This invention relates to Raman spectroscopy and Surface Enhanced Raman Scattering (SERS). More specifically, this invention relates to a stable form of colloidal metal particles that when reconstituted, produces a SERS active solution.
Raman spectroscopy stems from the inelastic scattering of light by molecular vibrational energy levels. Raman spectroscopy as an analytical tool has been known for decades, and is particularly popular for several reasons. For example, molecular composition can be determined in the presence of water. Visible light can be employed for analysis allowing for the use of conventional fiber optics. Unique spectral fingerprints allow for identification and quantification of a wide variety of solids, liquids, and gases. One of the significant disadvantages of Raman spectroscopy is the inadequate sensitivity for trace or ultratrace analysis. This stems from the inherently weak nature of Raman scattering.
In the early 1970s several researchers found an anomalous enhancement of Raman scattering at the surface of certain metals. It has subsequently been found that the metals that have both practicality and strong enhancing properties are silver, gold, and copper. The enhancement is believed to generally come from an electromagnetic effect and in some cases, an enhancement due to the nature of the chemical bond to the metal surface has also been found. The reported enhancement for SERS depends on the structure of the surface and ranges from about 105 to 108. This discovery immediately made it possible to detect very small amounts of material adsorbed to these surfaces. The SERS effect is limited to molecules attached to or in very close proximity with the surface.
The drawback to conventional SERS is that it is limited to analytes that will naturally adsorb to a SERS active metal surface. Thus, while in special cases SERS provides sensitive detection, in most cases it suffers from the inability of the molecule to adsorb to the surface and to benefit from the SERS effect.
A method to overcome the lack of adsorptivity to SERS surfaces by an analyte, is to provide surface coatings that have an affinity for the analyte. An example is an early publication which describes using a surface bound coating in the detection of hydrogen ions at a surface using SERS (Determination of pH with SERS Fiber Optic Probes. Ken I. Mullen, DaoXin Wang, L. Gayle Hurley, and Keith Carron Anal. Chem., 64, 930, 1992). This publication showed that it was possible to permanently attach a coating to a SERS surface and to have the coating provide the affinity for the analyte.
More recently, it has been demonstrated that an irreversible covalent bonding reagent could be used to achieve even more sensitive detection. Furthermore, it was shown that the surface need not be coated with the surface bound reagent, but rather, the reagent could have two reactive sites. One site is analyte specific and the other is surface binding specific. This produces a high affinity permanent bond to the analyte and a high affinity permanent bond to the surface. An example of a dual binding reagent for trace detection is a reagent that binds bilirubin and which has an argentiphillic sulfide group to bind to silver (Surface Enhanced Raman Assays (SERA): Measurement of Bilirubin and Salicylate, Roberta Sulk, Collin Chan, Jason Guicheteau, Cieline Gomez, J. B. B. Heyns, Robert Corcoran, and Keith Canon, J. Raman Spectrosc., 1999, 30, 853-859).
Accordingly, an assay is needed which is capable of producing a SERS active solution that is sensitive to a specific analyte or group of analytes.
An assay and method of making same is disclosed herein for use in SERS spectroscopy. The assay comprises lyophilized colloidal particles of a metal, which have been lyophilized. The lyophilized particles of metal produce a SERS active solution when reconstituted.
An assay system and method of making same is further disclosed herein for use in SERS spectroscopy. The assay system comprises a container with lyophilized colloidal particles of a metal disposed in a first section thereof. The lyophilized colloidal particles of a metal contained in the container produce a SERS active solution when reconstituted.
A method of analyzing a material is further disclosed herein. The method comprises the steps of: providing a container; placing colloidal particles of a metal in a first section of the container; lyophilizing the colloidal particles of the metal to produce an assay; simultaneously reconstituting and mixing the assay with the material to be analyzed to produce a SERS active solution; performing SERS spectroscopy on the SERS active solution.
One aspect of the present invention includes an assay and an assay system for use in Surface Enhanced Raman Scattering (SERS) spectroscopy. Another aspect of the present invention includes methods for preparing the assay and assay system. Still another aspect of the present invention includes a method of analyzing a material using the assay system of the present invention and SERS spectroscopy. Another aspect of the present invention includes a method of analyzing a material using the assay system of the present invention and Surface Enhanced Raman ImmunoAssay (SERIA).
The assay of the present invention comprises a colloidal suspension of noble metal particles, such as silver, gold, or copper particles, which have been lyophilized to dryness using conventional lyophilizing techniques. The lyophilized, colloidal particles of the present invention have long term stability, i.e., the colloidal particles can be stored for a long period of time, and are sensitive to a specific analyte or group of analytes. The lyophilized, colloidal noble metal particles of the present invention produce a SERS active solution, when reconstituted to a colloidal suspension. A specific advantage of having a SERS active solution is that the SERS phenomenon exhibits a signal from material localized near the particle surface. This phenomenon precludes the need for removing excess analyte, impurity, or reagent, that indicates the presence of an analyte, from the sample mixture. This aspect combined with the aspect of a coated particle with long-term stability makes the assay of the invention commercially important.
A particularly important aspect of the assay of the present invention is that the amount of colloidal particles is determined very accurately through a volumetric delivery of a known concentration of colloidal suspension, or delivery of a known mass of colloidal suspension. The mass delivery is enabling to an assay since a large mass of diluted colloid can be used to accurately deliver a small amount of colloid into the chamber of a sample container.
