WO2002096262A2 - Non-alloying core shell nanoparticles - Google Patents
Non-alloying core shell nanoparticles Download PDFInfo
- Publication number
- WO2002096262A2 WO2002096262A2 PCT/US2001/050825 US0150825W WO02096262A2 WO 2002096262 A2 WO2002096262 A2 WO 2002096262A2 US 0150825 W US0150825 W US 0150825W WO 02096262 A2 WO02096262 A2 WO 02096262A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- core
- nanoparticle
- shell
- gold
- nanoparticles
- Prior art date
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Definitions
- the present invention relates to core/shell nanoparticles, materials based on core/shell nanoparticles, kits containing core/shell nanoparticles, and methods of making and using core/shell nanoparticles for the detection of target molecules, including nucleic acids, peptides, and proteins.
- the present invention relates to specific binding substance-modified core/shell nanoparticles such as DNA-modified core/shell nanoparticles and their use for detecting target molecules such as nucleic acids.
- Gold particles are particularly easy to modify because they are often stabilized with a weakly binding layer of charged ligands (e.g. citrate) that can be replaced with molecules with chemical functionalities that bind more strongly (e.g. thiols, amines, and disulfides) to their surfaces than these ligands.
- ligands e.g. citrate
- chemical functionalities e.g. thiols, amines, and disulfides
- the CdSe and CdS quantum dots have proven more difficult to modify because they have a surfactant layer that is very strongly bound to their surfaces and, consequently, difficult to displace.
- the present invention relates to composite core/shell nanoparticles, compositions and kits including these core/shell nanoparticles, and methods for preparing and using composite core/shell nanoparticles, particularly Ag/gold core/shell nanoparticles, for the detection of target molecules such as nucleic acids, proteins and the like.
- These Ag/gold core/shell nanoparticles were prepared by reduction of HAuCl 4 by NaBH in the presence of Ag-nanop article "templates” and characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), and energy dispersive X-ray (EDX) microanalysis. Significantly, these particles do not alloy, yielding structures with the optical properties of silver and the surface chemistry and high stability of Au.
- the core/shell nanoparticles may be further modified with alkanethiol-oligonucleotides forming structures that undergo reversible hybridization with complementary ohgonucleotides to form extended nanoparticle network structures.
- alkanethiol-oligonucleotides forming structures that undergo reversible hybridization with complementary ohgonucleotides to form extended nanoparticle network structures.
- one object of the invention is to provide straightforward method of preparing core/shell nanoparticles with the optical, and many of the physical, properties of silver but the stability of gold.
- the surfaces of these nanoparticles can be modified with a variety of moieties such as, for example, natural and synthetic polymers, molecules capable of selective molecular recognition including, but not limited to, nucleotides, nucleosides, poly- or ohgonucleotides, proteins, peptides, carbohydrates, sugars, and haptens, thereby providing useful biorecognition properties to the nanoparticles.
- Another object of the invention is to provide a general method for preparing core/shell particles with tailorable physical properties by virtue of choice of core, e.g., Fe 3 O , Cu or Pt, but the surface chemistry and stability of the native, and oligonucleotide modified, pure gold particles.
- core e.g., Fe 3 O , Cu or Pt
- Another object of the invention is to provide methods for detection of molecules capable of selective molecular recognition comprising use of core/shell nanoparticle probes. These methods comprise contacting the core/shell nanoparticle probes with one or a plurality of target molecules under conditions that allow for selective molecular recognition, and the detection of an optical change.
- the physical properties of the particular core/shell nanoparticle probes can allow for various additional steps in these methods such as, for example, inducing their migration through application of electrical or magnetic fields.
- Another object of the invention is to provide nanomaterials based on the core/shell nanoparticles of the invention.
- FIG. 2A illustrates (A) Mercaptoalkyl-oligonucleotide-modified Ag/Au core/shell particles and an oligonucleotide target. Represents the core/shell nanoparticle and " ⁇ " represents a propyl (left) or hexyl (right) group linking S to the oligonucleotide probe.
- Figure 3 illustrates the UV-VIS spectra of a Pt core (dotted line) and Pt/gold core/shell nanoparticles (solid line).
- Figure 4 illustrates the UV-VIS spectra of gold growth on the surface of Fe 3 O nanoparticles at 0, 0.3 nm, 0.6 nm, and 0.9 nm thickness.
- Figure 5 illustrates the behavior of Fe O 4 /gold core/shell particles as super paramagnetic particles in the presence of an applied magnetic field, h the presence of a magnetic field, a solution containing the magnetic gold nanoparticles appears red. When a magnetic force is applied over a period of 2 hours, the solution becomes colorless as the nanoparticles migrate towards the magnetic force.
- Figure 6 illustrates the core/shell approach to magnetic gold nanaparticles.
- Figure 7 illustrates a comparison of the relative stabilities of Ag, Ag/Au alloy, and Ag@Au core/shell nanoparticle-DNA conjugates at different salt concentrations.
- the present invention provides for core/shell nanoparticles, comprising a nanoparticle core and a gold shell.
- the core material can comprise any nanoparticle known to those of skill in the art including, but not limited to, metal, semiconductor, and magnetic nanoparticles.
- the core material is comprised of metal or magnetic nanoparticles including, but not limited to, Ag, Pt, Fe, Co, Ni, FePt, FeAu, Fe 3 O 4 , and Co 3 O .
- Methods for preparing such nanoparticles are well known in the art. For example, see, e.g. Schmid, G. (ed.) Clusters and Colloids (VCH, Weinheim, 1994); Hayat, M.A.
- the present invention provides a method for preparation of non- alloying gold core/shell nanoparticles and product produced therefrom.
- the method of the invention comprises providing an inner nanoparticle core, treating the core simultaneously with a solution comprising a gold salt and a solution comprising a reducing agent, and isolating the core/shell nanoparticles.
- the method provides for the first time a non-alloying gold shell surrounding a nanoparticle core.
- non-alloying gold core/shell nanoparticles exhibit surprising superior spectroscopic properties not found in conventional gold core/shell nanoparticles and can be functionalized with molecules such as nucleic acids and receptors, to produce nanoparticle conjugates that can be used for targeting and detecting target analytes such as nucleic acids, antigens, proteins, carbohydrates and other substances.
- the method can be performed at any temperature favorable in producing a non-alloying gold shell surrounding the core.
- the temperature depends on the choice of reaction solvent used to generate the gold shell. Suitable, but non-limiting, examples of reaction solvents include water, aqueous buffer solutions, oleic acid and trioctylphosphine oxide. In practicing this invention, trisodium citrate solution is preferred. In practicing the method of the invention, the temperature generally ranges from about 0
- the temperature generally ranges from about 130°C to about 180°C when oleic acid and trioctylphosphine oxide are used.
- the gold salt can comprise any suitable gold salt including, but not limited to, HAuCl , NaAuCU, KAuCl 4 , or KAu(CN) 2 .
- the preferred gold salt is HAuCl 4 .
- the reducing agent can comprise any suitable reducing agent capable of reducing the valency of the gold that comprises the gold salt solution including, but not limited to, NaBH , ascorbic acid, NH 2 OH and N 2 H .
- the preferred reducing agent is NaBH 4 .
- the core/shell nanoparticles have specific binding substances bound to the gold shell surrounding the nanoparticle.
- the specific binding substance may be natural and synthetic nucleic acids, natural and synthetic polypeptides, antibodies, Fab and Fab' antibody fragments, biotin, avidin and haptens such as digoxin. Those skilled in these arts will recognize a wide variety of specific binding substances that can be linked to the gold shell surrounding the nanoparticles.
- the present invention provides for core/shell nanoparticle oligonucleotide conjugates, comprising a nanoparticle core, a gold shell surrounding the nanoparticle, and an oligonucleotide attached to the gold surface of the core/shell nanoparticle.
- Any suitable method for attaching ohgonucleotides onto a gold surface may be used.
- a particularly preferred method for attaching ohgonucleotides onto a gold surface is based on an aging process described in U.S. application nos.
- the method comprises providing ohgonucleotides preferably having covalently bound thereto a moiety comprising a functional group which can bind to the nanoparticles.
- the moieties and functional groups are those that allow for binding (i.e., by chemisorption or covalent bonding) of the ohgonucleotides to nanoparticles.
- ohgonucleotides having an alkanethiol, an alkanedisulfide or a cyclic disulfide covalently bound to their 5' or 3' ends can be used to bind the ohgonucleotides to a variety of nanoparticles, including gold nanoparticles.
- the ohgonucleotides are contacted with the nanoparticles in water for a time sufficient to allow at least some of the ohgonucleotides to bind to the nanoparticles by means of the functional groups.
- Such times can be determined empirically. For instance, it has been found that a time of about 12-24 hours gives good results.
- Other suitable conditions for binding of the ohgonucleotides can also be determined empirically. For instance, a concentration of about 10- 20 nM nanoparticles and incubation at room temperature gives good results.
- the salt can be any suitable water-soluble salt.
- the salt may be sodium chloride, magnesium chloride, potassium chloride, ammonium chloride, sodium acetate, ammonium acetate, a combination of two or more of these salts, or one of these salts in phosphate buffer.
