EP1606610A2 - Chemical enhancement in surface enhanced raman scattering using lithium chloride - Google Patents
Chemical enhancement in surface enhanced raman scattering using lithium chlorideInfo
- Publication number
- EP1606610A2 EP1606610A2 EP04749311A EP04749311A EP1606610A2 EP 1606610 A2 EP1606610 A2 EP 1606610A2 EP 04749311 A EP04749311 A EP 04749311A EP 04749311 A EP04749311 A EP 04749311A EP 1606610 A2 EP1606610 A2 EP 1606610A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- metallic structure
- enhancer
- raman
- substrate
- spectroscopy
- 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- Withdrawn
Links
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 title claims abstract description 59
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 title claims abstract description 36
- 239000000126 substance Substances 0.000 title description 9
- 239000003623 enhancer Substances 0.000 claims abstract description 26
- 239000002773 nucleotide Substances 0.000 claims abstract description 9
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 9
- 238000001069 Raman spectroscopy Methods 0.000 claims description 57
- 239000000758 substrate Substances 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 33
- 229910052751 metal Inorganic materials 0.000 claims description 28
- 239000002184 metal Substances 0.000 claims description 27
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 20
- 239000002082 metal nanoparticle Substances 0.000 claims description 20
- 229910052709 silver Inorganic materials 0.000 claims description 20
- 239000004332 silver Substances 0.000 claims description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 239000002105 nanoparticle Substances 0.000 claims description 16
- 239000012491 analyte Substances 0.000 claims description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 12
- 230000005284 excitation Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052737 gold Inorganic materials 0.000 claims description 9
- 239000010931 gold Substances 0.000 claims description 9
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 238000004611 spectroscopical analysis Methods 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 8
- 239000010949 copper Substances 0.000 claims description 8
- 229910052782 aluminium Inorganic materials 0.000 claims description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
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- 230000003213 activating effect Effects 0.000 claims 2
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- 238000002082 coherent anti-Stokes Raman spectroscopy Methods 0.000 claims 1
- 238000000881 hyper Raman spectroscopy Methods 0.000 claims 1
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- 238000004458 analytical method Methods 0.000 description 9
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 7
- 229910052710 silicon Inorganic materials 0.000 description 7
- 239000010703 silicon Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
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- 229910021426 porous silicon Inorganic materials 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- KHWCHTKSEGGWEX-RRKCRQDMSA-N 2'-deoxyadenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KHWCHTKSEGGWEX-RRKCRQDMSA-N 0.000 description 3
- 239000002923 metal particle Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
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- 239000011521 glass Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920006254 polymer film Polymers 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 229910052581 Si3N4 Inorganic materials 0.000 description 1
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- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- UJXZVRRCKFUQKG-UHFFFAOYSA-K indium(3+);phosphate Chemical compound [In+3].[O-]P([O-])([O-])=O UJXZVRRCKFUQKG-UHFFFAOYSA-K 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
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- 229910021423 nanocrystalline silicon Inorganic materials 0.000 description 1
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- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6825—Nucleic acid detection involving sensors
Definitions
- Raman scattering This phenomenon is known as Raman scattering, and the method to characterize and analyze the medium or molecule of interest with the Raman scattered light is called Raman spectroscopy.
- the wavelengths of the Raman emission spectrum are characteristic of the chemical composition and structure of the Raman scattering molecules in a sample, while the intensity of Raman scattered light is dependent on the concentration of molecules in the sample.
- SERS Surface enhanced Raman spectroscopy
- FIG. 1 is a block diagram of an overall surface-enhanced Raman spectroscopy system in accordance with one embodiment of the present invention
- FIG. 2 is a block diagram of a method for producing a solution for surface- enhanced Raman spectroscopy in accordance with one embodiment of the present invention:
- FIG. 3 is a diagram of a porous silicon substrate suitable for surface enhanced Raman spectroscopy in accordance with one embodiment of the present invention.
- FIG. 4 is a graphical representation of SERS spectra in accordance with an embodiment of the present invention.
- analyte may mean any atom, chemical, molecule, compound, composition or aggregate of interest for detection or identification, although the scope of the invention is not limited in this respect.
- Non-limiting examples of analytes may include, but are not limited to, an amino acid, peptide, polypeptide, protein, glycoprotein, lipoprotein, nucleoside, nucleotide, oligonucleotide, nucleic acid, deoxyribose nucleic acid, ribose nucleic acid, peptide nucleic acid, sugar, carbohydrate, oligosaccharide, polysaccharide, fatty acid, lipid, hormone, metabolite, cytokine, chemokine, receptor, neurotransmitter, antigen, allergen, antibody, substrate, metabolite, cofactor, inhibitor, drug, pharmaceutical, nutrient, prion, toxin, poison, explosive, pesticide, chemical warfare agent, biohazardous agent, bacteria, virus, radioisotope, vitamin, heterocyclic aromatic compound, carcinogen, mutagen, narcotic, amphetamine, barbiturate, hallucinogen, waste product, contaminant, quantum dots, or dye
- one or more analytes of weaker Raman signals may be labeled with or adsorbed to one or more molecules of stronger Raman signal, as disclosed below, although the scope of the invention is not limited in this respect.
