CN102072894A - Nano-structure-based spectrum detecting method for detecting chemical and biochemical impurities - Google Patents

Abstract

The invention detects chemical and biochemical impurities by a spectrum detecting method based on nano-structure, and particularly discloses a method for providing quality assurance for industrial production process. The method comprises the steps of: obtaining a manufacturing material from the industrial production process, contacting the manufacturing material with a nano surface so that the harmful substance is absorbed on the nano surface. The method further comprises the steps of: utilizing a spectrometer to obtain a Raman spectrum from the manufacturing material and the nano surface; using a spectrum analyzing system to find a spectrum signal of the harmful substance in a pre-determined spectrum range of the Raman spectrum; if the spectrum signal exists in the Raman spectrum, detecting the concentration of the harmful substance in the manufacturing material; and if the concentration exceeds a pre-determined acceptable limit, removing the manufacturing material from the industrial production process.

Description

Use spectral method of detection to detect chemicals and biological impurity based on nanostructured

The application requires U.S. US12/643, No. 689 patented claims and U.S. US12/625, the right of priority of No. 970 patented claims.Wherein, U.S. US12/643, No. 689 patented claims are that a part continues patented claim, and its title is " using the spectral method of detection based on nanostructured to detect chemicals and biological impurity ", and the applying date is on Dec 21st, 2009, require U.S. pending application application US12/625,970, US12/502,903, US12/403,522, US12/246,616 and US12/176,383 right of priority.Wherein, U.S. US12/625, the title of No. 970 patented claims is " the application of spectral method detects chemicals and biological substance ", the applying date is on November 25th, 2009; U.S. US12/502, No. 903 name of patent application are " the nanostructured detecting devices that are used for Surface enhanced raman spectroscopy ", the applying date is on July 14th, 2009; U.S. US12/403, the title of No. 522 patented claims is " system and methods that detect chemicals and biological substance ", the applying date is on March 13rd, 2009; U.S. US12/246, the title of No. 616 patented claims is " system and methods that are applied to food safety detection ", the applying date is on October 7th, 2008; U.S. US12/176, the title of No. 383 patented claims is " using the light scattering detector in the non-invasive diagnosing disease ", the applying date is on July 20th, 2008.U.S. US 12/176, No. 383 patented claims are U.S. US11/681, a part continuity application of No. 157 patented claims, U.S. US11/681, No. 157 patented claims are now authorized, and the patent No. is US7,428,046, title is " a trace chemistry material fluorescence detector ", and the applying date is on March 1st, 2007.U.S. US11/681, No. 157 patented claims are U.S. US10/987, a continuation application of No. 842 patented claims (now authorize, the patent No. is US7,242,469).U.S. US10/987, No. 842 patented claims are again the US10/852 of application on May 24th, 2004, a part continuity application of No. 787 patented claims (now authorize, the patent No. is 7,384,792).U.S. US10/852, No. 787 patented claims require the temporary patent application US60/473 that submitted on May 27th, 2003, and 283 and US60/473,287, and the temporary patent application US60/520 that submitted on November 17th, 2003,222 right of priority.Disclosing these related application at this is to incorporate it into the application by reference.

Technical field

The present invention relates to the material detection range, relate in particular to a kind of method of utilizing light scattering probe and chemical detector to detect and survey chemical substance, biochemical, radiomaterial and other materials.

Background technology

Light scattering technique for example Raman spectroscopy can detect chemical substance and biochemical.A major limitation using Raman spectroscopy is, the Raman scattering signal that obtains from chemical substance and biochemical very a little less than.Although people are doing many effort aspect the enhancing Raman scattering intensity, but still there is not to produce practical and economic detecting device based on Raman spectroscopy.Therefore, the application of detection chemical substance of Raman scattering method up to now and biochemical aspect is also very limited.

So, be necessary to provide a kind of effective and practical detecting device to quantize to learn material, biochemical, radiomaterial and other materials to detect and to survey microscratch based on Raman spectroscopy.

Summary of the invention the application discloses a kind of Raman spectrum detection (or detection) system and method that has supersensitive detection and survey chemical substance or biochemical.Biochemical that Raman spectrum detection system disclosed by the invention and method can detect or detect or chemical substance concentration level are than the low several magnitude of conventional detection technique.The sensitivity that the Raman spectrum detection system of the disclosure and method have superelevation, can satisfy the needs of for example pharmaceutical production, food production, semiconductor machining and manufacturing, petrochemical industry processing and industrial processes such as production, depollution of environment processing, this is that routine techniques can't be realized.For these industrial processes, the concentration of certain objectionable impurities in solid or powdered sample or product not only may be the low permission limit (for example concentration level is lower than 10ppm) of governments limit, and in order to detect objectionable impurities, solid sample need be diluted tens times, hundred times with the preparation sample solution toward contact, this may cause the concentration level of objectionable impurities in sample solution to be lower than 100ppb.

System and method disclosed by the invention also provides disease detection means simple, non-intrusion type for patient.The system of the disclosure can make portable, and operation easily, therefore helps very much early stage medical diagnosis on disease and drugs field screening.The system and method for the disclosure also has short advantage of cycle test duration, and this process for monitoring disease treatment and drug use is helpful.The detectable diseases range of system and method disclosed by the invention is wide, cancer for example, include but not limited to carcinoma of mouth, breast cancer, lung cancer, cancer of the stomach, ulcerocancer, oophoroma, the cancer of the uterus, cervical carcinoma, cancer of the esophagus, thyroid cancer, laryngocarcinoma, leukaemia, colon cancer, carcinoma of urinary bladder, prostate cancer, bronchiolar carcinoma, cancer of pancreas, liver cancer, kidney, cutaneum carcinoma, and cirrhosis, renal failure, diabetes, acquired immune deficiency syndrome (AIDS) (HIV), smoking state and dopy.

On the other hand, the application provides the special system and method that is suitable for using for Food Inspection, can be applicable to detect secondary product that produces in objectionable impurities in food and the medicine, the production run and the composition of not checking and approving (for example illegal food additives), and the concentration of measuring effective constituent in food and the medicine.The system and method for the disclosure can be implemented and be portable control laboratory (or portable laboratory), and its maneuverable program can realize the field quick detection of food and medicine.

On the one hand, the system of the disclosure can comprise a light scattering probe and a chemical detector, to detect microscratch amount biochemical or chemical substance.The solution that will contain biochemical or chemical substance is transferred to chemical detector, and the molecule of described material is adsorbed on the nanostructured surface of chemical detector.Be adsorbed in material molecule on the chemical detector nanostructured surface with laser beam irradiation.The scattered light spectrum that is adsorbed on the molecule generation on the nanostructured surface by analysis is measured this material.

On the other hand, the system of the disclosure can utilize light scattering probe and a solution that contains nano particle to detect microscratch amount biochemical or chemical substance.Described biochemical or chemical substance are dissolved in this solution, and this material molecule is adsorbed on the surface of nano particle.This solution of laser beam direct irradiation.Gather the scattered light that produces by the nano particle that is adsorbed with biochemical molecule or chemical molecular with light scattering probe to measure microscratch amount biochemical or chemical substance.

By Raman spectrum detector network disclosed by the invention system, can carry out the scene to the material in the broad area effectively and detect or survey.The Raman spectrum detection signal that obtains from described material is transferred to a control center by wired or wireless network moment.Control center comprises a database that is used to store a large amount of target chemical matter and biochemical substances spectral signal.Spectral signal is through a system module analyses local or central authorities, Real time identification target chemical or biological substance.Control center can be interrelated with the Raman spectrum detection signal that different detecting devices in the network obtain, with definite detected chemical substance or the position in biochemical substances source and the time of generation.Control center can comprise a warning system, and certain target chemical matter or the biochemical substances that detects or detect conveyed to people via wired or wireless system, and mode of communication includes but not limited to Email, instant message, calls out and network log automatically.The detection of the disclosure or the detection network scope of application are very wide, for example the explosive that carries out for national security, flammable liquid chemicals and chemical and biological weapons detect, drugs detect, food security, the application of criminal investigation/secret aspect (comprise in the air, the pollution detection in water or the soil, medical treatment and health care aspect are to infectious disease and epiphytotics control and prevention), the industrial processes monitoring, industrial hygiene and product are identified.The detection network of the disclosure can also help doctor and other medical experts patient or animal to be carried out the remote diagnosis of disease.

On the one hand, the present invention relates to manufacturing system, described manufacturing system comprises the production system of utilizing at least a starting material to produce product, and the quality assurance and the production control system that obtain manufactured materials from this production system, wherein said manufactured materials comprises starting material, product or intermediate materials or secondary product, just optionally takes from starting material in the production system or the material in the manufacturing process.Quality assurance and production control system add material in the sample solution, allow manufactured materials contact with the Nanosurface of nano particle in the sample solution, with this manufactured materials of a laser beam irradiation and Nanosurface, laser beam is produced a scattered light by this manufactured materials and nano grain surface scattering, utilize a spectrometer to obtain a Raman spectrum from scattered light, search the spectral signal of certain objectionable impurities in the spectral range of in Raman spectrum, being scheduled to, thereby measure and whether have this objectionable impurities in the described manufactured materials, if the concentration of this objectionable impurities is lower than predetermined permission limit, then this manufactured materials is qualified, otherwise, if the concentration of this objectionable impurities has exceeded predetermined permission limit, then this manufactured materials is got rid of from these industrial processes.

On the other hand, the present invention relates to provide the method for quality assurance in industrial processes.This method comprises: obtain a manufactured materials from industrial processes; Allow this manufactured materials contact, objectionable impurities is adsorbed onto on this Nanosurface with a Nanosurface; Utilize a spectrometer to obtain a Raman spectrum from this manufactured materials and Nanosurface; Utilize a spectroanalysis instrument in a predetermined spectral range of this Raman spectrum, to search the spectral signal of objectionable impurities, to detect whether there is this objectionable impurities in the described manufactured materials; If in this Raman spectrum, detect this spectral signal, then detect the concentration of this objectionable impurities, the concentration of this objectionable impurities is lower than 10ppm in the wherein said manufactured materials; If the concentration of objectionable impurities has exceeded a permission limit of being scheduled in the described manufactured materials, then this manufactured materials is got rid of from these industrial processes.

On the other hand, the present invention relates to provide the method for quality assurance in industrial processes.This method comprises: obtain a manufactured materials from industrial processes; This manufactured materials is added in the sample solution; Manufactured materials in the sample solution is contacted with a nano grain surface; With this manufactured materials of a branch of rayed and Nanosurface; This laser beam is produced scattered light by this manufactured materials and Nanosurface scattering; Utilize a spectroanalysis instrument to obtain a Raman spectrum from this scattered light; In the predetermined spectral range of this Raman spectrum, search the spectral signal of objectionable impurities, to detect whether there is this objectionable impurities in the described manufactured materials; If do not find this spectral signal in this Raman spectrum, then this manufactured materials is qualified; If in this Raman spectrum, found this spectral signal, then detect the concentration of objectionable impurities in this manufactured materials; If this concentration is lower than predetermined permission limit, then this manufactured materials is qualified; If this concentration has exceeded predetermined permission limit, then this manufactured materials is got rid of from these industrial processes.

System of the present invention when implementing, can comprise following aspect.Described objectionable impurities can comprise melamine (melamine), melamine cyanurate (melamine cyanurate), melamine compound or nitrogen-containing compound.Described objectionable impurities can comprise honey element (sodium cyclamate), sodium cyclohexylsulfamate (sodium cyclohexylsulfamate), nitrite (nitrite), nitrate (nitrate), Sudan red 1, II, III and IV (sudan I, II, III, and IV), malachite green (malachite green), acephatemet (methomidophos), orthene (acephate), DDT (dichloro-diphenyl-trichloroethane), DDV (DDVP), malathion (malathion), fenifrothion (fenitrothion), decis (deltamethrin), cypermethrin (cypermethrin), parathion-methyl (methyl parathion), phosmet (phosmet), Rogor (dimethoate), nitrofuran (nitrofuran), furazolidone (furanzolidole), chloromycetin (chloramphenicol), duomycin (chlortetracycline), Ciprofloxacin (ciprofloxacin), clenbuterol hydrochloride (clenbuterol), Enrofloxacin (enorfloxacin), carbofuran (sulfidecarbofuran), Talon (brodifacoum), tetramethylene two sulfone tetramines (tetramethylenedisulfotetramine is commonly called as Tetramine), sodium fluoroacetate (sodiumfluoroacetate), Fluorakil 100 (fluoroacetamide), (chlorphacinone), Duocide (pindone), Didion (diphacinone), amitraz (amitraz), Azodrin (monocrotophos), thimet (phorate), disulfoton (disulfoton), phosmet (phosmet), parathion (parathion), Entex (fenthion), phosphamidon (phosphamidon), basudin (diazinon), Aldicarb (aldicarb), metrifonate (trichlorfon), drinox (aldrin), Bentazon herbicide (bentazone), duomycin (chlortetracycline), clenbuterol hydrochloride (clenbuterol), rhodamine B (Rhodanmine B), benzoic acid (benzoic acid), hydrosulfurous acid (hyposulfurous acid), formaldehyde sodium (sodium formaldehyde), phthalate (phthalates) bioxin (dioxins), leaded (Pb), cadmium (Cd), mercury (Hg), arsenic (As), the compound of chromium (Cr) or copper (Cu), prussiate (cyanides), perchlorate (chlorates), sulfate (sulfates), (crysoidine G), boric acid (boric acid), borax (borax), sodium thiocyanate (sodium sulfocyanate), chrome green (lead chrome green), alkaline bright yellow O (basic Flavine O), NaOH, carbon monoxide, sodium sulphate, industrial sulphur (industrialsulfur), industrial dye, pappy shell (fructus papaveris), saccharin sodium (saccharin sodium salt), sucrose (sucrose easter of fatty acid), KAlSO ₄, NH ₄AlSO ₄, sulfur fumigation (sulfursuffumigation), TiO ₂Or benzoyl peroxide (benzoyl peroxide).Described manufactured materials can comprise peptide, free amino acid, the protein that contains described material, adenine, albumin, derive from the amino acid of casein protein hydrolysate, ammonium salt, calcium pantothenate, caseinate (Caseinate) or casein sodium (sodiumcaseinate), Derifil sodium salt (Chlorophyllin copper complex sodium), emulsification oatmeal (Colloidal oatmeal), copolyvidone (Copovidone), dihydroxyaluminum aminoacetate (Dihydroxyaluminum aminoacetate), gelatin (Gelatin), hyperglycemic factor (Glucagon), guar gum (Guar gum), hyaluronidase (Hyaluronidase), imidazolidinyl urea (Imidurea), lactose, melphalan (Melphalan), polyvinylpyrrolidone (Povidone), polyvinylpyrrolidone-iodine (Povidone-Iodine), protamine sulfate (Protamine sulfate), the injection protein hydrolysate, tarine (Taurine), 2-am-inopurine-6-thiol (Thioguanine), urea (Urea), wheat bran (Wheat bran) or zeins (Zein).This method can further comprise allows the objectionable impurities molecular adsorption to Nanosurface, is adsorbed to the objectionable impurities molecular scattering laser beam on the Nanosurface.Sample solution can comprise the nano particle with Nanosurface.Nano particle can comprise a material magnetic or ferromagnetic, or is selected from the material of metal, metal alloy, oxide material, silicon, polymeric material and their combination.The material that described nano particle comprises can be selected from titania, silicon dioxide, zinc paste, aluminium, silver, gold, copper, iron, cobalt, nickel, chromium, zinc, tin, palladium, platinum or their combination.Described nano particle can have the average-size of about 5nm-500nm.It is the size distribution of feature that nano particle has with the certain average-size and the dispersion of distribution, and wherein the ratio of the dispersion of distribution and average-size is in the scope of about 0.01-3.Described nano particle can comprise nanotube, Fu Leti (Fullerite), holder shape (torus), nanometer bud (nanobuds) or nanometer flower (nanoflowers) form of carbon.The inventive method can further comprise sample solution is incorporated on the Nanosurface that is formed at the nanostructured on the detecting device, wherein comprises a conductive material in this nanostructured.This detecting device can comprise a substrate, and wherein said nanostructured comprises a plurality of holes in suprabasil a plurality of cylinder or the substrate.Average neighbor distance between these a plurality of cylinders or the hole is in the 10nm-1000nm scope.This method can further comprise to be introduced an ionic material in the sample solution, and wherein this ionic material contains and is selected from Na ⁺, K ⁺, Li ⁺, Ca ²⁺, Ba ²⁺, Sr ²⁺, Mg ²⁺, Mn ²⁺, Al ³⁺, Zn ²⁺, Sn ²⁺And Sn ⁴⁺, F ^-, Cl ^-, Br ^-And I ^-Ion.Described spectral signal can comprise near at least one spectrum peak the predetermined wavelength in Raman spectrum.Identification step can comprise whether area, height or the signal to noise ratio (S/N ratio) of determining this spectrum peak in the Raman spectrum exceed a predetermined threshold; Exceed predetermined threshold if reach this spectrum peak or its signal to noise ratio (S/N ratio), then confirm to identify this objectionable impurities.Described objectionable impurities can comprise melamine or melamine cyanurate, and wherein said spectral signal comprises 678cm ^-1, 698cm ^-1Or 712cm ^-1Near, perhaps 1648cm ^-1Near one or more spectrum peaks.Described industrial processes can be made a kind of medicine, and wherein said manufactured materials can be the final products that a kind of starting material, a kind of inter-level, a kind of secondary product or this medicine are made.Described medicine can comprise vitamin, growth hormone, or the medicine of treatment or prevention of asthma, Alzheimer's, Parkinson's disease, arthritis, cancer, angiocardiopathy, SARS, influenza, leukaemia, diabetes or acquired immune deficiency syndrome (AIDS) and other biological medicine.Described industrial processes can be made food, comprise dairy products, candy, beverage, fruit juice, wine, meat, aquatic products, seafood, tealeaves, vegetables fresh or canning, fruit, grain, cereal, cornflakes, potato block, animal feed or contain the food of protein.The concentration that objectionable impurities in the manufactured materials can be measured is below 10ppm.The concentration that objectionable impurities can be measured in the sample solution is below 1ppm

