CN202614678U - Detection micro needle capable of strengthening Raman and fluorescence signals - Google Patents
Detection micro needle capable of strengthening Raman and fluorescence signals Download PDFInfo
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- CN202614678U CN202614678U CN 201120547417 CN201120547417U CN202614678U CN 202614678 U CN202614678 U CN 202614678U CN 201120547417 CN201120547417 CN 201120547417 CN 201120547417 U CN201120547417 U CN 201120547417U CN 202614678 U CN202614678 U CN 202614678U
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Abstract
The utility model discloses a detection micro needle capable of strengthening Raman and fluorescence signals and a preparation of the detection micro needle. The detection micro needle capable of strengthening the Raman and the fluorescence signals is characterized in that the preparation method is based on medical acupuncture needles. A metal nanometer layer and a high polymer material layer are covered on the surfaces of a needle body and a needle tip of a micro needle, wherein the metal nanometer material layer and the high polymer material layer are provided with functions of strengthening the Raman and the fluorescence signals. The detection micro needle structurally comprises a micro needle of surface hydrosulfuryl and amination, a metal nanometer particle layer, and the high polymer material layer. Metal nanometer particles are covered on the surface of the acupuncture needles through a covalent bond and electrostatic absorption, wherein the diameter of the metal nanometer particle ranges from 20 nanometers to 1000 nanometers. The high polymer material layer is covered on the outmost shell to protect the metal nanometer particles, and in vitro samples can be detected of the Raman and fluorescence by utilizing characteristics of the micro needle. And also minimally-invasive sampling and detections of the Raman and the fluorescence can proceed in an organism. The detection micro needle capable of strengthening the Raman and the fluorescence signals can provide rapid and ultra-sensitive detection methods for experiment researches in vivo and in vitro, a clinical diagnosis, and big sample screening.
Description
Technical field
The utility model relates to a kind of functional form and detects the micropin technical field, more specifically, has the detection micropin that strengthens Raman and fluorescence signal.
Background technology
It is more meaningful than measuring their concentration in blood to monitor the distribution in target organ of endogenous or exogenous molecules, comprises understanding physiological mechanism such as nerve signal conduction and estimating fields such as drug bioavailability such as cancer chemotherapy.Traditional original position analytical approach is because its invasive or complicated sample preparation can not be satisfied this monitoring requirement fully.Raman spectroscopy can provide based on the chemistry of molecular vibration and physical message, because need not consider the state of sample during raman detection, and temperature, physical states such as form and size are so this technology is the technology of desirable real-time in-situ monitoring bio sample.Through being designed and make, nano material can make nano material have SERS (SERS) effect; When sample concentration is low, still can obtain the higher enhancing Raman signal of intensity, so these nano materials often are used as qualitative or semiquantitative super sensitivity detection analysis tool.
Scientist just uses the target molecule in the Raman spectrum detection bodies to carry out many trials at present, remains a very big challenge but how to obtain the relevant SERS data of biopsy sample.For example; How under the situation of not damaging body and material; Implant also to take out and have the material that strengthens Raman signal, how to avoid body to having the immune response of the material production that strengthens Raman signal, and how in live body, to collect distinguishable enhancing Raman signal.In addition in the ordinary course of things, infrared laser is often as excitaton source, and it can almost zero-decremently penetrate some biological tissues, but corresponding Raman signal is difficult to penetrate these tissues.Therefore the hypodermic enhancing Raman signal that how to obtain certain depth also is a problem that can not be ignored.
In the traditional Chinese medical science, used several thousand through acupuncture needle being inserted the method that human body treats, its principal feature is the invasive in the therapeutic process, so acupuncture needle is a kind of instrument of desirable Wicresoft of the human body of coming in and going out.Here, acupuncture needle is used as the detection micropin that the carrier load has the active nano material formation discrepancy human body that strengthens Raman and fluorescence signal.In micropin gets into body or when organizing, tissue fluid can be diffused in the gap between the gold nanoshell, when micropin is pulled out, can the testing molecule in the tissue fluid be carried out.External SERS detects can avoid strengthening the decay of Raman signal in tissue, and the degree of depth of thrusting according to the detection micropin simultaneously can obtain the hypodermic enhancing Raman signal of certain depth.
The utility model content
The utility model is with the preparation main body of medical needle acupuncture needle as the detection micropin; Utilize the effect of enhancing Raman and the fluorescence signal of the metal nano material that the detector probe needle body covers to measure the Raman and the fluorescence signal of detecting probe surface biomolecule, invent a kind of detection method external and the quick Wicresoft that body is interior that can be used for.
Technical matters: the purpose of the utility model provides a kind of detection micropin that strengthens Raman and fluorescence signal that has, and has to be used in the body or the characteristics of external molecule Raman and fluoroscopic examination.
