Biodegradable nano-films for capture and non-invasive release of circulating tumor cells

Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and invitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips

Capillary Flow Layer-by-Layer: A Microfluidic Platform for the High-Throughput Assembly and Screening of Nanolayered Film Libraries

Layer-by-layer (LbL) assembly is a powerful tool with increasing real world applications in energy, biomaterials, active surfaces, and membranes; however, the current state of the art requires individual sample construction using large quantities of material. Here we describe a technique using capillary flow within a microfluidic device to drive high-throughput assembly of LbL film libraries. This capillary flow layer-by-layer (CF-LbL) method significantly reduces material waste, improves quality control, and expands the potential applications of LbL into new research spaces. The method can be operated as a simple lab benchtop apparatus or combined with liquid-handling robotics to extend the library size. Here we describe and demonstrate the technique and establish its ability to recreate and expand on the known literature for film growth and morphology. We use the same platform to assay biological properties such as cell adhesion and proliferation and ultimately provide an example of the use of this approach to identify LbL films for surface-based DNA transfection of commonly used cell types.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant W911NF-07-D-0004