Nanoparticulate chemical sensors using SERS

Information

  • Patent Grant
  • 8409863
  • Patent Number
    8,409,863
  • Date Filed
    Thursday, December 14, 2006
    17 years ago
  • Date Issued
    Tuesday, April 2, 2013
    11 years ago
Abstract
A system to selectively deliver relatively small analyte molecules of interest to a SERS-active nanoparticle surface while excluding dozens to hundreds of other species in the environment. In particular, the present invention provides a permselective film that renders the particles of interest as viable small molecule optically addressable sensors.
Description
TECHNICAL FIELD

The present invention relates to a system combining permselective films and surface enhanced Raman scattering (“SERS”)-active metal nanoparticles to make optically addressable, small-molecule chemical sensors.


BACKGROUND OF THE INVENTION

The development of methods and apparatus to detect small molecules using field-portable instrumentation is the ultimate goal of substantial research in the field of chemical analysis. In a research laboratory, small molecules are typically detected by gas chromatography (GC), liquid chromatography (LC), mass spectrometry (MS), or both (GC-MS, LC-MS). Despite intense effort, including efforts by the Defense Advanced Research Projects Agency (“DARPA”), over the past decade, miniaturization of this type of laboratory instrumentation while maintaining acceptable mass resolution and absolute sensitivity has proven impossible.


Field portable apparatus and methods for the detection of large molecules or proteins, cells, and DNA is possible. With respect to these large species, naturally-occurring detection molecules exist (such as antibodies or complementary sequences), to which detection tags (mostly optical) can be attached. Thus, 99% of all bioassays for these relatively large species involve a “sandwich” format, in which the analyte is immobilized by non-covalent interaction with a capture molecule, and quantified by non-covalent interaction with a labeled detection molecule.


Harnessing a New Detection Modality


Until recently, the only available optical detection tags were based on fluorescence. In U.S. Pat. No. 6,514,767, which patent is incorporated herein by reference in its entirety, Applicants described an optical detection tag based on surface enhanced Raman scattering (“SERS”). A tag consistent with the U.S. Pat. No. 6,514,767 patent is depicted in FIG. 1.1 With SERS, molecules in very close proximity to nanoscale roughness features on noble metal surfaces (typically gold, silver or copper) or suitably-sized metal nanoparticles give rise to million- to trillion-fold increases [known as enhancement factor (EF)] in scattering efficiency.2 With these tags, the SERS signal comes from submonolayers of reporter molecules sandwiched between the noble metal and a glass shell. In typical assays, the glass surface is coated with a biofuctional species that attaches to a bioanalyte of interest (e.g. an antibody for protein detection). These particles offer several significant advantages as optical detection tags: (i) they are excited in the near-infrared, eliminating the background visible fluorescence signal invariably associated with real-world measurements; (ii) different reporter molecules give rise to unique, narrow spectral features, allowing multiple signatures to be simultaneously detected; (iii) portable, robust and inexpensive instrumentation amenable to point-of-use implementation already exists; and (iv) exceptional sensitivity is possible.


Unfortunately, the SERS nanotags of FIG. 1 cannot be leveraged for detection of chemical warfare agents, e.g. sarin, because pairs of capture/detection molecules do not exist for low-molecular weight species, and more importantly, the Raman signal is (by design) locked in via the incorporation of a reporter molecule. Yet sarin and other low molecular weight species each have a distinctive SERS spectrum that could serve as a basis for ultrasensitive, accurate detection.


The present invention is directed toward overcoming one or more of the problems discussed above.


SUMMARY OF THE INVENTION

The present invention provides a system to selectively deliver relatively small analyte molecules of interest to a SERS-active nanoparticle surface while excluding dozens to hundreds of other species in the environment. In particular, the present invention provides a permselective film that renders the particles of interest as viable small molecule optically addressable sensors.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a schematic representation of a SERS nanotag structure;



FIG. 2 is a schematic and graphical representation of the structure and function of SERS-active nanoparticles consistent with the present invention;



FIG. 3 is a schematic representation of single point attached hyperbranched polymers; and



FIG. 4 is a graph of intensity as a function of wavelength depicting remote detection of SERS nanotags at 15 meters using a portable reader.



FIG. 5 is a graph of the SERS response of particles having permselective coatings in accordance with the present invention.



FIG. 6 is a graph of the SERS response of particles having permselective coatings in accordance with the present invention.



FIG. 7 is a graph of the SERS response of particles having permselective coatings in accordance with the present invention.





DETAILED DESCRIPTION OF THE INVENTION

The difficulty experienced in prior attempts to develop portable systems for the detection of smaller molecules may be addressed with specially prepared SERS-active nanoparticles. In particular, particles may be coated with thin films that exhibit molecular recognition capabilities that permit passage of species of interest to the nanoparticle surface while rejecting unwanted entities. One such system is depicted in FIG. 2. Once the analytes of interest reach the noble metal (typically Au) surface of the particle, they adsorb and give rise to a unique Raman spectrum. The selectivity of the thin molecular filtering film, which could comprise either discrete molecules or polymeric species, need not be perfect: low-level binding of undesired species (interferants) can be detected (and accounted for) because of their distinct Raman spectra. Nanoparticles modified with permselective films are referred to herein as “SERS nanofilters”.


