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Tenfold Boost in Ability to Pinpoint Proteins in Cancer Cells

Better diagnosis and treatment of cancer could hinge on the ability to better understand a single cell at its molecular level. New research offers a more comprehensive way of analyzing one cell’s unique behavior, using an array of colors to show patterns that could indicate why a cell will or won’t become cancerous.

A University of Washington team has developed a new method for color-coding cells that allows them to illuminate 100 biomarkers, a ten-time increase from the current research standard, to help analyze individual cells from cultures or tissue biopsies. The work is published in the March 19 issue of Nature Communications.

“Discovering this process is an unprecedented breakthrough for the field,” said corresponding author Xiaohu Gao, a UW associate professor of bioengineering. “This technology opens up exciting opportunities for single-cell analysis and clinical diagnosis.”

The research builds on current methods that use a smaller array of colors to point out a cell’s biomarkers – characteristics that indicate a special, and potentially abnormal or diseased, cell. Ideally, scientists would be able to test for a large number of biomarkers, then rely on the patterns that emerge from those tests to understand a cell’s properties.

The UW research team has created a cycle process that allows scientists to test for up to 100 biomarkers in a single cell. Before, researchers could only test for 10 at a time.

The analysis uses quantum dots, which are fluorescent balls of semiconductor material. Quantum dots are the smaller version of the material found in many electronics, including smartphones and radios. These quantum dots are between 2 and 6 nanometers in diameter, and they vary on the color they emit depending on their size.

Cyclical testing hasn’t been done before, though many quantum dot papers have tried to expand the number of biomarkers tested for in a single cell. This method essentially reuses the same tissue sample, testing for biomarkers in groups of 10 in each round.

“Proteins are the building blocks for cell function and cell behavior, but their makeup in a cell is highly complex,” Gao said. “You need to look at a number of indicators (biomarkers) to know what’s going on.”

The new process works like this: Gao and his team purchase antibodies that are known to bind with the specific biomarkers they want to test for in a cell. They pair quantum dots with the antibodies in a fluid solution, injecting it onto a tissue sample. Then, they use a microscope to look for the presence of fluorescent colors in the cell. If they see particular quantum dot colors in the tissue sample, they know the corresponding biomarker is present in the cell.

After completing one cycle, Gao and co-author Pavel Zrazhevskiy, a UW postdoctoral associate in bioengineering, inject a low-pH fluid into the cell tissue that neutralizes the color fluorescence, essentially wiping the sample clean for the next round. Remarkably, the tissue sample doesn’t degrade at all even after 10 such cycles, Gao said.

For cancer research and treatment, in particular, it’s important to be able to look at a single cell at high resolution to examine its details. For example, if 99 percent of cancer cells in a person’s body respond to a treatment drug, but 1 percent doesn’t, it’s important to analyze and understand the molecular makeup of that 1 percent that responds differently.

“When you treat with promising drugs, there are still a few cells that usually don’t respond to treatment,” said Gao. “They look the same, but you don’t have a tool to look at their protein building blocks. This will really help us develop new drugs and treatment approaches.”

The process is relatively low-cost and simple, and Gao hopes the procedure can be automated. He envisions a chamber to hold the tissue sample, and wire-thin pumps to inject and vacuum out fluid between cycles. A microscope underneath the chamber would take photos during each stage. All of the images would be quantified on a computer, where scientists and physicians could look at the intensity and prevalence of colors.

Gao hopes to collaborate with companies and other researchers to move toward an automated process and clinical use.

“The technology is ready,” Gao said. “Now that it’s developed, we’re ready for clinical impacts, particularly in the fields of systems biology, oncology and pathology.”

The research was funded by the National Institutes of Health, the U.S. National Science Foundation, the U.S. Department of Defense, the Wallace H. Coulter Foundation and the UW’s Department of Bioengineering.

Study: Quantum dot imaging platform for single-cell molecular profiling

Source: University of Washington

Advanced Cell Diagnostics Initiates Agreement to Study Biomarkers for Cancer Immunotherapy

Advanced Cell Diagnostics, Inc. (ACD) announced today that they have entered into an agreement with The Johns Hopkins University on behalf of its Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins to use ACD’s proprietary RNAscope® technology platform to validate novel biomarkers and drug targets for cancer immunotherapy.

Cancer immunotherapy, which aims to mobilize a patient’s immune system to fight cancer, has been gaining momentum recently with the FDA approval of anti-CTLA-4 therapy for melanoma and with the recent impressive and durable remissions produced by targeting PD1 in multiple solid tumors in early-phase clinical trials led by Johns Hopkins investigators. With many additional immune modulatory molecules identified for targeting that play major roles in specific subsets of cancer, it will be critical to develop standardized biomarkers to guide the application of the most effective immune therapies on a patient by patient basis.

