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Contents: News Stories, 2000


September 5, 2000

Nanoprobes awarded Phase I SBIR Grant on Gold Quenched Molecular Beacons

The National Institute of General Medical Sciences (National Institutes of Health) has recently awarded a Phase I SBIR grant to Nanoprobes, Incorporated (Yaphank, NY) of $ 138,457 for six months, effective September 1, to investigate the application of its gold labeling technology as a quencher for fluorescently labeled molecular beacons.

Nanogold®, a 1.4 nm metal cluster compound, is covalently linked to biologically active molecules for use as a structural probe in microscopy, where it is widely used for labeling cellular and tissue components for electron microscope observation. It has also been found to quench fluorescence by fluorescence resonance energy transfer and possibly other processes over short distances which are ideal for application to molecular beacons. In preliminary experiments, Nanogold® has already demonstrated a quenching ability which is equivalent to that of commonly used fluorescent quenchers. The grant will support the development of improved gold labels which will provide signal-to-noise ratios greater than those currently available with fluorescent quenchers; furthermore, because gold cluster labels absorb across a large part of the visible spectrum, the same gold cluster formulation can be used in a range of different beacons, potentially simplifying and streamlining beacon manufacture.

This technology will simplify and enhance the real-time detection of specific DNA sequences in cells and other highly localized systems. Because molecular beacons only fluoresce after binding to their target, the specific signal is not affected by the presence of unbound beacon, and therefore unbound beacons need not be removed before observation. This makes molecular beacons appropriate for use in fiber optic biosensors for quickly screening tissues during transplantation and other medical procedures. A variety of other applications, including rapid cancer screening and portable fetal testing, would also be enabled by this technology.

Gold cluster labels will be developed and optimized at Nanoprobes, Incorporated by Dr. Richard D. Powell, Dr. Wenqiu Liu, Joshua Stein, and Duane Hoch, with technical advice from Dr. James F. Hainfeld. Molecular beacons will be constructed and evaluated at The Rockefeller University, Department of Physics, by Prof. Albert Libchaber and Dr. Benoit Dubertret. The fluorescence quenching properties of different clusters will be compared, and it is hoped that the research will further elucidate the mechanisms by which energy is transferred between fluorescent groups and metal cluster compounds.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and labeling reagents, the combined fluorescent and gold immunoprobe FluoroNanogold which is used for correlative fluorescence and electron microscopy, and sensitive DNA detection reagents.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (919) 845-6324
E-mail rpowell@nanoprobes.com.
WWW: www.nanoprobes.com

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June 16, 2000

Nanoprobes wins Phase I STTR Grant to develop Chromogenic In Situ Hybridization Detection Assay

Nanoprobes, Incorporated has received a Phase I Small Business Technology Transfer (STTR) grant from the National Cancer Institute (National Institutes of Health). The award of $ 116,118 for one year will be used to develop a chromogenic in situ hybridization assay to detect and quantify Her-2/neu gene amplification, which will be used by pathologists and physicians to characterize and select treatment for breast cancer.

Preliminary results have shown that the Nanogold® system gives single copy gene detection in in situ hybridization in paraffin-embedded cells and biopsy sections, by light microscopy. The high resolution, black signal is permanent, easily seen in a standard light microscope, and readily distinguished from commonly used stains. It does not fade, and is not hampered by autofluorescence. For optimum performance in the Her-2/neu assay, Nanogold® will be evaluated with both silver and a new gold-based autometallographic system, GoldEnhance, which produces higher sensitivities and lower backgrounds. Although initially targeted to Her-2/neu gene amplification, the general method will be applicable to many other conditions in the future. Unlike fluorescence in situ hybridization (FISH), the new method will not require fluorescent optics, and therefore will be more convenient for many practicing pathologists. In addition, it is anticipated that the method and reagents may be readily adapted for use on automated staining instruments.

Reagents for the new method will be developed at Nanoprobes, Incorporated by Dr. Richard D. Powell, Dr. Wenqiu Liu, and Joshua Stein. The in situ hybridization assay will be developed and clinically validated at the Cleveland Clinic Foundation by Dr. Raymond R. Tubbs (Cleveland Clinic Foundation), with Mr. James Pettay. Dr. James F. Hainfeld (Nanoprobes) will provide assistance and direction.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical, chemical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes, chemically specific gold labeling reagents, and autometallographic enhancers which are used in light and electron microscopy, molecular biology and cellular studies.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (919) 845-6324
E-mail rpowell@nanoprobes.com.
WWW: www.nanoprobes.com

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April 19, 2000

Nanoprobes Receives Phase II of "Fast-Track" SBIR grant on large Covalent Gold Probes

The National Institute of General Medical Sciences (National Institutes of Health) has awarded a Phase II Small Business Innovation Research (SBIR) Grant to Nanoprobes, Incorporated (Yaphank, NY) of $ 757,045 for the two years beginning April 1, 2000. Entitled "Large Covalent Gold Labels and Probes," this grant is Phase II of a "Fast-Track" award to develop covalently linkable gold nanoparticles 3 to 40 nm in diameter. These will be used as improved replacements for colloidal gold labels for cell and structural biology research, and as detection agents in rapid, sensitive medical diagnostics and blotting applications. Promising results using covalently linked 3 and 10 nm gold particles suggest that the advantages of the successful Nanogold® technology may be applied to larger gold probes. Using chemical cross-linking, probes may be prepared using a wide range of molecules not available as in colloidal gold conjugates, such as oligonucleotides, peptides and lipids. This approach is expected to expand the experimental applications of gold labeling and enable new types of assays for rapid diagnostic tests.

