CN102080131B - Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof - Google Patents
Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof Download PDFInfo
- Publication number
- CN102080131B CN102080131B CN201010582898XA CN201010582898A CN102080131B CN 102080131 B CN102080131 B CN 102080131B CN 201010582898X A CN201010582898X A CN 201010582898XA CN 201010582898 A CN201010582898 A CN 201010582898A CN 102080131 B CN102080131 B CN 102080131B
- Authority
- CN
- China
- Prior art keywords
- hpdna
- gold size
- ssdna
- nanoparticle
- dna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses hairpin type DNA (hpDNA) modified gold colloid nano particles and a synthesizing method thereof, which relate to the technical field of biological nanomaterial synthesis. The method is characterized in that: an hpDNA (HS-hpDNA) one end part of which is connected with a sulfydryl and an ssDNA (HS-ssDNA) one end part of which is connected with a sulfydryl are highly modified onto the surfaces of the gold colloid nano particles together through gold-disulfide bonds; in order to inhibit the formation of dimers between different hpDNAs, a section of DNA sequence (CpDNA) which is complemented with a section of sequence at the free end of the hpDNA is introduced into a reaction system together with the HS-hpDNA; and after the synthetic reaction and ageing, the reaction product is repeatedly centrifuged and dispersed by a high-speed centrifuge at a low temperature, and the liquid of the final product is preserved at a low temperature. The oligonucleotide highly modified gold colloid nano particles have relatively high dispersibility, can serve as marks and signal amplifying means of biomolecules, such as proteins, nucleic acids and the like, are simple and quick in use and are convenient to use.
Description
Technical field
The present invention relates to the biological nano field of material synthesis technology, more particularly relate to gold size nanoparticle and compound method thereof that one type of novel oligonucleotide height is modified.
Background technology
It is big that nanoparticle has a specific surface, the signal factor characteristics that portability is a large amount of.Wherein, Advantages such as the gold size nanoparticle has the technology of preparing maturation, is easy to chemically modified, oxidation-resistance is strong, good biocompatibility, density height and photoelectric characteristic are good are being developed rapidly the light analysis of biomolecule detection such as nucleic acid, protein and the applied research in the electroanalysis in recent years.Recently pertinent literature has been reported that the oligonucleotide gold nano-particles modified is synthetic and has been used, and it is amplified means as detecting biomolecular labeling such as protein and nucleic acid and signal.The oligonucleotide of on the gold size nanoparticle, modifying all is a single stranded form but at present.For example there is research to be reported in and modifies two kinds of oligonucleotide strands (ssDNA) on the gold size nanoparticle simultaneously; Wherein a kind of strand is the probe of target DNA; Another kind of strand and bar code dna single chain are complementary (like document J.M. Nam, S.I. Stoeva, C.A. Mirkin; Bio-bar-code-based DNA detection with PCR-like sensitivity
J. Am. Chem. Soc.126 (2004) 5932-5933 report) or itself be labeled the back as biological barcode DNA (like document D.B. Zhu; Y.B. Tang; D. Xing; W.R. Chen, PCR-free quantitative detection of genetically modified organism from raw materials. An electrochemiluminescence-based bio bar code method
Anal. Chem.3571 reports of 80 (2008) 3566 –).When adopting the gold size nanoparticle of modifying through oligonucleotide like this that target DNA is detected, ubiquity detect or markers step loaded down with trivial details consuming time, need to use expensive detecting instrument, to shortcomings such as the detection background of blank sample are big.For overcoming the prior art deficiency, inquire into gold size nanoparticle ten minutes necessity of the novel oligonucleotide modification of biomolecules such as detection protein, nucleic acid, also be the focus that present biological nano material is synthetic and biological technical field is studied.
Summary of the invention
The object of the invention is to provide the gold size nanoparticle of one type of novel oligonucleotide height modification; It is the gold size nanoparticle that hair clip formula DNA (hpDNA) and ssDNA two-pack are modified; Simple when making it be applied to detect biomolecules such as protein, nucleic acid, quick, be convenient to use; Another purpose is to provide its compound method.