Nanoparticles suitable for use as SERS nanofilters preferably have a maximum length of at most 300 nm and may be rod shaped, spherical, prisms, cubes arrowheads or other shapes. The nanoparticle will preferably have a diameter of less than 200 nm and most preferably between 40 nm and 100 nm. The nanoparticles have a spectroscopy active outer region. Typically, the outer region contains or is made of a metal such as Au, Ag, Cu, Na, K, Cr, Al, or Li.


The present invention also includes methods of manufacture of the SERS nanofilters and applications for their use. The present invention includes a method of detecting an analyte of interest by associating a SERS nanofilter as described herein with an analyte of interest in the presence of one or more interfering analytes. The detection method is predicated upon the permselective film allowing the analyte of interest to associate with the particle and preventing the interferent from associating with the particle. The method also includes obtaining a spectrum of the particle and associated analyte of interest.


The use of permselective films to selectively filter molecules, allowing certain ones to reach a surface while excluding others, is a well-established technique of analytical chemistry. Super-acoustic wave (“SAW”) devices, Quartz Crystal microbalance (“QCM”) sensors and especially electrochemical sensors are dependent on selective binding/rejection phenomena. Indeed, electrochemical detection of glucose in commercial products relies extensively on permselectivity of glucose, and rejection of electroactive interferants (e.g. ascorbate).


Appropriate surface coatings to create SERS nanofilters as described above and shown in FIG. 2 must exhibit five specific properties:


(1)The films must selectively allow specific analyte molecules (or classes of molecules) of interest to rapidly diffuse to the particle surface, where they can be detected by their unique SERS spectral signature. The ratio of partition coefficients for a specific analyte of interest and molecules with similar structures would ideally be at least 10:1, although other ratios may prove workable.


(2) The film must not use up all binding sites on the SERS-active nanoparticle. In other words, there must be surface adsorption sites available for analyte molecules that diffuse through the film.


(3) The film must be robust enough to survive during use in harsh, interferantladen environments.


(4) The Raman spectra of the films themselves must be simple and weak, because all spectral features of the film will comprise background noise above or through which the analyte spectrum must be detected.


(5) Attachment of the permselective film layers to the particles must be achievable without irreversible nanoparticle aggregation, which would lead to precipitation (and thus poor reproducibility).


Permselective Films


Suitable permselective coatings may consist of globular polymers (hyperbranched polymers) that are single-point attached to the particle surface as shown in FIG. 3. Such polymers could be of polar nature, and synthesized in aqueous conditions, or of non-polar character, generally prepared in organic solvents of lower polarity. The single point attachment would result in a “tree-like” structure of the polymer on the particle surface, providing a dense polymer coating while leaving available space on the noble metal particle surface for binding and detection of analytes of interest. The selective permeation of a hyperbranched film coating is governed by the structure, functionality and/or polarity of the polymers, and can potentially be tuned. For example, selective permeation based on molecular size might be based upon the characteristics of the “polymer trees” which leave a small space between “branches” for smaller external molecules to go through and reach the metal surface, while large macromolecules or cells would be precluded from contacting the surface. In addition, non-polar or hydrophobic polymer coatings would act as a barrier for highly polar species (such as inorganic ions) while letting organic molecules penetrate the film layer. Accordingly, layered hyperbranched polymers with more than one permselectivity characteristic could be prepared, enabling “additive” filtration. Furthermore, the presence of specific functional groups at pre-defined locations in the polymers would be critical for controlling permeation selectivity via specific molecular interactions. This type of molecular recognition would be a pre-requisite for advancing the described technology from class-selective sensing to nanoparticle sensors tuned to distinct molecules within the class.


Several other types of films could potentially also be used to impart permselectivity. For example, polydimethylsiloxane (PDMS) has been shown to reject all ions from macroscopic SERS-active surfaces, while allowing candidate drug molecules to diffuse and adsorb (Mulvaney and Natan, unpublished results). Likewise, it may be possible to build porous glass films that exhibit permselectivity.


Films such as those described in Hydrophobic Interaction of Analytes with Permselective Poly(N-vinyl amide) Films on Electrodes2A or the Encyclopedia of Separation Science2B may be suitable for use with chemical sensors based upon SERS nanofilters. The present invention is not limited to films such as those described in these references.