Development and evaluation of the new probes will be conducted in collaboration with Dr. David L. Spector (Cold Spring Harbor Laboratory, NY) and Dr. Peter M. Takvorian and Dr. Ann Cali (Rutgers University, Newark, NJ). The grant also includes a subcontract to the State University of New York at Stony Brook, NY.

Nanoprobes, Incorporated, founded in 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® and 0.8 nm undecagold cluster immunoprobes, silver and gold enhancers, and sensitive DNA detection reagents. These are used in light and electron microscopy, molecular biology and cellular studies. The Company recently graduated from the Long Island High Technology Incubator at Stony Brook, New York and moved to larger premises in Yaphank, NY.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (919) 845-6324
E-mail rpowell@nanoprobes.com.
WWW: www.nanoprobes.com

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March 9, 2000

Nanoprobes Moves to Larger Facility in Yaphank, NY

Nanoprobes, Incorporated has moved its principal research, development and manufacturing operations to a larger suite of laboratories and offices located in Yaphank, NY. The new site will enable the company to expand its research and development activities, and at the same time allow us to provide faster and more responsive service to our existing customers.

Customers can now contact our technical support department directly using our new technical services number, (631) 205-9492, or our dedicated technical support e-mail address, tech@nanoprobes.com. For sales inquiries or requests, you can use our dedicated e-mail address, sales@nanoprobes.com. Altenatively, callers can use our new toll-free number, 1-877-447-6266, to quickly and easily reach anyone at the company through individual extensions. The new site is about ten miles from our previous location in Stony Brook, NY, and Nanoprobes will maintain its links with collaborators and facilities in the area. More information and directions for visitors are available on our web site at www.nanoprobes.com.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and sensitive DNA detection reagents which are used in light and electron microscopy, molecular biology and cellular studies.

For more information, contact:

James F. Hainfeld, Ph.D.
President
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (631) 205-9490
US Toll-Free: 1-877-447-6266 (1-877-447-NANO)
Technical Support: (631) 205-9492
Fax: (631) 205-9493
E-mail nano@nanoprobes.com
WWW: www.nanoprobes.com

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March 9, 2000

Nanoprobes wins Phase I SBIR to Develop Non-Radioactive Southern Blotting Detection Methods

The National Cancer Institute (National Institutes of Health) has awarded a new Phase I SBIR grant to Nanoprobes, Incorporated (Yaphank, NY) of $ 116,118 for up to one year to develop its Nanogold labeling technology as a method for fast sensitive Southern blotting detection.

Nanogold® with autometallographic enhancement has already exhibited detection sensitivities comparable with autoradiography and chemiluminescence. In in situ hybridization, Nanogold with silver acetate autometallography has been used to visualize as few as 1-2 copies of target viral DNA in paraffin-embedded cells and biopsy sections for light microscopy. For optimum performance in Southern blotting detection, Nanogold® will be used with both silver and a novel gold-based autometallographic system which produces higher sensitivities and lower backgrounds. Specialized blocking reagents will be developed to prevent non-specific membrane binding and ensure high signal-to-noise ratios. A reagent package and protocols will be developed for Southern blot hybridization detection in a few hours without film exposure, darkroom conditions or radioactivity.

Nanogold® Southern blotting detection will provide researchers pathologists and medical laboratories with faster, simpler and more sensitive methods for use in cancer diagnosis and research, without the hazard and expense of radioactive probes or the lengthy development times required for chemiluminescent detection. Nanogold® labeling has higher intrinsic resolution than chemiluminescence, which means that this method may be readily adapted to scanned microarrays or other high-throughput systems.

The new reagents will be clinically evaluated at the Cleveland Clinic Foundation (Cleveland OH) for the characterization of lymph node biopsies and abnormal lymphoid proliferations in the peripheral blood. The research will be performed by Dr. Richard D. Powell (Nanoprobes) and Dr. Raymond R. Tubbs (Cleveland Clinic Foundation), with Dr. Frederic R. Furuya and Dr. Wenqiu Liu. Dr. James F. Hainfeld will provide advice and technical direction to the project.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and sensitive DNA detection reagents which are used in light and electron microscopy, molecular biology and cellular studies.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (919) 845-6324
E-mail rpowell@nanoprobes.com.
WWW: www.nanoprobes.com

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