- the salt is added as a concentrated solution, but it could be added as a solid.
- the salt can be added to the water all at one time or the salt is added gradually over time. By “gradually over time” is meant that the salt is added in at least two portions at intervals spaced apart by a period of time. Suitable time intervals can be determined empirically.
- the ionic strength of the salt solution must be sufficient to overcome at least partially the electrostatic repulsion of the ohgonucleotides from each other and, either the electrostatic attraction of the negatively-charged ohgonucleotides for positively-charged nanoparticles, or the electrostatic repulsion of the negatively-charged ohgonucleotides from negatively-charged nanoparticles. Gradually reducing the electrostatic attraction and repulsion by adding the salt gradually over time has been found to give the highest surface density of ohgonucleotides on the nanoparticles. Suitable ionic strengths can be determined empirically for each salt or combination of salts. A final concentration of sodium chloride of from about 0.1 M to about 1.0 M in phosphate buffer, preferably with the concentration of sodium chloride being increased gradually over time, has been found to give good results.
- the ohgonucleotides and nanoparticles are incubated in the salt solution for an additional period of time sufficient to allow sufficient additional oligonucleotides to bind to the nanoparticles to produce the stable nanoparticle-oligonucleotide conjugates.
- an increased surface density of the oligonucleotides on the nanoparticles has been found to stabilize the conjugates.
- the time of this incubation can be determined empirically. A total incubation time of about 24-48, preferably 40 hours, has been found to give good results (this is the total time of incubation; as noted above, the salt concentration can be increased gradually over this total time).
- This second period of incubation in the salt solution is referred to herein as the "aging" step.
- Other suitable conditions for this "aging” step can also be determined empirically. For instance, incubation at room temperature and pH 7.0 gives good results.
- the conjugates produced by use of the "aging” step have been found to be considerably more stable than those produced without the “aging” step. As noted above, this increased stability is due to the increased density of the oligonucleotides on the surfaces of the nanoparticles which is achieved by the "aging” step.
- the surface density achieved by the “aging” step will depend on the size and type of nanoparticles and on the length, sequence and concentration of the oligonucleotides. A surface density adequate to make the nanoparticles stable and the conditions necessary to obtain it for a desired combination of nanoparticles and oligonucleotides can be determined empirically.
- a surface density of at least 10 picomoles/cm 2 will be adequate to provide stable nanoparticle-oligonucleotide conjugates.
- the surface density is at least 15 picomoles/cm 2 . Since the ability of the oligonucleotides of the conjugates to hybridize with nucleic acid and oligonucleotide targets can be diminished if the surface density is too great, the surface density is preferably no greater than about 35-40 picomoles/cm 2 .
- stable means that, for a period of at least six months after the conjugates are made, the nanoparticles remain dispersed, a majority of the oligonucleotides remain attached to the nanoparticles, and the oligonucleotides are able to hybridize with nucleic acid and oligonucleotide targets under standard conditions encountered in methods of detecting nucleic acid and methods of nanofabrication.
- the invention provides methods for the detection of a target analytes such as nucleic acids comprising contacting the core/shell nanoparticle oligonucleotide conjugates of the instant invention with a target nucleic acid sequence under conditions that allow hybridization between at least a portion of the oligonucleotides bound to the nanoparticle and at least a portion of the target nucleic acid sequence.
- protein receptors and other specific binding pair members can be functionalized with oligonucleotides and immobilized onto oligonucleotide-modified nanoparticles to generate a new class of hybrid particles (nanoparticle-receptor conjugates) that exhibit the high stability of the oligonucleotide modified particles but with molecular recognition properties that are dictated by the protein receptor rather than DNA.
- the invention further provides a method of nanofabrication based on the core-shell nanoparticle conjugates of the invention.
- Nanostructures and methods for prepare the materials from nanoparticles have been described in U.S. application nos. 09/344,667, filed June 25, 1999; 09/603,830, filed June 26, 2000; 09/760,500, filed January 12, 2001; 09/820,279, filed March 28, 2001; 09/927,777, filed August 10, 2001; and in International application nos. PCT US97/12783, filed July 21, 1997; PCT/USOO/17507, filed June 26, 2000; PCT/USOl/01190, filed January 12, 2001; PCT/USOl/10071, filed March 28, 2001, the disclosures which are incorporated by reference in their entirety.
- the method comprises providing at least one type of linking oligonucleotide having a selected sequence, the sequence of each type of linking oligonucleotide having at least two portions.
- the method further comprises providing one or more types of core/shell nanoparticles having oligonucleotides attached thereto, the oligonucleotides on each type of nanoparticles having a sequence complementary to a portion of the sequence of a linking oligonucleotide.
- the linking oligonucleotides and nanoparticles are contacted under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to the linking oligonucleotides so that a desired nanomaterials or nanostructure is formed.
- the invention provides another method of nanofabrication.
- This method comprises providing at least two types of core-shell nanoparticles of the invention having oligonucleotides attached thereto.
- the oligonucleotides on the first type of nanoparticles have a sequence complementary to that of the oligonucleotides on the second type of nanoparticles.
- the oligonucleotides on the second type of nanoparticles have a sequence complementary to that of the oligonucleotides on the first type of nanoparticle-oligonucleotide conjugates.
- the first and second types of nanoparticles are contacted under conditions effective to allow hybridization of the oligonucleotides on the nanoparticles to each other so that a desired nanomaterials or nanostructure is formed.
- the invention further provides nanomaterials or nanostructures composed of core-shell nanoparticles having oligonucleotides attached thereto, the nanoparticles being held together by oligonucleotide connectors.
- Example 1 Synthesis of A /AU core/shell nanoparticles prepared via a two-step synthesis
- This Example illustrates the inventive process for preparing Ag/Au core/shell nanoparticles.
- h part A methods for preparing silvercores are described.
- part B a method for preparing Ag/gold core/shell nanoparticles is provided.
- Silver nanoparticles are desired compositions for building blocks in material synthesis and as biological labels for two important reasons: (1) silver particles exhibit a surface plasmon band between -390 and 420 nm, depending on the particle size; 11 this is a spectral regime that is distinct from that of gold(520-580 nm). (2) The extinction coefficient of the surface plasmon band for a silver particle is approximately 4 times as large as that for an gold particle of the same size.
- silver particles functionalized with DNA would provide not only an opportunity to tailor the optical properties of DNA nanoparticle composite structures but also routes to new diagnostic systems that rely on the position and intensity of the surface plasmon band (e.g. colorimetric systems based on absorption or scattering, or SPR and SERS detection systems).
- new diagnostic systems e.g. colorimetric systems based on absorption or scattering, or SPR and SERS detection systems.
- silver nanoparticles cannot be effectively passivated by alkylthiol-modified-oligonucleotides using the established protocols for modifying goldparticles. 2 Indeed, silver particles prepared via such methods irreversibly aggregate when heated in a solution with a salt concentration necessary to effect DNA hybridization (0.05 M NaCl or greater).
- a core/shell approach was applied to overcome this problem.
- a thin goldshell was grown upon a silver nanoparticle, forming a particle with a gold outer surface that can be easily modified with alkylthiol-oligonucleotides.
- This approach could be generalized to prepare other particles such as Cu and Pt to create a series of core/shell particles with tailorable physical properties by virtue of choice of core but the surface chemistry and stability of the native, and oligonucleotide modified, pure gold particles.
- Silver nanoparticles were synthesized silver nanocrystals by reduction of silver nitrate by sodium borohydride in a trisodium citrate solution. Two methods for synthesizing the silver nanocrystals are described below and the resulting core nanocrystals are compared.
- Method No. 1 AgNO 3 (2.2 mg) and sodium citrate dihydrate (8.2 mg) were dissolved in 99 ml of Nanopure water in a 250-ml flask. With stirring and under Ar, this flask was placed in a ice bath for 15 min. Then 1 ml of sodium borohydride solution (0.14 M) was injected into the solution. After stirring for 1 hr, the solution was warmed to room temperature. The silver nanoparticles (- 12 nm in diameter) were obtained. Without further purification, these silver nanoparticles could be directly used for the gold shell growth.
- This step describes gold shell growth on the surface of silver cores described above.
- gold shells were grown on the silver core surface by reduction of HAuCl with the reducing silverent NaBH .
- the reduced gold has affinity for the silver surface, in part, because of the low surface chemical potential of the silver nanoparticles and near-zero lattice mismatch between these two materials.
- Two methods for growing gold shells on silver core nanocrystals are described below and the resulting core/shell nanoparticles were compared, silver core particles were prepared by method no. 1 described above.
- Gold shells (approximately one-monolayer thick) were grown on the surface of the silver nanoparticles (0.25 nmol of silver particles in 100 ml of 0.3 niM sodium citrate aqueous solution) by simultaneous dropwise addition, at a rate of between about 50 ⁇ L - 600 ⁇ L/min., of HAuCl and NaBH solutions (in Nanopure water) at 0 °C to the silver nanoparticle suspension.
- the simultaneous dropwise addition of dilute gold precursors inhibits the formation of gold cluster nucleation sites by keeping the concentration of these gold forming reagents at about 2 ⁇ M.
