Monitoring Dynamic Interactions of Tumor Cells with Tissue and Immune Cells in a Lab-on-a-Chip

Abstract

A complementary cell analysis method has been developed to assess the dynamic interactions of tumor cells with resident tissue and immune cells using optical light scattering and impedance sensing to shed light on tumor cell behavior. The combination of electroanalytical and optical biosensing technologies integrated in a lab-on-a-chip allows for continuous, label-free, and noninvasive probing of dynamic cell-to-cell interactions between adherent and nonadherent cocultures, thus providing real-time insights into tumor cell responses under physiologically relevant conditions. While the study of adherent cocultures is important for the understanding and suppression of metastatic invasion, the analysis of tumor cell interactions with nonadherent immune cells plays a vital role in cancer immunotherapy research. For the first time, the direct cell-to-cell interactions of tumor cells with bead-activated primary T cells were continuously assessed using an effector cell to target a cell ratio of 10:1.

Anisotropic Crystalline Protein Nanolayers as Multi‐Functional Biointerface for Patterned Co‐Cultures of Adherent and Non‐Adherent Cells in Microfluidic Devices

“…[ 4 ] Consequently a variety of surface patterning strategies have been developed in recent years to control the spatial orientation of cells for anchorage-dependent cell cultures, including those that infl uence adhesion, migration, proliferation, cell shape, cell differentiation and distinct linage commitment. [ 5 ] A range of nano-and microfabrication techniques have also been used to generate micropatterned co-culture systems, which exploit the different cell adhesion characteristics of various substrates, including photolithography, soft lithography and printing.…”

A simple in vitro method for evaluating dendritic cell-based vaccinations

“…Impedance measurements have been used in a number of different studies to determine morphological changes in real time;27 cisplatin-induced cell death;28 differentiation of 3T3 cells into adipocytes;29 effects of curcumin on physicochemical characterization and effects on MCF7 cancer cell proliferation;30 monitoring of dynamic interactions of tumor cells with tissues and immune cells on a lab-on-a-chip;31 cell senescence measurements of adipose tissue-derived stem cells;32 and real-time evaluation of nanoparticle-induced cytotoxic effects 33. By this method, Moodley et al34 conducted real-time profiling of NK cell killing of human astrocytes.…”

Recent advances and future applications of microfluidic live-cell microarrays

“…Routinely used immunofluorescence end-point analysis can now be replaced by complementary continuous monitoring techniques that assess the dynamic responses of cell cultures (Charwat et al, 2014, Charwat et al, 2013b, Picher et al, 2013. Additionally, several portable and miniaturized biosensors have been integrated into microfluidic cell analysis systems to detect transient cell responses in rapidly changing biological systems.…”

“…Cellular impedance spectroscopy is considered a robust analysis technique Heer, 2009, Sun andMorgan, 2010) and a variety of successful applications have been reported, including the detection of drug and nanomaterial cytotoxicity , Xiao and Luong, 2003, Yeon and Park, 2005, cell spreading (Wegener et al, 2000), endothelial cell stimulation and tight junction formation (Wegener et al, 1999), as well as IgE-mediated mast cell activation (Abassi et al, 2004) and stem cell differentiation (Cho et al, 2009, Hildebrandt et al, 2010. Another research group has also recently combined impedance spectroscopy with light scattering measurements, which are two well-established but independently used label-free cell analysis techniques, for cell analysis (Charwat, Rothbauer, 2013b). This dualparameter cell analysis system detects light scattering from adherent cells providing information on cell numbers and intracellular granularity while simultaneously performing impedance spectroscopy to monitor cell adhesion and cell-to-cell as well as cell-to-surface interactions without interfering with the physiological behavior of the in vitro cell culture.…”