APPLICATIONS OF TECHNOLOGY:
- Diagnostic testing
- Drug design
- Personalized medicine
ADVANTAGES:
- Highly sensitive labeling of tissues and cells
- Quantitative results
- Less expensive and time-consuming than conventional immunohistochemistry (IHC)
- High signal-to-noise ratio
- Compatible with conventional IHC and fluorescent microscopy
ABSTRACT:
Kevin Weng and Frank Chen at Berkeley Lab have developed multifunctional nanoparticles that combine targeting and reporting capabilities for sensitive detection of biomarkers on cells and in tissue. The invention consists of a nanocluster, such as a liposome or polymer, that acts as a scaffold. Attached to this scaffold are a targeting component (a secondary antibody or ligand), and fluorescent reporters (quantum dots or other luminescent nanocrystals).
As in standard IHC, tissue or cells are incubated with a primary antibody against a target antigen. The nanoclusters are then added, and their secondary antibody binds the primary antibody. When the sample is exposed to excitation light, the nanocrystals on the nanoclusters emit light in a narrow range of wavelengths, providing a high signal-to-noise ratio. The sensitivity is enhanced by attaching multiple secondary antibody fragments to each nanocluster, thereby facilitating avidity. In addition, the signal can be amplified by attaching multiple fluorescent reporters to each nanocluster. Thus, the technique combines the advantage of amplification, offered by conventional chromogenics, with processing efficiency and quantitative results, offered by immunofluorescence.
The scientists tested the invention by staining breast cancer cell lines and tissue for known targets. In the test with human epidermal growth factor receptor 2 (HER2/erbB2), for example, the resultant images showed quantifiable fluorescence intensities that accurately reflected known HER2 expression levels, indicating that the technique provides sensitivity, specificity, and signal amplification.
The testing of cells and biopsy tissues for biomarkers is a key component in disease diagnosis, selection of therapies, and drug development. This testing is usually done by conventional IHC—either chromogenics or immunofluorescence. However, chromogenics is limited by multiple, time-consuming steps and an inability to provide quantitative results, while immunofluorescence, though quantifiable, is limited by problems of signal amplification. The Berkeley Lab invention overcomes these limitations to advance the labeling of biomarkers.
DEVELOPMENT STAGE: Proof of principle.
STATUS: Patent pending. Available for licensing or collaborative research.
SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:
New Multimodal Probes Compatible with Fluorescence and MRI, JIB-2075
Predictive Methodology and Tools for Nanotoxicology, IB-2218b
Functionalized Semiconductor Nanocrystals for Imaging Organelles in Live Cells, IB-2045
Au-NP: High-Resolution Biomarkers as Indicators of Nanotoxicity, IB-2419
Cells-on-a-Chip: Apparatus for Real-Time and Label-Free Molecular Imaging of Live Cells and Bacteria, JIB-2201REFERENCE NUMBER: IB-2776