Single Molecule, Single-Particle SERS Has Been Demonstrated


Submonolayers of adsorbates on single particles have been shown to give rise to SERS spectra. The detection of single molecules by surface-enhanced Raman scattering (SERS) was first reported by two independent research groups in 1997.3,4 Nie and coworkers detected rhodamine 6G (R6G) on immobilized silver nanoparticles that were either single particles or small aggregates. They took advantage of the additional resonance enhancement gained by exciting the sample within the electronic absorption band of R6G and used a screening method to rapidly locate particles that were SERS-active. Conversely, Kneipp's group intentionally aggregated colloidal silver in the presence of crystal violet (CV) and detected the aggregates as they diffused through the focal volume of a microscope objective. Coupled with Poisson statistics, they surmised that many of the SERS events they recorded were from single CV molecules. It was also noteworthy that they excited the sol with 830 nm light, well outside of CV's absorption band. Furthermore, they employed similar methods to detect single adenine molecules,5 proving that single-molecule SERS detection was possible without taking advantage of additional resonance enhancement. Since that time, single-molecule SERS has been demonstrated on Au nanoparticles,6 for hemoglobin7 and for tyrosine.8 Applicant has already been quite successful with the preparation of spherical SERS nanotags of FIG. 1, and it is well understood that anistropic noble metal nanoparticles (rods, prisms, cubes, arrowheads), in which the particle surface plasmon band is tuned to the near-IR excitation frequency, will give exponential increases in SERS brightness;9.


Large-Scale Manufacture


Applicant currently manufactures colloidal Au nanoparticles in 1-2 liter batches, which provides approximately 1014 particles. A typical application of SERS tags (for example, for the detection of proteins or DNA) may involve 106-107 particles, meaning that a single batch is capable of generating enough material for one million tests. Applicant is in the process of scaling up to 10-liter preparations. Moreover, very large scale manufacture of the core particles has been demonstrated commercially. For example, British Biocell International (BBI), a UK concern that supplies colloidal Au to diagnostic companies for use in lateral flow immunoassays, manufactures particles in 250-liter batches.


Because the polymeric coating on the particles contemplated and described above will be thin (i.e. 10 nm), small amounts of raw material will be needed. For example, to cover 1017 particles of 60-nm diameter with a 10-nm thick coating of a polymer of density 1 gm/cm3 (an overestimate) would require only 1.6 grams of material.


Remote Detection of Raman Scattering


Recently, several groups10-13 demonstrated remote Raman detection as a viable detection technique. This advancement follows from the recent availability of highly-sensitive light detectors and relatively low-cost pulsed laser systems, along with knowledge built from sophisticated lock-in amplifier-based Light Detection and Ranging (“LIDAR”) systems, allowing for ultra-sensitive detection in ambient light conditions. For instance, Lawrence Livermore National Laboratory has explored passive detection of high-explosives using an 8″ Schmidt-cassegrain telescope coupled to an f/1.8 spectrograph.11 They were able to detect the Raman signal from TNT, RDX, PETN, and other nitrate/chlorate simulants embedded in a dry silica matrix at 50 meters with reasonable signal-to-noise ratios. Further development by this group12 generated a remote imaging Raman system which achieved detection of calcite, TiO2, and gypsum at approximately 1 cm-1 resolution at a 15 m distance using an AOTF (acousto-optical tunable filter)-based pulsed laser system.


Standoff Detection Has Already Been Demonstrated with SERS Nanotags


Due to large enhancement factors, SERS nanotags exhibit extremely strong signals compared to normal Raman spectra of solids or liquids. Accordingly, standoff detection of particles such as those produced by Applicant is becoming routine. See, for example, the graph of detection intensity as a function of wavelength included in FIG. 4. Importantly, the reporter molecules used in SERS tags are not resonantly enhanced, rather the SERS spectrum is merely obtained from a submonolayer of adsorbate. Thus, the SERS spectral intensity to be expected from analytes captured and detected with the proposed SERS nanofilters should be of similar magnitude.


Other Applications


While the initial application contemplated for the nanoparticulate chemical sensors of the present application may be the detection of chemical warfare agents, optically-detected, ultrasensitive detection of low molecular weight species is also of tremendous importance in bioanalysis. For example, the entire field of “metabolomics” is concerned with identification and quantition of the many hundreds of small molecules present in serum, many of these metabolites change in response to disease progression and/or therapeutic intervention. At present, the only way to analyze serum for these biomarkers is by LC-MS, which is slow, expensive, and not portable. The ability to design sensor particles for specific analytes that, by virtue of near-IR excitation, could be used in whole blood, would be of clinical significance.


Particles as described herein could also make up part of a system for air sampling at airport or other security checkpoints, where detection of explosives, narcotics or other agents, including substances on a passenger's skin, might be facilitated. In addition, in vivo imaging where the particles might be used to track the distribution of drug in living systems may be another possible application of the particles described herein.


Relevant References


1. U.S. Pat. No. 6,514,767, “Surface enhanced spectroscopy-active composite nanoparticles,” issued Feb. 4, 2003.


2. Campion, A.; Kambhampati, P. Chem. Soc. Rev. 1998, 27, 241-249.


2A. Hofbauer, M; Heineman, W.; Kreischman, G; Steckhan, E.; “Hydrophobic Interaction of Analytes with Permselective Poly(N-vinyl amide) Films on Electrodes” Anal. Chem. 1999, 71, 399-406.