- the molecule of stronger Raman signal is called a Raman label or Raman tag.
- Coupled may mean that two or more elements are in direct physical or electrical contact.
- coupled may also mean that two or more elements are not in direct contact with each other, but yet still cooperate or interact with each other.
- FIG. 1 a block diagram of an overall system for surface- enhanced Raman spectroscopy (SERS) will be discussed. As shown in FIG.
- SERS system 100 may include a Raman spectroscopy instrument 110 for analyzing molecules disposed on a Raman active substrate 112.
- Raman active substrate 112 may include a substrate that is suitable for Raman spectroscopy.
- Raman active substrate 112 may be a SERS active substrate in that the substrate is suitable for SERS analysis, although the scope of the invention is not limited in this respect.
- a computer 114 may be utilized to control the operation of Raman spectroscopy instrument 110, to receive an output from Raman spectroscopy instrument 110, and to compile, display, store, or otherwise organize and present a result of a Raman spectroscopy analysis provided by Raman spectroscopy instrument 110, although the scope of the invention is not limited in this respect.
- Raman active substrate 112 may be produced from a SERS solution 116 which may be prepared by combining metal nanoparticles 118 used for Raman spectroscopy enhancement with a target molecule 120 to be detected with Raman spectroscopy instrument 110.
- metal or metal nanoparticles may in general refer to and may encompass any metallic structure which may include any structure made wholly, partially, in mixture, or in layers of metal, and which may include rough metal, metal colloids, metal nanoparticles, metal films, and metal coatings, although the scope of the invention is not limited in this respect.
- the metal nanoparticles 118 may be enhanced or activated using an enhancer 122 that operates to further improve the enhancing effect of the metal nanoparticles 118 by increasing the Raman scattering intensity of the analyte, although the scope of the invention is not limited in this respect.
- enhancer 122 may be utilized to activate the metallic structure used in SERS to increase the overall enhancing effect of the SERS metallic structure.
- the enhancer 122 may be used before or after the target molecule in introduced to the metal nanoparticles.
- SERS solution 116 may be utilized to produce a Raman active substrate 112 by deposition of the SERS solution 116 onto the substrate, which may be inserted into Raman spectroscopy instrument 110 for analysis, although the scope of the invention is not limited in this respect.
- the Raman active substrate is obtained by utilizing a metal-coated substrate, using enhancer 122, and introducing target molecule 120.
- Raman active substrate 112 is not used, and a solution of a target molecule 120 and metal nanoparticles 118 enhanced or activated by enhancer 122 is directly analyzed in Raman spectroscopy instrument 110, although the scope of the invention is not limited in this respect.
- Such an arrangement is shown by optional path 124 by which SERS solution 116 is analyzed directly by Raman spectroscopy instrument 110 without requiring Raman active substrate 112.
- the process 200 for producing SERS solution 116 may include preparing metal nanoparticles for SERS analysis.
- the metal nanoparticles 118 may include silver, gold, copper, or any other metal or metallic structure, or a combination of the metals or metallic structures, although the scope of the invention is not limited in this respect.
- a silver nanoparticle solution 212 may be prepared using the following described method. Silver nitrate 118 is added to ultra pure water in a reflux flask with a stir bar.
- 0.2 milliliters of silver nitrate in 85 milligrams per milliliter solution is added to 97 milliliters of ultra pure water.
- a reflux apparatus including the reflux flask is assembled over a hotplate and the temperature is set 400 degrees Celsius to heat the liquid in the reflux flask.
- a solution of sodium citrate 210 is prepared, for example 0.2 milliliters of sodium citrate of 100 milligrams per milliliter concentration is diluted with water to a final volume of 2 milliliters in a 50-milliliter plastic tube. The sodium citrate solution is then added drop-wise to the boiling silver solution in the reflux flask over a five-minute period while stirring the silver solution at 350 revolutions per minute.
- the silver solution is refluxed for approximately one hour. After reflux, the solution is cooled, and the volume is adjusted to 100 milliliters and transferred to a glass bottle for storage of the resulting silver nanoparticle solution 212 at room temperature without exposure to direct sunlight.
- the metal nanoparticles may be made by laser ablation, mechanical grinding, or chemical etching of metals, although the scope of the invention is not limited in this respect.
