Cytotoxicity
Systematic automated phenotypic screening of living cells; profile cell responses to drug-perturbation(s) in parallel, to accelerate drug discovery in biotech and pharma Request a quote or demoAutomating phenotypic screening
Small-molecule kinase inhibitors have had success in the treatment of many diverse types of cancer. Here, we use Nanolive’s CX-A to test how cells respond to various inhibitors or modulators of kinase activities (Akt, JNK, CDK2, RTK, PKA, JAK, mTOR and AMPK). Images were taken using the automated 3×3 gridscan mode, at an acquisition rate of 1 scan every 25 mins, for 40 h.
Read our detailed blogpost here.
Quantifying non-homogeneous population responses to drug-perturbation
Ebastine is an antihistamine that simultaneously disrupts lysosomes and mitochondria. The cell stress response to Ebastine is highly non-homogeneous; a sub-population of cells die within hours of exposure to the drug, predominantly by apoptosis, but others are still alive 20 h later. This raises an important question: what makes certain cells more resistant than others?
The sub-cellular resolution delivered by Nanolive imaging reveals more resistant cells contain small black endocytic vacuoles in their cytoplasm. This, combined with global changes in granularity; a texture measurement that describes how a signal is distributed at a certain scale, suggests there is a reorganization of the subcellular distribution of organelles during the experiment, which could explain why certain cells survive longer than others.
Watch our dedicated cytotoxicity webinar here.
Increasing biological relevance and simplifying the discovery workflow
These are the results of a case study that was created to demonstrate how the CX-A and Eve Analytics can be used in drug screening. We feature the entire process from image acquisition to data analysis and interpretation in our webinar here. In the case study, we test to what extent the art of observing influences the outcome of our experiments; something too often ignored when running live cell experiments. The video, shows the effects that four different treatments: (1) label-free; (2) cytotoxic (MitoTracker only); (3) cytotoxic and low phototoxic (MitoTracker and 1% laser power) and (4) cytotoxic and high phototoxic (MitoTracker and 5% laser power), have on cell health.
Gaining insights into a drugs mechanism of action
Taxol is an anti-cancer chemotherapy drug that disrupts the formation of mitotic spindles during metaphase. The sub-cellular resolution of the CX-A allows us to visualize this process in spectacular detail; when cells enter mitosis, they successfully complete prophase and prometaphase but are unable to line their chromosomes up along the metaphasic plate leading to failure of cytokinesis and the development of multiple nuclei per cell.
With EVE Analytics, Nanolive’s quantitative software solution, we are able to quantify the multinucleation event from the increase in average dry mass density per cell.
Watch our dedicated cytotoxicity webinar here.
Scientific Publications
Nanolive label-free live cell imaging has already shed light on many important topics in the field of drug discovery research. To get inspired and learn how your research can benefit from our technology, we invite you to check out these scientific articles published by our clients.
Application Note
Feature Application: Multiparametric cytotoxicity assays
In this application note we demonstrate how the huge potential that Nanolive imaging holds for the drug discovery process, where cytotoxicity remains one of the major causes of drug withdrawal, and there is an urgent need for reliable and time-saving assay workflows. We show it is possible to quantify the onset and progression of stress with high precision, bringing greater accuracy to cell death research.
Feature Application: Drug Discovery
In this application note we demonstrate how the CX-A can be used for drug screening, target identification or mechanism of action studies. We feature the results of multiple, time-lapse imaging experiments featuring cells that have been perturbed by various anti-cancer drugs. We highlight the structural changes that the drugs have on cells and show that it is possible to analyze the images quantitatively.
Webinar
Watch our Webinar: do different cell death stimuli show unique signatures in cell metrics?
In this webinar, Dr. Emma Gibbin-Lameira, Communications Specialist at Nanolive reveals how Nanolive imaging can be used to conduct real-time, automated cytotoxicity assays, without the contribution of photo and cytotoxic methodological artefacts. Specifically, she will:
- Show high resolution, time-resolved footage of the dynamics of cell death following exposure to seven cell death stimuli (extreme shifts in external pH, thermal stress, phototoxicity, oxidative stress, Shikonin, Ebastine and Taxol)
- Feature relevant cell metrics and/or close-ups of changes in sub-cellular morphology induced by each experimental condition
- Discuss which cell metrics are best for distinguishing between different types of cell death
Sign up to watch the webinar:
Webinar
Watch our Webinar: Accelerating oncology drug discovery with label-free imaging
In this webinar, Dr. Emma Gibbin, Communications Specialist at Nanolive will discuss the advantages of using label-free live cell imaging in the drug discovery process and show how Nanolive’s automated live cell imaging solution the CX-A, can be used to:
- observe unique drug-induced phenotypes that fluorescence microscopy cannot capture
- record dynamic cellular responses to drug perturbations
- automate in vitro screening studies
Dr. Gibbin will present novel results from two experimental screens designed to test the phenotypic and morphological responses of pre-adipocyte and cancer cells to 8 inhibitors or modulators of kinase activity.
Sign up to watch the webinar:
Video Library
Nuclear changes following transcription inhibition
Read the blogpost here
Testing the efficacy of Selexipag
Norepinephrine effect on 3T3-derived pre-adipocyte cells
Read the blogpost here
VPA effects on mitochondrial morphology and LD behaviour
Read the blogpost here
Morphological changes in a population of pre-adipocyte cells following Rotenone-perturbation (blue lines)
Read the full case study in our Application note here.
Population level changes in granularity after Antimycin A addition.
Single cell changes in granularity after Antimycin A addition.
Read the full case study in our Application note here.
Cell death following oxidative stress
Watch our dedicated cytotoxicity webinar here.
Targeted cancer therapy
Read the blogpost here
Quantifying cell responses to anti-cancer drugs
Cytotoxicity-induced apoptosis
Watch the webinar here
Cyto- and phototoxicity-induced necroptosis
Watch the webinar here
Compare Nanolive's Products
CX-A
Automated live cell imaging: a unique walk-away solution for long-term live cell imaging of single cells and cell populations
3D CELL EXPLORER-fluo
Multimodal Complete Solution: combine high quality non-invasive 4D live cell imaging with fluorescence
3D CELL EXPLORER
Budget-friendly, easy-to-use, compact solution for high quality non-invasive 4D live cell imaging