A gentle approach to capturing individual cancer cells from patients’ blood could aid diagnosis and treatment while minimizing invasive procedures, say researchers [Li, et al., Biomaterials (2015), doi: 10.1016/j.biomaterials.2015.06.036, http://dx.doi.org/10.1016/j.biomaterials.2015.06.036].
Cancer can spread to new sites via the release of circulating tumor cells (CTCs) into the bloodstream. Isolated tumor cells can also provide useful information about cancer type and behavior, but detecting them in a throng of blood cells is difficult and capturing them without damage is a delicate business. So Paula T. Hammond of Massachusetts Institute of Technology and Shannon L. Scott of Harvard Medical School, together with colleagues from Texas Tech University and Howard Hughes Medical Institute, have devised a simple alternative based on a standard microfluidic chip coated with a biodegradable nano-film.
“The ability to selectively isolate extremely rare CTCs from whole blood holds major implications for both clinical medicine and biological research,” explains first author on the study, Wei Li of Texas Tech University. “Some current techniques place isolated tumor cells under excessive stresses, which reduce cell viability and potentially induce phenotype change, losing valuable information.”
Instead, the nano-film coating gently captures cancer cells from blood while preserving their functionality. The film is deposited onto the PDMS microfluidic chip using a layer-by-layer (LbL) approach, which allows the use of a ‘library’ of various coatings that can be readily functionalized with antibodies to bind to different types of cancer cell. At just 40 nm thick, the extremely thin coating easily conforms to the interior channels of the microfluidic chip.
In tests with blood spiked with cancer cells and samples from real patients, the modified microfluidic chip can achieve capture rates of up to around 80% for prostate and lung cancer cells. But just as important as capturing cancer cells is letting them go again. In a clinical setting, released cells might be needed for further analysis and characterization, or for further research. Here the new approach wins again as the nano-film can be degraded within 30 minutes after exposure to bacterial enzymes. Up to 95% of the captured cells are released with 90% remaining viable and unaffected by their temporary capture, which is important for subsequent analysis.
“Our approach has the capability to overcome practical hurdles in liquid biopsy and provide viable cancer cells in solution for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture,” says Wei.
The approach could be applied to the microfluidic chips already used in the clinic, believe the researchers, and could also be translated to a range of different device surfaces from silicon and glass to plastic or even paper for very low-cost detection devices.