The following accompanying drawing of description of drawings is the part of book as an illustration, and the diagram embodiments of the invention are used for illustrating principle of the present invention together with the invention description.

Figure 1A-1C for example understands the system that utilizes Raman scattering probe to detect chemical substance and biochemical substances.

Fig. 2 is the synoptic diagram of example probe that is applicable to the Raman scattering probe of Figure 1A-1C.

Fig. 3 A and 3B are respectively the synoptic diagram that uses the Raman scattering probe that passenger and luggage are checked on the airport.

Fig. 4 A is the synoptic diagram that is used for the Raman scattering probe wired connection network of monitoring building safety.Fig. 4 B is the synoptic diagram that is used for the Raman scattering probe wireless connections network of monitoring building safety.Fig. 4 C is an example structure figure that can carry out the probe assembly of radio communication with control center.Fig. 4 D is the time of hazard recognition substance source and an example flow diagram of position.

The synoptic diagram that Fig. 5 is to use the Raman scattering probe to carry out environmental monitoring.

Fig. 6 A is to use the Raman scattering probe to carry out the synoptic diagram that food security is checked.Fig. 6 B is to use the Raman scattering probe to carry out the synoptic diagram of long-range medical diagnosis on disease and the biomedical system that detects.Fig. 6 C is the synoptic diagram that uses a plurality of Raman scattering probes to carry out quality of production control in a multi-channel detection system.

Fig. 6 D uses a plurality of Raman scattering probes to carry out counterfeit goods detection, the safety of Food ﹠ Drink and the synoptic diagram of quality check and drug identification in a multi-channel detection system.

Fig. 7 utilizes the solution and the light scattering probe that contain nano particle to detect the synoptic diagram that microscratch quantizes to learn material or biochemical substances.

Fig. 8 utilizes the solution and the light scattering probe that contain nano particle to detect the process flow diagram that microscratch quantizes to learn material or biochemical substances.

Fig. 9 A is to use the micro-image example of the nano particle that sem observation arrives.Fig. 9 B is the size distribution exemplary plot of the nano particle in the solution shown in Figure 7.

Figure 10 is the cut-open view that is used to make the multilayer layer structure of nanostructured.

Figure 11 A is the cut-open view that forms hole by anodic oxidation in multilayer layer structure shown in Figure 10.Figure 11 B is the top view of the multilayer layer structure shown in Figure 11 A.Figure 11 C is that multilayer layer structure shown in Figure 11 B is along the cut-open view of A-A line.

Figure 12 is at the cut-open view of the structrural build up nanostructured of multilayer stratiform after wet chemical etching technique or chemically mechanical polishing.

Figure 13 is at the cut-open view of the structrural build up nanostructured of multilayer stratiform after removing the restraining barrier of hole bottom and being etched to conductive layer.

Figure 14 A is at the cut-open view of the structrural build up nanostructured of multilayer stratiform behind the depositing noble metal.Figure 14 B is the cut-open view of removing behind the noble metal of top layer in the structrural build up nanostructured of multilayer stratiform.

Figure 15 is the cut-open view of removing after the oxide layer in the structrural build up nanostructured of multilayer stratiform.

Figure 16 A-16D, 16G and 16H are at the cut-open view of the structrural build up nanostructured of multilayer stratiform after corresponding manufacture craft.Figure 16 E and 16F are at the top view of the structrural build up nanostructured of multilayer stratiform after corresponding manufacture craft.Figure 17 is the exemplary plot that detects the raman spectral signal of carcinoma of mouth by Raman scattering probe disclosed by the invention in an oral cavity carninomatosis people saliva.

Figure 18 is the exemplary plot that detects the raman spectral signal of breast cancer by Raman scattering probe disclosed by the invention in a breast cancer patient saliva.

Figure 19 A and 19B are to use Raman scattering disclosed by the invention probe to detect the exemplary plot of the raman spectral signal of lung cancer respectively in the saliva of a lung cancer patient and serum.

Figure 20 is the exemplary plot that detects the oophoroma raman spectral signal by Raman scattering probe disclosed by the invention in an oophoroma patient serum.

Figure 21 is the exemplary plot that detects the acquired immune deficiency syndrome (AIDS) raman spectral signal by Raman scattering probe disclosed by the invention in an acquired immune deficiency syndrome (AIDS) patient saliva.

Figure 22 is the exemplary plot that detects the raman spectral signal that uses forbidden drug by Raman scattering probe disclosed by the invention in a forbidden drug user saliva.Figure 23 example has illustrated by Raman scattering probe disclosed by the invention, through with N-first-2-5-pyrrolidone (can terraced Buddhist nun, the metabolic product of nicotine) raman spectral signal is made comparisons, and detects the raman spectral signal that can determine smoking state in a smoker saliva.

The process flow diagram that Figure 24 is to use Raman scattering probe disclosed by the invention to carry out the non-intrusion type medical diagnosis on disease.

Figure 25 A and 25B have shown the spectral signal of illegal and detrimental substance (melamine) in Raman spectrum of variable concentrations in the dairy products.

Figure 26 has shown with acetonitrile 918cm ^-1Raman peaks is interior mark reference, detects the spectral signal of melamine in Raman spectrum in the milk liquid.

Figure 27 has shown the spectral signal of illegal harmful chemical (melamine) in Raman spectrum of variable concentrations in the water.

Figure 28 is the exemplary plot by unauthorized chemical addition agent in the Raman spectrum identification milk powder.

Figure 29 is for guaranteeing the process flow diagram of harmful chemical in the food safety detection food.

Figure 30 utilizes Nanosurface and light scattering to detect the synoptic diagram of the industrial system of restricted objectionable impurities in the industrial goods by a quality assurance system.

Figure 31 is the process flow diagram that can detect and prevent the production run that objectionable impurities is polluted in the industrial goods.

Embodiment

Figure 1A-1C has illustrated respectively to use Surface enhanced raman spectroscopy to detect or survey the system that microscratch quantizes to learn material or biochemical substances.Referring to Figure 1A, light scattering probe 100 comprises that a probe 110 and is positioned at the detecting device 105 on probe 110 sides.Detecting device 105 comprises a Nanosurface structure.For example, this Nanosurface structure can comprise a plurality of nano-pillar 108 (shown in Figure 1B), a plurality of nanoaperture, or the surface structure of other nano-scale.In certain embodiments, as described below, the surface that can be coated in detecting device 105 by the colloidal suspension solution that will contain nano particle makes the Nanosurface structure.Then solution can be evaporated, and nanoparticle deposition is to the surface.In instructions of the present invention, term " nano particle " refers at least size a direction less than 1, the granule of 000nm.

Implement sample solution to be guided on the nano-pillar 108 of detecting device 105 in the example at some.Described sample solution can comprise patient or forbidden drug user's body fluid, to diagnose the illness and definite drug use situation.The example of body fluid includes but not limited to blood, saliva, urine, serum, tear, sweat, gastric juice, hydrothorax, ascites, celiolymph (CSF), seminal fluid and juice.Sample solution can also comprise food samples, for guaranteeing harmful or illegal adjuvant in the food safety detection food samples.The example of food includes but not limited to dairy products, and for example milk, milk powder, babies ' formula milk powder, cheese, sour milk, ice cream and other contain milk deli, for example contain candy, cake and the biscuit of milk, and proteinaceous food.Probe 110 and detecting device 105 can be to pack in the probe assembly 120.Probe assembly 120 can reduce pressure by a vacuum pump and reduce the pollution of impurity to sensitive surface.

Laser instrument 141 emitted laser bundles are transmitted to probe through optical fiber 125, are radiated on the Nanosurface structure of detecting device 105 (Figure 1A), shown in Fig. 1 C.The scattered light that sample solution on detecting device 105 Nanosurfaces produces is gathered by probe 110, is transmitted to spectrometer 140 through optical fiber 130.The output signal of spectrometer 140 obtains the Raman spectrum of scattered light by spectroanalysis instrument 150.Identify the one or more spectral signals in the Raman spectrum, and its spectral signal with the multiple molecule of being scheduled to is made comparisons.When detecting the threshold value of finding to have exceeded certain molecule, output signal 160 demonstrations recognize a disease.In instructions of the present invention, term " spectral signal " refers to one or more spectrum peaks, one or more spectrum paddy, and other wave spectrum shape, for example relative peak height, peak line width, peak shape or the like, they have characterized the one or more molecular links in biochemistry, medicine or the chemical substance.

Referring to Fig. 2, the laser beam that probe 110 receives from input optical fibre 125.This laser beam projects on the detecting device 105 by a bandpass filter 170, a lens combination 175-1 and 175-2 successively.The scattered light that comes out from detecting device 105 passes through another bandpass filter 185 through a reflector group 180-1 and 180-2 guiding, further enters through collimation lens 190 and collects optical fiber 130.

Detected microscratch quantizes to learn or biochemical preparation can be gas, liquid, solid, collosol and gel or aerocolloidal form.Its molecule is adsorbed on the Nanosurface or nano particle of detecting device 105.Compare with the molecule in freely being present in gas, liquid, solid, collosol and gel or gasoloid, these molecules that are attracted on Nanosurface or the nano particle have much bigger scattering cross-section under the irradiation of laser beam.When these branch period of the day from 11 p.m. to 1 a.m that are adsorbed, can obtain the raman scattering spectrum of these molecules with laser beam irradiation.The predetermined raman spectral signal comparison that is stored in system database by these molecules can identify target chemistry or biochemical preparation.

Fig. 3 A has shown an example that strengthens Raman scattering in traffic safety field application surface.Passenger 200-1,200-2 and the 200-3 by the walkway carried out examination.One or more probe assemblies 120 that have embed-type detecting device 105 are installed in the walkway 210.Near the spectroanalysis instrument 150 in office probe assembly 120 can connect by optical fiber or at a distance.In probe assembly 120, probe and detecting device (or detector) are packaged in together.The sensitive surface of probe direct detection device 105.Walkway 210 can be artificial draft and be under slight negative pressure and/or the high slightly temperature, with the volatilization that strengthens objectionable impurities or transport.If a passenger (for example passenger 200-2) carries explosive, harmful chemicals, chemical weapons, chemical and biological weapons, nuclear weapon or anaesthetic, these materials of microscratch amount will volatilize or transport and enter in the air, by the custom-designed sample collecting (U.S. US7 of system, 384, No. 792 Patent publish relevant details), these molecules are adsorbed to the surface of detecting device.The record Raman spectrum also compares the spectral signal of the known substance that stores in itself and the central office database.Just trigger alarm in case detect objectionable impurities, take suitable safety practice.

Referring to Fig. 3 B, goods 215 transports by goods examination passage 220 via a travelling belt 230.Embedding have the probe assembly 120 of detecting device 105 to place goods examination passage 220 everywhere.The spectroanalysis instrument 150 of probe assembly 120 in optical fiber coupling or distant place office.The pop one's head in surface of 120 aim detecting devices 105, and packaging together with detecting device 105, be used for detecting any explosive, chemistry or chemical and biological weapons or Harmful chemicals that is contained in goods 215.This facility can be applicable to the various places that need to check passenger baggage, for example airport, post office, railway station, customs inspection post, traffic control area or the like.Be easy to container or other dangerous goods implementing to detect gunpowder and other explosives, contain the liquid inflammable and explosive substances with this facility.

Wired detector network

Referring to Fig. 4 A, one detects (or detection) device network system 400 is applied to the safety monitoring of public building, and described public building is airport, railway or bus stop, stadiums, government bodies, auditorium, cinema, law court, shopping mall and other public buildings for example.A plurality of probe assemblies 401 are installed on the diverse location in public building 415 or other defence zone.Each probe assembly 401 comprises a probe and a detecting device (not showing respectively among Fig. 4 A).This probe can be similar with probe 110 (Figure 1A), but can also comprise a laser aid.This detecting device is consistent with the detecting device 105 shown in Figure 1B, comprises its lip-deep Nanosurface structure.This detecting device can also comprise one in order to receive the liquid solution that specimen material detects.This solution can comprise the nano particle of adsorption sample material molecule.Probe assembly 401 is used to monitor various material molecule, for the chemicals any danger or that be harmful to that enter into guarded region provide early detection.The light signal that probe assembly 401 is gathered is input to optical multiplexer 403 in the control roller office 408 through optical fiber 402 hyperchannels.Light signal decomposes the generation spectral signal through spectrometer 404, and spectral signal is analyzed by spectroanalysis instrument 405 again.Processor 407 utilizes the spectral information that is pre-stored in the database 406 to identify spectral signal in the spectroscopic data.Some special cases of supervision on hazardous substances include but not limited to explosive detection, comprise liquid explosive, chemistry or chemical and biological weapons (comprising anthrax), flammable liquid material, drugs etc.

Wireless detector network

In certain embodiments, detector network system 430 is shown in Fig. 4 B.Buildings 415 comprises an inlet and a multiaspect wall.Probe assembly 410A-410I is installed on the diverse location of buildings 415.Probe assembly 410A-410I connects together with antenna 411A-411I respectively, and antenna 411A-411I is transmitted into control center 450 with the detected spectral information in locality.