- the size of the metal nanoparticles in solution in one embodiment is approximately in the 50 to 100 nanometer range. It should be noted that the scope of the invention is not limited in any respect by the thus described process.
- the silver nanoparticle solution 212 may be prepared for SERS analysis via the following procedure.
- Lithium chloride may be used as enhancer 122, which is added to the silver nanoparticle solution at a final concentration of 0.18 M to enhance the metal nanoparticles in the silver nanoparticle solution 212 to arrive at a solution of enhanced silver nanoparticles 214.
- a target molecule 120 is then added to the enhanced silver nanoparticle solution 214 to arrive at the SERS solution 116.
- the target molecule may be any analyte of interest for analysis using Raman spectroscopy or SERS or the like.
- target molecule 120 was selected as the target molecule 120.
- target molecule 120 may include a mixture of different types of analytes.
- approximately 200 microliters of the SERS solution 116 was placed into a Raman spectroscopy instrument 110.
- target molecule 120 may be added to the silver nanoparticle solution, and then the lithium chloride 122 is added to the mixture of the silver nanoparticle solution and the target molecule.
- the SERS solution 116 may be added to a porous silicon substrate to produce a Raman activate substrate suitable for use in a Raman spectroscopy instrument 110, although the scope of the invention is not limited in this respect. It should be noted that although one example is shown in FIG. 2, the order in which nanoparticles 118, enhancer 122, and target molecule 120 are mixed may vary, so that the scope of the invention is not limited to any order of combining.
- FIG. 3 a silicon substrate suitable for use as a Raman active substrate in accordance with an embodiment of the invention will be discussed.
- Substrate 112 may comprise a silicon substrate to which a metal ion solution 312 containing metal ions 314 may be added in order to form a layer of metallic layer 310 on substrate 112.
- substrate 112 may comprise nanocrystalline silicon which may refer to silicon that comprises nanometer scale silicon crystals, for example in the range of 1 to 100 nanometers (nm), including but not limited to porous silicon, although the scope of the invention is not limited in this respect.
- substrate 112 may comprise porous silicon which may refer to silicon that has been etched or otherwise treated to form a porous structure.
- Other types of silicon substrates formed using various processes may also be utilized without departing from the scope of the invention, and without providing a substantial change thereto.
- substrate 112 may alternatively comprise silicon nitride, germanium, silicon carbide, gallium arsenide, indium phosphate, or silicon oxide, and may include minor amounts of other materials such as metal nucleation catalysts and dopants, although the scope of the invention is not limited in this respect.
- substrate 112 may be coated with a Raman active metallic structure, such as gold, silver, platinum, copper or aluminum, for example, as utilized in SERS solution 116.
- the composition and thickness of the metal layer 310 may be controlled to optimize the plasmon resonant frequency of substrate 112 as desired.
- metal layer 310 may be composed of metal colloid, or any other metallic structure, of gold or silver nanoparticles in accordance with the present invention, which may be suitable for detection of smaller sized target molecule analytes such a single nucleotides or amino acids, although the scope of the invention is not limited in this respect.
- a solution of nanoparticles such as
- SERS solution 116 may be added to a substrate 112 already having a metal layer 310 disposed thereon in order to enhance the Raman signal in accordance with surface enhanced Raman spectroscopy.
- substrate 112 may be incorporated into a larger apparatus, system, or article of manufacture such as a micro-electromechanical system (MEMS), which in one embodiment may refer to integrated systems comprising mechanical elements, sensors, actuators, electronics, and so on, although the scope of the invention is not limited in this respect.
- MEMS micro-electromechanical system
- Such a MEMS system may be utilized to measure or manipulate, for example, mechanical, thermal, biological, chemical, physical, optical, electrical, or magnetic phenomena.
- FIG. 3 shows one type of substrate that may be utilized for
- Raman active substrate 112 may comprise a metal nanoparticle island film that consists of isolated metal nanoparticles deposited on a base substrate.
- Raman active substrate 112 may comprise a metal-coated nanoparticle based substrate consists of a base substrate covered with nanoparticles in a first layer and then coated with a continuous layer of a SERS metal or metallic structure such as gold, silver, copper, platinum, aluminum or the like.
- Raman active substrate may comprise a polymer film with embedded nanoparticles. The polymer film may be disposed as a layer on a base substrate.
- the base substrate itself may comprise various materials, including but not limited to silicon, glass or quartz, or cellulose or paper based material, although the scope of the invention is not limited in this respect.
- Plot 400 shows Raman signal intensity of a SERS process on the vertical axis as measured by the counts of a charge coupled device (CCD) of Raman spectroscopy instrument 110, versus the wavelength of the Raman scattered light on the horizontal axis, in nanometer units.