Technical scheme: the utility model adopts following technical scheme:
The described detection micropin of the utility model with enhancing Raman and fluorescence signal; Comprise: the needle handle, the needle body and the needle point that connect successively; On the surface of the needle body and needle point, be coated with the metal nano material layer; On the metal nano material layer, be coated with polymer material layer, described metal nano material particle diameter is 20-1000nm.
Beneficial effect: compared with prior art, the utlity model has following advantage:
(1) this project utilizes the nano particle of structure homogeneous to make up the nanostructured that strengthens Raman and fluorescence signal, helps obtaining the consistent nanostructured of enhancer, improves detection signal to the full extent; Through carrying out specific detection at nanoparticle surface modified different functions molecule, the specificity Wicresoft that also can be used for different molecular in the body is detected.
(2) based on the Raman enhancement effect of nanometer aggregation, set up the detection method of fast super sensitivity, do not need pre-treatments such as sample concentrates are directly analyzed, can reduce the consumption of reagent and shorten the time of detecting.
(3) characteristic that utilize to detect micropin can provide when detecting in live body Wicresoft target molecule in hypodermic depth profile information, to be that other in-vivo analysis are technological be difficult to possess for this.
Description of drawings
Fig. 1 is a kind of detection microneedle configuration synoptic diagram that strengthens Raman and fluorescence signal that has.
Fig. 2 is that a kind of detection micropin with enhancing Raman and fluorescence signal prepares synoptic diagram.
Fig. 3 is a kind of detection micropin needle body A-A cross sectional representation that strengthens Raman and fluorescence signal that has.
Fig. 4 has been the Electronic Speculum figure of metal nano material layer that detected the micropin surface adsorption.
Fig. 5 is the Electronic Speculum figure that detects the metal nano material on micropin surface.
Fig. 6 is with detecting the Raman spectrogram that micropin detects Nile blue A.
Embodiment
Embodiment 1
A kind of detection micropin with enhancing Raman and fluorescence signal, as shown in Figure 1, detect micropin and comprise: the needle handle 13, the needle body 12 and the needle point 11 that connect successively.As shown in Figure 3, on the surface of the needle body 12 and needle point 11, be coated with metal nano material layer 2, on metal nano material layer 2, be coated with polymer material layer 3.Described metal nano material particle diameter is 20-1000nm, and referring to Fig. 5, the needle body and needle surface are coated with 1-2 layer golden nanometer particle layer, and the golden nanometer particle diameter is 180nm.In the present embodiment,
Said polymer material layer is a kind of in polystyrene layer, polylactic acid layers, layer of polyurethane or the polyethylene polypropylene layer.
Said metal nano material layer can be one of following:
1) the metal nano material layer is golden nanometer particle layer, nano grain of silver sublayer, copper nano-particle layer or nano platinum particle layer;
2) the metal nano material layer is the spherical composite nano particle layer, the metal composite nano particle layer of two or more that described spherical composite nano particle layer is gold, silver, copper and platinum.
3) the metal nano material layer is the composite nano-granule sublayer of the nucleocapsid structure of sphere, and the composite nano-granule sublayer of the nucleocapsid structure of described sphere comprises galactic nucleus gold shell composite nanometer particle layer, the compound core/shell nanoparticles layer of copper nuclear gold and silver, copper nuclear gold and silver double shells nanoparticle layers.
4) the metal nano material layer is nonmetallic SiO
2Examine golden shell, silver-colored shell, copper shell, platinum shell or compound core/shell nanoparticles layer, described compound core/shell nanoparticles is the core/shell nanoparticles of two or more metal composite in gold, silver, copper and the platinum.
A kind of preparation method with the detection micropin that strengthens Raman and fluorescence signal, step is following:
Step 1) is modified a kind of group in amino, aldehyde radical, carboxyl and the hydroxyl at least at the needle body and the needle surface of micropin;
Step 2) needle body and the needle point insertion concentration with step 1 is 10
8-10
18Individual particle/liter metal nanoparticle suspending liquid in leave standstill 12-48 hour after, take out micropin and get final product;
The high molecule mass that the needle body after step 3) is handled step 2 and needle point insert in the Polymer Solution leaves standstill 1-60 after second with the liquor capacity ratio in the Polymer Solution of 0.1-10%, takes out promptly to get and detects micropin.