For realizing the object of the invention, select for use hpDNA and ssDNA two-pack to modify the gold size nanoparticle, principle and concrete technical scheme are following:
HpDNA exists in the organism naturally, owing to contain the complementary base sequence of the identical sequence of reversed arrangement on its DNA chain, thus form the dna structure of base pairing in the chain.Double-stranded DNA (dsDNA) intercalator can combine with hpDNA specificity (with respect to ssDNA) through embedding between two adjacent base pairs.Utilize this character; The gold size nanoparticle that the novel oligonucleotide of synthetic of the present invention is modified can not need to carry out in advance chemical labeling; And directly combine, thereby realize that simple, quick, highly sensitive, high specific to target DNA, protein and other biomolecules detect with dsDNA intercalator with photolytic activity or electrochemical activity.
Compound method is following:
A, the employing tetra chlorauric acid salt-synthetic gold size nanoparticle of Trisodium Citrate reduction method: the tetra chlorauric acid salts solution is heated to boiling; The citric acid three sodium solution that adds preheating; Stirring and refluxing reaction 12-30 minute; Then reaction solution is naturally cooled to room temperature, membrane filtration is collected filtrating and is put refrigerator and keeps in Dark Place;
B, in the solution that contains HS-hpDNA, HS-ssDNA and CpDNA, add three (2-formyl ethyl) phosphonium salt acid salt aqueous solution, mix the back and in system, add 2 * TE damping fluid, activation 1-2 hour;
Add the colloidal gold solution that step (a) makes in c, the dna solution after step (b) activation, then both mixed solutions are put on the shaking table oscillatory reaction 10-20 hour (about 25 ℃, 150rpm);
D, reaction add 1 * TE damping fluid after accomplishing in reaction solution, room temperature is placed and worn out in 15-30 hour;
E, at last with reaction solution at a high speed (10000-20000rpm) centrifugal about 20 minutes at low temperatures, centrifugal gained deposition is dissolved in 1 * TE damping fluid again, low temperature is preserved down.
Centrifugal back is drawn supernatant and is measured its absorbancy at the 260nm place (solution only to contain CpDNA is done blank).HpDNA and ssDNA obtain at the absorbance ratio at the 260nm place product by HS-hpDNA and HS-ssDNA molar ratio and molar extinction coefficient ratio in the supernatant.Calculate in the supernatant hpDNA and ssDNA respectively in the absorbancy at 260nm place according to above data, and be not connected to concentration and the amount of the hpDNA and the ssDNA of gold size nanoparticle surface according to DNA concentration calculation formula.At last, the amount according to hpDNA and ssDNA in the reaction starting soln obtains nanoparticle surface modified hpDNA of gold size and ssDNA amount.HpDNA and ssDNA can be as required through adjusting its control recently that feeds intake at the ratio that is connected of gold size nanoparticle surface.
Gold size nanoparticle concentration is through measuring the absorbancy of gold size nano-particle solution in the 506nm wavelength, and
calculates by the Lambrt-Beer law.A is that absorbancy,
are that strength of solution, L are liquid layer thickness for molar extinction coefficient, c in the formula.Diameter is the molar extinction coefficient of the gold size nanoparticle of 14nm
=3.1548 * 10
8M
-1Cm
-1
When the gold size nanoparticle that synthetic hpDNA highly modifies, according to the difference of target molecule to be detected, with the co-modified molecule of hpDNA comprise can with target molecule specificity bonded ssDNA, ssRNA, polypeptide, antigen, antibody.Said hpDNA and ssDNA are respectively the hpDNA and the ssDNA of arbitrary sequence and length; Said CpDNA is and free-ended any one section sequence of hpDNA dna sequence dna of complementary random length mutually.HS-hpDNA is that hpDNA, the HS-ssDNA of end end connection sulfydryl is the ssDNA that an end end connects sulfydryl.
Centrifugal preferred when disperseing with the low-temperature and high-speed whizzer: as to repeat more than 2 times centrifugal and disperse; Final dispersive hpDNA/ gold size nanoparticle is preferably preserved down at 4 ℃-6 ℃.
Above-mentioned compound method also can be used to the hpDNA modification of synthetic Nano silver grain etc.
Innovative point of the present invention is: the hpDNA (HS-hpDNA) that an end end is connected sulfydryl is attached to the golden nanometer particle surface through gold-sulfide linkage; And with one section with the free-ended one section sequence of hpDNA mutually complementary dna sequence dna (CpDNA) introduce reaction system with HS-hpDNA, suppressed dimeric formation between the different hair clip DNA.Successfully synthesize gold size nanoparticle stable, that more independent dispersive hpDNA modifies.The nanoparticle surface modified DNA total amount of each gold size is on average at 10-200 dna molecular.