Shown in Fig. 4 C, each probe assembly 410A comprises that a probe 420A and is positioned at the detecting device 430A of probe 420A adjacent position.Detecting device 430A can gather the material in the surrounding environment.Implement in the example at some, detecting device 430A comprises a nanostructured surface, is adsorbed on the molecule of the material that collects in the surrounding environment.Probe 420A comprises the laser instrument 421A (for example semiconductor laser instrument) of a compactness, and laser instrument 421A is to being adsorbed in the sample molecule illuminating laser beam of detecting device 430A.Probe 420A further comprises optical signalling harvester 422A, and its collection is adsorbed in the light signal of the sample molecule scattering of detecting device 430A, and these scattering envelopes contain the correlation molecule information of sample molecule.Detecting device 430A is consistent with detecting device 105 (Figure 1B), has a nanostructured on its surface.Be adsorbed in the structural sample molecule scattering of this Nanosurface incident laser.Detecting device 430A can also comprise that one is used to receive the liquid solution (referring to following Fig. 7) of testing sample material.This solution contains the nano particle that is useful on the adsorption sample material molecule.

Probe 420A also comprises a compact spectrometer 440A, and the scattered light that probe 420A collects produces a spectrum through spectrometer 440A.Be transferred to wireless communication line 445A from the spectroscopic data of spectrometer 440A output.Wireless communication line 445A can comprise a radio frequency (RF) transceiver, one or more amplifiers and impedance matching circuit.Wireless communication line 445A is used for the detected spectroscopic data of probe assembly 410A is transferred to control center 450 (Fig. 4 B).

Referring to Fig. 4 B, control center 450 comprises that one has the wireless router 460 of antenna 455, is used to receive the wireless signal from antenna 411A-411I, and produces the electric signal that comprises spectroscopic data from this wireless signal.Control center 450 can be from signal source (for example, buildings 415) close together (for example, within several miles), allow the wireless signal that comprises spectroscopic data transmit, for example WiMax, WiBro, WiFi, WLAN, 802.16 and other home control network communication protocol according to a home control network communication protocol.Control center 450 can also be far away from signal source, the wireless signal that wherein comprises spectroscopic data can utilize wireless communication standard and agreement to transmit, for example gsm (GSM), universal mobile telecommunications service (UMTS) and CDMA (CDMA).GSM can comprise GPRS EDGE and CSD.UMTS can comprise that Wideband Code Division Multiple Access (WCDMA) (WCDMA), high-speed packet insert (HSPA), high-speed downlink packet inserts (HSDPA), universal mobile telecommunications system time division duplex (UMTS-TDD) and Long Term Evolution (LTE) technology.CDMA can comprise CDMA2000 and Ultra-Mobile Broadband (UMB) etc.

The spectroanalysis instrument 465 of control center 450 is used to receive the electronic signal that comprises spectroscopic data from wireless router 460.Analysis by spectroanalysis instrument 465 obtains a spectrum (for example Raman spectrum).As described below, different chemical substances or biochemical substances often have unique spectral signal.These spectral signals can utilize a known chemical substance or a biochemical substances, and one is similar to the detecting device that is installed among the probe assembly 410A-410I and measures in advance.These spectral signals can be kept in the database 470.Spectroanalysis instrument 465 can use the spectral signal that is kept in the database 470 spectral signal that identifies in the spectroscopic data for referencial use.The material that processor 475 can obtain a plurality of probe assembly 410A-410I that are positioned at buildings 415 diverse location places calculates and measures.If identify a dangerous substance from the spectroscopic data that one or more probe assembly 410A-410I obtain, processor 470 can be reported immediately to alarm and responding system 480.Described dangerous substance for example comprises explosive and fire goods, poison gas and other harmful chemical substances, and infective virus and bacterium.Alarm and responding system 480 are used for sending the early warning notice to wireless router 460, and wireless router 460 is then given mobile device 490 and other wireless devices with transmission of wireless signals, and warning safety and other responsible persons take the appropriate responsive action.Mobile device 490 can comprise portable personal computer, personal digital assistant system (PDA), a mobile internet device (MID), a portable phone, a smart mobile phone or a wireless server or router one by one.

In certain embodiments; referring to Fig. 4 D; the pre-position in probe assembly network installation place at buildings, airport, customs, goods or baggage conveyor system, doctor or healthy advisor's office, check-point, harbour, vehicle, boats and ships, submarine, aircraft, train, subway, industrial site, holiday resort, shopping mall, research laboratory, school or water source or the like, as above described about Fig. 3 B-4C.Each probe assembly comprises the probe in a detecting device and the detecting device, and probe is used to launch a laser beam and collects from the scattered light of testing molecule.Detecting device can have a nanostructured surface that is used for absorbing molecules.Probe assembly also comprises a spectrometer from scattered light generation spectroscopic data (for example Raman spectrum).Detector network can periodically be captured material (step 510) from the environment of each detecting device.Because detecting device has nanostructured surface, captive material molecule is to be attracted on the nanostructured surface of detecting device.Then the molecule from the nanostructured surface that is adsorbed in one or more detecting devices obtains spectroscopic data (step 520).Selectable, detected molecule can be by a sample solution capture, and/or is attracted on the nano particle that is suspended in the sample solution.As mentioned above, launching a laser beam irradiation by the laser instrument in the probe assembly is adsorbed on the detecting device nanostructured surface or the molecule in the sample solution.Through the light of these molecular scatterings by the probe assembly collection.Spectrometer in the probe assembly obtains spectroscopic data from scattered light, for example Raman spectrum.Nanostructured surface on the detecting device plays the amplification humidification to the signal intensity in the Raman spectrum.Capture material and obtain relevant spectroscopic data and can periodically carry out, for example at interval 1 minute, 10 minutes, 15 minutes or several hours.In certain embodiments, can respond the order that comes from control center and produce spectroscopic data.

Spectroscopic data is then from detecting device TCC traffic control center (step 530).The material capture time will transmit together with the spectrum data.Spectroscopic data can transmit by wired mode (shown in Fig. 4 A) or cordless communication network (shown in Fig. 4 B and 4C).Control center can comprise that a spectroanalysis instrument and stores the database of the spectral signal of predetermined known danger material.Spectroanalysis instrument is used for measuring in the spectroscopic data of self-detector whether have spectral signal.If in this spectroscopic data, found the spectral signal of a known danger material, then identify this dangerous substance (step 540).

This dangerous substance may be identified by a plurality of detecting devices in the detecting device network.This dangerous substance may be at different time by different detecting device identification.For example, when the passenger 200-2 walkway 210 (Fig. 3 A) of passing by, different detecting devices can obtain the dangerous substance at different time and diverse location place in this network.The processor 475 of control center (Fig. 4 B) can be measured the position and the life period of dangerous substance by the position of detecting device and the acquisition time of spectroscopic data are associated.Can measure the position of a dangerous substance of fixing by the position of detecting device.The position correlation of the detected dangerous substance of different detecting devices can be used as the exact position that weighting factor is measured this dangerous substance, and this can represent with a coordinate system two dimension (2D) or three-dimensional (3D).The different detecting devices of diverse location are used for measuring the space-time distribution situation (that is to say the function of position as the time) of this dangerous substance by the processor of control center to the capture time of dangerous substance.Can predict this dangerous substance position in the future by processor thus.

In certain embodiments, the spectroscopic data of detecting device collection can connect with the graphic materials that collects from spectroscopic detector periphery scene.For example, the video camera 405 that is positioned at the spectroscopic detector next door of identifying dangerous substance can be noted questionable person's thing or goods.The image of suspect or goods be stored and the positional information of the dangerous substance of reporting for work to take the appropriate responsive measure.

And then send alarm signal to the alarm response system, the alarm response system begins this dangerous substance is taked responsive measures (step 560).Described alarm signal can be forms such as Email, text message and voice call.Urgency level can be classified with the different hazard level of for example green (safety), blue, yellow, orange, red (the most dangerous) expression.Alarm signal can comprise the position that dangerous substance is current and/or expect, and has the suspect of dangerous substance or the appearance information of goods.The related personnel receives alarm, sends the guardian of the peace to arrive the dangerous substance place, begins to evacuate.

Fig. 5 utilizes detector monitors to be discharged into the synoptic diagram of the harmful chemical substance in the environment.Probe assembly 110 is distributed in the periphery of potential pollution source, for example near the highway that factory 260 or a large amount of automobile 270 pass through.Probe assembly 110 can be distributed in monitored area near, to spectroanalysis instrument 150, spectroanalysis instrument 150 is measured content and the concentration that is discharged into the material in the environment with transmission of stray light.The monitoring sample includes but not limited to soil, water (for example reservoir), lake, river, beach, well, plant or the like.This application may extend to vehicle exhaust inspection and monitoring, and probe assembly is positioned over the auto exhaust mouth.

Some are based on the spectral detection of nanostructured or the application of detection

In certain embodiments, the Raman detection system of compact has radio communication performance, can use in human body.For example, the Raman system chip can be made the tablet size, comprises little lasing light emitter in the chip, based on microminiature spectrometer, wireless module and little probe of MEMS or the like.An example application is the diagnosis of disease of digestive system.For example, patient can swallow the Raman spectrum detection system of next tablet size after cleaning its digestive system.Carry out Raman spectroscopy scans at interval according to preset time.Spectroscopic data is transferred to the outer wireless receiver of human body by a wireless module subsequently.The computer expert cross search and with spectroscopic data be stored in data in the database coupling of comparing, thereby identify disease.In the Another application example, the minimum invasive probe of a needle-like can be carried to little Raman detection probe the diagnostic region in the human body.Raman spectrum data can be by optical fiber or wireless module transmission.Such application includes but not limited to the diagnosis of cancer (for example breast cancer, colon cancer, cancer of the esophagus, lung cancer, liver cancer, carcinoma of urinary bladder and cancer of the stomach etc.), Alzheimer's, Parkinson's disease or the like.

Raman spectrum detection system disclosed by the invention and method are suitable for biotechnology and biomedical applications, for example A549 cell, DNA, RNA and the protein example of tissue by detecting the human or animal or body fluid, lung cancer, and biomarker (comprise CEA, CA-125, CA 19-9, PSA, AFP, A549, dna sequencing, DNA classification, or the like) carries out the early stage screening of major disease and the identity of biostatistics is veritified.

Raman spectrum detection system disclosed by the invention and method are applicable to the medicament research and development screening.The sample that is used for the medicament research and development screening can obtain by human body fluid test and/or breath test.Raman spectrum detection system disclosed by the invention and be equally applicable to criminal investigation.Sample can be saliva, urine and form of powder.Related application comprises that also identification forges a signature, and identifies and the examination individual by the DNA type, discerns small paint chipping, the fiber discriminating, or the like.

Raman spectrum detection system disclosed by the invention and method are suitable for Secure Application, for example detect dangerous substance, chemical weapons, biopreparate, explosive (powder, solid and liquid form), fire goods (comprising liquid, solid and powder), arcotic and radiomaterial.

Raman detection system and method disclosed by the invention is suitable for food security inspection and environmental monitoring.Can detect the harmful chemicals that exist with gas, liquid, powder, gel, gasoloid or solid form in food, fruit, beverage and the water.These harmful chemicals comprise heavy metal (including but not limited to contain the compound of Pd, Cd, Hg, As, Cr or Cu), prussiate (for example KCN, NaCN), perchlorate, the sulfate in remains of pesticide (for example acephatemet, cypermethrin, decis, malachite green etc.), bioxin, illegal man-made additive (for example Sudan red 1, Sudan red 1 I, Sudan red III, Sudan red 1 V, melamine, rhodamine B, sulfide (for example NaS), art green etc.), the water.Can utilize Raman spectrum detection technique disclosed by the invention to monitor secondary product (for example the potato block processing temperature is higher than the acrylamide of 120 ℃ of generations) in the food processing process to detect harmful chemicals, for example acrylamide.The food field of investigation includes but not limited to potato block, chips, fried potato, crisp chrisps, cooky, cracker, bread basket, crisp bread, bread, coffee, refining toast, the nut that toasted, biscuit, chocolate, puffed rice and comprises the aquatic products of fish, or the like.

Raman spectrum detection system disclosed by the invention and method are applicable to differentiates and detects packaging for foodstuff technology and preparation material, comprise that discriminating and screening are used for microwave food packaging paper, film for kitchen use, packaging for foodstuff, food and liquid container, and the polyvinylchloride rope (polyvinylchloride) and the phthalic ester material of processing and preparation material.

Raman spectrum detection system disclosed by the invention and method are suitable for differentiating the fake and inferior commodities for example ink signatures, the artwork, gasoline etc. of medicine, arcotic, milk powder, edible oil, wine, jewel, banknote, forgery.

Raman spectrum detection system disclosed by the invention and method are suitable for commercial production quality management and production safety monitoring.Application can comprise the process control of carrying out for the technology of product quality, gas and wet chemistry machining production line and production safety, comprise semiconductor wet chemical process line, air line and space shuttle, ship, boats and ships and submarine in refinery, chemical plant, the dust free room, or the like.

Raman spectrum detection system disclosed by the invention and detector network can be applicable to medical clinic office, Surgical Operating Room, shopping center, holiday resort, buildings, customs, road inspection post, harbour, airport, vehicle, ship, boats and ships, aircraft, space shuttle, commercial production place, R﹠amp; D research laboratory, Quality Control Office, institute of education, experiment office and water source (for example surface water, well, underground water) etc.

Fig. 6 A is that application surface enhancing Raman scattering technology use detecting device is the synoptic diagram that detects food quality and carry out matter monitoring safely.Light scattering probe 100 is placed on the places near food 280, and described food can be an apple or other fruit, vegetables, or other may be because of transportation, food processing and even the contaminated food of food growth course.The molecule of remains of pesticide or other pollutant is introduced into light scattering probe 100.Detecting device is used for detecting any suspicious harmful chemical in the food.

Fig. 6 B is that application Raman spectroscopy disclosed by the invention is the synoptic diagram that matter monitoring is carried out in early stage major disease screening and diagnosis.The doctor can remote monitoring and diagnosis at home and the patient in the hospital.Probe assembly 610 places patient 620 next door to carry out physical examination, the inspection of disease recovery situation or medical diagnosis on disease.The air that the people breathes out may carry special chemical substance for example alkene and benzene derivative.If the people by examination suffers from disease, cancer for example, include but not limited to lung cancer, breast cancer, liver cancer, cancer of pancreas, oophoroma etc., the Raman detection system and method can obtain the finger-print of some chemical substance in the breath test, thereby identifies for example cancer of some special diseases.Patient exhales to probe assembly 610.Detecting device in the probe assembly receives the air that enters, and produces from the corresponding scattered light of molecule in patient or breathe air sample supplier's the air-flow.The spectroscopic data of scattered light is produced by spectrometer 630.Wireless communication line 640 is converted into radiofrequency signal with spectroscopic data, and radiofrequency signal is launched radio signal through antenna 645.This radio signal can also comprise patient 620 information (for example patient's name, identity etc.).Terminal 650 and wireless communication line 640 couplings can show the information that derives from doctor's office and allow patient's input information to be transferred to doctor's office.

Receive radio signal at the antenna 655 of doctor or health consultation office from a plurality of patients outside the certain distance.Wireless server 660 will transform radio signal and take passages patient's spectroscopic data and other relevant informations.Spectroanalysis instrument 670 utilizes the spectral signal that is kept in the database 680 that spectroscopic data is analyzed.Spectral signal may show a plurality of predetermined diseases.Spectral signal in the spectroscopic data shows surely that really patient suffers from relevant disease or also recovery fully from the disease of past diagnosis.Signal intensity can show the order of severity of disease.Doctor 690 can also make the judgement of the disease character and the order of severity by checking spectroscopic data.The system and method that the present invention describes is suitable for early stage medical diagnosis on disease, and described disease includes but not limited to lung cancer, breast cancer, cancer of the stomach, cirrhosis, renal failure, ulcer etc.When testing human body fluid, body fluid manually or automatically is incorporated on the detecting device, or the Raman detection device is connected on the toilet water closet, thus sampling at an easy rate, with the abnormal signal of real-time monitoring of diseases and drug effect detection.This application also comprises to be identified and collating sort protein, DNA and RNA.All test specimens can engage with detecting device to strengthen sensitivity and the intensity that Raman scattering detects in the above-mentioned application.Utilize Raman scattering to detect microscratch quantification material and can also be used for other field, include but not limited to identify Alzheimer's, Parkinson's disease, for the non-intrusion type glucose that the monitoring diabetes are carried out is tested, for test of non-intrusion type carotenoid levels and the assessment that antioxidant status is carried out monitored in the early-stage cancer examination.

