New device for identifying aggressive breast cancers

Aggressive breast cancers with poor prognosis typically have abnormal levels of the protein HER2 (the tyrosine kinase human epidermal growth factor receptor 2). The new elastomeric, rubber-like device is designed to efficiently capture cancer cells overexpressing HER2 in circulating blood.

Finding a way to identify these cells is medically relevant because HER2 positive patients with early breast cancer have been found to significantly benefit from treatment with Herceptin or trastuzumab, the humanized monoclonal antibody against HER2, which can lower recurrence risk by about half. Given the cost ($50,000 – $65,000 per year in the United States) and possible side effects of Herceptin therapy, establishing HER2 status is crucial.

Current methodologies for determining HER2 status include immunohistochemistry and fluorescence in situ hybridization (FISH), both of which require biopsies. But biopsy-based testing may 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. This fact has made the non-invasive alternative of profiling circulating tumor cells 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, interest in microfluidic devices for capturing circulating tumor cells (CTCs) has intensified because of their greatly improved capabilities. A microfabricated device developed by researchers at the Massachusetts General Hospital and designed to bind to cells of epithelial origins (most cancers originate from epithelial tissues) circulating in the blood demonstrated near-perfect ability to isolate circulating tumor cells across a range of cancers.

In a study supported by the National Health and Medical Research Council Australia, Benjamin Thierry and colleagues at the Ian Wark Research Institute at the University of South Australia developed a plastic-based disposable microfluidic device offering several improvements for capturing circulating tumor cells. The device is designed to take advantage of the features of an organic silicone found in contact lenses and shampoos called polydimethylsiloxane (PDMS), which is compatible with soft molding techniques, transparent, and permeable to gasses.

The device is significantly easier and cheaper to make than the prior microfabricated one. 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 ~80% immuno-capture efficacy of HER positive cells from full blood in model and validation studies.

Thierry concluded, “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. We hope that our device will provide a fast, reliable and affordable methodology to establish HER2 status for breast cancer patients presenting metastases, thereby enabling the selection of more potent therapy based on trastuzumab. 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 article, “Herceptin-Functionalized Microfluidic PDMS Devices for the Capture of HER2 Positive Circulating Breast Cancer Cells Benjamin Thierry, Mahaveer Kurkuri, Jun Yan Shi, Lwin Ei Mon Phyo Lwin and Dennis Palms (University of South Australia) appears in the journal Biomicrofluidics.

ABOUT Biomicrofluidics

Biomicrofluidics is an online open-access journal published by the American Institute of Physics to rapidly disseminate research in elucidating fundamental physicochemical mechanisms associated with microfluidic and nanofluidic phenomena as well as novel microfluidic and nanofluidic techniques for diagnostic, medical, biological, pharmaceutical, environmental, and chemical applications. See: http://bmf.aip.org/

ABOUT AIP

The American Institute of Physics is a federation of 10 physical science societies representing more than 135,000 scientists, engineers, and educators and is one of the world's largest publishers of scientific information in the physical sciences. Offering partnership solutions for scientific societies and for similar organizations in science and engineering, AIP is a leader in the field of electronic publishing of scholarly journals. AIP publishes 12 journals (some of which are the most highly cited in their respective fields), two magazines, including its flagship publication Physics Today; and the AIP Conference Proceedings series. Its online publishing platform Scitation hosts nearly two million articles from more than 185 scholarly journals and other publications of 28 learned society publishers.