2B. Wilson, Ian; Poole, Colin; Cooke, Michael, eds., Encyclopedia of Separation Science, Academic Press (2000).


3. Nie, S.; Emory, S. R. Science. 1997, 275, 1102-1106.


4. Kneipp, K.; Wang, Y.; Kneipp, H.; Perelman, L. T.; Itzkan, I.; Dasari, R. R.; Feld, M. S. Phys. Rev. Lett. 1997, 78, 1667-1670.


5. Kneipp K, Kneipp H, Kartha V B, Manoharan R, Deinum G, Itzkan I, Dasari R R, Feld MS. Phys. Rev. E 1998; 57: R6281.


6. Kneipp K, Kneipp H, Itzkan I, Dasari R R, Feld M S. Chem. Phys. 1999; 247:155.


7. Xu H, Bjerneld E J, K all B orjesson ML. Phys. Rev. Lett. 1999; 83: 4357.


8. Bjerneld E J, Johansson P, K all M. Single Mol. 2000; 1, 329.


9. Kelly, K. L.; Coronado, E.; Zhao, L. L.; Schatz, G. C. J. Phys. Chem. B 2003, 298, 668-677.


10. Wiens, R. C.; Sharma, S. K.; Thompson, J. et al. Spectrochim. Acta A 2005, 61, 2324-2334.


11. Carter J C, Angel S M, Lawrence-Snyder M, et al., Appl. Spectrosc. 2005, 59, 769.


12. Carter J C, Scaffidi J, Burnett S, et al., Spectrochim Acta A 2005, 61, 2288.


13. Wu M, Ray M, Fung K H, et al., Appl. Spectrosc. 2000, 54, 800-806.


EXAMPLES

The following examples are provided for illustrative purposes only and are not intended to limit the scope of the invention.


Example 1
Experimental Procedure

30 ml of 50 nm diameter gold colloid (4×1010 particles/ml) was diluted with 30 ml of MQ water. A stirring bar (freshly washed with aqua regia) was added. Then 300 ul of polyvinylpyrrolidone solution (pvp, Mw=10000, 2.5 wt % in water) was added slowly while stirring. The mixture was gently stirred at room temperature for 24 h.


The pvp coated particles were transferred to dichloromethane as follows: the aqueous colloid was centrifuged at 3600 rpm for 2 hr. The supernatant was discarded and 60 ml of ethanol was then added. The particles were resuspended in ethanol by ultrasound. The centrifugation and solvent change was carried out for a second time. The resulting ethanolic dispersion was centrifuged, and after discarding the ethanol, 60 ml of dichloromethane was added and the particles redispersed by ultrasound. Centrifugation and addition of fresh dichloromethane was done one more time. Two aliquots of 10 ml each were taken from the final dichloromethane dispersion. To one of the aliquots it was added 500 ul of a 1M solution of pyridine in dichloromethane. To the second aliquot it was added 500 ul of a 1M solution of 4,4′-dipyridyl in dichloromethane. After 48 hr SERS was taken of both samples (FIG.5)



FIG. 5 clearly shows that pyridine penetrates the pvp coating and reaches the surface of the particle, resulting in enhanced Raman spectrum, while the larger 4,4′-dipyridyl does not. Knowing that 4,4′-dipyridyl shows a much larger SERS than pyridine when added to aqueous citrate colloids, it is reasonable to conclude that the results using pvp coated particles in dichloromethane are caused by size selective permeation by the polymer layer. Additional data is presented in FIGS. 6 and 7.

Claims
  • 1. A composition of matter comprising: a particle having a spectroscopy-active outer region; anda permselective film associated with at least a portion of the particle which selectively allows for specific molecules to reach the outer region of the particle and produce a spectrum when illuminated.
  • 2. The composition of matter of claim 1, wherein the particle comprises a metal.
  • 3. The composition of matter of claim 2, wherein said metal is selected from the group consisting of Au, Ag, Cu, Na, K, Cr, AI, and Li.
  • 4. The composition of matter of claim 1 wherein the permselective film is selected from the group consisting of a globular polymer, a hyperbranched polymer, polydimethylsiloxane, and a porous glass film.
  • 5. The composition of matter of claim 1 wherein the particle is a metal nanoparticle.
  • 6. The composition of matter of claim 5, wherein said metal nanoparticle has a diameter less than about 200 nm.
  • 7. The composition of matter of claim 6, wherein said metal nanoparticle has a diameter between about 20 nm and about 200 nm.
  • 8. The composition of matter of claim 7, wherein said metal nanoparticle has a diameter between about 40 nm and about 100 nm.
  • 9. The composition of matter of claim 1, wherein said permselective film has a thickness of about 10 nm.
  • 10. The composition of matter of claim 1, wherein said permselective film has a thickness less than 10 nm.
RELATED APPLICATIONS

This application claims priority from U.S. Provisional Application Ser. No. 60/825,676, filed on Sep. 14, 2006, entitled “Nanoparticulate Chemical Sensors Using SERS” and from U.S. Provisional Application Ser. No. 60/750,763, filed on Dec. 14, 2005, entitled “Nanoparticulate Chemical Sensors Using SERS”, the contents of each of which are incorporated herein in their entirety.

