Real time acoustic profiling of a live cancerous cell monolayer using QCM

Abstract

A Quartz Crystal Microbalance (QCM) is a well-established analytical weighing tool that can serve in the monitoring of the viscoelastic properties of a wide range of chemical and biological analytes, as well as investigating adsorption processes occurring at specifically engineered solid–liquid interfaces. More specifically, several recent works have reported the successful QCM-mediated acoustic profiling of various biophysical transformations of cancerous cells (cancer cell profiling). Such a cancer cell acoustic profiling is aimed at characterizing adsorption, adhesion, spreading, and the homeostatic processes of initially suspended cancer cells, seeded onto various chemically engineered nanostructured QCM sensors.The nanostructuration of sensing the QCM electrode surfaces, with well-defined ligand compositions, provides a unique tool for deeply featuring the physico-chemical interaction basis of multi-parameter bio-molecular recognition events. Even individual recognition ones can be tracked to precisely probe the functional behavior of tested cellular systems. In this regard, the well-recognized 2D organization of self-assembled monolayers (SAMs), of alkane-thiolates/disulfides, onto the bare surfaces of metals, such as gold, generates model chemically defined and structured organic surfaces, for cell interaction, when possessing specific ligands, enabling cell attachment and/or interaction.Herein, and in contrast to the most common suspended cell formats, the real-time in situ sensing, and biochemical profiling, of live raw non-processed cell line monolayers (cell monolayer formats) has been demonstrated to be felicitous. This bio-recognition event used a well-defined chemical composition of a cyclic disulfide-based SAM functional layer for QCM electrode nanostructuration/functionalization. This cyclic disulfide-based functional layer also has been shown to provide a robust sensing platform, quite well adapted to the non-planar nature of tested cancer cell monolayers, in a buffered aqueous environment. Corresponding bio-recognition events, for real-time in situ sensing and profiling, of non-suspended cell monolayers, enabled a significant reduction of the signal processing time, while keeping the interacting cells in their native state. As a matter of consequence, this new QCM-relating development may be considered as a significant step milestone, en-route to multiplexed in/ex vivo real-time diagnostics of tissue pathologies.