Drug Discovery

Systematic automated phenotypic screening of living cells; profile cell responses to drug-perturbation(s) in parallel, to accelerate drug discovery in biotech and pharma
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Automated 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.

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Quantifying the response of cell populations to drug-perturbation with single cell resolution

Modifications in respiration underpin a plethora of diseases. In this video, we quantify the response of a cell population to Rotenone-perturbation (a chemical inhibitor of electron transfer in complex I of the respiratory chain). Images were taken for 24 h using the 10×10 grid-scan mode on Nanolive’s CX-A at an acquisition rate of one image taken every 8.5 mins.

Rotenone-perturbation (blue line, video top left) generates a larger amount of morphological noise in a cell population compared to unperturbed conditions (green line, data not shown). Increased variability is observed in cell extent (spikiness), dry mass, and granularity (texture; indicative of a change in internal composition).

Read the full case study in our Application note 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. 

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Gaining insights into a drugs mechanism of action

Nanolive’s content rich, multiplexed images bring target context to drug discovery, and so, can provide insights into a drugs mechanism of action. Here, we applied a drug and quantified how cells responded at the population level. One metric, granularity, was disproportionately impacted by the addition of the drug (Video 1). Granularity describes the texture of an image and so changes in this metric often reflect changes in the internal composition of the cell.

 

Video 1. Changes in granularity at the population level following drug-perturbation 

Video 2. Changes in granularity at the single cell level following drug-perturbation 

The sub-cellular resolution of Nanolive imaging allowed us to test this hypothesis at the single cell level (Video 2). The change in granularity clearly corresponds to a change in mitochondrial morphology; from a functional elongated state, to a dysfunctional, ring shape. This allowed us to hypothesize that our drug is acting on mitochondria, possibly on the respiratory chain, giving us precious insights into our drugs mechanism of action.

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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: 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.

Download our Feature Application Note >

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.

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Webinar

Watch our Webinar: Increase biological relevance and simplify your discovery workflow

In this webinar, Dr. Emma Gibbin-Lameira, Communications Specialist at Nanolive:

  • A step-by-step guide to setting-up an experiment and acquiring images with Nanolive’s automated microscope the CX-A, and creating publication-ready data and images using Nanolive’s new quantification solution, EVE Analytics
  • A case study showing how different stress stimuli (cytotoxicity vs. phototoxicity) invoke different types of cell death
  • An in-depth discussion of how cell metrics can be used to quantify different types of cell death
 

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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

Targeted cancer therapy

Read the blogpost here

Restored phagocytosis of cancer cells

Read the blogpost here

Cytotoxicity-induced apoptosis

Cyto- and phototoxicity-induced necroptosis

 

Compare Nanolive's microscopes

CX-A

Automated live cell imaging: a unique walk-away solution for long-term live cell imaging of single cells and cell populations

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3D CELL EXPLORER-fluo

Multimodal Complete Solution: combine high quality non-invasive 4D live cell imaging with fluorescence

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3D Cell Explorer front view

3D CELL EXPLORER

Budget-friendly, easy-to-use, compact solution for high quality non-invasive 4D live cell imaging

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