- BSPP Bis(p- sulfonatophenyl)phenylphosphine
- Gold shells (approximately one-monolayer thick) were grown on the surface of the silver nanoparticles (0.25 nmol of silver particles in 100 ml of 0.3 mM sodium citrate aqueous solution) by simultaneously treating them with HAuCl 4 (2 mM) and NaBH (6 mM) via dropwise addition at room temperature at a rate of between about 50 ⁇ L - 600 ⁇ L/min.
- the simultaneous dropwise addition of dilute gold precursors inhibits the formation of gold cluster nucleation sites by keeping the concentration of these gold forming reagents at about 2 ⁇ M.
- the core/shell nanoparticles produced via method no. 1 (synthesis at 0 °C) were found to have better stability in 0.5 M NaCl solution compared to core/shell nanoparticles produced by method no. 2 (synthesis at room temperature). This result may be due, in part, to a slower rate of shell growth at 0 °C than the growth rate at room temperature.
- Silver nanoparticles were prepared by literature methods. 13 The particles were then passivated with BSPP (0.3 mM), purified by gradient centrifugation (collecting the primary fraction; -12 nm in diameter), and dispersed in Nanopure water. Gold shells, approximately one-monolayer thick, were grown on the surface of the silver nanoparticles (0.32 nmol of silver particles in 100 mL of 0.3 mM sodium citrate aqueous solution) by simultaneously treating them with HAuCl and sodium borohydride via dropwise addition at 0 °C. The reduced gold has an affinity for the silver surface, in part, because of its near zero lattice mismatch.
- Figure 1A shows a TEM image of silver/gold core/shell nanoparticles which was obtained using a Hitachi 8100 electron microscopy.
- a typical TEM sample was prepared by depositing one drop of nanoparticles solution onto a carbon coated copper grid. The excess solution was wicked away by filter paper and dry in vacuum. The silver:gold ratio in these core/shell particles was determined to be 5.2:1 by energy dispersive X-ray (EDX) microanalysis of the particles (Figure IB).
- Figure IB illustrates an EDX spectrum of silver core particles (dotted line) and silver/gold core/shell particles (solid line).
- L and M signify electron transitions into the L and M shell of the atoms, respectively, from higher states.
- EDX analysis was performed on a field emission scanning-electron microscopy (FESEM) Hitachi 4500.
- FESEM field emission scanning-electron microscopy
- the SEM samples were prepared by depositing of one drop of nanoparticle solution on a silicon plate.
- the silve ⁇ gold ratio corresponds to an gold shell thickness of 3.1 +/- 0.6 A, which correlates with approximately one monolayer of gold atoms.
- the extinction spectrum of the core/shell particles is very similar to that for the citrate-stabilized pure silver particles.
- the surface plasmon band of the silver remains at the same wavelength but is dampened by about 10%, and the gold plasmon band is observed as a slight buckle at 500 nm.
- the core/shell silver/gold nanoparticles prepared by the methods of the instant invention retain the optical properties of the core with no observed red shifting of the silver plasmon band, (Figure IC).
- Figure IC illustrates the UV- visible spectra of silver core (dotted line) and silver/gold core/shell (solid line) wherein the inset shows the calculated extinction spectra of silver particles (dotted line) and silver/gold core/shell particles (solid line).
- the UV/Vis spectra were obtained using a HP 8453 diode array spectrophotometer.
- Example 2 Preparation of silver/gold core/shell Nanoparticle-oligonucleotide Conjugates This Example describes the preparation of silver/gold core/shell nanoparticle oligonucleotide conjugates as probes for detecting a target nucleic acid. Two methods were employed and the resulting probes were then compared for stability. The oligonucleotide sequences used in making the conjugates are shown in Figure 2a. These sequences were synthesized using standard phosphoramidite chemistry according to the literature. (James J. Storhoff, Robert Elghanian, Robert C. Mucic, Chad A. Mirkin, and Robert L. Letsinger, J. Am. Chem. Soc, 1998, 120, 1959).
- Nanoparticle probes with appropriate probe oligonucleotides were prepared by derivatizing 10 mL of aqueous core/shell nanoparticle colloid (from method no. 1) with 8-10 OD (in about 500 uL) of alkanethiol-ohgonucleotide (final oligonucleotide concentration is about 2 ⁇ M).
- the solution was brought to 10 mM phosphate buffer (pH 7), using 100 mM concentrated phosphate stock buffer, and salt (from a 2 M aqueous NaCl solution) added to 0.05 M NaCl after 0.5 h, allowed to stand for about 8 h, then further addition of NaCl to 0.1 M, and after another standing time of about 8 h, another addition of NaCl to about 0.3 M and allowed to stand for a final ⁇ 8 h.
- colloids were centrifuged for 30 min at 18,000 rpm using 1.5 mL eppendorf tubes.
- Nanoparticle probes with appropriate probe oligonucleotides were prepared by derivatizing 10 mL of aqueous colloid with 8-10 OD of alkanethiol- ohgonucleotide (final oligonucleotide concentration is about 2 ⁇ M).
- the oily precipitate is washed with 0.3 M NaCl, 10 mM phosphate buffer (pH 7) solution in the same volume as the discarded supernatant, centrifuged, and dispersed in 0.3 M NaCl, 10 mM phosphate buffer (pH 7), 0.01% azide solution.
- the final colloids were refrigerated and stored for later use.
- the core/shell nanoparticle oligonucleotide conjugates prepared by the two methods described above were compared using a salting procedure as described in each of the above 2 methods.
- the salt concentration was increased from 0.05 M NaCl to 0.1 M NaCl, and then to 0.3 M NaCl.
- the salt concentration was increased in two steps: directly to 0.1 M NaCl and then to 0.3 M NaCl.
- Method 1 generates a higher quality nanoparticle-oligonucleotide conjugate when compared with those prepared by method 2. Via method 2, about 15% of the nanoparticle-oligonucleotide conjugates are not of adequate quality. Core/shell nanoparticle-oligonucleotide conjugate quality is evaluated by UV-Vis spectroscopy.
- Acceptable quality conjugates show a UV-Vis spectrum with the surface plasmon absorption peak centering at 400 nm, while poor (inadequate) quality conjugates show an absorption peak which is significantly damped and red-shifts to 450-550 mn.
- the core/shell particles undergo hybridization with complementary linking oligonucleotides to form aggregated structures with a concomitant darkening of the solution; ( Figure 2).
- the nanoparticles comprising these silver/gold core/shell aggregate structures can be disassembled by heating the aggregates above the "melting temperature" (T m ) of the duplex linkers ( Figure 1 D).
- UV- vis spectroscopy shows a red-shifting and dampening of the plasmon resonance of the core/shell particles upon DNA-induced assembly, ( Figure ID, inset).
- the oligonucleotide sequences are provided in Figure 2A.
- the Figure ID inset shows the UV- visible spectra of dispersed oligonucleotide-modified silver/gold core/shell particles (solid line) and aggregated (dotted line) oligonucleoti.de- modified silver/gold core/shell particles fonned via hybridization.
- UV-Vis spectra of silver and silver/gold core/shell particles were obtained using a HP 8453 diode array spectrophotometer.
- the thermal denaturation experiment ( Figure ID) was performed using an HP 8453 diode array spectrophotometer equipped with a HP 89090a Peltier temperature controller.
- the UV-Vis signature of the silver/gold core/shell probe/target oligonucleotide aggregates was recorded at 1 min intervals, as the temperature was increased from 25 to 70 °C with a holding time of 1 min/deg.
- the particle assembly process induced by the complementary DNA also can be monitored on a C 18 -reverse-phase alumina TLC plate, allowing for comparison with the pure gold system.
- the spot test results shown in Figure 2b and 2c were obtained as follows: a solution of the appropriate oligonucleotide target (24 pmol, 3 ⁇ L) was added to a 600 ⁇ L thin-wall PCR tube containing 200 ⁇ L of each silver/gold core/shell nanoparticle- oligonucleotide conjugates. After standing for 30 min at room temperature, the solution was transferred to a temperature controlled electro thermal heater.
- the mixture was allowed to equilibrate for 5 min at which time 2.5 ⁇ L aliquots of the silver-gold probe/target oligonucleotide solution were transferred with a pipet onto the reverse-phase alumina plate and allowed to dry.
- Example 3 Comparison of silver, silver/gold core/shell and silver/gold alloy nanoparticle oligonucleotide conjugates
- Example 1 (method no. 1) were compared to gold nanoparticles 2 and to silver/gold alloy nanoparticles.
- the silver/gold alloy nanoparticles were prepared by the method of Wang, Z. L.; El-
- the UV-Vis spectrum of the silver/gold core/shell nanoparticle exhibits a surface plasmon band at 400 nm with a FWHM of 58 nm (0.45 eV).
- Figure 7 shows a comparison of the relative stabilities of Ag, Ag/Au alloy, and Ag/Aucoresheil nanoparticle-DNA conjugates at different salt concentrations. The surface plasmon bands were monitored at 400 nm for Ag and Ag/Au particles, and at 430 nm for Ag/Au alloy particles, respectively.