US Referenced Citations (89)
Number Name Date Kind
3975084 Block Aug 1976 A
4039297 Takenaka Aug 1977 A
4313734 Leuvering Feb 1982 A
4802761 Bowen et al. Feb 1989 A
4853335 Olsen et al. Aug 1989 A
4920059 Moeremans et al. Apr 1990 A
5023139 Birnboim et al. Jun 1991 A
5059394 Phillips et al. Oct 1991 A
5096809 Chen et al. Mar 1992 A
5112127 Carrabba et al. May 1992 A
5137827 Mroczkowski et al. Aug 1992 A
5255067 Carrabba et al. Oct 1993 A
5266498 Tarcha et al. Nov 1993 A
5384265 Kidwell et al. Jan 1995 A
5441894 Coleman et al. Aug 1995 A
5445972 Tarcha et al. Aug 1995 A
5552086 Siiman et al. Sep 1996 A
5567628 Tarcha et al. Oct 1996 A
5580492 Bonnemann et al. Dec 1996 A
5609907 Natan Mar 1997 A
5637508 Kidwell et al. Jun 1997 A
5674699 Saunders et al. Oct 1997 A
5825790 Lawandy Oct 1998 A
5828450 Dou et al. Oct 1998 A
5833924 McClintock et al. Nov 1998 A
5864397 Vo-Dinh Jan 1999 A
5891738 Soini et al. Apr 1999 A
5935755 Kazmaier et al. Aug 1999 A
5958704 Starzl et al. Sep 1999 A
6020207 Liu Feb 2000 A
6027890 Ness et al. Feb 2000 A
6103868 Heath et al. Aug 2000 A
6136610 Polito et al. Oct 2000 A
6149868 Natan et al. Nov 2000 A
6200820 Hansen et al. Mar 2001 B1
6219137 Vo-Dinh Apr 2001 B1
6235241 Catt et al. May 2001 B1
6274323 Bruchez et al. Aug 2001 B1
6344272 Oldenburg et al. Feb 2002 B1
6361944 Mirkin et al. Mar 2002 B1
6422998 Vo-Dinh et al. Jul 2002 B1
6436651 Everhart et al. Aug 2002 B1
6451619 Catt et al. Sep 2002 B1
6500622 Bruchez, Jr. et al. Dec 2002 B2
6514767 Natan Feb 2003 B1
6514770 Sorin Feb 2003 B1
6558956 Carron et al. May 2003 B1
6562403 Klabunde et al. May 2003 B2
6587197 Rahbar-Dehghan Jul 2003 B1
6595427 Soni et al. Jul 2003 B1
6603537 Dietz et al. Aug 2003 B1
6610351 Shchegolikhin et al. Aug 2003 B2
6630307 Bruchez et al. Oct 2003 B2
6642012 Ashdown Nov 2003 B1
6646738 Roe Nov 2003 B2
6649138 Adams et al. Nov 2003 B2
6653080 Bruchez et al. Nov 2003 B2
6682596 Zehnder et al. Jan 2004 B2
6687395 Dietz et al. Feb 2004 B1
6699724 West et al. Mar 2004 B1
6730400 Komatsu et al. May 2004 B1
6743581 Vo-Dinh Jun 2004 B1
6750016 Mirkin et al. Jun 2004 B2
6750031 Ligler et al. Jun 2004 B1
6759235 Empedocles et al. Jul 2004 B2
6778316 Halas et al. Aug 2004 B2
6815064 Treadway et al. Nov 2004 B2
6815212 Ness et al. Nov 2004 B2
6838243 Lai et al. Jan 2005 B2
6861263 Natan Mar 2005 B2
6919009 Stonas et al. Jul 2005 B2
6970246 Hansen Nov 2005 B2
6972173 Su et al. Dec 2005 B2
7045049 Natan et al. May 2006 B1
7079241 Empedocles et al. Jul 2006 B2
7098041 Kaylor et al. Aug 2006 B2
7102747 Wang et al. Sep 2006 B2
7102752 Kaylor et al. Sep 2006 B2
7105310 Gray et al. Sep 2006 B1
7122384 Prober et al. Oct 2006 B2
7123359 Armstrong et al. Oct 2006 B2
7141212 Catt et al. Nov 2006 B2
7192778 Natan Mar 2007 B2
7443489 Natan Oct 2008 B2
20020142480 Natan Oct 2002 A1
20030232388 Kreimer et al. Dec 2003 A1
20050036148 Phelan Feb 2005 A1
20050037510 Sharrock et al. Feb 2005 A1
20050037511 Sharrock Feb 2005 A1
Foreign Referenced Citations (22)
Number Date Country
0 653 625 May 1995 EP
0 703 454 Mar 1996 EP
1 181 091 Feb 2002 EP
WO 8807680 Oct 1988 WO
WO 9217781 Oct 1992 WO
WO 9804740 Feb 1998 WO
WO 9810289 Mar 1998 WO
WO 9921934 May 1999 WO
WO 0011024 Mar 2000 WO
WO 0027645 May 2000 WO
WO 0108081 Feb 2001 WO
WO 0125002 Apr 2001 WO
WO 0125510 Apr 2001 WO
WO 0125758 Apr 2001 WO
WO 0229136 Apr 2002 WO
WO 02068932 Jun 2002 WO
WO 02079764 Oct 2002 WO
WO 03021231 Mar 2003 WO
WO 03021853 Mar 2003 WO
WO 2006036130 Apr 2006 WO
WO 2006042111 Apr 2006 WO
WO 2006105110 Oct 2006 WO
Non-Patent Literature Citations (76)
Entry
Michaels, Amy M., et al. Ag Nanocrystal Junctions as the Site for Surface-Enhanced Raman Scattering of Single Rhodaine 6G Molecules, J. Phys. Chem. B 2000, 104, 11965-11971.
