The polymer film forms nanodots: tiny bumps that can be functionalized with antibodies to grab passing cancer cells. Image: Ref. 1, 2011 WILEY-VHC Verlag GmbH & Co. |
Cancer
cells that break free from a tumor and circulate through the
bloodstream spread cancer to other parts of the body. But this process,
called metastasis, 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 at the RIKEN Advanced Science Institute in Wako,
Japan, in collaboration with colleagues at the University of California,
Los Angeles, and the Institute of Chemistry at the Chinese Academy of
Sciences, Beijing, has produced a polymer film that can capture specific
CTCs1. With further development, the system could help doctors to
diagnose an advancing cancer and assess the effectiveness of treatments.
The
researchers used 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, tiny bumps that measure 100 to 300 nm across, depending
on the voltage used (1 to 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. In turn, the
antibody could latch on to an antigen called epithelial cell adhesion
molecule (EpCAM), which is produced by most tumor cells. In this way,
the film could grab tumor cells from just a few milliliters of a blood
sample.
The
team tested 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 roughly 240 breast-cancer cells per square
millimeter of film. In contrast, it caught 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 50 or so breast cancer cells.
The
film’s efficiency depends on the size and spacing of the nanodots, and
the presence of the capturing antibody. Since these can be easily
modified, the same method could be used to make films that sense other
types of cells.
The
next step is to “further optimize the nanostructures of the conducting
polymers and understand in more detail the cell-capturing mechanism,”
says 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 corresponding author for this highlight is based at the Yu Initiative Research Unit, RIKEN Advanced Science Institute.