- the core/shell nanoparticle/DNA conjugate can reversibly hybridize with target DNA in a salt concentration range from 0.1 to 1.0 M, and the resulting nanoparticle aggregates can "melt" off when heated above the melting temperature. This hybridization/dehybridization process is completely reversible for core/shell particles.
- the core/shell particle/DNA conjugates show no degradation after 100 cycles. In sharp contrast, the silver/gold-alloy particle/DNA conjugates irreversibly aggregate even under minimal salt concentrations (-0.05 M NaCl) necessary to effect hybridization of oligonucleotides.
- This Example describes the preparation of magnetic gold nanoparticles by the inventive process.
- Fe 3 O magnetic core nanoparticles were prepared.
- goldshells were grown on the magnetic cores.
- Other magnetic cores could be used in place of Fe 3 O such as Co, Fe, Ni, FePt, and FeAu.
- Figure 6 illustrates the core/shell approach to preparing magnetic gold nanoparticles.
- Fe 3 O 4 nanoparticles were prepared as follows. First, 0.86 g FeCl »4H 2 O and 2.35 g FeCl 3 »6H O were dissolved in 50 mL nanopure water under an inert Ar(g ) atmosphere. The solution was heated to 80 °C with vigorous stirring. A solution of 100 mg of neat decanoic acid in 5 mL of acetone was added to the Fe solution, followed by 5 mL of 28%) (w/w) NH 3 /H 2 O. Additional neat decanoic acid was added to the suspension in 5x 0.2 g amounts over 5 min. The reaction was allowed to proceed for 30 min at 80 °C with stirring to produce a stable, water-based suspension.
- the procedure for growing goldshell is similar to that of core/shell silver/goldpreparation described in Example 1.
- the UV-Vis spectrum, of the Fe 3 O /gold shell growth is shown in Figure 4.
- Figure 5 illustrates that in an applied magnetic field, Fe 3 O /gold core/shell particles behave as super paramagnetic particles.
- Figure 5 illustrates that the gold nanoparticles become colorless after 12 hours in a magnetic field.
- This Example describes the preparation of magnetic gold nanoparticles by the inventive process.
- Co magnetic core nanoparticles were prepared.
- goldshells were grown on the Co magnetic cores.
- O-dichlorobenzene (15.9 g), trioctylphosphine oxide (0.1 g), and 0.2 ml of oleic acid were placed into a 50-ml tri-neck flask, and heated to 180 °C.
- a solution of Co 2 (CO) 8 (0.65 g in 3 ml of O-dichlorobenzene) was added by injection into the heated solution. After this addition, the reaction temperature was maintained at 180 °C for an hour. The reaction solution was then cooled to room temperature. Co nanoparticles of about 12 nm in diameter were produced in a yield of 95%.
- reaction solution 50 ⁇ l - 500 ⁇ l/min. After sufficient amount of stock solutions 1 and 2 were added (about 5% excess), the reaction solution was maintained at 180 °C for another 30 mins. Subsequently, the reaction was cooled to room temperature in order to halt it.
- the gold shell stock solutions were prepared as follows: stock solution 1, HAuCl 4 »3H O (0.1 g) and n-hexadecyltrimetyl ammonium bromide (O.lg) were dissolved in O-dichlorobenzene (10 g); stock solution 2, 1,1-hexadecanediol (0.12g) was dissolved in O- dichlorobenzene (10 g).
Abstract
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Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003081202A2 (en) | 2001-11-09 | 2003-10-02 | Nanosphere, Inc. | Bioconjugate-nanoparticle probes |
WO2003095973A2 (en) | 2002-05-07 | 2003-11-20 | Northwestern University | Nanoparticle probes with raman spectroscopic fingerprints for analyte detection |
EP1532274A2 (en) * | 2002-06-28 | 2005-05-25 | Purdue Research Foundation | Magnetic nanomaterials and methods for detection of biological materials |
US7485471B1 (en) | 2004-12-17 | 2009-02-03 | Intel Corporation | Detection of enhanced multiplex signals by surface enhanced Raman spectroscopy |
WO2009056401A1 (en) | 2007-09-27 | 2009-05-07 | Basf Se | Isolable and redispersable transition metal nanoparticles their preparation and use as ir absorbers |
WO2009156990A1 (en) * | 2008-06-23 | 2009-12-30 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Core-shell metallic nanoparticles, methods of production thereof, and ink compositions containing same |
WO2010016798A1 (en) * | 2008-08-06 | 2010-02-11 | Agency For Science, Technology And Research | Nanocomposites |
US7807372B2 (en) | 2007-06-04 | 2010-10-05 | Northwestern University | Screening sequence selectivity of oligonucleotide-binding molecules using nanoparticle based colorimetric assay |
WO2011113054A2 (en) | 2010-03-12 | 2011-09-15 | Aurasense Llc | Crosslinked polynucleotide structure |
CN102298055A (en) * | 2011-07-21 | 2011-12-28 | 南京博天科智生物技术有限公司 | Human blood H-FABP nano-gold labeled test paper and preparation method thereof |
US8323888B2 (en) | 1996-07-29 | 2012-12-04 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
WO2013036974A1 (en) | 2011-09-11 | 2013-03-14 | Aurasense, Llc | Cellular uptake control systems |
CN103159771A (en) * | 2013-03-29 | 2013-06-19 | 山东科技大学 | Technique for synthesizing porphyrin-functionalized cobalt oxide nanoparticles by one-step method |
WO2015013675A1 (en) | 2013-07-25 | 2015-01-29 | Aurasense Therapeutics, Llc | Spherical nucleic acid-based constructs as immunoregulatory agents |
US9139827B2 (en) | 2008-11-24 | 2015-09-22 | Northwestern University | Polyvalent RNA-nanoparticle compositions |
US9719089B2 (en) | 2005-06-14 | 2017-08-01 | Northwestern University | Nucleic acid functionalized nonoparticles for therapeutic applications |
US9757475B2 (en) | 2009-10-30 | 2017-09-12 | Northwestern University | Templated nanoconjugates |
US9889209B2 (en) | 2011-09-14 | 2018-02-13 | Northwestern University | Nanoconjugates able to cross the blood-brain barrier |
US9890427B2 (en) | 2007-02-09 | 2018-02-13 | Northwestern University | Particles for detecting intracellular targets |
US10098958B2 (en) | 2009-01-08 | 2018-10-16 | Northwestern University | Delivery of oligonucleotide functionalized nanoparticles |
US10301622B2 (en) | 2013-11-04 | 2019-05-28 | Northwestern University | Quantification and spatio-temporal tracking of a target using a spherical nucleic acid (SNA) |
US10370656B2 (en) | 2006-06-08 | 2019-08-06 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
US10837018B2 (en) | 2013-07-25 | 2020-11-17 | Exicure, Inc. | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
US11213593B2 (en) | 2014-11-21 | 2022-01-04 | Northwestern University | Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
US11957788B2 (en) | 2014-06-04 | 2024-04-16 | Exicure Operating Company | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
Families Citing this family (147)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6506564B1 (en) * | 1996-07-29 | 2003-01-14 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US7098320B1 (en) | 1996-07-29 | 2006-08-29 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US7169556B2 (en) * | 1996-07-29 | 2007-01-30 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6750016B2 (en) * | 1996-07-29 | 2004-06-15 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6984491B2 (en) * | 1996-07-29 | 2006-01-10 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6974669B2 (en) * | 2000-03-28 | 2005-12-13 | Nanosphere, Inc. | Bio-barcodes based on oligonucleotide-modified nanoparticles |
US20050037397A1 (en) * | 2001-03-28 | 2005-02-17 | Nanosphere, Inc. | Bio-barcode based detection of target analytes |
US20030096321A1 (en) * | 1999-05-19 | 2003-05-22 | Jose Remacle | Method for the identification and/or the quantification of a target compound obtained from a biological sample upon chips |
AU774593C (en) * | 2000-01-13 | 2005-06-23 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6743395B2 (en) * | 2000-03-22 | 2004-06-01 | Ebara Corporation | Composite metallic ultrafine particles and process for producing the same |
AU7687001A (en) * | 2000-07-11 | 2002-01-21 | Nanospherre Inc | Method of detection by enhancement of silver staining |
