Scientists have developed a disposable microfluidics device that may help identify advanced breast cancer patients who are candidates for therapy with Herceptin (trastuzumab). It is designed to efficiently capture cancer cells overexpressing Her2 in circulating blood.
“Microfluidic-based devices offer a unique opportunity to efficiently isolate CTCs from patient's blood, thereby opening a window on the pathophysiology of cancer and its progression,” notes Benjamin Thierry, Ph.D., at the Ian Wark Research Institute at the University of South Australia. “We are aiming to achieve clinical validation in the coming months and, with the support of a fellowship from the Prostate Cancer Foundation of Australia, to extend the study to the detection of aggressive forms of prostate cancer.”
The device is described in a paper titled “Herceptin-Functionalized Microfluidic PDMS Devices for the Capture of Her2 Positive Circulating Breast Cancer Cells” and is published in Biomicrofluidics.
Current methodologies for determining Her2 status include immunohistochemistry and FISH, both of which require biopsies. Biopsy-based testing has the potential to lead to ineffective treatment choices, because in about 20% of breast cancers the Her2 status of the primary tumor may differ from that of a metastatic tumor, according to the researchers.
This fact has made the noninvasive alternative of profiling circulating tumor cells (CTCs) a long-sought but elusive goal. Isolating circulating tumor cells, which are present at ratios as low as 1 to 10 per billion blood cells, is extremely challenging.
Recently, researchers at Massachusetts General Hospital developed a microfabricated device to bind to cells of epithelial origins circulating in the blood. They reported near-perfect ability to isolate circulating tumor cells across a range of cancers.
Dr. Thierry’s team has now developed a plastic-based disposable microfluidic device that they believe offers several improvements for capturing circulating tumor cells. It is significantly easier and cheaper to make than the prior microfabricated device, according to Dr. Thierry.
The device uses an organic silicone called polydimethylsiloxane (PDMS), which is compatible with soft molding techniques, transparent, and permeable to gasses. The major challenge associated with PDMS use in biodiagnostic applications is its lack of chemical reactivity.
The team used a novel plasma-based polymerization process to overcome that problem. The process creates a durable polymeric layer on the device's surface containing a high number of reactive molecules, which can readily be used to attach proteins able to capture cancer cells but not normal blood cells.
With a commonly used breast cancer cell line (SK-BR-3) as a model for cells overexpressing Her2, Dr. Thierry's device demonstrated an approximately 80% immunocapture efficacy of Her-positive cells from full blood in model and validation studies.