WO2007023452A1 - Spectroscopie raman amelioree - Google Patents
Spectroscopie raman amelioree Download PDFInfo
- Publication number
- WO2007023452A1 WO2007023452A1 PCT/IB2006/052899 IB2006052899W WO2007023452A1 WO 2007023452 A1 WO2007023452 A1 WO 2007023452A1 IB 2006052899 W IB2006052899 W IB 2006052899W WO 2007023452 A1 WO2007023452 A1 WO 2007023452A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- frequency
- sample
- scattering signal
- raman scattering
- analytes
- Prior art date
Links
- 238000001069 Raman spectroscopy Methods 0.000 title claims abstract description 55
- 238000010521 absorption reaction Methods 0.000 claims abstract description 17
- 230000001678 irradiating effect Effects 0.000 claims abstract description 16
- 230000005855 radiation Effects 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 239000000084 colloidal system Substances 0.000 claims description 5
- 239000002923 metal particle Substances 0.000 claims description 2
- 239000000523 sample Substances 0.000 abstract description 39
- 230000000694 effects Effects 0.000 description 9
- 239000002184 metal Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000012491 analyte Substances 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 230000005284 excitation Effects 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000005672 electromagnetic field Effects 0.000 description 2
- 239000002082 metal nanoparticle Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000002772 conduction electron Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000005274 electronic transitions Effects 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001945 resonance Rayleigh scattering spectroscopy Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001774 stimulated Raman spectroscopy Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
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
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/636—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited using an arrangement of pump beam and probe beam; using the measurement of optical non-linear properties
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
- G01J3/28—Investigating the spectrum
- G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
-
- 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
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
- G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
-
- 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
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
- G01N2021/653—Coherent methods [CARS]
- G01N2021/655—Stimulated Raman
Definitions
- the present invention relates to an improved Raman spectroscopy apparatus and method.
- Raman Scattering is a well known technique for detecting the presence of molecules.
- RS Raman Scattering
- a sample is irradiated with light and photons from the incident light are scattered by molecules in the sample. Most of the scattered photons scatter elastically but a small fraction scatter in-elastically at different wavelengths to the incident wavelength. The process behind this in-elastic scattering is termed the Raman effect.
- a plot of intensity of the scattered light verses the wavelength difference of the incident and scattered light is termed a Raman spectra and is indicative of the scattering molecules.
- the Raman effect is weak and hence not very sensitive to analyte concentration.
- Several techniques have been developed to enhance the Raman effect.
- the sample receives the normal laser light beam, and an additional beam of photons tuned to the wavelength that the sample Raman scatters to. This "stimulates” or amplifies the Raman effect by a factor of four to five.
- SERS Surface - Enhanced Raman Scattering
- Another technique is termed Surface - Enhanced Raman Scattering (SERS) which utilises the fact that Raman scattering from an analyte that is located close to certain metal surfaces can be many times greater than that from the analyte alone in solution. SERS is strongest on silver but may be observed on gold and copper as well. It is has been proposed that SERS arises from two mechanisms. The first is an enhanced electromagnetic field produced at the surface of the metal. When the wavelength of the incident light is close to the plasmon wavelength of the metal, conduction electrons in the metal surface are excited into an extended surface electronic excited state called a surface plasmon resonance. Molecules adsorbed or in close proximity to the surface experience an exceptionally large electromagnetic field. Vibrational modes normal to the surface are thus strongly enhanced.
- the second mode of enhancement is by the formation of a charge-transfer complex between the surface and analyte molecule.
- the electronic transitions of many charge transfer complexes are in the visible, so that resonance enhancement occurs.
- So called Surface enhanced resonance spectroscopy (SERRS) is a technique which can detect analyte concentrations in the femto-molar range.
- the method involves analysing a colloid solution or solid metal substrates of noble, for example silver or gold nano-particles in solution and target molecules, for example, DNA strands which are in contact with or in close proximity to the nano-particles.
- specific capture molecules may be used to bind the target molecules and attach them to the metal surface.
- Raman spectroscopy techniques having sensitivities in the sub- femto molar detection limit, particularly when used to detect small quantities of analytes . For example for identification of bacterial DNA in infectious diseases.
- Embodiments of the present invention aim to provide a sensitive Raman spectroscopy technique.
- a method of detecting Raman active analytes located at a conducting surface comprising: irradiating a sample containing the Raman active analytes with radiation having a frequency substantially tuned to a plasmon resonance band of the conducting surface to generate an enhanced Raman scattering signal; irradiating the sample with radiation having a frequency substantially tuned to a frequency of the enhanced Raman scattering signal to stimulate the enhanced Raman scattering signal; detecting the stimulated enhanced Raman scattering signal.