3 one kinds of preparations of embodiment with the detection micropin that strengthens Raman and fluorescence signal
Modify the micropin (method of modifying sulfydryl is known in this area) that sulfydryl gets functionalization at the needle body that detects micropin and needle surface, it is 1 * 10 that adjusting golden nanometer particle suspending liquid makes its concentration
8-18Individual/liter.Again the micropin of functionalization is left standstill in golden nanometer particle suspending liquid and take out after 12-48 hour.Because the sulfydryl on micropin surface and the chemical b ` of golden nanometer particle, golden nanometer particle can be adsorbed on the acupuncture needle surface, and is as shown in Figure 5, forms nanostructured 1-2 layer structure homogeneous, that enhancing Raman and fluorescence signal are arranged.Referring to Fig. 2, metal nanoparticle layer can be connected with needle surface with the needle body through groups such as sulfydryl or hydroxyls.Again the part that is coated with golden nanometer particle of micropin is inserted in the polystyrene solution of quality and volume ratio 0.1-10% and left standstill 1-60 after second, take out the room temperature placement and get final product.The polystyrene layer that forms can not rubbed off by the protective money nano particle in the process of inserting and taking out pin.
Embodiment 4 has the application of detection micropin in vitro detection---the surface-enhanced Raman signal that strengthens Raman and fluorescence signal
The surface is not immersed in the Nile blue A solution that concentration is 1 micromoles per liter through the micropin of any processing and the micropin of above-mentioned preparation simultaneously, soaks after 30 minutes and take out, washing, Raman spectrometer is measured the Raman signal on two micropin surfaces.Method therefor is known in this area, and can be used.With reference to figure 6; Curve 1 is the Raman signal of surface without the Nile blue A molecule on the micropin surface of any processing; The Raman signal of the Nile blue A molecule on the micropin surface of the above-mentioned preparation of curve 2 expressions; Can find out do not possess the function of amplifying Raman signal when micropin is unprocessed, and surface adsorption there is the micropin of metal nanoparticle layer can strengthen the Raman signal of molecule.
Embodiment 5 has the application of detection micropin in vitro detection---the detection of nucleic acids (Raman signal) that strengthens Raman and fluorescence signal
The micropin of above-mentioned preparation is immersed in 10 microlitre sulfhydrylation nucleic acid probe molecules (10 nanomoles/liter), and 4 ℃ are spent the night, the unreacted nucleic acid probe molecules of flush away.This micropin is inserted in the solution to be measured again, hybridized 5 minutes for 72 ℃, 3 times (60 ℃/4 ℃) are handled in thermal cycle again.37 ℃ add endonuclease again and handled washing, Raman spectrometer mensuration nucleic acid characteristic signal 5 minutes.Method therefor is known in this area, and can be used.
Embodiment 6 has the application of micropin in vitro detection---the Protein Detection (Raman signal) that strengthens Raman and fluorescence signal
The micropin of above-mentioned preparation is immersed in the 10 microlitre sulfhydrylation folate molecules (1 nanomole/liter), and 4 ℃ are spent the night, the unreacted folate molecule of flush away.Again this micropin is immersed in the epicyte protein extract, 37 ℃ of incubations 30 minutes, washing, Raman spectrometer is measured the characteristic signal of folacin receptor protein molecular.Method therefor is known in this area, and can be used.
Embodiment 7 has the application of detection micropin in vitro detection---the detection of nucleic acids (fluorescence signal) that strengthens Raman and fluorescence signal
With the sulfhydrylation nucleic acid probe molecules (10 nanomoles/liter) that the micropin of above-mentioned preparation soaks 10 microlitre mark fluorescent signaling molecules, 4 ℃ are spent the night, and the unreacted nucleic acid molecules of flush away is measured the signal intensity of fluorescence.This micropin is inserted in the solution to be measured again, hybridized 5 minutes for 72 ℃, 3 times (60 ℃/4 ℃) are handled in thermal cycle again.37 ℃ add single-chain nucleic acid hydrolytic enzyme processing 5 minutes again, wash, and measure the signal intensity of fluorescence once more, calculate the decay of fluorescence signal, obtain the amount of bind nucleic acid.Method therefor is known in this area, and can be used.
Embodiment 8 has application---the tissue fluid composition detection of the detection micropin that strengthens Raman and fluorescence signal in detecting in vivo
The micropin of above-mentioned preparation is directly inserted in the tissue that needs to detect, and be inserted into the degree of depth that needs detection.Be detained 5-30 minute, the taking-up micropin directly detects the Raman collection of illustrative plates of the tissue fluid on micropin surface with Raman spectrometer, and the Raman collection of illustrative plates with normal tissues liquid compares then, and the kind of molecule in the tissue fluid of pin front and back and the variation of quantity are executed in analysis.Method therefor is known in this area, and can be used.
Embodiment 9 has application---the tissue fluid glucose detection of the detection micropin that strengthens Raman and fluorescence signal in detecting in vivo
The 3-sulfydryl phenyl boric acid solution that the micropin of above-mentioned preparation is soaked 5 mg/ml spends the night for 4 ℃, is stored in the physiological saline behind the unreacted 3-sulfydryl of the flush away phenyl boric acid.In the tissue that directly insertion needs to detect, and be inserted into the degree of depth that needs detection.Be detained 5-30 minute, and took out directly and detect with Raman spectrometer, the glucose Raman collection of illustrative plates that the 3-sulfydryl phenyl boric acid of mensuration combines calculates glucose content by intensity.By same principle, other specific moleculars of functionalization can carry out other specific detection on the micropin of preparation.Method therefor is known in this area, and can be used.