Fig. 6 C is the synoptic diagram that Raman scattering is applied to the commercial production quality management.This application can comprise that the monitoring of chemical concentrate on-line monitoring in the wet chemistry machining production line, chemical vessel sealing benchmark, long-range microscratch quantize to learn material inspection, semiconductor wafer defect testing, and food, fruits and vegetables storage monitoring, or the like.Spectral signal carries out spectroscopic data analysis by optical fiber by the spectroanalysis instrument that hyperchannel is transferred to control center through the probe collection of a plurality of positions.Identify the objectionable impurities in the samples such as food according to the spectral signal in the spectroscopic data.

Fig. 6 D is the synoptic diagram of a hyperchannel Raman scattering detection system, and it can carry out identification and the examination and the food security examination of fake and inferior commodities.This application can comprise operations such as food, medicine examination, wherein may comprise or not comprise the nanometer technology module in the detecting device.But the laser beam direct irradiation test specimen of detection system.Scattered light from test material is collected by probe.The Raman spectrum of this scattered light demonstrates spectral signal, and this spectral signal can be pointed out whether to have added illegal adjuvant in these commodity.Potential fake and inferior commodities, for example milk powder, wine and tablet can be used as to be detected and material examination places under the Raman detector.Gathered and passed through hyperchannel from the spectral signal of different samples and given the spectroanalysis instrument that is arranged on central office, to carry out the analysis of spectroscopic data by Optical Fiber Transmission.This application can extend to the signature and the evaluation of banknote, the raman scattering spectrum of signature and banknote generation is compared with the spectrum of legal signature and banknote, thereby check out forgery signature and counterfeit money.

Utilize the spectral detection of nano particle

In some implemented examples, referring to Fig. 7 and 8, sample solution 720 placed container 710, and container 710 is the cuvette (step 810) of an optical sample bottle or quartz, glass plastic material for example.Container 710 can be an optical sample bottle, a beaker or a cuvette, or the like.Sample solution 720 contains nano particle 750.Nano particle 750 can be present in the sample solution 720 with the form of colloidal suspension.The specimen material that contains chemical substance or biochemical substances is introduced in the sample solution 720 (step 820).Specimen material can exist with solid, liquid, gasoloid, collosol and gel or gas form.Specimen material is dissolved in the sample solution 720, allows chemical substance or biochemical substances molecule be adsorbed on the surface of nano particle 750 (step 830).Probe 110 (shown in Figure 1A) send an incident light 701 (a for example laser beam), nano particle 750 and chemical substance or biochemical substances (step 840) in the irradiation sample solution 720.The scattered light 702 that comes from nano particle 750 and chemical substance or biochemical substances is gathered (shown in Figure 1A) (step 850) by probe 110.Analyze through spectroanalysis instrument 150 from the signal of probe assembly output.Detail is seen following Example, obtains a Raman spectrum (step 860) from scattered light.Spectral signal in the Raman spectrum can be used for measuring the microscratch that is adsorbed on the nano particle and quantizes to learn material or biochemical substances (step 870).

One side disclosed by the invention, the material of the nano particle 750 in the sample solution 720 are formed and are wanted to strengthen scattered light 702 and from the intensity of the raman spectral signal of nano particle.For example, nano particle 750 comprises metal material (as Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt and their alloy), oxide material (as titania, silicon dioxide, zinc paste etc.), silicon and polymeric material.Nano particle 750 can be charged in sample solution 720, and this helps the separation between the nano particle and the formation of colloidal suspension.Nano particle 750 can also comprise the polymkeric substance that is tethered in particle surface, helps them to repel mutually in sample solution 750.

In certain embodiments, nano particle 750 can comprise carbon nano-tube.The diameter of carbon nano-tube is less than 1,000nm, and for example the diameter of carbon nano-tube can be 0.3nm-100nm, length can be that 5nm arrives several millimeters.The length-to-diameter ratio of carbon nano-tube can be up to 5,000 ten thousand.Carbon nano-tube can be walls single wall or many.Carbon nano-tube can be the form of Fu Leti (fullerite), holder shape (torus), nanometer bud (nanobuds) and nanometer flower (nanoflowers).

In the system and method disclosed by the invention, carbon nano-tube can place sample solution 720 to form the suspending liquid of a nano particle, and specimen material also is added into.Carbon nano-tube can also be introduced in one very on the even curface or one have on the surface of nanostructured, and specimen material is introduced on this surface of containing carbon nano-tube subsequently.Under any situation, laser beam irradiation is on carbon nano-tube and specimen material.Strengthen electromagnetic field and can help the electric charge between target chemical matter or the biochemical substances molecule to shift, thereby strengthen the signal of Raman spectrum.

Another aspect of the present invention, nano particle 750 can be made of magnetic or ferromagnetic material, for example iron (Fe), cobalt (Co), nickel (Ni), the compound that perhaps contains iron, cobalt, nickel, as the alloy or the oxide of iron, cobalt, nickel, can strengthen raman spectral signal by sample solution 750 is applied electric field, magnetic field or electromagnetic field like this.This electric field, magnetic field or electromagnetic field can be fix or alternation.Another aspect of the present invention, sample solution 720 can comprise the potpourri of the nano particle of different composition materials.For example, described nano particle can comprise the potpourri of silicon nanometer or micron particles and metal nanoparticle, the perhaps potpourri of silicon nanometer or micron particles and polymer nano granules, the perhaps potpourri of silicon nanometer or micron particles, metal nanoparticle, metal oxide nanoparticles and polymer nano granules.Can strengthen the intensity of Raman signal by the composition of potpourri.

Another aspect of the present invention, the solvent in the sample solution 720 are used to strengthen the light scattering intensity of nano particle equally.Ion can significantly strengthen the intensity of Raman signal, and therefore, ionic material is added in the sample solution 720.The contained ion of ionic material that is added in the sample solution 720 can include but not limited to Na ⁺, K ⁺, Li ⁺, Ca ²⁺, Ba ²⁺, Sr ²⁺, Mg ²⁺, Mn ²⁺, Al ³⁺, Zn ²⁺, Sn ²⁺, Sn ⁴⁺, F ^-, Cl ^-, Br ^-And I ^-Or the like.The ion of sample solution 720 can be a unit price, or divalence or more the high price.Described ion can have positive charge or negative charge.Sample solution 720 can have an ionic compound, includes but not limited to LiF, NaF, LiCl, NaCl, KCl, KI etc.Ion concentration can be from 10mM to the saturated level.

Shown in Fig. 9 A, nano particle 750 can be circle or irregular shape.Nano particle can be separated from one another in sample solution 720, also can be that gathering is agglomerating.Shown in Fig. 9 B, nano particle 750 can have a size distribution, characterizes size distribution with average particle size particle size da and particle diameter distribution width dw here.Average particle size particle size da can be 1nm-10,000nm, perhaps 2nm-500nm.The value of dw/da can be 0.01-3, and this can limit and singly be distributed to polydisperse distribution of particles.The value of dw/da is generally 0.03-1.In certain embodiments, sample solution can comprise nano particle and as the little section of the tumor tissues of specimen material.The temperature of sample solution can by-TE refrigeratory and well heater be controlled at one predetermined among a small circle in, temperature variation is less than 1 ℃ or 2 ℃.Temperature can be from-18 ℃ to 60 ℃, or from 0 ℃ to 40 ℃.Dry sample solution on a substrate surface makes nano particle and specimen material stay substrate surface.With this nano particle of laser beam irradiation and specimen material.Collection has the scattered light of the specimen material generation of the nano particle that is adsorbed with testing molecule.Obtain Raman spectrum by this scattered light.Utilize spectral signal in the Raman spectrum can identify chemical substance or biochemical substances in the specimen material.

Utilize the spectral detection of Nanosurface structure

Implement in the example at some, the material that contains microscratch quantification material or biochemical substances can be introduced on the surface of chemical detector or detector, and as shown in Figure 1, incident light is scattered, and obtains Raman spectrum to carry out substance-measuring.Figure 10-15 has shown the processing step of the nanostructured precious metal surface of a series of making chemical detectors (or detecting device among Fig. 1 105).One sandwich construction 302 (Figure 10) comprises a substrate 305, a conductive layer 310 and an alumina layer 315.Substrate 305 can be, for example n type silicon chip (the 3-8 Ω-cm) or (the 30-50nm SiO of oxidation ₂) p type silicon (5-10m Ω-cm).Conductive layer 310 can comprise Ti and Ni, and it is deposited in the substrate 305, has not only conducted electricity but also heat conduction.The thickness of conductive layer 310 can be optimised, makes it i) adhere to the noble metal film of deposition, for example Ag or Au film or the like subsequently; Be conductive film ii), in the practical application sensitive surface applied electrical bias; Iii) be heat-conducting layer, reduce the temperature of sensitive surface.The thickness of conductive layer 310 generally can be controlled at 100

-1,000 Scope in.

Aluminium lamination 315 is deposited on the conductive layer 310.Aluminium lamination 315 can have 99.999% purity, and thickness is in the 1.0-10.0 mu m range.Substrate 305, conductive layer 310 and alumina layer 315 are filling N ₂Reacting furnace in 400 ℃-500 ℃ annealing 2-5 hour, make aluminium film recrystallization.Carry out anodic oxidation subsequently, on alumina layer 315, form porous structure, shown in Figure 11 A and 11B.The porous structure that forms on the alumina layer 315 comprise many by inwall 314 around hole 312, its along the cut-open view of horizontal line A-A shown in Fig. 1 lC.In Figure 12, carry out the wet oxidation corrosion, to remove the porous Al at top ₂O ₃Layer and restraining barrier.Carry out anodic oxidation for the second time and consume all metallic aluminiums, make the Al of the porous at restraining barrier and top ₂O ₃Layer just in time is positioned on the conductive metal layer.

In Figure 13, carry out restraining barrier and reaming that oxide etch is removed the hole bottom.Wet etching makes hole 312 extend downward conductive layer.The thickness of formed porous oxide coatings can be controlled by the technological parameter of control aluminium physical vapor deposition (PVD), oxidation and wet etching course subsequently.The porous structure of self assembly is formed naturally a hexagonal array.Aperture (d) and interpore distance (D) depend on the character of the oxidation voltage (V), current density (i) and the electrolytic solution that are applied, and wet etching reaming process afterwards.

Referring to Figure 14 A, noble metal for example Ag is deposited on the porous layer 315 with filling pore 312 and layer 320 of formation.Layer 320 can form with PVD or plating mode.In Figure 14 B, one deck noble metal 320 is removed, and has kept the noble metal 320-N in the hole 312.Carry out wet method metal erosion or CMP once more and be filled in the height of the noble metal 320-N in the hole with further control.In Figure 15, the aluminium film 315-AL of aluminium oxide 315 and porous aluminium lamination 315 bottom remnants is removed, and forms a nanostructured surface 300, and it contains a nano-pillar 320-N array.

Nano-pillar 320-N is straight basically, perpendicular to substrate 305 and conductive layer 310.Nano-pillar 320-N can have substantially the same or close width.Adjacent nano-pillar 320-N is separated by the gap, and the distance of these gaps and conductive layer 310 remains unchanged basically.

The photoetching of using in the above-mentioned manufacturing process is complementary with the geometric configuration of mask and the dimensional requirement of sensing chip and the zone of metal gasket, and metal gasket is positioned on the corner of chip.For field studies, chemicals detects sensing chip and adopts different semiconductor packagings to encapsulate, for example, and lead-in wire bonding, upside-down method of hull-section construction, system level chip (SOC), or the like.

In certain embodiments, nanostructured can be made by different technology, shown in Figure 16 A-16F.Pair of lamina structure 362 comprises a conductive layer 335 and a substrate 330.Conductive layer 335 can be made by titanium (Ti) or nickel (Ni), can be not only to have conducted electricity but also heat conduction.Substrate 330 can be a n type silicon chip (the 3-8 Ω-cm) or (the 30-50nm SiO of oxidation ₂) p type silicon chip (5-10m Ω-cm).The controllable thickness of conductive metal layer 335 is in scope.Adhesion layer (for example can be made by Ag) can be to be deposited on the metal level 335.The thickness of conductive layer 335 can be optimized, thereby microscratch quantification material detection sensitive surface is applied electrical bias, further, reduces the temperature of sensitive surface for the sensitivity that strengthens the detection of microscratch quantification material.

In Figure 16 B, layer of precious metal 340 is deposited on the top of conductive layer 335.Noble metal can be a silver layer, and for example thickness is the Ag of 10-200nm.In Figure 16 C, second metal level 345 is deposited on the top of layer of precious metal 340.Second metal level 345 can comprise that purity is about 99.999% aluminium, and thickness is in the 1.0-10.0 mu m range.Aluminium lamination 345 is filling N subsequently ₂Annealed 2-5 hour for 400 ℃-500 ℃ in the reacting furnace, make aluminium film recrystallization.

In Figure 16 D, make the porous structure of Woelm Alumina 345 ' form by oxidation technology.Figure 16 E is its top view, and this porous structure is formed naturally the hexagon nanoaperture array of self assembly, and it comprises many holes 348 that centered on by hexagon hole wall 349.The centre distance of adjacent pores 348 is D.Remove the anodic oxide coating and restraining barrier at top by a wet chemical process after, carry out for the second time that anode oxidation process consumes all metallic aluminiums, so that the porous Al at restraining barrier and top ₂O ₃Layer 345 ' is positioned on the layer of precious metal 340 just.Carry out wet etching then and widen hole 348, and remove the restraining barrier of hole 348 bottoms.When carrying out wet etching, shown in Figure 16 F, hole 348 is widened, around inwall 349 attenuation of hole.Can control etching process to form a large amount of nano-pores 348 that is centered on by inwall 349.Can also corrode between hole 348 and contact each other, produce the hexagonal array of an accurate triangle nano-pillar 349 '.

In Figure 16 G, layer of precious metal 340 is corroded, and hole 348 extends downwardly into the titanium layer 335 of conduction.In Figure 16 H, carry out wet oxidation erosion removal aluminium oxide, remove the aluminium that remains in hole 348 bottoms succeeded by the wet method metal erosion.The aluminium film 315 of aluminium oxide 315 and porous aluminium lamination 315 bottom remnants is removed, and forms the nano column array with controllable height, diameter and intercolumnar distance.This array can have accurate leg-of-mutton periodic hole.

Nano-pillar is straight basically, perpendicular to substrate 330 and conductive layer 335.Nano-pillar 320-N can have substantially the same or close width.Adjacent nano-pillar is separated by the gap, and the distance of these gaps and conductive layer 335 remains unchanged basically.

In some implemented examples, as mentioned above, the preparation that is suitable for the detecting device of Figure 1A and 1C can or not have in ad hoc structure (the being smooth) substrate or introduces nano particle in the sample solution at tool one fixed structure.Microscratch quantizes to learn material or biochemical substances can mix with nano particle in solution earlier mutually, the molecule that makes microscratch quantize learn material or biochemical substances is adsorbed on the nano particle, and the sample solution that contains this nano particle is introduced in tool one fixed structure of this chemical detector subsequently or does not have on the surface of ad hoc structure.In other words, the nanoscale surface structure is produced on the surface that can be coated on detecting device 105 by the colloidal suspension solution that will contain nano particle.Described nano particle can be made by metal material (for example Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt, and their alloy), oxide material (for example titania, silicon dioxide, zinc paste etc.) or polymeric material.Oxide or polymer beads can cover with the metallic ion coating or with conductive material.Colloidal suspension solution can comprise single nano particle or nano particle group.This solution forms the nanoscale surface structure after being applied in detector surface.This solution is volatilizable, stays nano particle target molecule is adsorbed onto detector surface.

