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Patent Issued for Compositions Comprising Nanomaterials and Method for Using Such Compositions for Histochemical Processes

May 6, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- A patent by the inventors Jackson, Merrill (Tucson, AZ); Herman, Michael (Tucson, AZ); Hoben, Grace (Marana, AZ); Sebastiao, Noemi (Tucson, AZ); Cockayne, Scott (Tucson, AZ); Ferrea, Heather (Tucson, AZ), filed on June 1, 2009, was published online on April 22, 2014, according to news reporting originating from Alexandria, Virginia, by NewsRx correspondents (see also Ventana Medical Systems, Inc.).

Patent number 8703490 is assigned to Ventana Medical Systems, Inc. (Tucson, AZ).

The following quote was obtained by the news editors from the background information supplied by the inventors: "I. Histochemical Processes

"Histology is the microscopic examination of tissue samples to identify structural and other changes in cells, tissues and organs. Histochemical processes include examining biological molecules that cause or are otherwise associated with disease to elucidate information about patient diagnosis, prognosis, and treatment options, and generally are divided into two main areas: (i) analysis of DNA, mRNA, and proteins in intact cells (in-situ); and (ii) analysis of these biological materials after they have been extracted from tissues. The first category allows a pathologist to study the histopathologic architecture or morphology of the tissue specimen while nucleic acids or proteins are being assayed. These techniques include immunohistochemistry (IHC) for analyzing proteins, in-situ hybridization (ISH) for analyzing nucleic acids, histochemistry (HC) for analyzing carbohydrates, and enzyme histochemistry (EHC) for enzyme chemistry.

"IHC uses antibodies to bind specifically to unique epitopes, such as epitopes found on proteins that may be expressed only in certain types of diseased cellular tissue, and more particularly involves selectively detecting such epitopes in a tissue section or cells (e.g. blood or bone marrow) mounted on a glass slide. Typical IHC process steps include pretreating the tissue section to remove embedding paraffin and to reduce non-specific binding, retrieval of antigens masked by cross-linking of proteins by chemical fixatives, antibody treatment and incubation, enzyme labeled secondary antibody treatment and incubation, substrate reaction with the enzyme to produce a fluorophore or chromophore highlighting areas of the tissue section having epitopes bound with the antibody, counterstaining, and the like. In particular, antigen retrieval typically is performed at elevated temperatures.

"ISH uses nucleic acid probes to detect target nucleic acid sequences in a sample. For example, ISH can be used to detect oncogenes, such as Her2, EGFR and TOPIIA gene sequences. ISH can be used to detect a genetic abnormality or condition, such as amplification of cancer causing genes specifically in cells that, when viewed under a microscope, morphologically appear to be malignant. ISH also is useful for diagnosing infectious diseases. Typical ISH process steps include pretreating the tissue section to remove embedding paraffin and to reduce non-specific binding, retrieval of target nucleic acid sequences, hybridization of nucleic acid probes to target sequences, and detection of the probe bound to its target. In particular, target retrieval and probe hybridization steps are performed at elevated temperatures.

"II. Automated Systems

"Automated sample staining systems have been developed to reduce human labor, error rate and expense. Representative microprocessor-controlled systems include a slide carousel that is rotated by a stepper motor to serially place sample slides adjacent dispensers to receive processing reagents or compositions for performing histochemical processes. Bar codes on the slides and dispensers allow the computer to control different treatment regimens for various tissue samples. These staining systems also include a heat source to heat the samples for steps requiring elevated temperatures, or steps that are facilitated by temperatures greater than ambient, such as to increase reaction kinetics.

"Recently, users of automated systems have noticed anomalous staining results under certain conditions, particularly during processing of samples using steps performed at temperatures above room temperature, and more particularly at temperatures near the boiling point of water or aqueous solutions. For example, such anomalous staining results have been more particularly noted during staining protocols that include processing steps performed at temperatures above 60.degree. C., such as temperatures between about 90.degree. C. and about 101.degree. C. Certain such staining protocols result in well-defined, generally circular, areas of anomalously reduced staining intensity surrounded by areas of appropriately stained tissue. These areas of reduced staining intensity are referred to herein as spots. While spots are not known to have compromised sample examination, a preferred staining process nevertheless would address production of anomalously stained samples."

In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "The present invention provides reagents, compositions, and methods for their use, particularly in automated apparatuses, that reduce or substantially eliminate the occurrence of spots upon staining. Disclosed embodiments concern histochemical process compositions, exemplified herein by particular reference to cell conditioning compositions, comprising at least one nanoparticle in amounts effective to reduce the average number of spots per slide. Compositions comprising nanoparticles also may be referred to herein as nanosolutions.

"One embodiment of an exemplary cell conditioning composition, referred to as CC1, comprises Tris borate-ethylene diamine tetraacetic acid (EDTA) buffer, at a pH of about 8, and from greater than zero to at least about 25 parts per million, more typically from about 2 parts per million to about 20 parts per million, and even more typically from about 2.5 parts per million to about 15 parts per million, of at least one nanoparticle. Another exemplary embodiment of a cell conditioning composition, referred to as CC2, comprises from about 5 mM to about 50 mM citrate buffer at a pH of from about 4 to about 8, about 1% to about 10% ethylene glycol, about 0.1 to about 10 mM sodium metabisulfite, about 0.1% to about 10% sodium dodecyl sulfate (SDS), and again from greater than zero to at least about 25 parts per million, more typically from about 2 parts per million to about 20 parts per million, and even more typically from about 2.5 parts per million to about 15 parts per million, of at least one nanoparticle.

"The nanoparticle or nanoparticles used to form such compositions can be any of various nanoparticles, or combinations thereof, that reduce the average number of spots that may occur as a result of using a particular histochemical process reagent or composition. Classes of nanoparticles that can be used include metals, metalloids, functionalized metals or metalloids, metal alloys, metal oxides, ceramics, and other miscellaneous nanoparticles, such as carbon nanoparticles and diamond nanoparticles. Metal oxides, such as alumina (Al.sub.2O.sub.3), silica (SiO.sub.2) and titania (TiO.sub.2), have been used in working embodiments.

"Embodiments of a method for using histochemical process nanosolutions also are disclosed. One embodiment concerns applying a histochemical process composition to a sample, the composition comprising at least one nanoparticle in an amount effective to reduce the average number of spots per slide relative to performing the process without using a nanosolution. A histochemical staining process is then performed on the sample. For example, the method may concern performing cell conditioning on the sample using a cell conditioning composition. The method also can include performing at least one or plural additional process steps typically practiced in a sample staining protocol. Additional staining processes, such as counter staining, also can be performed. Particular embodiments concern automated histochemical processes comprising dispensing a nanosolution onto a sample using an automated system, heating the sample, and performing a sample staining process on the sample.

"The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures."

URL and more information on this patent, see: Jackson, Merrill; Herman, Michael; Hoben, Grace; Sebastiao, Noemi; Cockayne, Scott; Ferrea, Heather. Compositions Comprising Nanomaterials and Method for Using Such Compositions for Histochemical Processes. U.S. Patent Number 8703490, filed June 1, 2009, and published online on April 22, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=90&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=4481&f=G&l=50&co1=AND&d=PTXT&s1=20140422.PD.&OS=ISD/20140422&RS=ISD/20140422

Keywords for this news article include: Antibodies, Antigens, Epitopes, Peptides, Immunology, Amino Acids, Nanomaterial, Nanoparticle, Blood Proteins, Nanotechnology, Immunoglobulins, Emerging Technologies, Enzymes and Coenzymes, Ventana Medical Systems Inc.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Life Science Weekly


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