The lyophilized, colloidal particle assay of the present invention may further comprise one or more reagents. The type or types of reagents used will depend upon the particular application or sample to be analyzed. Further, the lyophilized, colloidal particle assay may further comprise one or more antibodies, thereby forming a Surface Enhanced Raman ImmunoAssay (SERIA).
The assay system of the present invention comprises a sample container which contains the lyophilized, colloidal noble metal particles of the present invention. The container typically includes a pretreatment which prevents the lyophilized, colloidal particles from binding to the surface of the chamber of the container, or from binding with each other, thus inhibiting the lyophilized, colloid's ability to be reconstituted to a colloidal suspension. The pretreatment may comprise a wax-like material, such as polyethylene glycol (PEG), or combination of materials, which is applied to the chamber of the container. It should be understood, however, that the pretreatment can be omitted when the sample container is made from a material which possesses the ability to contain the lyophilized, colloid without inhibiting its ability to be reconstituted.
In addition or alternative to pretreating the chamber surface(s) of the container, a material or combination of materials may be added to the colloidal particles, prior to lyophilization, which also immobilizes the lyophilized, colloidal particles within the container and prevents the colloidal particles from binding to the surface of the chamber of the container, or from binding with each other. This pretreatment may also be omitted. This material may also comprise a wax-like material, such as PEG. Another example would be a surfactant material such as sodium dodecylsulfate (SDS). In view of the above, it should be apparent that the assay system of the present invention affords long term stability such that a pretreated assay can be provided for a customer for later use.
In certain applications, one or more reagents must be added in sequential fashion to the assay of the present invention.
Assays are typically performed either individually or multiply. Multiple assays have an advantage that many of the steps involved in the assay can be performed in parallel, thus decreasing the time of the assay. Accordingly, the assay system of the present invention may also comprise a sample container with multiple sample chambers, which enables multiple assays to be performed in parallel, if desired.
Additionally, as the assay of the present invention takes special advantage of the SERS effect to produce a one-step assay, the sample chamber or chambers include closures, e.g. Critoseal 17 (
While the foregoing invention has been described with reference to the above embodiments, various modifications and changes can be made without departing from the spirit of the invention. Accordingly, all such modifications and changes are considered to be within the scope of the appended claims.
This application is a divisional application of U.S. application Ser. No. 10/177,194, filed Jun. 21, 2002 which application claims the benefit of U.S. Provisional Application No. 60/300,270, filed Jun. 21, 2001.
Number | Name | Date | Kind |
---|---|---|---|
3799742 | Coleman | Mar 1974 | A |
4043678 | Farrell et al. | Aug 1977 | A |
4450231 | Ozkan | May 1984 | A |
4920061 | Poynton et al. | Apr 1990 | A |
5102788 | Cole | Apr 1992 | A |
5169789 | Bernstein | Dec 1992 | A |
5252459 | Tarcha et al. | Oct 1993 | A |
5255067 | Carrabba et al. | Oct 1993 | A |
5376556 | Tarcha et al. | Dec 1994 | A |
5637508 | Kidwell et al. | Jun 1997 | A |
5705207 | Cook et al. | Jan 1998 | A |
5759774 | Hackett et al. | Jun 1998 | A |
5869346 | Xiaoming et al. | Feb 1999 | A |
6391652 | Okada et al. | May 2002 | B2 |
6770488 | Carron et al. | Aug 2004 | B1 |
7776610 | Carron et al. | Aug 2010 | B2 |
7993933 | Carron et al. | Aug 2011 | B2 |
20030231304 | Chan et al. | Dec 2003 | A1 |
20040135997 | Chan et al. | Jul 2004 | A1 |
Number | Date | Country |
---|---|---|
9859234 | Dec 1998 | WO |
Entry |
---|
L. Rivas et al, “Growth of Silver Collodial Particles Obtained by Citrate Reduction to Increase the Raman Enhancement Factor,” Instituto de Estructura de la Materia, CSIC, Serrano 121, E-28006 Madrid, Spain and Departamento de Quimica Organica y Biologia, Universidad Nacional de Educacion a Distancia, Senda del Rey s/n E-28040 Madrid Spain, pp. 574-577, Langmuir 2001. |
1982 American Chemical Society—J. Phys. Chem 1982, 86, 3391-3395—“Adsorption and Surface-Enhanced Raman of Dyes on Silver and Gold Sols,” by P.C. Lee and D. Meisel. |
Roberta Sulk, Collin Chan, Jason Guicheteau, Cieline Gomez, J.B.B. Heyns, Robert Corcoran and Keith Carron, “Surface Enhanced Raman Assays (SERA): Measurement of Bilirubin and Salicylate,” J. Raman Spectrose, 1999, 30, 853-859. |
Non-Final Office Action dated Jul. 5, 2005 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Non-Final Office Action dated Dec. 29, 2005 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Final Office Action dated Jun. 14, 2006 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Non-Final Office Action dated Feb. 23, 2007 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Final Office Action dated Nov. 1, 2007 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Non-Final Office Action dated Jul. 28, 2008 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Final Office Action dated Jul. 24, 2009 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Non-Final Office Action dated Dec. 20, 2010 issued in co-pending U.S. Appl. No. 10/177,194, filed Jun. 21, 2002 of Keith T. Carron. |
Number | Date | Country | |
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20110294230 A1 | Dec 2011 | US |
Number | Date | Country | |
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60300270 | Jun 2001 | US |
Number | Date | Country | |
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Parent | 10177194 | Jun 2002 | US |
Child | 13160985 | US |