Healthcare appliances based on the spectral detection of nanostructured

In certain embodiments, use as above Figure 1A-2,6B, the described light scattering probe 100 of 7-9B associated description obtains the Raman spectrum of patient's body fluid, can be used to identify disease by analyzing this Raman spectrum.Human body fluid can be introduced directly into detecting device (as 105 among Figure 1A) upward or with the sample solution that contains nano particle (as 720 among Fig. 7) to be mixed mutually.Light scattering and Raman spectrum analysis can be as Figure 1A-1C or carrying out shown in Figure 7.In addition, as mentioned above, the sample solution that contains nano particle can be transferred on having of a detecting device surface fixed structure or that do not have ad hoc structure, is used for light scattering and Raman spectrum analysis subsequently.

Referring to Figure 17, shown the spectrum peak of two features from a Raman spectrum that obtains from carcinoma of mouth patient's saliva sample, respectively at 560cm ^-1(at 520cm ^-1-580cm ^-1In the zone) and 1100cm ^-1(at 1080cm ^-1-1110cm ^-1In the zone) near, and the healthy individual of not suffering from carcinoma of mouth does not show this two spectrum peaks.560cm ^-1And 1100cm ^-1The characteristic spectrum peak at place and C-S, S-S, O-P-O, PO ₂, the molecular vibration that causes of C-N or C-C key is relevant, for example contains halfcystine, ATP, ADP, DNA, RNA, protein and other contain the biological sample of phosphoric acid.The identification of spectral signal can comprise the following steps: to be cm in the Raman frequency shift unit with each spectral signal at first ^-1Select a spectrum peak in the Raman peaks of (wave number); Determine background scattering intensity; Calculate intensity, relative intensity or the integral area at peak.Calculate signal to noise ratio (S/N ratio) with peak intensity and background.If signal to noise ratio (S/N ratio) is higher than a predetermined threshold (for example 3 or higher), the spectral signal of Raman peaks just is identified.Detection can be adopted statistical study and several algorithm (for example Dendrograph and principal component analysis (PCA)) with the identification of the spectral signal of disease and the relevant chemical substance of drug use.If 560cm ^-1And 1100cm ^-1Near two spectral signals are all identified, can recognize to be chosen as detecting and the Cancer-Related chemical substance in oral cavity so, and the detected person may suffer from carcinoma of mouth or early stage carcinoma of mouth.Doctor and detected person should use same or other diagnostic techniques further detects, and whether suffer from carcinoma of mouth or early stage carcinoma of mouth with diagnosis.

System and method disclosed by the invention can also be used to measuring glucose level to be used to assess diabetic conditions.1115cm ^-1To 1135cm ^-1Characteristic spectrum peak in the zone, for example 1124cm ^-1Near, relevant with the molecular vibration of glucose, the Raman spectrum that obtains from the saliva sample of diabetic can provide the key foundation of diagnosing diabetes.The intensity of this Raman peaks, relative intensity or integral area can be used for the concentration of glucose of evaluating patient body fluid, thereby determine the diabetes rank.Similarly, referring to Figure 18-20, relevant chemical substance with breast cancer also can be at about 560cm of the Raman spectrum of saliva ^-1And 1100cm ^-1The place demonstrates spectral signal (Figure 18).Relevant chemical substance with lung cancer and oophoroma may be at about 745cm of the Raman spectrum of saliva and blood serum sample ^-1The place has a spectral signal (about 740cm ^-1-760cm ^-1In the scope) (Figure 19 B and Figure 20).745cm ^-1Characteristic spectrum peak and the C-S key in protein or the phosphate at place, the perhaps O-P-O key among Z-DNA, the T-DNA perhaps contains the atom of S, N or P or molecular vibration that molecular radical causes and is correlated with.Relevant chemical substance with acquired immune deficiency syndrome (AIDS) may be at the 865cm of the Raman spectrum of blood serum sample ^-1-885cm ^-1In the zone, 870cm for example ^-1Near have a spectral signal (Figure 21).System and method disclosed by the invention can also be used to whether using the detection of forbidden drug, for example heroin (heroin), dexoxyn (methamphetamine), ***e (***e), caffeine (caffeine), morphine (morphine), codeine (codeine), amphetamine (amphetamine), ephedrine (ephedrine), papaverine (papaverine), narcotine (narcotine), acetyl codeine (acetylcodeine), methamphetamine hydrochloride (methamphetamine HCl), ketamine hydrochloride (ketamine HCl), codeine phosphate (codeine H ₃PO ₄), dolantin hydrochloride (meperidine HCl claims pethidine again), triazole benzene phenodiazine (triazolam), quinalbarbitone (secobarbital), hypaconitine (hypaconitine), MDMA or the like.Figure 22 shows is Raman spectrum from the saliva sample of a dexoxyn solid (a kind of forbidden drug), a medication individuality and a dexoxyn user's saliva sample.From the Raman spectrum of drug use person's saliva sample at about 1030cm ^-1And 1535cm ^-1Near a characteristic peak is respectively arranged, this characteristic peak shows that it may use forbidden drug.Method and system disclosed by the invention can also be used for detecting the excitant (for example hormone) in sportsman's body in international athletic competition (such as the Olympic Games).

Similarly, referring to Figure 23, the state of smoking state and passive smoking also shows spectral signal, at about 1029cm of smoker's saliva sample Raman spectrum ^-1The spectral signal that the place demonstrates is not present in the healthy individual of non-smoking.About 1029cm ^-1The characteristic spectrum peak at place is relevant with the molecular vibration pattern of N-first-2-5-pyrrolidone (cotinine), and N-first-2-5-pyrrolidone is the metabolic product of nicotine.

Utilize Raman disclosed by the invention probe to carry out one or more in can comprising the following steps of non-invasive disease detection and diagnosis:, at first to obtain body fluid (step 2010) from a patient or forbidden drug user referring to Figure 24.Because Raman scattering detecting device disclosed by the invention has high sensitivity, the amount of body fluid can be quite little.For example, the body fluid volume that obtains from patient can be from about 100pl to 4ml.The example of body fluid can comprise blood, saliva, urine, serum, tear, sweat, gastric juice, hydrothorax, ascites, celiolymph, seminal fluid and juice.Centrifugal back body fluid is introduced on the Nanosurface (step 2020).For example, this Nanosurface can comprise the nanoscale structures on the detector surface.Body fluid can be transferred on the Nanosurface of detecting device.The body fluid of staying detector surface after the drying forms a drying layer.In another example, Nanosurface is provided by the nano grain surface that is suspended in the solution.Body fluid be directed in the solution that comprises nano particle.Molecule in the body fluid is adsorbed on the Nanosurface.With this Nanosurface of laser beam irradiation and the molecule (step 2030) that is adsorbed on the Nanosurface.Collection is through Nanosurface and the scattered light (step 2040) that is adsorbed molecule.

Obtain Raman spectrum (step 2050) from scattered light.One or more spectral signals in the spectrum are identified with diagnose the illness (step 2060).Can comprise cancer by detected disease example, include but not limited to lung cancer, breast cancer, cancer of the stomach, cancer of the esophagus, thyroid cancer, laryngocarcinoma, ulcerocancer, oophoroma, liver cancer, head and neck cancer, the cancer of the uterus, cervical carcinoma, carcinoma of mouth, leukaemia, colon cancer, carcinoma of urinary bladder, prostate cancer, cutaneum carcinoma, bronchiolar carcinoma, kidney, cirrhosis, renal failure, acquired immune deficiency syndrome (AIDS) and dopy.As mentioned above, one or more spectral signals predetermined wavelength place in Raman spectrum.The wavelength of spectral signal and feature are special for disease to be detected.For example, the spectral signal in carcinoma of mouth and the breast cancer saliva sample may be at about 560cm ^-1Or 1100cm ^-1Near.Spectral signal 745cm in Raman spectrum greatly in the lung cancer blood serum sample ^-1Near.One spectral signal can comprise a spectrum peak.When this spectrum peak during greater than certain predetermined threshold, spectral signal is identified.For example, with respect to noise background, when the signal to noise ratio (S/N ratio) of spectrum peak just identified greater than 3 the time.

Should be noted that Figure 24 and Fig. 8 are consistent, can add the one or more steps among Fig. 8 in the step of Figure 24, comprise and utilize the sample solution that contains nano particle.

Utilization is based on the food security safeguard of the spectral detection of nanostructured

The high detection sensitivity and the specificity of light scattering probe disclosed by the invention and material detection method make it to be applicable to the food security field, comprise the illegal adjuvant in the examination food and verify effective constituent.Described food is dairy products for example, and dairy products can comprise milk, milk powder (as babies ' formula milk powder), cheese, cheese cake, sour milk, ice cream, toffee, contain milk biscuit, contain milk deli and contain protein food.Nearest serious together food security incident is about the illegal melamine that adds in dairy products (for example babies ' formula milk powder, ice cream and biscuit etc.).Method and system disclosed by the invention can be used for detecting the wine product for example existence and the content thereof of grape wine methyl alcohol equally, and nitrite, honey element (sodium cyclohexylsulfamate) and other illegal or excessive food additives in the food, beverage, wine product.

As above with Figure 1A-2,6A, the description that 6C is relevant with 7-9B, food samples can be made into solution, is incorporated into detecting device (as 105 among Figure 1A) then and goes up or mix mutually with the sample solution that contains nano particle (as 720 among Fig. 7).Light scattering and Raman spectrum analysis can be as Figure 1A-1C or carrying out shown in Figure 7.In addition, as mentioned above, the sample solution that contains nano particle can be transferred on having of a detecting device surface fixed structure or that do not have ad hoc structure, is used for light scattering and Raman spectrum analysis subsequently.

As above with Figure 1A-2; 6A; the description that 6C is relevant with 7-9B, chemical substance or biochemical substances sample can be prepared into solution, are incorporated into detecting device (as 105 among Figure 1A) then and upward or with the sample solution that contains nano particle or carbon nano-tube (as 720 among Fig. 7) mix mutually.A kind of method of preparation sample solution is that the chemical substance and the biochemical substances (for example liquid, solid, powder, collosol and gel, gasoloid etc.) that directly will contain sample are mixed in the test solution that contains nano particle; Another kind method is, the gas sample tube that end is had many micropores inserts in the solvent solution, again the gas that contains chemical substance or biochemical substances is blown in the solvent solution by gas sample tube, and then with this solvent solution with contain nanoparticles solution and mix.The time of blowing is 1 minute to 2 hours, and the pressure of air blowing is 1atm-5atm.The terminal hole of gas sample tube is of a size of 5 μ m-50mm, and the internal diameter of gas sample tube is 20 μ m-500mm.The chemical substance of gas or aerosol form comprises ammoniacal liquor, benzene, toluene, m-xylene, o-xylene, P-xylene, sulphuric dioxide, nitrous oxide, nitrogen dioxide, monoethanolamine, dimethyl formamide etc.If sample solution places on the surface of detecting device, the carrying out that light scattering and Raman spectrum analysis can be shown in Figure 1A-1C, or by light scattering and the Raman spectrum analysis of carrying out shown in Figure 7.On the other hand, contain the nano particle sample solution and also can be transferred to having a fixed structure or not having on the surface of ad hoc structure of detecting device, as mentioned above, carry out light scattering and Raman spectrum analysis subsequently.

In certain embodiments, referring to Fig. 1,8 and 9, the milk sample solution is the milk liquid that has added the melamine of 1ppm, 2ppm, 5ppm and 50ppm respectively.These milk sample solutions are added to respectively that detecting device (as 105 among Fig. 1) is gone up or add contain in the sample solution (as 720 among Fig. 7) of nano particle.The melamine adjuvant comprises melamine and melamine cyanurate.Use above-mentioned light scattering probe method to obtain Raman spectrum.The volume of food samples solution is generally 100pl-1ml.

Illegal and the harmful chemical (as melamine) of variable concentrations can detect the correlation spectrum signal at Raman spectrum in the dairy produce.Figure 25 A shows is to have added the Raman spectrum of milk sample solution that concentration is the melamine of 0ppm (not containing melamine), 1ppm, 2ppm and 5ppm respectively.Raman spectrum shown in Figure 25 A and the 25B is at 700cm ^-1Near have Raman peaks, lay respectively at about 678cm ^-1(peak A), 698cm ^-1(peak B) and 710cm ^-1Near (peak C).These observed Raman peaks are relevant with ring around suction II pattern (the ring breathing II mode) vibration, relate to the plane deformation (in-plane deformation) of triazine ring in the melamine molecule or the out-of-plane bending vibration ring of melamine cyanurate molecule (a ring out of-plane bending vibration).In addition, as can be seen, 678cm in these three Raman peaks ^-1The concentration that the relative intensity of peak A near increases the expression melamine increases.By contrast, 710cm ^-1Near peak C relative intensity reduces to represent that melamine concentration increases.By melamine concentration relatively is that the Raman spectrum of 5ppm (Figure 25 A) and 50ppm (Figure 25 B) can clearly be seen this two trend.Attention melamine cyanurate (the minute white precipitation of needle-like) is that the cyanuric acid in melamine and the solution forms under specific circumstances.

In another example, acetonitrile solvent is added to the interior mark reference of measuring as Raman scattering in the sample milk solution.Discover, do with acetonitrile that solvent does not influence or the faint Raman scattering intensity that influences test solution.Referring to Figure 26, use said system and method to obtain Raman spectrum as the milk solution of 5ppm from a melamine concentration of having added acetonitrile, spectral signal is positioned at 700cm ^-1Neighbouring (peak A, B and C).About 918cm ^-1-921cm ^-1The Raman peaks of position (peak D) can be as the interior mark reference of calibration Raman peaks frequency and intensity.Another Raman peaks is at 1640cm ^-1Near.

In another example, Raman spectrum detects the spectral signal (Figure 27) that in aqueous solution concentration is respectively the illegal and detrimental substance (melamine) of 1ppb and 100ppb.

In certain embodiments, referring to Figure 1B, Figure 16 F, 16E and 16H, go up coating one metallic film in the nano-pillar 108 (or hole) of the Nanosurface of detecting device 105.This metallic film is electrically connected with electrode.This metallic film can form by a noble metal is for example golden.Detecting device is immersed in the sample solution, and sample solution just is applied on the detector surface like this.On electrode and metallic film, apply electrical bias.Electrical bias can be controlled in-3.0V～+ scope of 3.0V in, this can strengthen the absorption of Nanosurface to sample molecule (for example melamine molecule), strengthen local electro permanent magnetic, reach the electric charge transfer that strengthens between sample molecule and the nanoscale surface structure, thereby make the Raman scattering strength-enhanced of the sample molecule that is adsorbed onto Nanosurface.The laser beam of incident projects on the detecting device, detects scattered light when sample solution is applied electrical bias.Can carry out Raman light scattering after cancelling electrical bias measures.

In certain embodiments, use ion exchange column and from sample, separate chaff interference.Sample flow is through pillar, and chaff interference is trapped and analyte stream comes out.Such pillar, for example the C18 post can be used for equally according to the similar compound of (retention time) separation chemistry performance of the different residence time.Final concentrated and purified sample will increase the concentration of target substance, therefore make detection sensitivity improve the 1-2 order of magnitude.

In certain embodiments, the detection of chemical substance or medical diagnosis on disease can use an integrating device to carry out in the food, and this device can carry out Chemical Decomposition and the light scattering detection that microscratch quantizes to learn material, biomaterial etc.The details of this integrating device discloses in common 11/761, No. 453 patented claim of U.S. US of transferring the possession of, and this application is called " integrated chemical separated light scattering device ", and the applying date is on June 12nd, 2007, incorporates its disclosure by reference at this.

