A high-throughput QCM chip configuration for the study of living cells and cell-drug interactions

Abstract

In this study, we present a novel design of interference-free, negligible installation-induced stress, suitable for the fabrication of high-throughput quartz crystal microbalance (HQCM) chips. This novel HQCM chip configuration was fabricated using eight independent yet same-batch quartz crystal resonators within a common glass substrate with eight through-holes of diameter slightly larger than that of the quartz resonator. Each quartz resonator's rim was adhered to the inner part of the through-hole via silicone glue to form the rigid (quartz)-soft (silicone)-rigid (glass) structure (RSRS) which effectively eliminates the acoustic couplings among different resonators and largely alleviates the installation-induced stresses. The consistence of the eight resonators was verified by very similar equivalent circuit parameters and very close response slopes to liquid density and viscosity. The HQCM chip was then employed for real-time and continuous monitoring of H9C2 cardiomyoblast adhesions and viscoelastic changes induced by the treatments of two types of drugs: drugs that affect the cytoskeletons, including nocodazole, paclitaxel, and Y-27632, and drugs that affect the contractile properties of the cells: verapamil and different dosages of isoprenaline. Meanwhile, we compared the cytoskeleton affecting drug-induced viscoelastic changes of H9C2 with those of human umbilical vein endothelial cells (HUVECs). The results described here provide the first solution to fabricate HQCM chips that are free from the limitation of resonator number, installation-induced stress, and acoustic interferences among resonators, which should find wide applications in areas of cell phenotype assay, cytotoxicity test, drug evaluation and screening, etc. Graphical abstract Schematic illustration of the principle and configuration of interference-free high-throughput QCM chip to evaluate and screen drugs based on cell viscoelasticity.

A Quartz Crystal Microbalance Immunosensor for Stem Cell Selection and Extraction

“…The immunoassay format, based on antibody–antigen (Ab–Ag) interactions, remains a robust, ubiquitous analytical tool [ 21 ]. Indeed, a number of QCM immunosensors [ 22 ] have been reported for the determination of different analytes, such as glucose [ 4 ], microbes [ 23 , 24 , 25 , 26 , 27 ], nucleic acids [ 28 , 29 ], environmental pollutants [ 30 ], cells [ 31 ], and food pathogens [ 32 ], for drug discovery applications, and for diagnostics and biomedical applications [ 33 ].…”

Quartz Crystal Microbalance as Cell‐Based Biosensor to Detect and Study Cytoskeletal Alterations and Dynamics

“…Such configuration, as a consequence, may originate a softer layer with an increase of dissipation value. The softening effect of Y27632 has been reported for different cell lines as H9C2 cardiomyoblasts investigated by high-throughput QCM chips [45] and MDA-MB-231 metastatic breast cancer cells using Atomic Force Microscopy. [46] The dissipation increase is also consistent with a previous confocal microscopy observation for MCF7 transfected cells [47] that described the ability of Y27632 to sever actin filaments in addition to softening it, and by our CLSM experimental findings that demonstrated the disappearance of elastic and compact stress fibers ( Figure 4B).…”

Quartz Crystal Microbalance with Dissipation Monitoring of Dynamic Viscoelastic Changes of Tobacco BY-2 Cells under Different Osmotic Conditions

“…High-throughput QCM (HQCM) chip for the study of cell-drug interactions Configuration of interference-free, negligible installation-induced stress Fabricated using independent yet same-batch quartz crystal resonators within a common glass substrate through the rigid (quartz)-soft (silicone)-rigid (glass) structure [17] Cell−material interactions Tuning the surface free energy of materials…”