Product is through perspective Electronic Speculum, ultraviolet-visible pectrophotometer and infrared absorption spectrum characterizes and stability analysis.Product has good result of use in biomolecules application facet such as detecting protein, nucleic acid.The hpDNA that gold size nanoparticle surface height is modified and every hpDNA go up a plurality of intercalator signaling molecules that insert, and can carry out dual multistage amplification to the detection signal of target molecule.Except signal amplifies; The gold size nanoparticle that hpDNA modifies also comprises in the advantage that detects biomolecules application facet such as protein, nucleic acid: hpDNA combines with it with the dsDNA intercalator with photolytic activity or electrochemical activity without discharging directly; Sensed light signal or electrochemical signals, simple and efficient; DsDNA intercalator signaling molecule optionally combines with dsDNA (with respect to ssDNA), and is little to the detection background of blank sample, can further improve detection sensitivity.
Description of drawings
Fig. 1Perspective sem image for gold size nanoparticle and hpDNA, the ssDNA gold size nanoparticle after co-modified.A wherein, b are respectively that gold size nanoparticle low power is amplified, high magnification map; C, d are respectively that hpDNA, the ssDNA gold size nanoparticle low power after co-modified is amplified, high magnification map.
The perspective sem image b and the d that are amplified by high power among Fig. 1 can find out that synthetic gold size nanoparticle of the present invention is the spherical particle of rule, and particle size distribution is even.Dna modification does not change the form of gold size nanoparticle.Perspective sem image particle size analysis software DigitalMicrograph through specialty carries out analysis revealed to the perspective sem image, and the particle diameter of synthetic gold size nanoparticle of the present invention is 13 ± 1 nm.HpDNA, the co-modified not influence of particle diameter of ssDNA to the gold size nanoparticle.The low power magnification fluoroscopy Electronic Speculum figure a of gold size nanoparticle shows that the gold size nanoparticle is uniformly dispersed, and does not reunite.Gold size nanoparticle subgraph c after hpDNA, ssDNA are co-modified shows; Gold size nanoparticle after hpDNA modifies still is in the independent dispersion state uniformly of comparison; Though contain the agglomerating particles of minute quantity, be owing to produce through the intermolecular hybridization between the hpDNA of its finishing between particle.
Fig. 2For the UV-Vis of gold size nanoparticle (long and short dash line) and hpDNA, the ssDNA gold size nanoparticle (solid line) after co-modified absorbs collection of illustrative plates (Tianjin, island UV-2400 ultraviolet-visible pectrophotometer).
UV-Vis absorbs collection of illustrative plates and shows that synthetic gold size nanoparticle of the present invention maximum absorption band occurs at the 520nm place.Since quantum size effect, maximum absorption wavelength red shift that the surface of metal particles plasma resonance absorbs along with the increase of particle size.Can estimate that by maximum absorption wavelength the particle diameter of gold size nanoparticle is 13～14nm, consistent with the particle diameter result of the gold size nanoparticle that obtains through the analysis of perspective sem image.
At 528 nm places, the maximum absorption wavelength that the surface plasma body resonant vibration of the gold size nanoparticle before modifying absorbs has red shift to gold size nanoparticle after hpDNA, ssDNA are co-modified slightly in the absorbing wavelength of visible region.The maximum absorption wavelength that the surface plasma body resonant vibration of gold size nanoparticle absorbs is responsive to the dielectric environment and the variable in distance between the particle of gold size nanoparticle.A spot of particle agglomeration causes the nanoparticle dielectric environment to increase, and spacing of particle is from reducing to cause nanometer gold to absorb red shift simultaneously.Slight red shift reflects that the reunion between the gold size nanoparticle is very slight, and this is consistent with the result that the perspective electron microscopic observation arrives.In addition, the gold size nanoparticle after hpDNA, ssDNA are co-modified the absorption peak at 260 nm places with modify before compare more obviously, show that hpDNA and ssDNA successfully are modified at the gold size nanoparticle surface.
Fig. 3Modify the infrared absorption pattern (ir lamp is dry for Nicolet 6700 FT-IR, membrane process) of hpDNA front and back and pure hpDNA for the gold size nanoparticle.Wherein, a is a gold size nanoparticle infrared absorption pattern; B is the gold size nanoparticle infrared absorption pattern after hpDNA modifies; C is the hpDNA infrared absorption pattern.