In certain embodiments, light scattering probe disclosed by the invention and chemical detection method not only can be used for detecting the illegal or objectionable constituent in the food, can also be used to detect effective or neutral composition.As shown in figure 28, be starch, sucrose, milk powder A (the first milk powder brand) from top to bottom, added the milk powder B (the second milk powder brand) of sucrose, the Raman spectrum of milk powder C (the 3rd milk powder brand).Should not contain starch and sucrose in the normal milk powder.Because starch and sucrose are white powder, be not easy to detect with common test method if they are mixed in the milk powder.The Raman spectrum of starch is at about 473cm ^-1Near a very strong peak (Figure 28 topmost) is arranged, this feature Raman peaks can be used for detecting the starch that whether illegally mixed in the milk powder.Because the Raman spectrum of milk powder C has shown stronger 473cm ^-1Raman peaks shows among the milk powder C and contains starch.This detection method is applicable to and detects mixing up of unauthorized starch-containing material that described starch-containing material is flour, ground rice, soy meal, dehydrated potato powder, sweet potato flour or the like for example.

The open system and method for the present invention can also be used to the existence of sucrose in the examination milk powder.From the top down second Raman spectrum demonstrates several strong Raman peaks (greatly about 850cm among Figure 28 ^-1, 940cm ^-1, 1020cm ^-1, 1130cm ^-1At the place).The set feature of these Raman peaks clearly (is mixed with sucrose since relate on the packaging label of milk powder B in the spectrum of the milk powder B that is mixed with sucrose (among Figure 28 the 4th from the top down), it is legal that Here it is), but be not present in the spectrum (among Figure 28 the 3rd from the top down) of the milk powder A that does not add sucrose.On the other hand, the set feature of the Raman peaks that sucrose is relevant in the spectrum (Figure 28 bottom) of milk powder C clearly because its packaging label does not relate to sucrose, this milk powder mark and interpolation starch and sucrose are illegal.Note that Raman test shows the starch that both mixed among the milk powder C sucrose that also mixed, and in its packing, do not indicate.

In addition, method and system disclosed by the invention can be applied to measure for example protein content in the dairy products of food.The high concentration of protein can reflect that its Raman peaks is at 1658cm by higher acid amides I concentration in the food ^-1Near.With respect to other spectral signature, 1658cm ^-1The intensity at place can be used for for example assessment of protein level in the milk powder of food.For example, three different powdered milk samples among Figure 28 (among Figure 28 lower three spectrum) have similar protein content level.Be positioned at 1658cm in the milk powder A spectrum ^-1More significant peak show that the protein content of milk powder A is higher slightly than milk powder B and milk powder C.

Therefore, method and system disclosed by the invention is to detect protein content in the milk powder, and whether has sucrose and starch, whether has the effective ways of illegal adjuvant (for example melamine).In addition, the disclosure system is simply compact, is easy to carry.Because of its fast detecting time cycle (30 second-3 minute, even the shorter time), material detects and can carry out at the scene easily, thereby can be to dairy produce in very wide environmental field, for example fresh milk and milk powder are identified timely and effectively with quality and are examined.

The intensity of Raman signal can increase by the experimental pretreatment sample.For example, after test specimen is dissolved in the solution, solid particle, unnecessary ionic molecule or not clear material can pass through with a solid phase extractions (solid-phaseextraction, SPE) the post filtering solution removes, key step comprises the preparation solvent, makes sample solution pass through pillar, with selecting eluant solution, obtain final elution analysis thing, identify according to light-scattering analysis subsequently.The removal of solid particle, unnecessary molecule or not clear material can effectively strengthen from the nanostructured surface of chemical detector or contain the scattered light of the sample solution of nano particle, thereby can carry out quantitative test to the concentration of target molecules of known base substance, for example can measure the melamine that concentration in fresh milk or finished milk or the milk powder is low to moderate 0.5ppm.

When method and system disclosed by the invention was used to Food Inspection, illegal food additives molecule can be separated from the food substrate material by the temperature of control (for example improve or reduce) sample solution (for example 720 among Fig. 7).Illegal food additives Sudan red 1 or Sudan red 1 V can separate with capsorubin by temperature being controlled at 20 ℃-100 ℃ (preferred 40 ℃-80 ℃) 1sec-30min or 1min-10min.Other can include but not limited to rhodamine B (RhodanmineB) by the food additives that method and system disclosed by the invention detects, benzoic acid (being present in the dairy produce sometimes), hyposulfurous acid (hyposulfurous acid), formaldehyde sodium (sodium formaldehyde), chrysoidine (chrysoidine G), boric acid and sodium borate, sodium thiocyanate, chrome green (Lead chrome green), alkaline bright yellow O (Basic Flavine O), industrial formaldehyde and NaOH, carbon monoxide, sodium sulphate, industrial sulphur, industrial dye, pappy shell (fructus papaveris), excessive food dye is (for example carmine, lemon yellow, lure red AC (allura red AC), sunset yellow or the like), food preservative, sweetener (saccharin sodium for example, sodium cyclohexyl sulfamate), emulsifying agent (sucrose ester of fatty acid etc.), excessive leavening agent (KAlSO ₄, NH ₄AlSO ₄Or the like), bleaching agent, sulfur fumigation (sulfersuffumigation), color stabilizer (nitrate, nitrite or the like), TiO ₂, benzoyl peroxide and KAlSO ₄In certain embodiments, before detecting melamine, protein is separated from sample with Raman scattering.Protein can precipitate from fresh milk or milk power solution or Chemical Decomposition is come out.In one example, will the suckle salt (for example NaCl) of solution and a high concentration (for example supersaturated concentration) mixes mutually and comes precipitating proteins.In another example, at acid condition acetone is added to milk solution and comes precipitating proteins.With post for example the SPE post can remove the protein of milk in the solution equally.The colourless transparent solution that obtains carries out aforesaid Raman scattering test subsequently.The removal of protein or precipitation can effectively reduce random-position scattering and the interference in the raman spectral signal, therefore can effectively strengthen the signal to noise ratio (S/N ratio) of this technology, can detect the melamine of 0.2ppm concentration in the fresh milk.

The harmful chemical that uses Raman scattering probe disclosed by the invention to detect in the food can comprise following one or more step: referring to Figure 29, at first determine to appear at the spectral signal (step 2200) harmful or unauthorized, effective composition or protein (acid amides I) in the food.As mentioned above, this can realize by carrying out the Raman scattering measurement on the Nanosurface structure that a reference solution harmful or effective constituent is applied to a light scattering detector.Wavelength and spectral characteristic (peak area, peak height, peak width and peak shape etc.) can be saved in the database of spectroanalysis instrument (150 among Fig. 6 A).Determine a threshold value for the peak area or the peak height of this spectral signal, this threshold value corresponds to a certain predetermined concentration of this chemical substance in the reference solution.In certain embodiments, calculate the signal to noise ratio (S/N ratio) of this spectrum peak.If this signal to noise ratio (S/N ratio) exceeds certain threshold value (for example 3), confirm to identify this chemical substance.

In certain embodiments, the detecting device that is used for determining spectral signal contains and is used to detect or the quantitative essentially identical nanostructured of detecting device of food chemical substance.In other words, for the detecting device that is used for determining the detecting device of spectral signal and is used to carry out the food field test, the size and dimension of their nano-pillar or nanoaperture, the spacing of nano-pillar and nanoaperture, and the material of nano-pillar and nanoaperture composition is essentially identical.For example, identical detector module can be used for two purposes.This method can guarantee the optimum matching of spectral characteristic between measure spectrum and the spectral signal.This method can also make those come from the noise minimization of the difference of different detecting devices on structure and material is formed.

Implement in the example at some, be used for determining that the Nanosurface structure of compound raman spectral signal can prepare by a test solution that comprises target compound and nano granule suspension.Initial detector surface can be a relatively flat.Test solution is applied to detector surface.After evaporation or the drying, one deck is adsorbed with the nanoparticle deposition of target compound molecule on detector surface, is used to determine the Raman scattering measurement of Raman signal.Except target compound was substituted by a food samples solution or patient's body fluid, identical program was followed in the detection of material in food composition or the patient's body fluid.In order to improve assay sensitivity and to reduce noise, the identical nano particle and identical solvent of preferred use in Raman signal test and open-air material detect.In other words, be used for determining that the Size Distribution of raman spectral signal and the open-air nano particle that detects and material composition are basic identical.

At first obtain food samples (step 2210 Figure 29) from a food.In view of the high sensitivity of disclosed Raman scattering detecting device, the amount of food samples solution can be quite little.For example, the amount of food samples solution can be in the scope of 100pl-1ml.The example of food samples includes but not limited to dairy products, candy, beverage, fruit juice, wine, meat, aquatic products (for example fish, shrimp etc.), tealeaves, fresh or canning vegetables, fruit, grain, cereal, cornflakes, animal, aquatic products and poultry feed or potato block, or the like.Food samples is produced or is dissolved in the solution, changes a detecting device (step 2220) that comprises the Nanosurface structure then over to.Molecule in the food samples solution is adsorbed on the Nanosurface structure.With laser beam irradiation Nanosurface structure be adsorbed to the structural molecule of Nanosurface (step 2230).Collection is through Nanosurface structure and the light (step 2240) that is adsorbed to the structural molecular scattering of Nanosurface.Nano particle can comprise mean grain size be 2-100nm contain particles such as argent Ag, golden Au.

Obtain Raman spectrum (step 2250) from scattered light.One or more spectral signals in the identification spectrum to measure harmful or illegal adjuvant and composition, are perhaps verified the existence and the concentration (step 2260) of effective constituent.Harmful or the illegal adjuvant or the example of composition include but not limited to the compound in the common fertilizer, herbicide, pesticide, insecticide, microbiotic, hormone, heavy metal, toxic material, hazardous chemical and antiseptic, melamine for example, honey element (sodium cyclohexylsulfamate), sucrose, starch, nitrite, nitrate, sulfide (for example NaS), Sudan red 1, II, III and IV, malachite green, formaldehyde, acephatemet, orthene, DDT, DDV, the malathion, fenifrothion, carbofuran (carbofuran), Talon (brodifacoum), tetramethylene two sulfone tetramines, sodium fluoroacetate, Fluorakil 100, chloradion (chlorphacinone), Duocide, Didion, amitraz, Azodrin, thimet, disulfoton, phosmet, parathion, Entex, phosphamidon, basudin, Aldicarb, metrifonate, drinox, Bentazon herbicide, decis, cypermethrin, parathion-methyl, phosmet, nitrofuran (for example furazolidone), Rogor, chloromycetin, duomycin, Ciprofloxacin, clenbuterol hydrochloride, Enrofloxacin, phthalate bioxin, heavy metal in the water (includes but not limited to contain Pd, Cd, Hg, As, Cr, or the compound of Cu), prussiate (KCN for example, NaCN), perchlorate, sulfate, or the like.The wavelength of correlation spectrum signal and feature are special for each detected compound and amount thereof in the Raman spectrum, as above to the description of Figure 25 A-28.One spectral signal can comprise a spectrum peak.When this spectrum peak exceeded certain threshold value, this spectral signal was identified, and described threshold value can pre-determine by the reference solution that analysis contains this compound, as mentioned above.For example, this spectrum peak with respect to the signal to noise ratio (S/N ratio) of noise background greater than determining to identify this spectral signal at 3 o'clock.

Should be noted that Figure 29 and Fig. 8 are consistent, can add the one or more steps among Fig. 8 in the step of Figure 24, comprise and utilize the sample solution that contains nano particle.

Utilization is based on the industrial processes control of the spectral detection of nanostructured

Light scattering probe disclosed by the invention and material detection method are equally applicable to the quality assurance in the industrial processes and produce and regulate control.Referring to Figure 30, manufacturing system 3000 comprises a production system 3010, quality assurance system 3050 and production run control assembly 3090.Production system 3010 can comprise that selectable regional 3020, one zones 3025 and that produce final products that receive and prepare raw-material regional 3015, one or more generation inter-level (or secondary product) transport the transport zone 3030 of final products.Should be noted that industrial products for example can produce to be permitted different ways by medicine, food, beverage and wine.The composition of shown production system 3010 is an example and be not to be used for the limit production system among Figure 30.Quality assurance system 3050 can comprise a zone 3060 of preparing sample, and it comprises, for example is diluted in the sample solution producing composition.Quality assurance system 3050 also comprises light scattering device 3065, spectrometer 3070, spectroanalysis instrument 3075 and controller 3080.In some cases, quality assurance system 3050 and production run control assembly 3090 can unify to be quality assurance and production control system.

The starting material that milk powder is produced for example, can comprise the fresh milk that transport the cattle farm.For pharmaceutical production, starting material and inter-level can comprise calcium pantothenate (Calcium pantothenate), caseinate (Crospovidone) or casein sodium (sodium caseinate), Derifil sodium salt (Chlorophyllin coppercomplex sodium), emulsification oatmeal (Colloidal oatmeal), copolyvidone (Copovidone), crospovidone (Crospovidone), dihydroxyaluminum aminoacetate (Dihydroxyaluminumaminoacetate), gelatin (Gelatin), hyperglycemic factor (Glucagon), guar gum (Guargum), hyaluronidase (Hyaluronidase), imidazolidinyl urea (Imidurea), lactose (Lactose), melphalan (Melphalan), polyvinylpyrrolidone (Povidone), polyvinylpyrrolidone-iodine (Povidone-Iodine), protamine sulfate (Protamine sulfate), injection protein hydrolysate (powder), tarine (Taurine), thioguanine (Thioguanine), urea (Urea), wheat bran (Wheat bran), zeins (Zein), amino acid (comprises 4-hydroxyproline (4-Hydroxy Proline), alanine (Alanine), arginine list hydrochloric acid (Arginine mono-HCl), asparagine (Asparagine), aspartic acid (Aspatic Acid), halfcystine (Cysteine), cystine (Cystine), glutamic acid (Glutamic Acid), glutamine (Glutamine), glycocoll (Clycine), histidine hydrochloric acid (Histidine HCl), isoleucine (Isoleucine), leucine (Leucine), lysine hydrochloric acid (Lysine HCl), methionine (Methionine), phenylalanine (Phenylalaine), proline (Proline), serine (Serine), threonine (Threonine), tryptophane (Tryptophan), tyrosine (Tyrosine), valine (Valine)), vitamin (includes but not limited to the B family vitamin, vitamin E), or the like.Industrial medicine can comprise vitamin, growth hormone, or the medicine of treatment or prevention of asthma, Alzheimer's, Parkinson's disease, arthritis, cancer, angiocardiopathy, influenza, SARS, leukaemia, diabetes or acquired immune deficiency syndrome (AIDS).

In view of sanitarian importance, national governments usually all strict regulations in medicine, food, the beverage etc. various objectionable impuritiess to greatest extent admissible.For example, the regulation of Ministry of Health of the People's Republic of China in 2008, dairy produce comprises that the highest level of melamine in milk, milk powder, the ice cream etc. will be lower than 2.5ppm, will be lower than 1ppm in the babies ' formula milk powder.2009, FDA (FDA) delivered and has prevented drug ingedient by the regulation that melamine pollutes, and required that the melamine level is lower than 2.5ppm in starting material, secondary product and the final products.Be listed in and comprised adenine by the drug ingedient that melamine pollutes in the FDA policy paper, albumin, derive from the amino acid of casein protein hydrolysate, ammonium salt, calcium pantothenate, caseinate or casein sodium, the Derifil sodium salt, the emulsification oatmeal, copolyvidone, dihydroxyaluminum aminoacetate, gelatin, hyperglycemic factor, guar gum, hyaluronidase, imidazolidinyl urea, lactose, melphalan, polyvinylpyrrolidone, polyvinylpyrrolidone-iodine, protamine sulfate, the injection protein hydrolysate, tarine, thioguanine, urea, wheat bran or zeins.Other may be comprised amino acid (AA) by the drug ingedient that melamine pollutes, 4-hydroxyproline, alanine, arginine list hydrochloric acid, asparagine, aspartic acid, halfcystine, cystine, glutamic acid, glutamine, glycocoll, histidine hydrochloric acid, isoleucine, leucine, lysine hydrochloric acid, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, valine and urea.These drug ingedients through be often used as pharmaceutical production or inter-level.