US20060040286A1 (en) * | 2001-03-28 | 2006-02-23 | Nanosphere, Inc. | Bio-barcode based detection of target analytes |
US20030113740A1 (en) * | 2001-04-26 | 2003-06-19 | Mirkin Chad A. | Oligonucleotide-modified ROMP polymers and co-polymers |
US7147687B2 (en) * | 2001-05-25 | 2006-12-12 | Nanosphere, Inc. | Non-alloying core shell nanoparticles |
US7238472B2 (en) | 2001-05-25 | 2007-07-03 | Nanosphere, Inc. | Non-alloying core shell nanoparticles |
GR1004178B (en) * | 2001-11-29 | 2003-03-05 | "����������" | Integrated optoelectronic silicon biosensor for the detection of biomolecules labeled with chromophore groups or nanoparticles |
US7282710B1 (en) * | 2002-01-02 | 2007-10-16 | International Business Machines Corporation | Scanning probe microscopy tips composed of nanoparticles and methods to form same |
WO2003072830A1 (en) * | 2002-02-22 | 2003-09-04 | Purdue Research Foundation | Magnetic nanomaterials and methods for detection of biological materials |
US20030190475A1 (en) * | 2002-04-09 | 2003-10-09 | Everett Carpenter | Magnetic nanoparticles having passivated metallic cores |
JP2005532456A (en) * | 2002-07-02 | 2005-10-27 | ナノスフェアー インコーポレイテッド | Nanoparticle polyanion complex and its use in the detection of analytes |
TWI242478B (en) * | 2002-08-01 | 2005-11-01 | Masami Nakamoto | Metal nanoparticle and process for producing the same |
US20040156846A1 (en) * | 2003-02-06 | 2004-08-12 | Triton Biosystems, Inc. | Therapy via targeted delivery of nanoscale particles using L6 antibodies |
EP1597399A2 (en) * | 2003-02-27 | 2005-11-23 | Nanosphere, Inc. | Label-free gene expression profiling with universal nanoparticle probes in microarray assay format |
JP4603487B2 (en) * | 2003-03-12 | 2010-12-22 | インテル・コーポレーション | Chemical sensitization of surface-sensitized Raman spectroscopy using lithium salts |
US7029514B1 (en) * | 2003-03-17 | 2006-04-18 | University Of Rochester | Core-shell magnetic nanoparticles and nanocomposite materials formed therefrom |
US20050250094A1 (en) * | 2003-05-30 | 2005-11-10 | Nanosphere, Inc. | Method for detecting analytes based on evanescent illumination and scatter-based detection of nanoparticle probe complexes |
US7232474B2 (en) * | 2003-07-09 | 2007-06-19 | National Research Council Of Canada | Process for producing gold nanoparticles |
JP5082187B2 (en) * | 2003-10-06 | 2012-11-28 | 日産自動車株式会社 | Method for producing electrode catalyst particles for polymer electrolyte fuel cell |
JP4207754B2 (en) * | 2003-10-31 | 2009-01-14 | 和光純薬工業株式会社 | Immunological measurement method using magnetic substance |
US20050191665A1 (en) * | 2003-12-29 | 2005-09-01 | Xing Su | Composite organic-inorganic nanoclusters |
JP3912391B2 (en) * | 2004-05-26 | 2007-05-09 | ソニー株式会社 | Metallic magnetic nanoparticles and production method thereof |
US7718094B2 (en) * | 2004-06-18 | 2010-05-18 | The Research Foundation Of State University Of New York | Preparation of metallic nanoparticles |
CA2572178A1 (en) * | 2004-07-26 | 2006-03-16 | Nanosphere, Inc. | Method for distinguishing methicillin resistant s. aureus from methicillin sensitive s. aureus in a mixed culture |
US9494581B2 (en) | 2004-08-24 | 2016-11-15 | University Of Wyoming | System and method for Raman spectroscopy assay using paramagnetic particles |
US7776547B2 (en) * | 2004-08-26 | 2010-08-17 | Intel Corporation | Cellular analysis using Raman surface scanning |
WO2007018562A2 (en) * | 2004-09-22 | 2007-02-15 | Nanolab, Inc. | Nanospearing for molecular transportation into cells |
CA2583729A1 (en) | 2004-10-21 | 2006-05-04 | Englebienne & Associates | Stable metal/conductive polymer composite colloids and methods for making and using the same |
US7855021B2 (en) * | 2004-12-22 | 2010-12-21 | Brookhaven Science Associates, Llc | Electrocatalysts having platium monolayers on palladium, palladium alloy, and gold alloy core-shell nanoparticles, and uses thereof |
US8084275B2 (en) * | 2005-02-08 | 2011-12-27 | Fujifilm Corporation | Magnetic composite body, production method thereof, method for removing substance with mannose on its surface, and method for concentrating substance with mannose on its surface |
JP4791867B2 (en) * | 2005-03-31 | 2011-10-12 | 日立マクセル株式会社 | Detection method of test substance using precious metal coated magnetic particles |
JP4665144B2 (en) * | 2005-03-31 | 2011-04-06 | 独立行政法人物質・材料研究機構 | Humidity sensor using stress change with volume expansion of polymer film |
US7700193B2 (en) * | 2005-04-08 | 2010-04-20 | Industrial Technology Research Institute | Core-shell structure with magnetic, thermal, and optical characteristics and manufacturing method thereof |
WO2006125124A2 (en) * | 2005-05-18 | 2006-11-23 | Nanosphere, Inc. | Substrate functionalization method for high sensitivity applications |
US8062552B2 (en) * | 2005-05-19 | 2011-11-22 | Brookhaven Science Associates, Llc | Electrocatalyst for oxygen reduction with reduced platinum oxidation and dissolution rates |
WO2007002567A2 (en) * | 2005-06-23 | 2007-01-04 | Nanosphere, Inc. | Selective isolation and concentration of nucleic acids from complex samples |
JP2007040978A (en) * | 2005-06-30 | 2007-02-15 | Fujifilm Corp | Method for separating objective element using magnetic nanoparticles |
US7704919B2 (en) * | 2005-08-01 | 2010-04-27 | Brookhaven Science Associates, Llc | Electrocatalysts having gold monolayers on platinum nanoparticle cores, and uses thereof |
TWI428937B (en) | 2005-08-12 | 2014-03-01 | Cambrios Technologies Corp | Nanowires-based transparent conductors |
ATE489482T1 (en) * | 2005-08-19 | 2010-12-15 | Nanosphere Inc | METHOD FOR PRODUCING HYBRID SUBSTRATES WITH DNA AND ANTIBODIES AND USES THEREOF |
US7736910B2 (en) * | 2005-10-04 | 2010-06-15 | Calypte Biomedical Corporation | One-step production of gold sols |
US20070098640A1 (en) * | 2005-11-02 | 2007-05-03 | General Electric Company | Nanoparticle-based imaging agents for X-ray/computed tomography |
JP2009523071A (en) * | 2005-11-28 | 2009-06-18 | ナショナル リサーチ カウンシル オブ カナダ | Multifunctional nanostructure and manufacturing method thereof |
US20070166730A1 (en) * | 2006-01-19 | 2007-07-19 | Menon & Associates, Inc. | Magnetic resonance system and method to detect and confirm analytes |
JP2007205911A (en) * | 2006-02-02 | 2007-08-16 | Sekisui Chem Co Ltd | Gold/iron oxide composite magnetic particle, magnetic particle for measuring immunity, and immunoassay |
US7790066B2 (en) * | 2006-03-03 | 2010-09-07 | William Marsh Rice University | Nanorice particles: hybrid plasmonic nanostructures |
CA2643691A1 (en) * | 2006-03-08 | 2007-09-13 | Northwestern University | Photoinduced phase separation of gold in two-component nanoparticles to form nanoprisms |
WO2007121032A2 (en) | 2006-03-23 | 2007-10-25 | The Research Foundation Of State University Of New York | Optical methods and systems for detecting a constituent in a gas containing oxygen in harsh environments |
GB0605965D0 (en) | 2006-03-24 | 2006-05-03 | Univ East Anglia | Fluorescence based detection of substances |
US20080085508A1 (en) * | 2006-05-11 | 2008-04-10 | Nanosphere, Inc. | Non-nucleic acid based biobarcode assay for detection of biological materials |
US7625637B2 (en) * | 2006-05-31 | 2009-12-01 | Cabot Corporation | Production of metal nanoparticles from precursors having low reduction potentials |
US20100035243A1 (en) * | 2006-07-10 | 2010-02-11 | Nanosphere, Inc. | Ultra-sensitive detection of analytes |
ITFI20060180A1 (en) * | 2006-07-20 | 2008-01-21 | Acta Spa | ANODIC CATALYSTS CONSISTING OF NOBLE METALS SPONTANEOUSLY DEPOSITED ON NANOSTRUCTURED CATALYSTS BASED ON TRANSITIONAL METALS, THEIR PREPARATION AND USE AND FUEL CELLS THAT CONTAIN THEM. |
US7502106B2 (en) * | 2006-09-21 | 2009-03-10 | Honeywell International Inc. | SERS analyzer |
US8018568B2 (en) | 2006-10-12 | 2011-09-13 | Cambrios Technologies Corporation | Nanowire-based transparent conductors and applications thereof |
CN102324462B (en) | 2006-10-12 | 2015-07-01 | 凯博瑞奥斯技术公司 | Nanowire-based transparent conductors and applications thereof |