After the gold size nanoparticle is modified hpDNA, at 1060 cm
-1One tangible absorption peak appears in the place, with the absorption peak position consistency of pure hpDNA sample.Usually the absorption peak ownership with this position is phosphate group (PO in the DNA chain
2 -Bands) symmetrical stretching vibration.Infared spectrum shows that hpDNA successfully is modified at the gold size nanoparticle surface.
Embodiment
For the present invention is better explained, it is following to lift embodiment:
EmbodimentHpDNA and ssDNA two-pack height are modified the synthetic of gold size nanoparticle
A, the employing tetra chlorauric acid salt-synthetic gold size nanoparticle of Trisodium Citrate reduction method: get 20ml 0.01% tetra chlorauric acid salts solution; Be heated to boiling; The citric acid three sodium solution that adds fast 1ml 1% preheating after being stirred to solution and being transparent wine red, continues reaction 12min.After reaction solution naturally cools to room temperature,, collect filtrating and put 4 ℃ of refrigerators and keep in Dark Place with 0.45 μ m membrane filtration.
B, contain the solution (total concn 10 of HS-hpDNA, HS-ssDNA and CpDNA (mol ratio HS-hpDNA:HS-ssDNA:CpDNA=2:1:4) to 70 μ l
-5M) tris (the 2-carboxyethyl)-phosphine hydrochloride [three (2-formyl ethyl) phosphonium salt hydrochlorate] that adds 10 μ l in is the aqueous solution (TCEP).Mix the back and in system, add 0.93ml 2 * TE damping fluid, activation 1hrs.
Add the colloidal gold solution that 1ml is made by step (a) in c, the dna solution after step (b) activation; Both mixed solutions are put oscillatory reaction on the shaking table (25 ℃, 150rpm, 16hrs).
In reaction solution, add 1m l 1 * TE damping fluid after d, reaction are accomplished, room temperature is placed 20hrs and is worn out.
E, at last with reaction solution at the centrifugal 20min of high-speed low temperature under the 14000rpm (about 4 ℃), centrifugal gained deposition is dissolved in 1 * TE damping fluid again.Repeated centrifugation and twice of dissolving.The gold size nanoparticle that final gained oligonucleotide is modified is preserved under 4 ℃ in 1 * TE damping fluid.
Through assaying reaction when initial and reaction accomplish after the centrifugal supernatant at the absorbance at 260 nm places; And, obtain each gold size nanoparticle surface and on average connect about 87 hpDNA and 43 ssDNA molecular chains according to molar ratio and the molar extinction coefficient of HS-hpDNA and HS-ssDNA.
The perspective sem image of product, UV, visible light absorb collection of illustrative plates, infrared absorption pattern is seen Fig. 1, Fig. 2, Fig. 3 respectively.HpDNA is identical with hpDNA single-component modification gold size nanoparticle infrared absorption pattern with ssDNA two-pack modification gold size nanoparticle.
Above show be merely embodiments of the invention, can not limit interest field of the present invention with this.Therefore the equivalent variations of being done with claim of the present invention still is encompassed among the novel nano particle and synthetic technology scheme scope thereof that the present invention asks for protection.
Application examples
The gold size nanoparticle that synthetic according to the method described above hpDNA and ssDNA two-pack are modified: the ssDNA that is modified at the gold size nanoparticle surface for can with the specific nucleic acid sequence fragment of Hp: 14 nucleotide base complementary dna sequence dnas that 3 ' of 5 '-TAA TCG TGG ATT ACA CCG GTA TTT ATA AAG CGG ATA TTG GTA T-3 ' holds: 5 '-ATA CCA ATA TCC GC-(CH
2)
3-SH.
Gold size nanoparticle with synthetic hpDNA of the present invention and the modification of ssDNA two-pack; Be applied to assemble the DNA electrochemical sensor of sandwich structure; With pentaamine ruthenium [3-(2-phenanthren-9-yl-vinyl)-pyridine] complex is that [3-(2-(phenanthrene-9-yl) vinyl) pyridine five ammino ruthenium complexees] are as the dsDNA intercalator with electrochemical activity; Detect the above-mentioned specific nucleic acid sequence fragment of Hp, the limit of detection of target molecule has been reached 10
-17M.
