(601ai) Device to Capture Circulating Tumor Cells on a Layer-By-Layer Assembled Transparent Substrate

The charge of cancer morbidity and mortality is led by metastasis, the cause of over 90% of cancer deaths. The solution may lie in the agents of metastasis, those cells which are shed from the primary tumor and intravasate into the blood stream. If recovered, these circulating tumor cells (CTCs) could provide answers to questions concerning an individual’s cancer as well as the biological principles behind metastasis. Although accessible by a simple blood draw, the challenge in fully utilizing the information presented by CTCs is largely a function of their low frequency on the order of one CTC per 1 billion blood cells. Graphene oxide (GO) is a biocompatible nanomaterial that can be reduced to increase conductivity for use in transparent conducting electrodes, but can also have applications in drug delivery and cell culture. It was recently used in a CTC capture device that featured high specificity and high purity, but this chip is based in silicon, limiting the high magnification and brightfield imaging necessary to conduct useful downstream analysis.

Layer-by-Layer (LbL) is an assembly method by which layers are sequentially deposited on a surface, and the integrity of the resulting composite is a function of the interactions between the layers. There is precedent for the use of graphene oxide in LbL films, inspiring the decision to use this method as the basis for a transparent graphene oxide circulating tumor cell capture device. Graphene oxide was deposited on to glass slides in alternating layers with polymers previously used in anti-adhesive films to create a transparent surface which was subsequently functionalized to ultimately present the capture antibody against the epithelial cellular adhesion molecule (anti-EpCAM). Device performance was optimized in terms of layer composition and operating flow rate using cell line spike experiments into buffer and blood, the latter to better simulate the processing of cancer patient whole blood samples. The device was ultimately evaluated with genitourinary cancer patient samples to demonstrate clinical utility.