Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation

Wu, Shangquan; Liu, Xiaoli; Zhou, Xuanru; Liang, Xin; Gao, Dayong; Liu, Hong; Zhao, Gang; Zhang, Qingchuan; Wu, Xiaoping

doi:10.1016/j.bios.2015.09.024

Cited by 48 publications

(35 citation statements)

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“…The design and operation of the SMR have been previously described 13–15 . In short, single cells in suspension are passed through the SMR resulting in a frequency shift that is proportional to cell buoyant mass.…”

Section: Methodsmentioning

confidence: 99%

“…1a) 11–13 , either in the presence or absence of cancer therapeutics. Resonator-based approaches have been used to measure an array of cellular physical properties 14 , and, in one preliminary study, response to therapeutics 15 . Following the incubation of tumor cells with drug, the SMR can detect changes in the growth of single cells to predict therapeutic response without the need for extended culture.…”

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confidence: 99%

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Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate

et al. 2016

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Assays that can determine the response of tumor cells to cancer therapeutics could greatly aid the selection of drug regimens for individual patients. However, no functional assays are currently implemented clinically, and predictive genetic biomarkers are available for only a small fraction of cancer therapies. Here we demonstrate that the single-cell mass accumulation rate (MAR), profiled over many hours with a suspended microchannel resonator, accurately defines the drug sensitivity or resistance of glioblastoma multiforme (GBM) and B-cell acute lymphocytic leukemia (B-ALL) cells. MAR reveals heterogeneity in drug sensitivity not only between different tumors but also within individual tumors and tumor-derived cell lines. MAR measurement predicts drug response using samples as small as 25 μL of peripheral blood while maintaining cell viability and compatibility with downstream characterization. MAR measurement is a promising approach for directly assaying single-cell therapeutic responses and for identifying cellular subpopulations with phenotypic resistance within heterogeneous tumors.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate

et al. 2016

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“…Mechanical biosensors have been widely used for ultrasensitive detection of pathogens [18], and also some work has attempted to dynamically inspect living cells [19–24]. There is also some recent work which addresses dynamic (>1 h) qualification of cell viability by a micromechanical mass sensor [25]. …”

Section: Introductionmentioning

confidence: 99%

Real-time, label-free monitoring of cell viability based on cell adhesion measurements with an atomic force microscope

et al. 2017

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BackgroundThe adhesion of cells to an oscillating cantilever sensitively influences the oscillation amplitude at a given frequency. Even early stages of cytotoxicity cause a change in the viscosity of the cell membrane and morphology, both affecting their adhesion to the cantilever. We present a generally applicable method for real-time, label free monitoring and fast-screening technique to assess early stages of cytotoxicity recorded in terms of loss of cell adhesion.ResultsWe present data taken from gold nanoparticles of different sizes and surface coatings as well as some reference substances like ethanol, cadmium chloride, and staurosporine. Measurements were recorded with two different cell lines, HeLa and MCF7 cells. The results obtained from gold nanoparticles confirm earlier findings and attest the easiness and effectiveness of the method.ConclusionsThe reported method allows to easily adapt virtually every AFM to screen and assess toxicity of compounds in terms of cell adhesion with little modifications as long as a flow cell is available. The sensitivity of the method is good enough indicating that even single cell analysis seems possible.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0256-7) contains supplementary material, which is available to authorized users.

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“…It must be noted that conventional and NMS assays monitor different metabolic parameters. In most conventional analyses, the MIC is identified by the bacterial ability to replicate, while for the NMS, this concentration is associated with the reduction of the sensor's fluctuations, associated with alterations in the bacterial membrane elasticity (36,37) or to their internal metabolic activity. Indeed, while the information is similar, the concentration at which one or the other phenomenon occurs can be different.…”

Section: Resultsmentioning

confidence: 99%

“…The sensitivity of the technique enables the detection of energy consumption of a few ATP molecules, as demonstrated in previous works using finite elements mod-eling or studying conformational changes in quaternary protein structures (31,33). Thus, the NMS can been used to evaluate the fluctuations of a very limited number of viable specimens (single mammalian cells or tens of bacteria) (32,(34)(35)(36)(37).…”

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confidence: 95%

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

Mustazzolu

Venturelli

Dinarelli

et al. 2019

Antimicrob Agents Chemother

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The development of antibiotic-resistant bacteria is a worldwide health-related emergency that calls for new tools to study the bacterial metabolism and to obtain fast diagnoses. Indeed, the conventional analysis time scale is too long and affects our ability to fight infections. Slowly growing bacteria represent a bigger challenge, since their analysis may require up to months. Among these bacteria, Mycobacterium tuberculosis, the causative agent of tuberculosis, has caused more than 10 million new cases and 1.7 million deaths in 2016 only. We employed a particularly powerful nanomechanical oscillator, the nanomotion sensor, to characterize rapidly and in real time tuberculous and nontuberculous bacterial species, Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium abscessus, respectively, exposed to different antibiotics. Here, we show how high-speed and high-sensitivity detectors, the nanomotion sensors, can provide a rapid and reliable analysis of different mycobacterial species, obtaining qualitative and quantitative information on their responses to different drugs. This is the first application of the technique to tackle the urgent medical issue of mycobacterial infections, evaluating the dynamic response of bacteria to different antimicrobial families and the role of the replication rate in the resulting nanomotion pattern. In addition to a fast analysis, which could massively benefit patients and the overall health care system, we investigated the real-time responses of the bacteria to extract unique information on the bacterial mechanisms triggered in response to antibacterial pressure, with consequences both at the clinical level and at the microbiological level.

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Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation

Cited by 48 publications

References 50 publications

Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate

Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate

Real-time, label-free monitoring of cell viability based on cell adhesion measurements with an atomic force microscope

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

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