- an apparatus for detecting Raman active analytes located at a conducting surface in a sample comprising: a radiation source for irradiating the sample containing the Raman active analytes with radiation having a frequency substantially tuned to a plasmon resonance band of the conducting surface to generate an enhanced Raman scattering signal; a radiation source for irradiating the sample with radiation having a frequency substantially tuned to a frequency of the enhanced Raman scattering signal to stimulate the enhanced Raman scattering signal; and a detector for detecting the stimulated enhanced Raman scattering signal.
- the sample is also irradiated with radiation having a frequency substantially tuned to an absorption band of the analytes.
- the sample may comprise a colloid solution of metal particles which together form the conducting surface.
- the analytes each comprise a target molecule, which may comprise protein or DNA.
- Each target molecule may be linked to a dye molecule, the absorption band being an absorption band of the dye molecules.
- Figure 1 is a schematic diagram of a system embodying the present invention
- Figure 2 is a schematic diagram of an analyte absorbed at a metal surface.
- a spectroscopy system 1 comprises a pump laser source 2 for irradiating a sample 3 with a pump laser beam 2a comprising laser light of frequency/;.
- the sample 3 is a colloid solution comprising noble, for example silver or gold, or copper nano-particles and target molecules, for example DNA strands, in close proximity to the nano-particles.
- a target molecule 10 typically protein or a DNA strand in the sample 3 is bound to the surface of a nano-particle 11 by a specific capture molecule 12.
- a dye molecule 13 is attached to the capture molecule 12.
- DNA in itself is not very sensitive to Raman spectroscopy when excited in the visible wavelength range and so the purpose of the Dye molecules is to generate a strong scattering signal and hence indicate the presence of the specific target molecules to which they are linked.
- Such solutions and methods for their preparation are well known to those skilled in the art of Raman spectroscopy of biological molecules.
- the frequency of the pump laser beam is selected so that it is within the surface plasmon resonance band of the metal nano-particles in the colloid solution of sample 3 and an electronic absorption band of the dye molecules.
- the pump laser source 2 thus causes SERRS scattering from the sample 3.
- the system further comprises a probe laser source 4 for irradiating the sample 3 with a probe laser beam 4a of tunable frequency /2.
- the probe laser beam is directed by a mirror 5 to a beam splitter 6. From the beam splitter 6 both the pump laser beam 2a and the probe laser beam 4a pass collinearly to the sample 3.
- the system 1 may be arranged so that both beams are spatially separated when they enter the sample 3.
- the probe laser beam 4a is tunable across the frequency range of the Raman signal generated by the pump laser beam 2a.
- the frequency of probe laser may be tuned to match the frequency of each peak in the Raman signal generated by the pump laser beam.
- the probe laser beam thus causes the stimulated Raman gain effect described above in the introduction to amplify further the SERRS effect caused by the pump laser beam 2a.
- the combined effect of the pump laser source 2 and the probe laser source 4 gives rise to a new triple enhanced RAMAN effect having enhancement via 1) pump laser excitement of the dye molecules in their electronic resonance band 2) surface plasmon excitation by the pump laser and 3) the stimulated Raman effect of probe laser.
- SESRRS Surface Enhanced Stimulated Resonance Raman Spectroscopy
- Figures 3a and 3b each shows a intensity v wavelength plot of a possible plasmon resonance band 20 and a dye absorption band 21 and also indicates a pump beam wavelength ⁇ i and a probe beam wavelength ⁇ 2 for generating SESRRS.
- the SESRRS signal 7 generated in this may be measured in the probe forward direction by a detector 8, for example a photodiode or photo multiplier tube, having passed through a filter 9 which filters out elastically scattered photons.
- a signal 8a is fed from the detector 8 to a chopper 8b which in a standard way chops the pump beam to enable phase lock loop measurements to be made.
- the gain from the stimulated Raman effect depends on sample length. There is an optimum sample length for maximising the gain resulting from the electronic excitation of the dye molecules. If the sample length is too long the gain resulting from the electronic excitation of the dye molecules decreases because of self-absorption of the light. It will therefore be appreciated that an optimum sample length for the SEERRS system 1 exists that will depend upon the sample under analysis. Improved results will be obtained even if the frequency of the pump laser beam is not tuned to an electronic absorption band of the dye molecules and thus the pump laser beam is generating SERS rather than SERRS.