- the signals 410 and 412 shown in plot 400 were generated by using dAMP as target molecule 120 with excitation light of 785 nanometers in wavelength in accordance with the procedure described herein. In one case, sodium chloride was used as enhancer 122, and the resulting spectrum is shown at 412.
- lithium chloride was used as enhancer 122 in accordance with the present invention, and the resulting spectrum is shown at 410.
- the intensity of the lithium chloride spectrum 410 is greater than the intensity of the sodium chloride spectrum 412.
- the selection of inorganic salts may help to optimize chemical enhancement effects in SERS.
- the investigation of the ionic effect consisted of screening 18 salts against three classes of target molecules: nucleotides, nucleosides, and bases. Even when the same anion is used, it has been discovered that different cations may affect the SERS signal significantly. It has been particularly discovered that lithium chloride (LiCl) may provide a SERS signals of greater intensity than other salts such as sodium chloride (NaCl). Thus, the selection of the cation in an enhancer may result in enhanced SERS signal intensity. It has been discovered that a strong SERS enhancement with LiCl may be particularly suitable for at least one group of target molecules.
- the colloidal particles When ions are introduced into colloidal solutions, the colloidal particles may form aggregates and alter the electromagnetic enhancement of the SERS process.
- the increased SERS signal intensity was observed to occur at multiple wavelengths, including both the visible and near-infrared spectrum, for example at 514 nm, 785 nm, and 830 nm.
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| PCT/US2004/002989 WO2004085988A2 (en) | 2003-03-12 | 2004-02-04 | Chemical enhancement in surface enhanced raman scattering using lithium chloride |
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| US20050147980A1 (en) * | 2003-12-30 | 2005-07-07 | Intel Corporation | Nucleic acid sequencing by Raman monitoring of uptake of nucleotides during molecular replication |
| US7583379B2 (en) | 2005-07-28 | 2009-09-01 | University Of Georgia Research Foundation | Surface enhanced raman spectroscopy (SERS) systems and methods of use thereof |
| GB0605752D0 (en) * | 2006-03-23 | 2006-05-03 | Univ Lincolnshire The | Preparation of stable silver colloids |
| JP5110254B2 (ja) * | 2006-10-10 | 2012-12-26 | 富士レビオ株式会社 | 蛍光測定法と、蛍光測定のための測定用チップ及びその製造方法 |
| WO2011078794A1 (en) | 2009-12-22 | 2011-06-30 | Agency For Science, Technology And Research | Sers-based analyte detection |
| US9063836B2 (en) * | 2010-07-26 | 2015-06-23 | Intel Corporation | Methods and apparatus to protect segments of memory |
| GB201307013D0 (en) * | 2013-04-18 | 2013-05-29 | Renishaw Diagnostics Ltd | Seers based assays for oligonucleotides |
| JP2014228323A (ja) * | 2013-05-20 | 2014-12-08 | ウシオ電機株式会社 | 検査方法、センサ |
| JP2014228321A (ja) * | 2013-05-20 | 2014-12-08 | ウシオ電機株式会社 | 検査方法 |
| JP2014228322A (ja) * | 2013-05-20 | 2014-12-08 | ウシオ電機株式会社 | センサ、検査方法 |
| KR101494131B1 (ko) | 2014-02-27 | 2015-02-16 | 숭실대학교산학협력단 | 은나노 구조체와 라만 분광법을 이용한 진균독소 시트리닌 검출방법 |
| CN104568908B (zh) * | 2015-02-06 | 2017-12-01 | 上海师范大学 | 基于表面增强拉曼散射的高效测定谷物中微量呕吐毒素的新方法 |
| CN107167834B (zh) * | 2017-07-21 | 2018-12-14 | 东南大学 | 检测热中子辐射的sers活性基底及其制备方法和应用 |
| JP7190277B2 (ja) * | 2018-07-31 | 2022-12-15 | 浜松ホトニクス株式会社 | 被検体分析方法 |
| CN109939664A (zh) * | 2019-04-16 | 2019-06-28 | 天津工业大学 | 一种多尺度纳微米氧化铝纤维光催化剂载体的制备方法 |
| CN110579465A (zh) * | 2019-10-24 | 2019-12-17 | 汎锶科艺股份有限公司 | 二硫代氨基甲酸盐类农药的检测方法 |
| JP7344140B2 (ja) * | 2020-01-27 | 2023-09-13 | 浜松ホトニクス株式会社 | 細胞分析方法 |
| CN113588626B (zh) * | 2021-08-24 | 2024-05-24 | 上海师范大学 | 一种苯丙氨酸对映体的拉曼光谱检测方法 |
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| KOMPAN M E ET AL.: "Enhancement of Raman scattering intensity in porous silicon", PHYSICS OF THE SOLID STATE, vol. 41, no. 7, July 1999 (1999-07-01), pages 1207 - 1209, XP019309665 * |
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