US7727776B2 (en) * | 2006-10-24 | 2010-06-01 | Honeywell International Inc. | Core-shell nanoparticles for detection based on SERS |
EP2092077A2 (en) * | 2006-11-08 | 2009-08-26 | Northwestern University | Colorimetric detection of metallic ions in aqueous media using functionlized nanoparticles |
JP2008196927A (en) * | 2007-02-13 | 2008-08-28 | Fujifilm Corp | Detection method of object material accompanied by removal of probe |
JP2010520749A (en) * | 2007-02-27 | 2010-06-17 | ノースウェスタン ユニバーシティ | Binding molecules to nanoparticles |
JP4854547B2 (en) * | 2007-03-09 | 2012-01-18 | 独立行政法人科学技術振興機構 | Silver fine particle and nucleic acid complex and method for producing the same |
JP6098860B2 (en) | 2007-04-20 | 2017-03-22 | シーエーエム ホールディング コーポレーション | Composite transparent conductor and device |
CN101674906A (en) * | 2007-04-25 | 2010-03-17 | 丰田自动车株式会社 | Make the method for core/shell composite nanoparticle |
US20080293588A1 (en) * | 2007-05-11 | 2008-11-27 | Northwestern University | Nanodisk codes |
PT2178796T (en) | 2007-07-11 | 2021-03-29 | Clene Nanomedicine Inc | Continuous methods for treating liquids and manufacturing certain constituents (e.g., nanoparticles) in liquids, apparatuses and nanoparticles and nanoparticle/liquid solution(s) resulting therefrom |
US7829735B2 (en) * | 2007-10-26 | 2010-11-09 | Northwestern University | Universal phosphoramidite for preparation of modified biomolecules and surfaces |
US8679458B2 (en) | 2007-11-07 | 2014-03-25 | Battelle Memorial Institute | Functionalized magnetic nanoparticle analyte sensor |
US20100105024A1 (en) * | 2008-01-14 | 2010-04-29 | Transgenex Nanobiotech, Inc. | Rapid test including genetic sequence probe |
US20090181361A1 (en) * | 2008-01-14 | 2009-07-16 | Weidong Xu | Rapid test for detecting infection |
WO2009090748A1 (en) * | 2008-01-17 | 2009-07-23 | Applied Nanoparticle Laboratory Corporation | Silver composite nanoparticle and process and apparatus for producing the same |
JP5539962B2 (en) | 2008-04-25 | 2014-07-02 | ノースウェスタン、ユニバーシティ | Nanostructure suitable for sequestering cholesterol |
KR101153748B1 (en) * | 2008-05-07 | 2012-06-14 | 재단법인서울대학교산학협력재단 | NOVEL Au/Ag CORE SHELL COMPOSITE USEFUL FOR BIOSENNOVEL Au/Ag CORE SHELL COMPOSITE USEFUL FOR BIOSENSOR SOR |
US8304365B2 (en) * | 2008-05-16 | 2012-11-06 | Utc Power Corporation | Stabilized platinum catalyst |
WO2009139749A1 (en) * | 2008-05-16 | 2009-11-19 | Utc Power Corporation | A fuel cell having a stabilized cathode catalyst |
US7879625B1 (en) | 2008-12-03 | 2011-02-01 | The United States Of America As Represented By The Secretary Of The Navy | Preparation of SERS substrates on silica-coated magnetic microspheres |
US9387452B2 (en) | 2009-01-14 | 2016-07-12 | Gr Intellectual Reserve, Llc. | Continuous methods for treating liquids and manufacturing certain constituents (e.g., nanoparticles) in liquids, apparatuses and nanoparticles and nanoparticle/liquid solution(s) resulting therefrom |
DK2387478T3 (en) | 2009-01-15 | 2018-10-29 | Clene Nanomedicine Inc | CONTINUOUS PROCESS AND APPARATUS FOR THE CREATION OF GOLD-BASED NANOPARTICLES |
KR101546673B1 (en) * | 2009-01-15 | 2015-08-25 | 삼성전자주식회사 | Toner for electrophotographic and process for preparing the same |
US20110033940A1 (en) * | 2009-01-30 | 2011-02-10 | Northwestern University | Click chemistry, molecular transport junctions, and colorimetric detection of copper |
EP2411402B1 (en) * | 2009-03-23 | 2014-02-12 | Yeditepe Universitesi | Synthesis of oligonucleotide mediated gold core- silver shell nanoparticles |
KR20170072367A (en) | 2009-04-15 | 2017-06-26 | 노오쓰웨스턴 유니버시티 | Delivery of oligonucleotide-functionalized nanoparticles |
KR101040903B1 (en) | 2009-06-24 | 2011-06-16 | 성균관대학교산학협력단 | A platinium catalyst coated by gold nanoparticle and a method for preparation thereof |
SG10201403497QA (en) | 2009-07-08 | 2014-10-30 | Gr Intellectual Reserve Llc | Novel gold-based nanocrystals for medical treatments and electrochemical manufacturing processes therefor |
WO2011031999A2 (en) * | 2009-09-10 | 2011-03-17 | Purdue Research Foundation | Multi-component nanoparticle structure having detectable magnetic resonance properties |
US20130029360A1 (en) * | 2009-12-11 | 2013-01-31 | Snu R&Db Foundation | Dimeric core-shell nanostructure labeled with raman active molecule localized at interparticle junction, use thereof, and method for preparing the same |
US20130034599A1 (en) | 2010-01-19 | 2013-02-07 | Northwestern University | Synthetic nanostructures including nucleic acids and/or other entities |
SG10201500798UA (en) | 2010-02-05 | 2015-03-30 | Cambrios Technologies Corp | Photosensitive ink compositions and transparent conductors and method of using the same |
JP5543021B2 (en) * | 2010-06-13 | 2014-07-09 | オーシャンズ キング ライティング サイエンスアンドテクノロジー カンパニー リミテッド | Preparation method of core-shell magnetic alloy nanoparticles |
FR2965719B1 (en) * | 2010-10-07 | 2014-05-23 | Oreal | PARTICLE COMPRISING TWO PLASMONIC METALS |
CN102554252A (en) * | 2010-12-17 | 2012-07-11 | 中国科学技术大学 | Synthesizing method of porous bimetal nanostructure |
WO2012104831A1 (en) | 2011-02-03 | 2012-08-09 | Metallo Therapy Ltd. | Surface-modified heavy metal nanoparticles, compositions and uses thereof |
CN102672167B (en) * | 2011-03-16 | 2014-04-02 | 首都师范大学 | Preparation and application of novel triangular sliver-silver sulfide nanocomposite particle |
CN102407340B (en) * | 2011-04-18 | 2013-06-12 | 中国人民解放军总后勤部军需装备研究所 | Preparation method of micro powder with silver/carbon nuclear shell structure |
US9605304B2 (en) * | 2011-07-20 | 2017-03-28 | The Hong Kong Polytechnic University | Ultra-stable oligonucleotide-gold and-silver nanoparticle conjugates and method of their preparation |
CN102380335B (en) * | 2011-09-15 | 2014-03-12 | 东南大学 | Core-shell hydrogel colloid crystal microballoon, its preparation method and its purpose |
US9079249B2 (en) * | 2011-09-30 | 2015-07-14 | Uchicago Argonne, Llc | Intermetallic nanoparticles |
CN102519948B (en) * | 2011-11-24 | 2014-05-07 | 中国科学院宁波材料技术与工程研究所 | Detection method for hexavalent chromium ions |
WO2013170229A1 (en) * | 2012-05-11 | 2013-11-14 | Vanderbilt University | Detecting antigens such as bacterial quorum sensing proteins |
CN104507574B (en) * | 2012-07-09 | 2017-09-01 | 丰田自动车株式会社 | Exhaust gas purification catalyst and its manufacture method |
US9512468B2 (en) | 2012-11-06 | 2016-12-06 | Industrial Technology Research Institute | Detection method uses magnetic and detectable nanoparticles with oligonucleotides attached thereto |
CN102962474B (en) * | 2012-12-13 | 2014-10-22 | 北京航空航天大学 | Controllable synthetic method for preparing gold-nickel core-shell nanostructure with ethylene glycol system |
US9557324B2 (en) * | 2013-02-19 | 2017-01-31 | Samsung Electronics., Ltd. | Conjugate of a metal nanoparticle and a light emitting material |
CN103265950B (en) * | 2013-06-09 | 2015-09-02 | 南京大学 | Boron nitride nanosheet/gold nanoclusters matrix material and method for making thereof and the application in bioanalysis |
US10568898B2 (en) | 2013-08-13 | 2020-02-25 | Northwestern University | Lipophilic nanoparticles for drug delivery |
CN103447547B (en) * | 2013-08-28 | 2015-06-24 | 同济大学 | Method for preparing ferroferric oxide/gold nano-composite particles of star-like structure in micro-emulsion |
KR101427146B1 (en) | 2013-11-13 | 2014-08-07 | 단국대학교 산학협력단 | Kit for analyzing biomolecules and method for analyzing biomolecules using the same |
US20170199185A1 (en) * | 2014-05-30 | 2017-07-13 | Dai Nippon Toryo Co., Ltd. | Suspension of Gold-Coated Silver Nanoplates |
CN104096849B (en) * | 2014-07-15 | 2016-10-19 | 中国石油大学(华东) | The preparation method of gold core silver shell nano-probe and the application in cyanide ion colorimetric detection thereof |
CA2963931A1 (en) | 2014-10-06 | 2016-04-14 | Exicure, Inc. | Anti-tnf compounds |
CN104439276B (en) * | 2014-11-30 | 2016-04-13 | 湖南科技大学 | A kind of quick method and product preparing hollow porous silica/argentum nano composite material |