Other detrimental substance or the biochemical substances of monitoring in the industrial processes can comprise melamine, and the melamine compound is melamine cyanurate for example, nitrite, nitrate, other nitrogen-containing compound, honey element, sodium cyclohexylsulfamate, sucrose, starch, nitrite, nitrate, sulfide, Sudan red 1, II, III and IV, malachite green, acephatemet, orthene, DDT, DDV, the malathion, fenifrothion, carbofuran, Talon, tetramethylene two sulfone tetramines, sodium fluoroacetate, Fluorakil 100, chloradion, Duocide, Didion, amitraz, Azodrin, thimet, disulfoton, phosmet, parathion, Entex, phosphamidon, basudin, Aldicarb, metrifonate, drinox, Bentazon herbicide, decis, cypermethrin, parathion-methyl, phosmet, Rogor, nitrofuran, furazolidone, chloromycetin, duomycin, Ciprofloxacin, clenbuterol hydrochloride, Enrofloxacin, rhodamine B, benzoic acid (in dairy produce, finding sometimes), hydrosulfurous acid, formaldehyde sodium, formaldehyde, phthalate ， bioxin, contain Pd in the water, Cd, Hg, As, the compound of Cr or Cu, prussiate, perchlorate, sulfate, chrysoidine, boric acid and borax, sodium thiocyanate, chrome green, alkaline bright yellow O, industrial formaldehyde and NaOH, carbon monoxide, sodium sulphate, industrial sulphur, industrial dye, pappy shell, excessive food dye is (for example carmine, lemon yellow, Allura Red AC, sunset yellow etc.), food preservative, sweetener (saccharin sodium for example, honey element), emulsifying agent (sucrose fatty acid ester etc.), excessive leavening agent (KAlSO ₄, NH ₄AlSO ₄Deng), bleaching agent, sulfur fumigation, color stabilizer (nitrate, nitrite etc.), TiO ₂And benzoyl peroxide.Referring to Figure 30 and 31, for example find one or more spectral signals (step 3100) in the Raman spectrum of melamine in objectionable impurities.Can to be governments limit for example use in dairy products and the medicine at a certain industrial goods described objectionable impurities.One or more starting material, inter-level, final products and secondary product in the production run can be monitored by quality assurance system 3050.For example, be restricted objectionable impurities in food (particularly dairy products) at Chinese melamine or melamine cyanurate.The spectral signal of melamine for example spectrum peak can be at the 678cm of spectral region ^-1, 698cm ^-1Or 710cm ^-1, or 1648cm ^-1Near measure (as above about Figure 25 A-28 associated description).In another example, urea is a kind of common raw materials of drug manufacture.Urea is received by production system 3010 as a kind of solid powder material.3015 small samples that may contain the urea of objectionable impurities are gathered in the zone, deliver to sample then and prepare zone 3060.The pressed powder of urea is dissolved in the aqueous solution, and for example deionized water contains water-acetonitrile, aqueous methanol, or contain acetate, methanoic acid trifluoro acetate, ammonium acetate, acetonitrile or methanol in water (step 3110).Similarly, manufactured materials can obtain (step 3110) from zone 3020 (inter-levels) or zone 3025 (final products).

Since the many manufactured materials for example principal ingredient of urea may cause tangible background Raman scattering, this shows as noise in Raman spectrum, to manufactured materials for example the urea powder to carry out suitable dilution very important.In order to improve signal to noise ratio (S/N ratio), identify the spectral signal in the Raman spectrum, urea sample can be diluted 10 times, 50 times, 100 times or higher, suppressing the interference and the raman spectral characteristics thereof of urea, thereby can identify the spectral signal of the objectionable impurities that may exist.

The perparation of specimen of dilution comprises main industrial components and the objectionable impurities that may comprise, and then is introduced into a Nanosurface (step 3120), and Nanosurface can strengthen the sensitivity of Raman scattering.As mentioned above, this Nanosurface can be provided by nano particle, that is to say, is present in the sample solution with the form of suspending liquid.As above Fig. 7 and 8 associated description, nano particle can be by metal material (for example Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt and their alloy), oxide material (for example titania, silicon dioxide, zinc paste etc.), silicon and polymeric material form.Manufactured materials is introduced in the solution that contains nano particle, allows on the surface of molecular adsorption nano particle of potential objectionable impurities.

Nanosurface also can be provided by the nanostructured (for example nano-pillar or nanoaperture) in detector surface.The nanostructured of detector surface to small part comprises metal material.Contain the sample solution of producing composition (for example urea) and potentially harmful substance and be introduced in the nanostructured of detector surface, the molecule of potentially harmful substance is adsorbed on the surface of this nanostructured (step 3120).

In laser instrument scattering unit 3065, comprise the sample solution of nano particle subsequently, or shine the detecting device (step 3130) that has the Nanosurface structure that scribbles sample solution with a laser beam irradiation.Then gather the scattered light (step 3140) of potentially harmful substance and Nanosurface; Obtain Raman spectrum (step 3150) by spectrometer 3070 and spectroanalysis instrument 3075.In Raman spectrum, search the spectral signal (step 3160) of objectionable impurities with spectroanalysis instrument 3075.

If do not find the spectral signal of objectionable impurities (for example melamine) in Raman spectrum, this manufactured materials is qualified so, production run can go on (step 3170).If found the spectral signal of one or more objectionable impuritiess (for example melamine) in Raman spectrum, spectroanalysis instrument 3075 can be measured the concentration (step 3180) of this objectionable impurities so.If the concentration of objectionable impurities is lower than allowable concentration, starting material (for example urea) are qualified so.Follow-up production run can be carried out (step 3190).If the concentration of this objectionable impurities is higher than maximum acceptable concentration (for example consistent with the effective concentration 2.5ppm in drug ingedient of U.S. FDA regulation), controller 3080 sends warning messages to production run control assembly 3090 so, and production run control assembly 3090 these starting material of refusal also prevent that it from continuing to use (step 3190) in process of production.

An advantage of method and system disclosed by the invention is the detection sensitivity of microscratch quantity of material very high.Certain content of harmful often is the low tolerance range of statutory regulation in these industrial processes, for example the maximum level of 100ppm, 50ppm, 10ppm or 2.5ppm in solid sample.For example, U.S. FDA requires the middle melamine of starting material (for example urea powder) should be lower than 2.5ppm.With 1: 100 dilution urea powder, the maximum acceptable concentration of melamine was 25ppb in the sample solution.Usually, conventional Raman scattering technology can detect the material of about 1000ppm concentration, and method and system disclosed by the invention is proved the objectionable impurities (for example melamine) that can detect 1ppb in the sample solution even lower concentration, than sensitive high several orders of magnitude of classic method.Therefore, method and system disclosed by the invention provides a kind of and can satisfy business and government about the more strong of objectionable impurities relevant regulations in the manufactured materials and in unavailable detection means in the past.Should be noted that the described process of Figure 31 do not get rid of the Raman optical spectrum method that does not utilize Nanosurface to come recognition material.For example, do not utilize the Raman optical spectrum method of Nanosurface can be used for determining in chemical substance and the biochemical substances spectral signal and in industrial processes the material in examination starting material, inter-level, final products and the secondary product.

Although invention has been described by preferred enforcement example, should be understood that so openly can not be understood that limitation of the present invention.For a person skilled in the art, above-mentionedly openly make various conversion and to revise all be conspicuous.Therefore, in the spirit and scope of essence of the present invention, appended claims should be interpreted as having contained all conversion and modification.For example, the detectable material of system and method disclosed by the invention is not limited to those chemical substances recited above and biochemical substances example.Other material comprises medicine and radiomaterial.The Nanosurface structure that is applicable to system and method disclosed by the invention equally also is not limited to described example.The Nanosurface structure can comprise nano-pillar, nanoaperture and other Nanosurface structures, and the nano particle that is deposited on detector surface.Communication between probe assembly and the control center can be in conjunction with utilizing wireless and the wire communication mode.Radio communication can utilize agreement and the standard outside above-mentioned to realize.The data of spectrum can be analyzed with the spectral method except that Raman spectrum.The nanostructured of detector surface is not limited to example recited above to strengthen scattered light signal.In addition, probe assembly also can be installed on the fixed object, rather than must be installed on vehicle and the flyer.

Claims (65)

1. manufacturing system comprises:

One utilizes at least a starting material to produce the product production system of product; With

One quality assurance and production control system, obtain manufactured materials from product production system, wherein said manufactured materials comprises starting material, product and intermediate materials or secondary product, quality assurance and production control system are incorporated into a sample solution with described manufactured materials, in gas or the gasoloid, allow sample solution, this manufactured materials contacts with Nanosurface in gas or the gasoloid, with this manufactured materials of a laser beam irradiation and this Nanosurface, laser beam is produced a scattered light by this manufactured materials and this Nanosurface scattering, utilize a spectrometer to obtain a Raman spectrum from this scattered light, search the spectral signal of an objectionable impurities in the predetermined spectral range in this Raman spectrum, detect and whether have this objectionable impurities in this manufactured materials, if in this Raman spectrum, do not find this special spectrum signal, think that then this manufactured materials is qualified, if in this Raman spectrum, found this spectral signal, then detect the concentration of objectionable impurities in this manufactured materials, if this concentration is lower than a predetermined permission limit, then this manufactured materials is qualified, if the concentration of objectionable impurities has exceeded a permission limit of being scheduled in this manufactured materials, then refuse this manufactured materials.

2. manufacturing system as claimed in claim 1 is characterized in that the concentration of objectionable impurities is lower than 10ppm in the described manufactured materials.

3. manufacturing system as claimed in claim 1 is characterized in that, described objectionable impurities comprises melamine, melamine cyanurate, melamine compound or nitrogen-containing compound.

4. manufacturing system as claimed in claim 1 is characterized in that described objectionable impurities comprises honey element, sodium cyclohexylsulfamate, nitrite, nitrate, Sudan red 1, II, III and IV, malachite green, acephatemet, orthene, DDT, DDV, the malathion, fenifrothion, decis, cypermethrin, parathion-methyl, phosmet, Rogor, nitrofuran, furazolidone, chloromycetin, duomycin, Ciprofloxacin, clenbuterol hydrochloride, Enrofloxacin, furans pellet, Talon, tetramethylene two sulfone tetramines, sodium fluoroacetate, Fluorakil 100, chloradion, Duocide, Didion, amitraz, Azodrin, thimet, disulfoton, phosmet, parathion, Entex, phosphamidon, basudin, Aldicarb, metrifonate, drinox, Bentazon herbicide, duomycin, clenbuterol hydrochloride, rhodamine B, benzoic acid, hydrosulfurous acid, formaldehyde sodium, phthalate ， bioxin contains Pd, Cd, Hg, As, the compound of Cr or Cu, prussiate, perchlorate, sulfate, chrysoidine, boric acid, borax, sodium thiocyanate, chrome green, alkaline bright yellow O, NaOH, carbon monoxide, sodium sulphate, industrial sulphur, industrial dye, pappy shell, saccharin sodium, sucrose fatty acid ester, KAlSO ₄, NH ₄AlSO ₄, sulfur fumigation, TiO ₂Or benzoyl peroxide.

5. manufacturing system as claimed in claim 1 is characterized in that described manufactured materials comprises peptide, amino acid, proteinaceous material, adenine, albumin derives from the amino acid of casein protein hydrolysate, ammonium salt, calcium pantothenate, caseinate or casein sodium, Derifil sodium salt, the emulsification oatmeal, copolyvidone, dihydroxyaluminum aminoacetate, gelatin, hyperglycemic factor, guar gum, hyaluronidase, imidazolidinyl urea lactose, melphalan, polyvinylpyrrolidone, polyvinylpyrrolidone-iodine, protamine sulfate, the injection protolysate, tarine, thioguanine, urea, wheat bran or zeins.

6. manufacturing system as claimed in claim 1, it is characterized in that, if described manufactured materials contains hazardous substance, described quality assurance and production control system allow the molecular adsorption of described objectionable impurities to Nanosurface, and this is adsorbed in the objectionable impurities molecular scattering laser beam on the Nanosurface.

7. manufacturing system as claimed in claim 1 is characterized in that described sample solution comprises nano particle, and this nano particle size at least in one direction is less than 1,000 nanometer, and this nano particle has Nanosurface.

8. manufacturing system as claimed in claim 7 is characterized in that described nano particle comprises magnetic or ferromagnetic material, or a kind of material that is selected from metal, metal alloy, oxide material, silicon, polymeric material or their combination.

9. manufacturing system as claimed in claim 7, it is characterized in that described nano particle comprises one or more in the following material: titania, silicon dioxide, zinc paste, aluminium, silver, gold, copper, iron, cobalt, nickel, chromium, zinc, tin, palladium, platinum and their combination.

10. manufacturing system as claimed in claim 7 is characterized in that, described nano particle range of size at least in one direction is 5nm-500nm.

11. manufacturing system as claimed in claim 1, it is characterized in that, described sample solution contains the carbon of nanotube, Fu Leti, holder shape, nanometer bud or nanometer flower form, and wherein said Nanosurface is positioned on the carbon of nanotube, Fu Leti, holder shape, nanometer bud or nanometer flower form.

12. manufacturing system as claimed in claim 1 is characterized in that, described quality assurance and production control system are guided to sample solution on the Nanosurface of the nanostructured on the detecting device, and wherein said nanostructured comprises a conductive material.

13. manufacturing system as claimed in claim 12, it is characterized in that, described detecting device comprises a substrate, and wherein said nanostructured comprises a plurality of suprabasil cylinders or a plurality of in the substrate mesoporosity that are positioned at, and wherein the average neighbor distance between these a plurality of cylinders or the hole is 10nm-1000nm.

14. manufacturing system as claimed in claim 1 is characterized in that, described spectral signal comprises that at least one is arranged near the spectrum peak of Raman spectrum predetermined wavelength.

15. manufacturing system as claimed in claim 14, it is characterized in that, described quality assurance and production control system are used for determining whether the spectrum peak of Raman spectrum or the signal to noise ratio (S/N ratio) of this spectrum peak exceed a predetermined threshold, if this spectrum peak or its signal to noise ratio (S/N ratio) have exceeded this predetermined threshold, then confirm to identify this objectionable impurities.

16. manufacturing system as claimed in claim 14 is characterized in that, described quality assurance and production control system utilize the area of the spectrum peak in the described spectral signal or the concentration of strength detection objectionable impurities.

17. manufacturing system as claimed in claim 14 is characterized in that, described objectionable impurities comprises melamine or melamine cyanurate, and wherein said spectral signal comprises 678cm ^-1, 698cm ^-1Or 710cm ^-1Near, perhaps 1648cm ^-1Near one or more spectrum peaks.

18. manufacturing system as claimed in claim 1, it is characterized in that, described product is a medicine, comprise vitamin, growth hormone, the medicine of treatment or prevention of asthma, Alzheimer's, Parkinson's disease, arthritis, cancer, angiocardiopathy, SARS, influenza, leukaemia, diabetes or acquired immune deficiency syndrome (AIDS).

19. manufacturing system as claimed in claim 1, it is characterized in that, described product is a food, comprises dairy products, candy, beverage, fruit juice, wine, meat, seafood, tealeaves, vegetables fresh or canning, fruit, grain, cereal, cornflakes, potato block, animal feed or protein-contg food.