Use dosage New Zealand's male rabbit to be carried out intraperitoneal administration and anaesthetize, after arcotic works, the hair on the thigh lateral tendon is cut off with scissors as the yellow Jackets of 50mg/kg.With 200 μ l, the NBA solution of 2 * 10-4M injects the thigh lateral tendon.After 5-10 minute, the micropin of above-mentioned preparation is directly inserted in the tendon tissue, the degree of depth must be enough deeply.Be detained after 5-30 minute, take out micropin and directly detect, and spectrum is compared, can analyze the degree that medicine spreads in tissue with the different parts of Raman spectrum to needle point, needle body.Method therefor is known in this area, and can be used.
Claims (3)
1. one kind has the detection micropin that strengthens Raman and fluorescence signal; Comprise: the needle handle (13), the needle body (12) and the needle point (11) that connect successively; It is characterized in that; On the surface of the needle body (12) and needle point (11), be coated with metal nano material layer (2), on metal nano material layer (2), be coated with polymer material layer (3), described metal nano material particle diameter is 20-1000nm.
2. the detection micropin with enhancing Raman and fluorescence signal according to claim 1 is characterized in that the metal nano material layer is golden nanometer particle layer, nano grain of silver sublayer, copper nano-particle layer or nano platinum particle layer.
3. according to claim 1 have a detection micropin that strengthens Raman and fluorescence signal, it is characterized in that, polymer material layer is a kind of in polystyrene layer, polylactic acid layers, layer of polyurethane or the polyethylene polypropylene layer.
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| CN201120161868.1 | 2011-05-18 | ||
| CN201120161868 | 2011-05-18 | ||
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525421A (en) * | 2011-05-18 | 2012-07-04 | 东南大学 | Detecting micro-needle with strengthened Raman and fluorescence signal and preparation method thereof |
| CN103099604A (en) * | 2013-01-15 | 2013-05-15 | 东南大学 | An imaging method of tumor targeting based on enhancement effect of zinc ion signals |
| CN105784667A (en) * | 2014-12-22 | 2016-07-20 | 深圳先进技术研究院 | Surface enhanced Raman scattering substrate, preparation method and applications thereof |
| CN107167834A (en) * | 2017-07-21 | 2017-09-15 | 东南大学 | Detect SERS active-substrate of thermoneutron radiation and its preparation method and application |
| CN110151160A (en) * | 2019-05-20 | 2019-08-23 | 深圳市问库信息技术有限公司 | A kind of electronic channel detecting device and its detection method |
| CN110567933A (en) * | 2019-06-28 | 2019-12-13 | 华东理工大学 | SERS substrate and preparation method thereof |
| CN111551725A (en) * | 2020-04-10 | 2020-08-18 | 浙江正熙生物医药有限公司 | Method for improving antibody fluorescent dye labeling signal |
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2011
- 2011-12-24 CN CN 201120547417 patent/CN202614678U/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525421A (en) * | 2011-05-18 | 2012-07-04 | 东南大学 | Detecting micro-needle with strengthened Raman and fluorescence signal and preparation method thereof |
| CN103099604A (en) * | 2013-01-15 | 2013-05-15 | 东南大学 | An imaging method of tumor targeting based on enhancement effect of zinc ion signals |
| CN103099604B (en) * | 2013-01-15 | 2015-05-06 | 东南大学 | An imaging method of tumor targeting based on enhancement effect of zinc ion signals |
| CN105784667A (en) * | 2014-12-22 | 2016-07-20 | 深圳先进技术研究院 | Surface enhanced Raman scattering substrate, preparation method and applications thereof |
| CN107167834A (en) * | 2017-07-21 | 2017-09-15 | 东南大学 | Detect SERS active-substrate of thermoneutron radiation and its preparation method and application |
| CN107167834B (en) * | 2017-07-21 | 2018-12-14 | 东南大学 | Detect the SERS active-substrate and its preparation method and application of thermoneutron radiation |
| CN110151160A (en) * | 2019-05-20 | 2019-08-23 | 深圳市问库信息技术有限公司 | A kind of electronic channel detecting device and its detection method |
| CN110567933A (en) * | 2019-06-28 | 2019-12-13 | 华东理工大学 | SERS substrate and preparation method thereof |
| CN111551725A (en) * | 2020-04-10 | 2020-08-18 | 浙江正熙生物医药有限公司 | Method for improving antibody fluorescent dye labeling signal |
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Granted publication date: 20121219 Termination date: 20131224 |