Liz-Marzan Luis M., et al. Synthesis of Nanosized Gold-Silica Core-Shell Particles, Langmuir, 1996, 12, 4329-4335.
Khlebtsov, N.G., Optical models for conjugates of gold and silver nanoparticles with biomacromolecules, Journal of Quantitative Spectroscopy & Radiative Transfer, 2004, 89, 143-153.
U.S. Appl. No. 09/598,395, filed Jun. 20, 2000, Natan et al.
U.S. Appl. No. 09/676,890, filed Oct. 2, 2000, Natan et al.
U.S. Appl. No. 09/677,198, filed Oct. 2, 2000, Natan et al.
Akbarian F. et al., “Porous Sol-Gel Silicates Containing Gold Particles as Matrices for Surface-Enhanced Raman Spectroscopy”, Journal of Raman Spectroscopy; vol. 27, Issue 10, Oct. 1996, pp. 775-783.
Akerman et al., “Nanocrystal targeting in vivo” PNAS, 99 (20), 2002, p. 12621.
Ascencio et al, “A truncated icosahedral structure observed in gold nanoparticles”, Jorge A. Ascencio, Mario Surface Science, vol. 447, Issues 1-3, Feb. 20, 2000, pp. 73-80.
Averitt et al., “A metal nanoshell consists of a nanometer-scale dielectric core surrounded by a thin metallic shell. The plasmon resonance of metal nanoshells displays a geometric tunability”, JOSA B, vol. 16, Issue 10, 1999, pp. 1824-1832.
Ballou et al., “Nonivasive imaging of quantum dots in mice”, Bioconjugate Chem., 15 (1), 2004, pp. 79-86.
Brazdil et al., “Resonance Raman spectra of adsorbed species at solid-gas interfaces. Nitrosodimethylaniline adsorbed on silica and alumina surfaces”, J. Phys. Chem., 1981, 85 (8), pp. 995-1004.
Bruchez et al., “Semiconductor nanocrystals as fluorescent biological labels”, Science, Sep. 25, 1998, 281(5385), pp. 2013-2016.
Byahutet al., “Direct comparison of the chemical properties of single crystal Ag(111) and electrochemically roughened Ag as substrates for surface Raman scattering”, Langmuir, 1991, 7 (3), pp. 508-513.
Chan et al., “Quantum dot bioconjugates for ultrasensitive nonisotopic detection”, Science, 1998, 281, pp. 2016-2018.
Co-Pending U.S. Appl. No. 11/051,222, filed Feb. 4, 2005.
Co-Pending U.S. Appl. No. 11/113,601, filed Apr. 25, 2005.
Co-Pending U.S. Appl. No. 11/132,510, filed May 18, 2005.
Co-Pending U.S. Appl. No. 11/132,974, filed May 18, 2005.
Co-Pending U.S. Appl. No. 11/133,926, filed May 20, 2005.
Co-Pending U.S. Appl. No. 11/134,129, filed May 20, 2005.
Co-Pending U.S. Appl. No. 11/134,145, filed May 20, 2005.
Co-Pending U.S. Appl. No. 11/622,915, filed Jan. 12, 2007.
Co-Pending U.S. Appl. No. 12/245,538, filed Oct. 3, 2008.
Co-Pending U.S. Appl. No. 12/245,555, filed Oct. 3, 2008.
Dhere et al., “Twinned colloidal gold particles”, Ultramicroscopy, vol. 18, Issues 1-4, 1985, pp. 415-417.
Duff et al., “The Morphology and Microstructure of Colloidal Silver and Gold Angewandte Chemie”, International Edition in English, vol. 26, Issue 7, 1987, pp. 676-678.
El-Kouedi et al., “Optical Properties of Gold-Silver Nanoparticle Pair Structures”, J. Phys. Chem. B, 104, 2000, pp. 4031-4037.
Emory et al., “Direct Observation of Size-Dependent Optical Enhancement in Single Metal Nanoparticles”, Journal of the American Chemical Society, 1998, 120 (31), 8009-8010.
Emory et al., “Near-Field Surface-Enhanced Raman Spectroscopy on Single Silver Nanoparticles”, Analytical Chemistry, 1997, 69 (14), pp. 2631-2635.
Emory et al., “Screening and Enrichment of Metal Nanoparticles with Novel Optical Properties”, J. Phys. Chem. B, 1998, 102 (3), pp. 493-497.
European Patent Office, EP Supplementary Search Report prepared Apr. 18, 2008, for European Patent Application No. EP 05 85 6641, 4 pages.
