche métallique (5) réfléchissante. Ainsi, la divergence des rayons reste maintenue dans le plan d'incidence, lequel comporte tous les angles d'incidence entrant en ligne de compte pour une résonance qui sont déterminés par le détecteur (8). Perpendiculairement au plan d'incidence, le chemin des rayons est toutefois collimaté, ce qui permet l'obtention d'une construction compacte et l'agencement de plusieurs cellules de mesure disposées les unes derrière les autres, perpendiculairement au plan d'incidence.
EP01940431A 2000-05-12 2001-05-09 Capteur a resonance de plasmon Withdrawn EP1281062A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10023363 2000-05-12
DE10023363A DE10023363C1 (de) 2000-05-12 2000-05-12 Plasmonenresonanzsensor
PCT/EP2001/005287 WO2001086262A1 (fr) 2000-05-12 2001-05-09 Capteur a resonance de plasmon

Publications (1)

Publication Number Publication Date
EP1281062A1 true EP1281062A1 (fr) 2003-02-05

Family

ID=7641845

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01940431A Withdrawn EP1281062A1 (fr) 2000-05-12 2001-05-09 Capteur a resonance de plasmon

Country Status (5)

Country Link
US (1) US6801317B2 (fr)
EP (1) EP1281062A1 (fr)
AU (1) AU2001274010A1 (fr)
DE (1) DE10023363C1 (fr)
WO (1) WO2001086262A1 (fr)

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Publication number Priority date Publication date Assignee Title
US6804007B2 (en) * 2002-09-10 2004-10-12 Reichert, Inc. Apparatus for multiplexing two surface plasma resonance channels onto a single linear scanned array
DE60232689D1 (de) 2002-12-25 2009-07-30 Bio Rad Laboratories Oberflächenplasmonenresonanzsensor
JP4076962B2 (ja) * 2003-04-23 2008-04-16 独立行政法人科学技術振興機構 差動式表面プラズモン共鳴現象測定装置及びその測定方法
JP4298392B2 (ja) * 2003-06-16 2009-07-15 Ｎｔｎ株式会社 等速自在継手
WO2005052644A2 (fr) * 2003-11-21 2005-06-09 Perkinelmer Las, Inc. Dispositif optique integre a une cupule
US7271885B2 (en) * 2004-03-25 2007-09-18 Perkinelmer Las, Inc. Plasmon resonance measuring method and apparatus
US7436596B2 (en) * 2005-08-30 2008-10-14 Robertson William M Optical sensor based on surface electromagnetic wave resonance in photonic band gap materials and method for using same
US8355136B2 (en) 2005-12-16 2013-01-15 Indiana University Research And Technology Corporation Sub-micron surface plasmon resonance sensor systems
KR20080082976A (ko) * 2005-12-16 2008-09-12 인디애나 유니버시티 리서치 앤드 테크놀로지 코포레이션 서브-미크론 표면 플라즈몬 공진 센서 시스템들
DE102006041338B3 (de) 2006-09-01 2007-11-22 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Plasmonenresonanzsensor
US7652767B2 (en) * 2006-10-19 2010-01-26 Sporian Microsystems, Inc. Optical sensor with chemically reactive surface
DE102007005147A1 (de) * 2007-02-01 2008-08-07 Hofmann, Andreas Verfahren und Vorrichtung zur Untersuchung der Anheftung oder Ablösung lebender oder toter Zellen oder zellähnlicher Partikel oder sonstiger Oberflächenbelegung an Oberflächen mittels Plasmonenresonanz sowie Verwendung dieses Verfahrens und dieser Vorrichtung
US8743367B2 (en) * 2007-05-21 2014-06-03 Bio-Rad Laboratories Inc. Optical resonance analysis using a multi-angle source of illumination
US20090181857A1 (en) * 2008-01-15 2009-07-16 Academia Sinica System and method for producing a label-free micro-array biochip
WO2012129196A2 (fr) 2011-03-20 2012-09-27 Robertson William M Ondes électromagnétiques de surface dans des multicouches à bande interdite photonique
EP3028033B1 (fr) 2013-08-04 2020-10-07 Photonicsys Ltd. Capteur optique à base de structure plasmonique multicouche comprenant une couche métallique nanoporeuse
TWI567376B (zh) * 2015-03-25 2017-01-21 Nat Chin-Yi Univ Of Tech A Novel Localized Plasma Resonance Biochemical Sensor with High Sensitivity and Its Simulation Test Method
CN108027313B (zh) 2015-08-26 2021-01-29 光子系统有限责任公司 谐振周期性结构以及使用它们作为滤光器和传感器的方法
JP6854134B2 (ja) * 2017-01-16 2021-04-07 矢崎総業株式会社 高選択性腐食センサーシステム

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US4844613A (en) * 1986-11-03 1989-07-04 Stc Plc Optical surface plasmon sensor device
US5164589A (en) * 1988-11-10 1992-11-17 Pharmacia Biosensor Ab Reusable optical interface for non-permanent passive light coupling

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US4844613A (en) * 1986-11-03 1989-07-04 Stc Plc Optical surface plasmon sensor device
US5164589A (en) * 1988-11-10 1992-11-17 Pharmacia Biosensor Ab Reusable optical interface for non-permanent passive light coupling

Non-Patent Citations (1)

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Title
See also references of WO0186262A1 *

Also Published As

Publication number Publication date
US20030076501A1 (en) 2003-04-24
DE10023363C1 (de) 2001-12-20
WO2001086262A1 (fr) 2001-11-15
AU2001274010A1 (en) 2001-11-20
US6801317B2 (en) 2004-10-05

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