20. the method that quality assurance is provided in industrial processes comprises:

Obtain a manufactured materials from these industrial processes;

Allow this manufactured materials contact, the objectionable impurities in the manufactured materials is adsorbed onto on this Nanosurface with a Nanosurface;

Utilize a spectrometer to obtain a Raman spectrum from this manufactured materials and this Nanosurface;

Utilize a spectroanalysis instrument to search objectionable impurities spectral signal in the predetermined spectral range in Raman spectrum, thereby measure whether there is this objectionable impurities in this manufactured materials;

If in this Raman spectrum, have this spectral signal really, then measure the concentration of this objectionable impurities in manufactured materials; With

If this concentration exceeds a predetermined limit that allows, then this manufactured materials is got rid of from these industrial processes.

21. the method that quality assurance is provided in industrial processes comprises:

Obtain a manufactured materials from these industrial processes;

This manufactured materials is introduced a sample solution;

Allow the manufactured materials in the sample solution contact with Nanosurface;

With this manufactured materials of a laser beam irradiation and this Nanosurface;

This manufactured materials and this this laser beam of Nanosurface scattering produce a scattered light;

Utilize a spectroanalysis instrument to obtain a Raman spectrum from this scattered light;

Search the spectral signal of an objectionable impurities in the predetermined spectral range in this Raman spectrum, thereby measure whether there is this objectionable impurities in this manufactured materials;

If do not find this spectral signal in this Raman spectrum, then this manufactured materials is qualified;

If there is this spectral signal in this Raman spectrum, then detect the concentration of objectionable impurities in this manufactured materials;

If the concentration of objectionable impurities is lower than a predetermined limit that allows in this manufactured materials, and is then that this manufactured materials is qualified;

If the concentration of objectionable impurities exceeds a predetermined limit that allows in this manufactured materials, then this manufactured materials is got rid of from these industrial processes.

22. method as claimed in claim 21 is characterized in that, described objectionable impurities comprises melamine, melamine cyanurate, melamine compound or nitrogen-containing compound.

23. method as claimed in claim 21 is characterized in that, described objectionable impurities comprises honey element, sodium cyclohexylsulfamate, nitrite, nitrate, Sudan red 1, II, III and IV, malachite green, acephatemet, orthene, DDT, DDV, the malathion, fenifrothion, decis, cypermethrin, parathion-methyl, phosmet, Rogor, nitrofuran, furazolidone, chloromycetin, duomycin, Ciprofloxacin, clenbuterol hydrochloride, Enrofloxacin, furans pellet, Talon, tetramethylene two sulfone tetramines, sodium fluoroacetate, Fluorakil 100, chloradion, Duocide, Didion, amitraz, Azodrin, thimet, disulfoton, phosmet, parathion, Entex, phosphamidon, basudin, Aldicarb, metrifonate, drinox, Bentazon herbicide, duomycin, clenbuterol hydrochloride, rhodamine B, benzoic acid, hydrosulfurous acid, formaldehyde sodium as the ， bioxin, contains Pd, Cd, Hg, As, the compound of Cr or Cu, prussiate, perchlorate, sulfate, chrysoidine, boric acid, borax, sodium thiocyanate, chrome green, alkaline bright yellow O, NaOH, carbon monoxide, sodium sulphate, industrial sulphur, industrial dye, pappy shell, saccharin sodium, sucrose fatty acid ester, KAlSO ₄, NH ₄AlSO ₄, sulfur fumigation, TiO ₂Or benzoyl peroxide.

24. method as claimed in claim 21 is characterized in that, described manufactured materials comprises adenine, albumin derives from the amino acid of casein protein hydrolysate, ammonium salt, calcium pantothenate, caseinate or casein sodium, Derifil sodium salt, the emulsification oatmeal, copolyvidone, dihydroxyaluminum aminoacetate, gelatin, hyperglycemic factor, guar gum, hyaluronidase, imidazolidinyl urea lactose, melphalan, polyvinylpyrrolidone, polyvinylpyrrolidone-iodine, protamine sulfate, injection protolysate, tarine, thioguanine, urea, wheat bran or zeins.

25. method as claimed in claim 21 is characterized in that, this method further comprises allows the molecular adsorption of objectionable impurities to Nanosurface, is adsorbed to the objectionable impurities molecular scattering laser beam of Nanosurface.

26. method as claimed in claim 21 is characterized in that, described sample solution comprises nano particle, and this nano particle size at least in one direction is less than 1,000 nanometer, and this nano particle has Nanosurface.

27. method as claimed in claim 26 is characterized in that, described nano particle comprises magnetic or ferromagnetic material, or a kind of material that is selected from metal, metal alloy, oxide material, silicon, polymeric material and their combination.

28. method as claimed in claim 27, it is characterized in that described nano particle comprises one or more in the following material: titania, silicon dioxide, zinc paste, aluminium, silver, gold, copper, iron, cobalt, nickel, chromium, zinc, tin, palladium, platinum and their combination.

29. method as claimed in claim 26 is characterized in that, described nano particle range of size at least in one direction is 5nm-500nm.

30. method as claimed in claim 21, it is characterized in that, described sample solution contains the carbon of nanotube, Fu Leti, holder shape, nanometer bud or nanometer flower form, and wherein said Nanosurface is positioned on the carbon of this nanotube, Fu Leti, holder shape, nanometer bud or nanometer flower form.

31. method as claimed in claim 21 is characterized in that, this method further comprises to be guided to sample solution on the Nanosurface of the nanostructured on the detecting device, and wherein said nanostructured comprises a conductive material.

32. method as claimed in claim 31 is characterized in that, described detecting device comprises a substrate, and wherein said nanostructured comprises a plurality of holes in suprabasil a plurality of cylinder or the substrate.

33. method as claimed in claim 32 is characterized in that, the average neighbor distance of described a plurality of cylinders or a plurality of holes is 10nm-1000nm.

34. method as claimed in claim 21 is characterized in that, this method further comprises to be introduced an ionic material in the sample solution, and wherein this ionic material contains and is selected from Na ⁺, K ⁺, Li ⁺, Ca ²⁺, Ba ²⁺, Sr ²⁺, Mg ²⁺, Mn ²⁺, Al ³⁺, Zn ²⁺, Sn ²⁺, Sn ⁴⁺, F ^-, Cl ^-, Br ^-And I ^-Ion.

35. method as claimed in claim 21 is characterized in that, described spectral signal comprises a near spectrum peak the predetermined wavelength in Raman spectrum at least.

36. method as claimed in claim 35 is characterized in that, described identification step comprises:

Area, intensity or the signal to noise ratio (S/N ratio) of measuring the spectrum peak in the described Raman spectrum whether have exceeded a pre-threshold value of measuring; With

If exceeding this predetermined threshold, this spectrum peak or this signal to noise ratio (S/N ratio) identify this objectionable impurities.

37. method as claimed in claim 35 is characterized in that, described objectionable impurities comprises melamine or melamine cyanurate, and wherein said spectral signal comprises 678cm ^-1, 698cm ^-1Or 710cm ^-1Near, perhaps 1648cm ^-1Near one or more spectrum peaks.

38. method as claimed in claim 21 is characterized in that, described industrial processes are used to make a kind of medicine, and wherein said manufactured materials is the final products that a kind of starting material, a kind of inter-level, a kind of secondary product or this medicine are made.

39. method as claimed in claim 38, it is characterized in that, described medicine comprises vitamin, growth hormone, the medicine of treatment or prevention of asthma, Alzheimer's, Parkinson's disease, arthritis, cancer, angiocardiopathy, SARS, influenza, leukaemia, diabetes or acquired immune deficiency syndrome (AIDS).

40. method as claimed in claim 21, it is characterized in that, described industrial processes are used to make food, and described food comprises dairy products, candy, beverage, fruit juice, wine, meat, seafood, tealeaves, vegetables fresh or canning, fruit, grain, cereal, cornflakes, potato block, animal feed or protein-contg food.

41. method as claimed in claim 21 is characterized in that, the concentration of objectionable impurities is lower than 10ppm in the described manufactured materials.

42. method as claimed in claim 21 is characterized in that, the concentration of objectionable impurities is lower than 1ppm in the described sample solution.

43. a detector network system that is used to detect chemical substance or biochemical substances comprises:

A plurality of probe assemblies, each probe assembly comprises:

One has the detecting device of nanostructured surface, and wherein this nanostructured surface is used to adsorb near this detecting device and the molecule of the specimen material of being captured by this detecting device;

One is used for the laser instrument that the emission of lasering beam irradiation is adsorbed to the molecule of described nanostructured surface;

With

One is used to obtain to be adsorbed to the spectrometer of spectroscopic data of scattered light of the molecule of described nanostructured surface; With

One control center comprises:

One is used to store the computer memory of the one or more spectral signals relevant with a chemical substance or biochemical; With

One and the spectroanalysis instrument that interrelates of computer memory, wherein this spectroanalysis instrument is used to detect spectroscopic data, search and be kept at the spectral signal that at least one spectral signal in the computer memory is complementary, thereby identify chemical substance or biochemical relevant in the specimen material with this spectral signal.

44. detector network as claimed in claim 43 system, it is characterized in that, have at least one further to comprise in described a plurality of probe assembly: to be used to gather the scattered light of the molecule that is adsorbed in described nanostructured surface, and this transmission of stray light to be given the collection optical devices of described spectrometer.

45. detector network as claimed in claim 43 system is characterized in that, the spectroscopic data from described probe assembly to control center is by cable network transmission.

46. detector network as claimed in claim 43 system, it is characterized in that, described control center further comprises an alarm and a responding system that interrelates with described spectroanalysis instrument, and wherein said alarm and responding system are used for the signal that gives the alarm when the chemical substance that identifies or biochemical are an objectionable impurities.

47. detector network as claimed in claim 43 system, it is characterized in that, this detector network system further comprise one with described probe assembly in first antenna that interrelates, this first antenna is used to launch first radio signal that comprises spectroscopic data; Control center comprises:

One receives second antenna of first radio signal; With

One wireless router that interrelates with described spectroanalysis instrument, this wireless router extracts spectroscopic data from first radio signal.

48. detector network as claimed in claim 47 system, it is characterized in that, described control center further comprises alarm and a responding system and a described wireless router that interrelates with described spectroanalysis instrument, described alarm and the responding system signal that gives the alarm when the chemical substance that identifies or biochemical are an objectionable impurities, this wireless router emission comprises second radio signal of this alarm signal.

49. detector network as claimed in claim 43 system is characterized in that the nano particle that is provided by a solution is provided the nanostructured surface on the described detecting device.

50. detector network as claimed in claim 49 system is characterized in that described substrate comprises a basic even curface that is provided with nano particle on it.

51. detector network as claimed in claim 43 system; it is characterized in that described a plurality of probe assemblies are installed near buildings, airport, customs, goods or baggage conveyor system, doctor or health consultation person office, check-point, harbour, vehicle, vessel, submarine, aircraft, train, subway, industrial site, holiday resort, shopping mall, research laboratory, school or place, water source or its.

52. detector network as claimed in claim 43 system is characterized in that described spectroscopic data comprises a Raman spectral information.

53. the detector network system as claim 43 is characterized in that, described specimen material extracts from food.

54. detector network as claimed in claim 43 system is characterized in that described specimen material comprises the body fluid from the human or animal, this method further comprises: based on the diagnosis of the spectral signal in Raman spectrum human or animal's disease.

55. detector network as claimed in claim 43 system is characterized in that described a plurality of probe assemblies are used for security monitoring, wherein the detecting device specimen material of capturing comprises chemistry or chemical and biological weapons, explosive, fire goods, arcotic or radiomaterial.

56. the detector network system of specific detection chemical substance or biochemical comprises:

Be arranged on a plurality of probe assemblies of a plurality of positions, each probe assembly comprises:

One detecting device is used to receive near this detecting device and the molecule of the specimen material of being captured by this detecting device;

One laser instrument is used for emission of lasering beam and shines this molecule; With

One spectrometer is used for from the scattered light acquisition spectroscopic data of the molecule of this detecting device; With a control center, comprising:

One computer memory is used to store the one or more spectral signals relevant with a chemical substance or biochemical; With

One and the spectroanalysis instrument that interrelates of computer memory, wherein this spectroanalysis instrument is used to detect spectroscopic data, search and be kept at the spectral signal that at least one spectral signal in the computer memory is complementary, thereby identify chemical substance or biochemical relevant in the specimen material with this spectral signal; With

One processor, this processor utilizes from two or more probe assemblies and obtains spectroscopic data, and the position calculation of these two or more probe assemblies goes out the position of specimen material at special time.

57. detector network as claimed in claim 56 system, it is characterized in that, this detector network system further comprises near at least one the camera in the described probe assembly, the image of this camera record is judged through described processor, identifies the suspect's goods that has described specimen material source.

58. detector network as claimed in claim 56 system, it is characterized in that, described processor utilization obtains spectroscopic data from two or more probe assemblies, and the position finding of these two or more probe assemblies goes out the space-time distribution plan in specimen material source.

59. detector network as claimed in claim 56 system is characterized in that, the spectroscopic data from described probe assembly to control center is by a cable data line or a wired computer network transmission.

60. detector network as claimed in claim 56 system, it is characterized in that, described control center further comprises an alarm and a responding system that interrelates with described processor, wherein said alarm and the responding system signal that gives the alarm when described chemical substance or biochemical are measured as an objectionable impurities.

61. detector network as claimed in claim 56 system, it is characterized in that, this detector network system further comprise one with described probe assembly in first antenna that interrelates, this first antenna is used to launch first radio signal that comprises spectroscopic data; Control center comprises:

One receives second antenna of first radio signal; With

One and the described spectroanalysis instrument wireless router that interrelates, wireless router extracts spectroscopic data from first radio signal, when identified chemical substance or biochemical were an objectionable impurities, this wireless router emission comprised second radio signal of alarm signal.

62. detector network as claimed in claim 56 system is characterized in that, this detecting device comprises that one is used to adsorb the nanostructured surface near the specimen material molecule of this detecting device.

63. detector network as claimed in claim 56 system; it is characterized in that described a plurality of probe assemblies are installed near buildings, airport, customs, goods or baggage conveyor system, doctor or health consultation person office, hospital, check-point, harbour, vehicle, vessel, submarine, aircraft, train, subway, industrial site, holiday resort, shopping mall, research laboratory, school or place, water source or its.

64. detector network as claimed in claim 56 system is characterized in that described spectroscopic data comprises a Raman spectrum.

65. the detector network system of specific detection chemical substance or biochemical comprises:

A plurality of probe assemblies, each probe assembly comprises:

One has the detecting device of nanostructured surface, and wherein this nanostructured surface is used to adsorb near this detecting device and the molecule of the specimen material of being captured by this detecting device; With

One laser instrument is used to launch the molecule that a laser beam irradiation is adsorbed to described nanostructured surface, and the scattered light that probe assembly will be adsorbed to the molecule of described nanostructured surface passes through an Optical Fiber Transmission to a control center; With

Control center comprises:

One optical multiplexer receives from the scattered light of the molecule that is adsorbed in described nanostructured surface of a plurality of probe assemblies of a plurality of paths and exports road scattered light in these a plurality of paths;

One spectrometer is used for from one road scattered light acquisition spectroscopic data of a plurality of paths of being exported by optical multiplexer;

One computer memory is used to store the one or more spectral signals relevant with a chemical substance or biochemical; With

One and the spectroanalysis instrument that interrelates of computer memory, wherein this spectroanalysis instrument is used to detect spectroscopic data, search and be kept at the spectral signal that at least one spectral signal in the computer memory is complementary, thereby identify chemical substance or biochemical relevant in the specimen material with this spectral signal.

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