Félidj et al., “A new approach to determine nanoparticle shape and size distributions of SERS-active gold-silver mixed colloids”, New J. Chem., 1998, 22, pp. 725-732.
Freeman et al., “Ag-Clad Au Nanoparticles: Novel Aggregation, Optical, and Surface-Enhanced”, Raman Scattering Properties, M.J, J. Phys. Chem., vol. 100, No. 2, 1996, pp. 718-724.
Gao et al., “In vivo cancer targeting and imaging with semiconductor quantum dots”, Nature Biotechnology, 22 (8), 2004, pp. 969-976.
Grabar et al., “Preparation and Characterization of Au Colloid Monolayers”, Analytical Chemistry, 1995, 67 (4), pp. 735-743.
Hall et al., “Cocondensation of Organosilica Hybrid Shells on Nanoparticle Templates: A Direct Synthetic Route to Functionalized Core-Shell Colloids”, Langmuir, 2000, 16 (3), pp. 1454-1456.
Hoadk et al., “Laser-Induced Inter-Diffusion in AuAg Core-Shell Nanoparticles”, J. Phys. Chem. B, 2000, vol. 104, pp. 11708-11718.
Horkans et al., “Pulsed Potentiostatic Deposition of Gold from Solutions of the Au(I) Sulfite Complex”, Electrochem. Soc., 124, 1977, p. 1499.
Hua-Zhong Yu et al., “Surface-Enhanced Raman Scattering (SERS) from Azobenzene Self-Assembled Sandwiches”, Langmuir, vol. 15, No. 1, 1999, pp. 16-19.
Jin et al., “Photoinduced Conversion of Silver Nanospheres to Nanoprisms”, Science, Nov. 30, 2001, 294, pp. 1901-1903.
Keating et al., “Heightened Electromagnetic Fields Between Metal Nanoparticles: Surface Enhanced Raman Scattering from Metal-Cytochrome c-Metal Sandwiches”, J. Phys. Chem. B, vol. 102, No. 47, 1998, pp. 9414-9425.
Keating et al., “Protein: Colloid Conjugates for Surface Enhanced Raman Scattering: Stability and Control of Protein Orientation”, J. Phys. Chem. B, vol. 102, No. 47, 1998, pp. 9404-9413.
Kneipp et al., “Approach to Single Molecule Detection Using Surface-Enhanced Resonance Raman Scattering (SERRS): A Study Using Rhodamine 6G on Colloidal Silver”, Applied Spectroscopy, vol. 49, Issue 6, pp. 12A-20A and 691-860, Jun. 1995, pp. 780-784.
Kneipp et al., “Detection and identification of a single DNA base molecule using surface-enhanced Raman scattering (SERS)”, Rev. E 57, 1998, pp. R6281-R6284.
Kneipp et al., “Extremely Large Enhancement Factors in Surface-Enhanced Raman Scattering for Molecules on Colloidal Gold Clusters”, Applied Spectroscopy, vol. 52, Issue 12, pp. 443A-455A and 1493-1626, Dec. 1998, pp. 1493-1497.
Kneipp et al., “Population Pumping of Excited Vibrational States by Spontaneous Surface-Enhanced Raman Scattering”, Phys. Rev. Lett. 76, 1996, pp. 2444-2447.
Kneipp et al., “Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS)”, Phys. Rev. Lett. 78, 1997, pp. 1667-1670.
Kneipp et al., “Single-Molecule Detection of a Cyanine Dye in Silver Colloidal Solution Using Near-Infrared Surface-Enhanced Raman Scattering”, Applied Spectroscopy, vol. 52, Issue 2, pp. 72A-73A and 175-321, Feb. 1998, pp. 175-178.
Kneipp et al., “Surface-enhanced Raman scattering: A new tool for biomedical spectroscopy”, Current Science, vol. 77, No. 7, Oct. 1999, pp. 915-926.
Kneipp et al., “Ultrasensitive Chemical Analysis by Raman Spectroscopy”, Chem. Rev., 1999, 99 (10), pp. 2957-2976.
Kneipp, K., “High-sensitive SERS on colloidal silver particles in aqueous solution”, Journal: Experimentelle Technik der Physik; vol. 36, No. 2, 1998, pp. 161-166.
Kovtyukhova et al., “Layer-by-Layer Assembly of Rectifying Junctions in and on Metal Nanowires”, J. Phys. Chem. B, 2001, 105 (37), pp. 8762-8769.
Liz-Marzán et al., “Synthesis of Nanosized Gold-Silica Core-Shell Particles”, Langmuir, 1996, 12 (18), pp. 4329-4335.
Lyon et al., “Confinement and Detection of Single Molecules in Submicrometer Channels”, Analytical Chemistry, 1997, 69 (16), pp. 3400-3405.