In physiologically sample, the concentration of DNA is at femtomolar (fM:10
-15M) or attomolar (aM:10
-18M) scope.The DNA electrochemical sensor that the gold size nanoparticle that uses the novel oligonucleotide of synthetic of the present invention to modify is assembled detects the requirement that has reached direct detection physiologically sample to the nucleotide sequence of Hp; Detection signal is realized multistage number amplification, simple and efficient, little to the detection background of blank sample, thereby further improved detection sensitivity.
Claims (3)
1. the compound method of the gold size nanoparticle modified of hair clip formula hpDNA is characterized in that, the gold size that said hair clip formula hpDNA modifies is nanoparticle surface modified to have hpDNA and ssDNA, realizes through following steps:
A, employing tetra chlorauric acid salt-Trisodium Citrate reduction method gold size nanoparticle: the tetra chlorauric acid salts solution under agitation is heated to boiling; The citric acid three sodium solution that adds preheating; Stirring and refluxing reaction 12-30 minute; Then reaction solution is naturally cooled to room temperature, membrane filtration is collected filtrating and is put refrigerator and keeps in Dark Place;
B, in the solution that contains HS-hpDNA, HS-ssDNA and CpDNA, add three (2-formyl ethyl) phosphonium salt acid salt aqueous solution, mix the back and in system, add 2 * TE damping fluid, activation 1-2 hour;
Add the gold size nanoparticle that step (a) makes in c, the dna solution after step (b) activation, then both mixed solutions were put on the shaking table oscillatory reaction 10-20 hour;
D, reaction add 1 * TE damping fluid after accomplishing in reaction solution, room temperature is placed and worn out in 15-30 hour;
E, at last that reaction solution is centrifugal is dissolved in centrifugal gained deposition again in 1 * TE damping fluid and preserves;
The said HS-hpDNA of step (b) is that hpDNA, the HS-ssDNA of end end connection sulfydryl is the ssDNA that an end end connects sulfydryl; Said CpDNA is and free-ended any one section sequence of hpDNA dna sequence dna of complementary random length mutually.
2. the compound method of the gold size nanoparticle that hair clip formula hpDNA as claimed in claim 1 modifies is characterized in that, the nanoparticle surface modified DNA total amount of each gold size is on average at 10-200 dna molecular.
3. the compound method of the gold size nanoparticle that hair clip formula hpDNA as claimed in claim 1 modifies is characterized in that, when the gold size nanoparticle that synthetic hpDNA modifies, comprises ssDNA, ssRNA, antigen or antibody with the co-modified molecule of hpDNA.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010582898XA CN102080131B (en) | 2010-12-10 | 2010-12-10 | Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010582898XA CN102080131B (en) | 2010-12-10 | 2010-12-10 | Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102080131A CN102080131A (en) | 2011-06-01 |
| CN102080131B true CN102080131B (en) | 2012-11-21 |
Family
ID=44086320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010582898XA Expired - Fee Related CN102080131B (en) | 2010-12-10 | 2010-12-10 | Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102080131B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102556959B (en) * | 2011-12-30 | 2014-04-16 | 中国科学院苏州纳米技术与纳米仿生研究所 | Preparation method of metal nanoparticle dimer |
| CN103045460B (en) * | 2012-12-31 | 2014-07-02 | 北京师范大学 | Visual plastic substrate biochip taking hairpin-type DNA as probe, as well as preparation method and application thereof |
| CN103487576B (en) * | 2013-09-27 | 2015-01-07 | 无锡市产品质量监督检验中心 | Quick test-paper detection method for porcine-derived material adulteration |
| CN103484549B (en) * | 2013-09-27 | 2014-10-22 | 无锡市产品质量监督检验中心 | Quick identification method for porcine-derived material adulteration |
| CN103773756B (en) * | 2013-10-18 | 2017-10-31 | 南京农业大学 | A kind of preparation method of the golden DNA probe of specific nano |
| CN104923777A (en) * | 2015-03-18 | 2015-09-23 | 华南理工大学 | High-salt-tolerance metal nanoparticle assembly and preparing method thereof |
| CN106498077B (en) * | 2016-12-09 | 2019-09-06 | 青岛千卓分子生物科技有限公司 | DNA cloning product rapid detection method |
| CN106596487B (en) * | 2016-12-14 | 2019-08-27 | 中国科学院苏州生物医学工程技术研究所 | Intracellular protein detection method based on droplet and namo fluorescence probe |
