False colored scanning electron microscope image of prostate cancer tumor cell cluster captured in one of the >100,000 cluster traps on the Cluster-Wells.
Cancer cells that have detached from the primary tumor and flow into the blood circulation are called circulating tumor cells (CTCs), and they may become seeds for the growth of additional tumors. Clusters of CTCs, while extremely rare, are 100 times more efficient at spreading cancer than single CTCs.
Until now, technology has been limited in detecting CTC clusters. But in a study recently published in Nature Communications, researchers at Winship Cancer Institute of Emory University and Georgia Institute of Technology have developed a device that reliably and efficiently detects cell clusters that spread cancer, enabling minimally invasive prognosis and diagnosis and improving the clinical management of cancer.
The research led by corresponding author A. Fatih Sarioglu, PhD, MS, a member of the Cancer Immunology Research Program at Winship Cancer Institute of Emory University and assistant professor in the School of Electrical and Computer Engineering at Georgia Institute of Technology, developed a novel device called Cluster-Wells; this device detects and collects CTC clusters from peripheral blood. It is designed to be disposable and have low manufacturing cost to make it accessible in a variety of research and clinical settings.
"The technology allows routine biopsies on patients' cells that are spreading inside the body," said Sarioglu. "Studying these cells can provide information on the patient’s tumor that can help doctors develop effective treatment strategies."
Historically, it has been difficult to reliably and efficiently isolate viable CTC clusters because the technologies used for CTC isolation weren't sensitive and specific enough as they were calibrated to detect single cells, not clusters. What’s more, CTC clusters can reorganize themselves as single-file, chain-like structures and slip through extraordinarily fine "sieves." The higher shear forces experienced during microfiltration could also damage CTC clusters or break them into single cells. Recent microfluidic chips specifically made to target CTC clusters are relatively more sensitive, but they also risk damaging the clusters because of their processing rates.
To address these limitations, Sarioglu and his team co-developed Cluster-Wells, a device that is both more sensitive and more efficient in its processing rate than previous technologies. It gently isolates small and large CTC clusters from unprocessed whole blood specimens without needing to target tumor-specific antigens. The Cluster-Wells can filter CTC clusters as tiny as a single cell—from blood samples of people with all sorts of cancers.
Finding CTCs in circulation means the primary tumor is already shedding cancer cells that can eventually lead to metastasis "if the seed matches the soil," said Sarioglu. "Isolating these tumor cells will provide the information that can be used to treat them effectively and potentially lead to the development of therapies that can target cancer metastasis."
Other Winship researchers who collaborated on this research include: Mehmet Asim Bilen, MD, associate professor, Department of Hematology and Medical Oncology at Emory University School of Medicine and director of Winship's Genitourinary Medical Oncology Program; Omer Kucuk, MD, professor and Correll Chair in Genitourinary Cancer in the Department of Hematology and Medical Oncology at EUSM; Carlos S. Moreno, PhD, associate professor, Department of Pathology and Laboratory Medicine, and Bioinformatics at EUSM and member of Winship's Cell and Molecular Biology Research Program; Bassel Nazha, MD, MPH, assistant professor, Department of Hematology and Medical Oncology at EUSM and member of Winship's Discovery and Developmental Therapeutics Research Program; and Martin G. Sanda, MD, professor and chair, Department of Urology at EUSM, and director of Winship's Prostate Cancer Center.