Michaels et al., “Ag Nanocrystal Junctions as the Site for Surface-Enhanced Raman Scattering of Single Rhodamine 6G Molecules”, J. Phys. Chem. B, 2000, 104 (50), pp. 11965-11971.
Michaels et al., “Surface Enhanced Raman Spectroscopy of Individual Rhodamine 6G Molecules on Large Ag Nanocrystals”, J. Am. Chem. Soc., 1999, 121 (43), pp. 9932-9939.
Moskovits et al., “SERS and the Single Molecule: Near Field Microscopy and Spectroscopy”, SPIE, 2001, vol. 4258, pp. 43-49.
Mucic et al., “DNA-Directed Synthesis of Binary Nanoparticle Network Materials”, J. Am. Chem. Soc., 120 (48), 1998, pp. 12674-12675.
Nicewarner Sr. et al., “Synthesis and characterization of well-defined metal nanoparticle-protein-metal nanoparticle sandwiches”, Penn State University/University Pk//Pa/16802, Abstracts of Papers of The American Chemical Society , Aug. 23, 1998, vol. 216 , 1, pp. 172-COLL.
Nicewarner-Peña et al., “Submicrometer Metallic Barcodes”, Science, Oct. 5, 2001, 294, pp. 137-141.
Nie et al., “Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering”, Emory, Science, Feb. 21, 1997, vol. 275, No. 5303, pp. 1102-1106.
Nie, S., “Optical detection of single molecules; Annual Review of Biophysics and Biomolecular Structure”, vol. 26, 1997, pp. 567-596.
Nikoobakht et al., “Preparation and Growth Mechanism of Gold Nanorods (NRs) Using Seed-Mediated Growth Method”, Chem. Mater., 15, 2003, pp. 1957-1962.
Ron et al., “Self-Assembled Monolayers on Oxidized Metals. 2. Gold Surface Oxidative Pretreatment, Monolayer Properties, and Depression Formation”, Langmuir, 14 (5), 1998, pp. 1116-1121.
Sandrock et al., “Synthesis and Second-Harmonic Generation Studies of Noncentrosymmetric Gold Nanostructures”, J. Phys. Chem. B, 103, 1999, pp. 2668-2673.
Sandrock, “Synthesis and Linear Optical Properties of Nanoscopic Gold Particle Pair Structures”, J. Phys. Chem. B, 103, 1999, pp. 11398-11406.
Shibata et al., “Preparation of Silica Microspheres Containing Ag Nanoparticles”, Journal of Sol-Gel Science and Technology, vol. 11, No. 3, Aug. 1998, pp. 279-287.
Stöber et al., “Controlled growth of monodisperse silica spheres in the micron size range”, Journal of Colloid and Interface Science, vol. 26, Issue 1, Jan. 1968, pp. 62-69.
Sun et al., “Fabrication of nanoporous single crystal mica templates for electrochemical deposition of nanowire arrays”, Journal of Materials Science, vol. 35, No. 5, Mar. 2000, pp. 1097-1103.
Switzer et al., “Electrochemical Self-Assembly of Copper/Cuprous Oxide Layered Nanostructures”, J. Am. Chem. Soc., 1998, 120 (14), pp. 3530-3531.
Ung et al., “Controlled Method for Silica Coating of Silver Colloids. Influence of Coating on the Rate of Chemical Reactions”, Langmuir, 1998, 14 (14), pp. 3740-3748.
Van Duyne et al., “Atomic force microscopy and surface-enhanced Raman spectroscopy. I. Ag island films and Ag film over polymer nanosphere surfaces supported on glass”, Chem. Phys., vol. 99, Issue 3, pp. 2101-2115.
Vo-Dinh, T., “Surface-enhanced Raman Spectroscopy using metallic nanostructures”, Trends in Analytical Chemistry, vol. 17, No. 8-9, 1998, XP002314222.
Walton et al., “Particles for Multiplexed Analysis in Solution: Detection and Identification of Striped Metallic Particles Using Optical Microscopy”, Analytical Chemistry, 74 (10), 2002, pp. 2240-2247.
Wasileski et al., “Surface-Enhanced Raman Scattering from Substrates with Conducting or Insulator Overlayers: Electromagnetic Model Predictions and Comparisons with Experiment”, Applied Spectroscopy, 2000, vol. 54, pp. 761-772.
Related Publications (1)
Number Date Country
20070259437 A1 Nov 2007 US
Provisional Applications (2)
Number Date Country
60825676 Sep 2006 US
60750763 Dec 2005 US