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Spectroscopy & Molecular Physics (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nonlinear Science (AREA)
- Optics & Photonics (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
La présente invention concerne un système (1) de spectroscopie Raman qui détecte les analytes actifs Raman situés au niveau d'une surface conductrice (11) d'un échantillon (3). Le système (1) comprend un laser de pompage (2) qui irradie l'échantillon (3) avec de la lumière laser dont la fréquence est sensiblement accordée sur une bande de résonance du plasmon de la surface conductrice (11) mais aussi sensiblement accordée sur la bande d'absorption électronique des analytes pour générer un signal de diffusion Raman amélioré. Le système (1) comprend également un laser sonde (4) qui irradie l'échantillon avec de la lumière laser dont la fréquence est sensiblement accordée sur une fréquence du signal de diffusion Raman amélioré en vue de stimuler plus encore le signal de diffusion Raman amélioré.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP05300696.1 | 2005-08-25 | ||
EP05300696 | 2005-08-25 |
Publications (1)
Publication Number | Publication Date |
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WO2007023452A1 true WO2007023452A1 (fr) | 2007-03-01 |
Family
ID=37667198
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/IB2006/052899 WO2007023452A1 (fr) | 2005-08-25 | 2006-08-22 | Spectroscopie raman amelioree |
Country Status (1)
Country | Link |
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WO (1) | WO2007023452A1 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103712960A (zh) * | 2013-12-26 | 2014-04-09 | 无锡利弗莫尔仪器有限公司 | 一种采用级联锁相检测的光热检测装置及其检测方法 |
KR101401634B1 (ko) | 2013-02-25 | 2014-06-02 | 한국광기술원 | 나노 구조체의 광-기계식 효과를 이용한 플라즈몬 파장 가변 가시광 레이저 |
CN106153600A (zh) * | 2015-05-14 | 2016-11-23 | 汎锶科艺股份有限公司 | 成品农药检测装置 |
CN117980728A (zh) * | 2021-08-24 | 2024-05-03 | 堀场仪器株式会社 | 用于检测样品流体中的污染物的系统和方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040135997A1 (en) * | 2002-06-12 | 2004-07-15 | Selena Chan | Metal coated nanocrystalline silicon as an active surface enhanced raman spectroscopy (SERS) substrate |
GB2408796A (en) * | 2003-12-01 | 2005-06-08 | Stephen Richard Elliott | Raman gain or loss effect optical sensor chip |
US20050147980A1 (en) * | 2003-12-30 | 2005-07-07 | Intel Corporation | Nucleic acid sequencing by Raman monitoring of uptake of nucleotides during molecular replication |
US20050147976A1 (en) * | 2003-12-29 | 2005-07-07 | Xing Su | Methods for determining nucleotide sequence information |
-
2006
- 2006-08-22 WO PCT/IB2006/052899 patent/WO2007023452A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040135997A1 (en) * | 2002-06-12 | 2004-07-15 | Selena Chan | Metal coated nanocrystalline silicon as an active surface enhanced raman spectroscopy (SERS) substrate |
GB2408796A (en) * | 2003-12-01 | 2005-06-08 | Stephen Richard Elliott | Raman gain or loss effect optical sensor chip |
US20050147976A1 (en) * | 2003-12-29 | 2005-07-07 | Xing Su | Methods for determining nucleotide sequence information |
US20050147980A1 (en) * | 2003-12-30 | 2005-07-07 | Intel Corporation | Nucleic acid sequencing by Raman monitoring of uptake of nucleotides during molecular replication |
Non-Patent Citations (1)
Title |
---|
GRAHAM D ET AL: "SURFACE ENHANCED RESONANCE RAMAN SCATTERING (SERRS) - A FIRST EXAMPLE OF ITS USE IN MULTIPLEX GENOTYPING", CHEMPHYSCHEM - A EUROPEAN JOURNAL OF CHEMICAL PHYSICS & PHYSICAL CHEMISTRY, WILEY VCH, WEINHEIM, DE, no. 12, 2001, pages 746 - 748, XP002328954, ISSN: 1439-4235 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101401634B1 (ko) | 2013-02-25 | 2014-06-02 | 한국광기술원 | 나노 구조체의 광-기계식 효과를 이용한 플라즈몬 파장 가변 가시광 레이저 |
CN103712960A (zh) * | 2013-12-26 | 2014-04-09 | 无锡利弗莫尔仪器有限公司 | 一种采用级联锁相检测的光热检测装置及其检测方法 |
CN106153600A (zh) * | 2015-05-14 | 2016-11-23 | 汎锶科艺股份有限公司 | 成品农药检测装置 |
CN117980728A (zh) * | 2021-08-24 | 2024-05-03 | 堀场仪器株式会社 | 用于检测样品流体中的污染物的系统和方法 |
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