Polymer Film Packed with Antibodies Used to Capture Tumor Cells

Metastasis, the process when cancer cells that break free from a tumor and circulate through the bloodstream spread cancer to other parts of the body, is extremely difficult to monitor because the circulating tumor cells (CTCs) can account for as few as one in every billion blood cells.

Research led by scientists from the RIKEN Advanced Science Institute (Wako, Japan), in collaboration with colleagues at the University of California, Los Angeles (UCLA; USA) and the Institute of Chemistry at the Chinese Academy of Sciences (Beijing, China), has created a polymer film that can capture specific CTCs. With additional modifications, the system could help clinicians to identify an advancing cancer and assess the effectiveness of treatments.

The researchers utilized a small electrical voltage to help deposit a conducting polymer film of poly(3,4-ethylenedioxythiophene) (PEDOT) bearing carboxylic acid groups on to a 2-cm2 glass base. The polymer formed nanodots, minuscule bumps that measure 100-300 nm across, depending on the voltage used (1-1.4 V).

Adding a chemical linker to the film allowed it to bind a protein called streptavidin; this protein then joined to an antibody. After that, the antibody could latch on to an antigen called epithelial cell adhesion molecule (EpCAM), which is generated by most tumor cells. In this manner, the film could capture tumor cells from only a couple of milliliters of a blood sample.

The scientists evaluated several types of tumor cells on films with various sizes and densities of nanodots, and used a microscope to observe how well they captured the cells. The most effective film, with nanodots measuring about 230 nm across and containing about 8 dots per square micrometer, captured approximately 240 breast-cancer cells per mm2 of film. In contrast, it captured fewer than 30 cervical cancer cells that do not express EpCAM, proving that the antibody used on the film is highly selective. A smooth PEDOT-carboxylic acid film with the same antibody captured only about 50 breast cancer cells.

The film’s effectiveness depends on the size and spacing of the nanodots, and the presence of the capturing antibody. Because these can be easily modified, the same application could be used to produce films that sense other types of cells.

The next phase of the research is to “further optimize the nanostructures of the conducting polymers and understand in more detail the cell-capturing mechanism,” said RIKEN unit leader Hsiao-hua Yu. “We are also currently working on a direct electrical readout of the captured cells, without needing to use a microscope.”

The study’s findings were published November 2, 2012, in the journal Advanced Materials.

Related Links:
RIKEN Advanced Science Institute
University of California, Los Angeles
Institute of Chemistry at the Chinese Academy of Sciences