WO2016141193A1 (en) | 2015-03-03 | 2016-09-09 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Enhanced plasmonic nanoparticles for cancer therapy and diagnostics |
CN104668580A (en) * | 2015-03-06 | 2015-06-03 | 天津大学 | Preparation of ferroferric oxide/gold nanometer composite material and method for rapidly detecting rhodamine molecules by using ferroferric oxide/gold nanometer composite material |
US10078092B2 (en) | 2015-03-18 | 2018-09-18 | Northwestern University | Assays for measuring binding kinetics and binding capacity of acceptors for lipophilic or amphiphilic molecules |
JP6944438B2 (en) * | 2015-08-04 | 2021-10-06 | ゾエティス サービシズ リミテッド ライアビリティ カンパニー | Signal amplification in solution-based plasmon-specific binding partner assay |
US9627114B2 (en) * | 2015-09-14 | 2017-04-18 | Elwha Llc | Magnetic plasmonic nanoparticle positioned on a magnetic plasmonic substrate |
US9627115B2 (en) * | 2015-09-14 | 2017-04-18 | Elwha Llc | Magnetic plasmonic nanoparticle dimer |
JP2017150865A (en) * | 2016-02-23 | 2017-08-31 | コニカミノルタ株式会社 | Gas detection method and gas detection device |
CN105598442B (en) * | 2016-02-25 | 2019-01-22 | 天津工业大学 | One-dimensional chain Au-Ag core-shell nanostructure, self-assembly preparation method thereof and SERS application |
WO2017193087A1 (en) | 2016-05-06 | 2017-11-09 | Exicure, Inc. | Liposomal spherical nucleic acid (sna) constructs prsenting antisense oligonucleotides(aso) for specific knockdown of interleukin 17 receptor mrna |
CN105903979B (en) * | 2016-05-13 | 2017-12-26 | 吉林师范大学 | A kind of Fe3O4The preparation method of@Au nucleocapsid functional materials |
CN106111974B (en) * | 2016-07-26 | 2017-11-28 | 江南大学 | A kind of preparation method and application of gold and silver core-shell particles gold nanorods self-assembled structures |
JP7254349B2 (en) * | 2016-10-26 | 2023-04-10 | インテグレーテッド ナノ-テクノロジーズ,インコーポレイティド | System and method for optical detection of biomolecular targets |
CN106735287B (en) * | 2016-11-28 | 2018-08-28 | 东北大学 | A kind of monodispersed FePt/Fe3O4Mix the preparation method of nano particle |
US11696954B2 (en) | 2017-04-28 | 2023-07-11 | Exicure Operating Company | Synthesis of spherical nucleic acids using lipophilic moieties |
US10178735B1 (en) | 2017-08-22 | 2019-01-08 | Northrop Grumman Systems Corporation | Dynamically tunable materials for parity-time symmetric electro-optical devices |
KR102064961B1 (en) * | 2017-12-13 | 2020-01-10 | 주식회사 포스코 | Magnetic nanoparticles and method for amplification of signal in lateral flow assay by using the same |
CN108097950A (en) * | 2017-12-25 | 2018-06-01 | 浙江理工大学 | A kind of nucleocapsid Ag@Fe3O4Complex microsphere, preparation method and applications |
CN110756796B (en) * | 2018-07-25 | 2021-08-27 | 石家庄铁道大学 | Composite powder with core-shell structure and preparation method thereof |
CN110227816B (en) * | 2019-07-15 | 2021-11-02 | 福州大学 | Honeysuckle nano-flower particles with core-shell structure and preparation method and application thereof |
KR102357642B1 (en) * | 2019-11-12 | 2022-02-07 | 충남대학교산학협력단 | Magnetoplasmonic particle |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000033079A1 (en) * | 1998-11-30 | 2000-06-08 | Nanosphere, Inc. | Nanoparticles with polymer shells |
Family Cites Families (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4193983A (en) * | 1978-05-16 | 1980-03-18 | Syva Company | Labeled liposome particle compositions and immunoassays therewith |
NL7807532A (en) * | 1978-07-13 | 1980-01-15 | Akzo Nv | METAL IMMUNO TEST. |
US4318707A (en) * | 1978-11-24 | 1982-03-09 | Syva Company | Macromolecular fluorescent quencher particle in specific receptor assays |
US4256834A (en) * | 1979-04-09 | 1981-03-17 | Syva Company | Fluorescent scavenger particle immunoassay |
US4261968A (en) * | 1979-05-10 | 1981-04-14 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4650770A (en) * | 1981-04-27 | 1987-03-17 | Syntex (U.S.A.) Inc. | Energy absorbing particle quenching in light emitting competitive protein binding assays |
US4713348A (en) * | 1983-04-05 | 1987-12-15 | Syntex (U.S.A.) Inc. | Fluorescent multiparameter particle analysis |
US5288609A (en) * | 1984-04-27 | 1994-02-22 | Enzo Diagnostics, Inc. | Capture sandwich hybridization method and composition |
US4868104A (en) * | 1985-09-06 | 1989-09-19 | Syntex (U.S.A.) Inc. | Homogeneous assay for specific polynucleotides |
US4996143A (en) * | 1985-12-23 | 1991-02-26 | Syngene, Inc. | Fluorescent stokes shift probes for polynucleotide hybridization |
US5137827A (en) * | 1986-03-25 | 1992-08-11 | Midwest Research Technologies, Inc. | Diagnostic element for electrical detection of a binding reaction |
US5514602A (en) * | 1986-06-09 | 1996-05-07 | Ortho Diagnostic Systems, Inc. | Method of producing a metal sol reagent containing colloidal metal particles |
US5360895A (en) * | 1987-04-22 | 1994-11-01 | Associated Universities, Inc. | Derivatized gold clusters and antibody-gold cluster conjugates |
US4853335A (en) * | 1987-09-28 | 1989-08-01 | Olsen Duane A | Colloidal gold particle concentration immunoassay |
US5460831A (en) * | 1990-06-22 | 1995-10-24 | The Regents Of The University Of California | Targeted transfection nanoparticles |
US5665582A (en) * | 1990-10-29 | 1997-09-09 | Dekalb Genetics Corp. | Isolation of biological materials |
AU8951191A (en) * | 1990-10-29 | 1992-05-26 | Dekalb Plant Genetics | Isolation of biological materials using magnetic particles |
US5294369A (en) * | 1990-12-05 | 1994-03-15 | Akzo N.V. | Ligand gold bonding |
EP0613585A4 (en) * | 1991-11-22 | 1995-06-21 | Univ California | Semiconductor nanocrystals covalently bound to solid inorganic surfaces using self-assembled monolayers. |
US5225064A (en) * | 1992-01-15 | 1993-07-06 | Enzyme Technology Research Group, Inc. | Peroxidase colloidal gold oxidase biosensors for mediatorless glucose determination |
US5472881A (en) * | 1992-11-12 | 1995-12-05 | University Of Utah Research Foundation | Thiol labeling of DNA for attachment to gold surfaces |
US5384265A (en) * | 1993-03-26 | 1995-01-24 | Geo-Centers, Inc. | Biomolecules bound to catalytic inorganic particles, immunoassays using the same |
US5637508A (en) * | 1993-03-26 | 1997-06-10 | Geo-Centers, Inc. | Biomolecules bound to polymer or copolymer coated catalytic inorganic particles, immunoassays using the same and kits containing the same |
US5681943A (en) * | 1993-04-12 | 1997-10-28 | Northwestern University | Method for covalently linking adjacent oligonucleotides |
US5543158A (en) * | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
DE4405156C1 (en) * | 1994-02-18 | 1995-10-26 | Univ Karlsruhe | Process for the production of coated polymeric microparticles |
US5521289A (en) * | 1994-07-29 | 1996-05-28 | Nanoprobes, Inc. | Small organometallic probes |
US5599668A (en) * | 1994-09-22 | 1997-02-04 | Abbott Laboratories | Light scattering optical waveguide method for detecting specific binding events |
US5609907A (en) * | 1995-02-09 | 1997-03-11 | The Penn State Research Foundation | Self-assembled metal colloid monolayers |
US6025202A (en) * | 1995-02-09 | 2000-02-15 | The Penn State Research Foundation | Self-assembled metal colloid monolayers and detection methods therewith |
CA2253710A1 (en) * | 1996-04-25 | 1997-10-30 | Spectrametrix Inc. | Analyte assay using particulate labels |
US6361944B1 (en) * | 1996-07-29 | 2002-03-26 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US7169556B2 (en) | 1996-07-29 | 2007-01-30 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6750016B2 (en) * | 1996-07-29 | 2004-06-15 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6984491B2 (en) | 1996-07-29 | 2006-01-10 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6506564B1 (en) * | 1996-07-29 | 2003-01-14 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
CA2262018C (en) * | 1996-07-29 | 2007-10-02 | Nanosphere Llc | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6582921B2 (en) * | 1996-07-29 | 2003-06-24 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses thereof |