| CN108048906A (en) * | 2017-12-08 | 2018-05-18 | 中山大学 | A kind of DNA is oriented to gold nano-crystal and preparation method and application |
| CN108261548B (en) * | 2018-01-10 | 2020-04-10 | 浙江大学 | Nano composite and preparation method and application thereof |
| CN110625138B (en) * | 2019-10-30 | 2022-07-22 | 中山大学 | DNA-oriented gold-silver bimetallic nanoparticle and preparation method and application thereof |
| CN113186254B (en) * | 2021-03-17 | 2022-06-24 | 中国地质大学（武汉） | Biosensor for ctDNA detection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101368198A (en) * | 2008-09-24 | 2009-02-18 | 江南大学 | Preparation method for self-assembly material of nano golden and Lambda DNA chain connection |
-
2010
- 2010-12-10 CN CN201010582898XA patent/CN102080131B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101368198A (en) * | 2008-09-24 | 2009-02-18 | 江南大学 | Preparation method for self-assembly material of nano golden and Lambda DNA chain connection |
Non-Patent Citations (2)
| Title |
|---|
| Shiping Song etal..Gold-Nanoparticle-Based Multicolor Nanobeacons for Sequence-Specific DNA Analysis.《Angew. Chem.Int.Ed》.2009,第48卷第8670-8674. * |
| 周波等.应用纳米与分子探针技术对IgG抗原水平的检测.《科技导报》.2009,第27卷(第22期),第38-43页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102080131A (en) | 2011-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102080131B (en) | Hairpin type DNA modified gold colloid nano particles and synthesizing method thereof | |
| Tang et al. | Plasmon-based colorimetric nanosensors for ultrasensitive molecular diagnostics | |
| JP5400297B2 (en) | Fluorescent nanosilica particles, nanofluorescent material, biochip using the same, and assay method thereof | |
| Knopp et al. | Bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles | |
| Vietz et al. | Broadband fluorescence enhancement with self-assembled silver nanoparticle optical antennas | |
| Soto et al. | Fluorescent signal amplification of carbocyanine dyes using engineered viral nanoparticles | |
| Zanoli et al. | Functionalized gold nanoparticles for ultrasensitive DNA detection | |
| Zhou et al. | Liposome–quantum dot complexes enable multiplexed detection of attomolar DNAs without target amplification | |
| Nguyen et al. | Controlled synthesis and biomolecular probe application of gold nanoparticles | |
| Nath et al. | A colorimetric gold nanoparticle sensor to interrogate biomolecular interactions in real time on a surface | |
| Hennig et al. | Scope and limitations of surface functional group quantification methods: exploratory study with poly (acrylic acid)-grafted micro-and nanoparticles | |
| Huang et al. | AuNanostar@ 4-MBA@ Au core–shell nanostructure coupled with exonuclease III-assisted cycling amplification for ultrasensitive SERS detection of ochratoxin A | |
| Guo et al. | Conformational details of quantum dot-DNA resolved by forster resonance energy transfer lifetime nanoruler | |
| Su et al. | Surface plasmon-assisted fluorescence enhancing and quenching: From theory to application | |
| AU2009317878B2 (en) | Analyte detection assay | |
| Guo et al. | Ultrasensitive simultaneous detection of multiplex disease-related nucleic acids using double-enhanced surface-enhanced Raman scattering nanosensors | |
| EP1639370B1 (en) | Method for detecting analytes based on evanescent illumination and scatter-based detection of nanoparticle probe complexes | |
| Gunnarsson et al. | Liposome-based chemical barcodes for single molecule DNA detection using imaging mass spectrometry | |
| Lin et al. | DNA functionalized gold nanoparticles for bioanalysis | |
| Liu et al. | Fluorescence enhancement of terminal amine assembled on gold nanoclusters and its application to ratiometric lysine detection | |
| Choi et al. | Progress in molecularly imprinted polymers for biomedical applications | |
| Obliosca et al. | Probing quenched dye fluorescence of Cy3–DNA–Au-nanoparticle hybrid conjugates using solution and array platforms | |
| Zhang et al. | Fluorescent metal nanoshells: lifetime-tunable molecular probes in fluorescent cell imaging | |
| Lee et al. | Controlled protein embedment onto Au/Ag core–shell nanoparticles for immuno-labeling of nanosilver surface | |
| Uddayasankar et al. | Isolation of monovalent quantum dot–nucleic acid conjugates using magnetic beads |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121121 Termination date: 20131210 |