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Angle, BioView Demonstrate Integrated Workflow to Detect CTCs in Feasibility Study

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NEW YORK – Angle this week presented results from an internal feasibility study that integrated its Parsortix cell-sorting platform with BioView's Duet imaging system to improve detection of circulating tumor cells (CTCs) in cancer patients' blood samples.

The group found a higher number of CTCs in metastatic breast, lung, and melanoma cancer patients than previously possible by combining their collection and automated detection platforms.

UK-based Angle's Parsortix cell-sorting instrument contains a microfluidic chip that captures CTCs based on their physical properties, including size and deformability. By filtering out white blood cells and other particles in the patients' bloodstream, Parsortix then isolates CTCs for downstream applications.

In an interview at the Molecular Med Tri-Con Conference in San Francisco this week, Anne-Sophie Pailhes-Jimenez, head of research and development at Angle and study lead author, explained that her team needed an immunofluorescence assay to identify CTCs after running blood samples on the Parsortix platform.  

Previously applying handheld microscopes, Pailhes-Jimenez's team realized that user-dependent immunofluorescence could lead to varying results and instead decided to use a standardized method to produce consistent and accurate results. After identifying Israel-based BioView and its Duet instrument as a potential partner, Angle began collaborating with the firm early last year.

BioView's Duet platform integrates an automated scanning microscope and imaging system, which pathologists can use to detect, classify, and count cells based on color, intensity, size, pattern, and shape.

"At the beginning, we were not looking for a collaboration, but instead to simply to buy an instrument," Pailhes-Jimenez said. "We had been in contact with BioView for a few years for prior work, but the team was very proactive, and we [therefore] began working with them and asked them to standardize the system for our assay."

In the study, Angle's researchers processed 10-ml blood samples from 42 metastatic breast cancer, 32 non small lung cancer (NSCLC), and 20 melanoma cancer patient through the Parsortix system.

The group then used proprietary chemistry to immunostain the enriched samples to mark CTCs from the specific cancer types and from nucleated cells, and to apply exclusion markers for red blood cells in the samples' background.

Pailhez-Jimenez's team then ran the samples through BioView's Duet analysis system.

By combining the Parsortix and Duet systems, the researchers successfully collected and identified CTCs in about 27 breast cancer patients, 10 NSCLC patients, and 13 melanoma patients. Pailhes-Jimenez said the integrated workflow allowed her team to detect higher amounts of CTCs in cancer patients than they had previously found in prior internal studies.

Pailhes-Jimenez explained that Parsortix requires about 1.5 to 2.5 hours to enrich for CTCs in a patient's bloodstream. The immunostaining step takes about 2.5 to three hours, followed by imaging and analysis steps on the Duet system that require up to an hour. Depending on the sample size, she noted that the overall workflow takes about five to six hours to produce actionable results. 

Because of the improvements in CTC detection via the integrated workflow, Pailhes-Jimenez's team is now collaborating with BioView on a larger study focusing on detecting CTCs in breast and lung cancers. The researchers also hope to provide information about the integrated system's clinical utility for different cancer subtypes.

"In the current study, we only looked at CTC markers for specific cancer types," Pailhes-Jimenez explained. "In the subsequent study, we will look at subpopulations, such as mesenchymal and epithelial, or epithelial-mesenchymal transition cells, which will hopefully show more clinical utility."

In the new study, the researchers will process a separate cohort of 200 blood samples, including approximately 50 breast and 50 lung cancer patients, as well as 100 controls through the integrated workflow.

According to Pailhes-Jimenez, the team is purchasing blood samples from Biomedica, a contract research organization based out of Ukraine.

Pailhez-Jimenez also highlighted that the Duet system's flexibility will allow Angle to adapt the workflow to assays that firm envisions developing for additional cancers. She hopes to present the results at the American Association of Cancer Research Conference in May, which she noted will also include clinical sensitivity and specificity data.

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