US5830986A (en) * | 1996-10-28 | 1998-11-03 | Massachusetts Institute Of Technology | Methods for the synthesis of functionalizable poly(ethylene oxide) star macromolecules |
US5900481A (en) * | 1996-11-06 | 1999-05-04 | Sequenom, Inc. | Bead linkers for immobilizing nucleic acids to solid supports |
US5922537A (en) * | 1996-11-08 | 1999-07-13 | N.o slashed.AB Immunoassay, Inc. | Nanoparticles biosensor |
US5939021A (en) * | 1997-01-23 | 1999-08-17 | Hansen; W. Peter | Homogeneous binding assay |
JP4209471B2 (en) | 1997-02-20 | 2009-01-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Plasmon resonant particles, methods, and apparatus |
US6852252B2 (en) * | 1997-03-12 | 2005-02-08 | William Marsh Rice University | Use of metalnanoshells to impede the photo-oxidation of conjugated polymer |
US6344272B1 (en) * | 1997-03-12 | 2002-02-05 | Wm. Marsh Rice University | Metal nanoshells |
US6974669B2 (en) | 2000-03-28 | 2005-12-13 | Nanosphere, Inc. | Bio-barcodes based on oligonucleotide-modified nanoparticles |
US6149868A (en) * | 1997-10-28 | 2000-11-21 | The Penn State Research Foundation | Surface enhanced raman scattering from metal nanoparticle-analyte-noble metal substrate sandwiches |
US5990479A (en) * | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US5972615A (en) * | 1998-01-21 | 1999-10-26 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate disease |
US6428811B1 (en) * | 1998-03-11 | 2002-08-06 | Wm. Marsh Rice University | Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery |
US6699724B1 (en) * | 1998-03-11 | 2004-03-02 | Wm. Marsh Rice University | Metal nanoshells for biosensing applications |
DE19822996C1 (en) * | 1998-05-22 | 1999-04-22 | Siemens Ag | Temperature-resistant gradient material for heat shield or gas turbine blade |
US6290839B1 (en) * | 1998-06-23 | 2001-09-18 | Clinical Micro Sensors, Inc. | Systems for electrophoretic transport and detection of analytes |
US6406921B1 (en) * | 1998-07-14 | 2002-06-18 | Zyomyx, Incorporated | Protein arrays for high-throughput screening |
US6738163B2 (en) * | 1998-07-17 | 2004-05-18 | Gary Hochman | Method for transmission of facsimile image data |
US6306610B1 (en) * | 1998-09-18 | 2001-10-23 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6251303B1 (en) * | 1998-09-18 | 2001-06-26 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6203989B1 (en) * | 1998-09-30 | 2001-03-20 | Affymetrix, Inc. | Methods and compositions for amplifying detectable signals in specific binding assays |
US6277489B1 (en) * | 1998-12-04 | 2001-08-21 | The Regents Of The University Of California | Support for high performance affinity chromatography and other uses |
US6159378A (en) * | 1999-02-23 | 2000-12-12 | Battelle Memorial Institute | Apparatus and method for handling magnetic particles in a fluid |
JP2003504642A (en) * | 1999-07-16 | 2003-02-04 | ダブリューエム・マーシュ・ライス・ユニバーシティー | Metallic fine shell for biosensing applications |
CA2381568A1 (en) * | 1999-07-30 | 2001-02-08 | The Penn State Research Foundation | Instruments, methods and reagents for surface plasmon resonance |
AU774593C (en) * | 2000-01-13 | 2005-06-23 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6530944B2 (en) * | 2000-02-08 | 2003-03-11 | Rice University | Optically-active nanoparticles for use in therapeutic and diagnostic methods |
US6773823B2 (en) * | 2000-04-07 | 2004-08-10 | University Of New Orleans Research And Technology Foundation, Inc. | Sequential synthesis of core-shell nanoparticles using reverse micelles |
AU7687001A (en) * | 2000-07-11 | 2002-01-21 | Nanospherre Inc | Method of detection by enhancement of silver staining |
WO2002059226A2 (en) * | 2000-11-03 | 2002-08-01 | Wm. Marsh Rice University | Partial coverage metal nanoshells and method of making same |
WO2002046483A2 (en) * | 2000-12-06 | 2002-06-13 | Northwestern University | Silver stain removal from dna detection chips by cyanide etching or sonication |
US20030113740A1 (en) | 2001-04-26 | 2003-06-19 | Mirkin Chad A. | Oligonucleotide-modified ROMP polymers and co-polymers |
US7238472B2 (en) | 2001-05-25 | 2007-07-03 | Nanosphere, Inc. | Non-alloying core shell nanoparticles |
US7147687B2 (en) | 2001-05-25 | 2006-12-12 | Nanosphere, Inc. | Non-alloying core shell nanoparticles |
WO2003053535A2 (en) | 2001-08-03 | 2003-07-03 | Nanosphere, Inc. | Nanoparticle imaging system and method |
KR100438408B1 (en) * | 2001-08-16 | 2004-07-02 | 한국과학기술원 | Method for Synthesis of Core-Shell type and Solid Solution type Metallic Alloy Nanoparticles via Transmetalation Reactions and Their Applications |
ATE519438T1 (en) * | 2001-09-26 | 2011-08-15 | Rice University | OPTICALLY ABSORBING NANOPARTICLES FOR IMPROVED TISSUE REPAIR |
US6778316B2 (en) * | 2001-10-24 | 2004-08-17 | William Marsh Rice University | Nanoparticle-based all-optical sensors |
DE60228128D1 (en) | 2001-11-09 | 2008-09-18 | Nanosphere Inc | Bioconjugate NANOPARTICLE PROBES |
US6875475B2 (en) * | 2002-04-01 | 2005-04-05 | William Marsh Rice University | Methods for producing submicron metal line and island arrays |
US20030211488A1 (en) * | 2002-05-07 | 2003-11-13 | Northwestern University | Nanoparticle probs with Raman spectrocopic fingerprints for analyte detection |
JP2005532456A (en) | 2002-07-02 | 2005-10-27 | ナノスフェアー インコーポレイテッド | Nanoparticle polyanion complex and its use in the detection of analytes |
-
2001
- 2001-12-28 US US10/034,451 patent/US7238472B2/en not_active Expired - Lifetime
- 2001-12-28 AU AU2002239726A patent/AU2002239726A1/en not_active Abandoned
- 2001-12-28 WO PCT/US2001/050825 patent/WO2002096262A2/en not_active Application Discontinuation
-
2002
- 2002-05-22 JP JP2003514082A patent/JP3885054B2/en not_active Expired - Fee Related
- 2002-05-22 WO PCT/US2002/016382 patent/WO2003008539A2/en active IP Right Grant
- 2002-05-22 DE DE60218840T patent/DE60218840T2/en not_active Expired - Lifetime
- 2002-05-22 AT AT02775688T patent/ATE356826T1/en not_active IP Right Cessation
- 2002-05-22 AU AU2002341539A patent/AU2002341539B2/en not_active Ceased
- 2002-05-22 EP EP02775688A patent/EP1392872B1/en not_active Expired - Lifetime
-
2003
- 2003-03-26 US US10/397,579 patent/US7135055B2/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000033079A1 (en) * | 1998-11-30 | 2000-06-08 | Nanosphere, Inc. | Nanoparticles with polymer shells |
Cited By (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8323888B2 (en) | 1996-07-29 | 2012-12-04 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
WO2003081202A2 (en) | 2001-11-09 | 2003-10-02 | Nanosphere, Inc. | Bioconjugate-nanoparticle probes |
US7985539B2 (en) | 2002-05-07 | 2011-07-26 | Northwestern University | Nanoparticle probes with raman spectroscopic fingerprints for analyte detection |
WO2003095973A2 (en) | 2002-05-07 | 2003-11-20 | Northwestern University | Nanoparticle probes with raman spectroscopic fingerprints for analyte detection |
EP1532274A2 (en) * | 2002-06-28 | 2005-05-25 | Purdue Research Foundation | Magnetic nanomaterials and methods for detection of biological materials |
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US7485471B1 (en) | 2004-12-17 | 2009-02-03 | Intel Corporation | Detection of enhanced multiplex signals by surface enhanced Raman spectroscopy |
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AU2002341539B2 (en) | 2007-06-28 |
EP1392872A4 (en) | 2004-08-11 |
WO2003008539A2 (en) | 2003-01-30 |
US7135055B2 (en) | 2006-11-14 |
US20020177143A1 (en) | 2002-11-28 |
WO2003008539A3 (en) | 2003-08-21 |
DE60218840D1 (en) | 2007-04-26 |
JP2005520125A (en) | 2005-07-07 |
US20040038255A1 (en) | 2004-02-26 |
ATE356826T1 (en) | 2007-04-15 |
US7238472B2 (en) | 2007-07-03 |
JP3885054B2 (en) | 2007-02-21 |
AU2002239726A1 (en) | 2002-12-09 |
WO2002096262A3 (en) | 2003-02-20 |
EP1392872B1 (en) | 2007-03-14 |
EP1392872A2 (en) | 2004-03-03 |
DE60218840T2 (en) | 2007-11-29 |
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