The NANIVID – or Nano Intravital Device – is an implantable delivery tool designed to locally affect the tumor microenvironment in vivo. This technology is being redesigned and validated as a cell collection tool for the study of metastatic cancer cells. A methodology has been developed to facilitate this transition, consisting of microfluidic analysis of the device microchannels and a series of cell-related collection experiments building up to in vivo collection. Single-chamber designs were first used to qualitatively demonstrate the feasibility of cell collection ex vivo. This was followed by the development and implementation of devices containing a second, negative-control chamber for quantitative analysis. This work sets the foundation for in vivo cancer cell migration studies utilizing the NANIVID.
The tumor microenvironment is a complex system which is not fully understood. New technologies are needed to provide a better understanding of the role of the tumor microenvironment in promoting metastasis. The Nano Intravital Device, or NANIVID, has been developed as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a custom hydrogel blend that contains selected factors for delivery to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel swells and releases these entrapped molecules, forming a sustained concentration gradient. The NANIVID has previously been successful in manipulating the tumor microenvironment both in vitro as well as in vivo. As metastatic cells intravasate, it has been shown that some are able to do so unscathed and reach their new location, while others are cleaved during the process1. There appears to be a correlation between cell migration and the mechanical properties of these cells. It is believed that these properties can be detected in real time by atomic force microscopy. In this study, metastatic MTLn3 rat mammary cells are seeded onto 1-dimensional microfibers and directed up a stable gradient of growth factor. The NANIVID device is placed behind our AFM tip, where it generates a stable chemotactic gradient of epidermal growth factor. Scanning confocal laser microscopy is also used to monitor movement of the cells over time. This experiment will shed light on the mechanical changes in metastatic cells as they undergo directed migration.