Targeting the immune checkpoints that are often suppressed in many cancers has demonstrated tremendous potential. However, to identify biomarkers useful for guiding therapy, conventional approaches to biomarker analysis have proven inadequate, leading to conflicting results.

“The complex interplay between cancer cells and the immune system in the tumor microenvironment matches perfectly with RNAscope’s capability of single molecule sensitivity and single cell resolution, which can help pinpoint which cell is talking to which other cell,” said Dr. Yuling Luo, Founder, President and CEO of ACD. Dr. Luo added, “That knowledge will be essential for selecting optimal targets for drug development and predicting which patient will benefit from it. We feel extremely fortunate to be able to provide such a tool to the pioneers in this emerging and exciting field.”

Source: Advanced Cell Diagnostics

Definiens and Advanced Cell Diagnostics Introduce RNAscope SpotStudio – Early Access Program Started

Definiens and Advanced Cell Diagnostics (ACD) recently unveiled the details of the RNAscope SpotStudio image analysis software to attendees at the Molecular Medicine Tri-Conference meeting in San Francisco, USA. The software has already been sold to a top pharmaceutical company and a leading academic medical center under an early access program. This advanced image analysis solution brings objective and accurate quantification to RNA in situ hybridization and enables a new generation of diagnostic applications based on single cell analysis. For the first time, gene expression can be measured quantitatively at single-cell resolution and interpreted by pathologists within histopathological context.

Empowering Pathologists with an Easy-to-Use Tool for Quantitative Biomarker Analysis

Quantitative RNA in situ hybridization analysis has recently been made possible by the single molecule sensitivity and digital nature of RNAscope® assay technology. However, manual scoring is time consuming and prone to subjectivity and poor reproducibility. RNAscope SpotStudio software is designed for pathologists with no prior training in image analysis. It is an intuitive automated solution that generates standardized and objective results in minutes. Testing has shown that results obtained with RNAscope SpotStudio are comparable to careful manual annotations by pathologists. The software is compatible with image data from whole slide scanners and microscopes.

“In situ biomarker analysis tools such as immunohistochemistry (IHC) have been limited to subjective semi-quantitative scoring. RNAscope and the SpotStudio image analysis software take in situ biomarker analysis to a whole new level, where quantitative data at the single cell level can be obtained and interpreted within the histopathological context of the clinical specimen”, said Yuling Luo, Founder, President and CEO of ACD. “RNAscope combines the advantages of IHC and PCR, making it a superior tool for tissue-based diagnostics and companion diagnostics”, Dr. Luo added. “Definiens’ invaluable expertise with tissue image analysis made it an ideal partner for the joint development of RNAscope SpotStudio.”

“Coming from a leading position in providing image analysis solutions to the life sciences market, Definiens is rapidly expanding its footprint in tissue diagnostics. We are very excited about this partnership with ACD representing a great example of advanced diagnostic solutions based on Definiens image and data analysis capabilities that will drive next generation diagnostics to truly enable personalized medicine”, said Thomas Heydler, CEO of Definiens.

Definiens and ACD will showcase RNAscope SpotStudio at the Molecular-Med Tri-Con in San Francisco (booth 210). The solution will be marketed and distributed by ACD and is currently being distributed to selected customers in an early access program. General availability is planned for the second quarter of 2013.

While RNAscope Spot Studio supports the analysis of brightfield images, RNA FISH assays can be quantified with Definiens Tissue Studio. With over 450 deployed licenses, Definiens Tissue Studio is the leading image analysis solution for digital pathology. Beyond the detection of spot-like stains, Definiens Tissue Studio provides morphological and molecular expression profiles from any solid tissue (IHC and IF) on a cell-by-cell basis.

Source: Definiens

Nodality Enters into a Multi-year Strategic Collaboration with Pfizer in Autoimmune Disease

Nodality, Inc. recently announced a strategic collaboration with Pfizer Inc. for the use of Nodality’s proprietary Single Cell Network Profiling (SCNP) technology as a tool for the development of Pfizer compounds. The agreement establishes a multi-year, collaborative effort that will initially focus on providing biological bases for streamlining the development of potential Pfizer compounds for autoimmune disease with an initial focus on Lupus, including characterizing mechanisms of action, disease analysis, and drug profiling. The agreement also provides Pfizer the option to engage Nodality in companion diagnostics development. The terms of the agreement include an upfront payment, R&D funding, and success-based milestone payments.

Frost & Sullivan Lauds Advanced Cell Diagnostics for Its Highly Innovative In Situ Biomarker Detection Assay Kit

Based on its recent analysis of the in situ biomarker detection assay market, Frost & Sullivan recognizes Advanced Cell Diagnostics, Inc. with the 2011 North American Frost & Sullivan Technology Innovation Award for its RNAscope platform.