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Operetta CLS High-Content Analysis System

Uncover deep biological understanding in your everyday assays and innovative applications using the Operetta CLS high-content analysis system. Featuring a unique combination of technologies, the system delivers all the speed, sensitivity and resolution you need to reveal fine sub-cellular details. And with our simple, powerful Harmony 4.5 software, Operetta CLS lets you find even subtle phenotypic changes.

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For research purposes only, not intended for diagnostic use

Overview

The Operetta CLS system combines speed and sensitivity with the powerful and intuitive data analysis you’ve come to trust from the Operetta platform. The all-new Operetta CLS delivers everything you need from high-content analysis. What’s more, the Operetta CLS system is part of our comprehensive HCS workflow – everything from HCS systems and microplates to automation and informatics for every application. All from one knowledgeable, trusted vendor. Put that together with our Harmony® high-content imaging and analysis software – the easy-to-learn, easy-to-use software that empowers biologists to do their own analysis – and you have everything you need to run your everyday (and complex) analyses right away.

A Unique Combination of Technologies

At the core of the Operetta CLS high-content analysis system is a new light path that ensures efficient excitation of your samples and careful collection of emitted signals.

  • Powerful, stable 8x LED light source for optimal excitation of your fluorophores and confidence in results
  • Proprietary automated water-immersion objectives with very high numerical aperture enable high resolution and fast read times with minimal photodamage
  • Confocal spinning disk technology provides a fast and gentle imaging process, enabling efficient background rejection, live cell experiments, and 3D imaging
  • Large format sCMOS camera delivers low noise, wide dynamic range, and high resolution – perfect for sensitive and quantitative measurements at short exposure times
  • User accessible bar-coded emission filters provide flexibility, sensitive imaging and error-free operation
  • Simple, powerful Harmony 4.5 high-content imaging and analysis software for easy set-up of assays, automation of experiments, image acquisition, data analysis, and storage and retrieval of results

A Solution Configured To Suit Every Need;

Whatever your application, there’s an Operetta CLS system configured to meet your requirements. And it’s modular, so it can change with your research demands. Several configuration options are available, Typical configurations include:

Operetta CLS Quattro

  • With four LEDs and widefield fluorescence, the basic configuration of the Operetta CLS system is ideal for common applications that need sensitivity and resolution, with the capacity to grow if the need arises.

Operetta CLS FLEX

  • With eight LEDs, and confocal and widefield fluorescence, the FLEX configuration offers flexibility in excitation and imaging modes for many challenging applications – and it can be upgraded to even higher performance.

Operetta CLS LIVE

  • With all the features of the FLEX configuration, plus gas and temperature control and water-immersion objectives, this system is ideal for gentle yet highly sensitive live cell imaging.

Applications

From everyday assays to more demanding applications, the Operetta CLS high-content analysis system delivers just the right combination of flexible excitation, sensitive optics, and advanced software features to enable you to gain deeper biological insight from all your critical applications.

Fixed-cell assays

  • Up to eight high-power excitation sources and user-accessible emission filters enable maximum flexibility of fluorescent stains and labels, plus the system features widefield and spinning-disk fluorescent imaging.

Live-cell assays

  • The spinning disk confocal optics and synchronized LED illumination provide stable excitation and minimize phototoxicity and bleaching for meaningful live-cell assays. You can also choose brightfield or digital-phase contrast imaging modes.

Complex cellular models

  • The large-format sCMOS camera with water-immersion objectives provides sensitivity and high resolution, while advanced software helps you address the imaging and analysis challenges presented by complex cellular models.

Advanced assays

  • FRET is a powerful tool for investigating conformational changes and protein-protein interactions. The Operetta CLS system’s sensitive imaging and dedicated analysis tools for ratiometric imaging, facilitate robust results.

Phenotypic fingerprinting

  • The Operetta CLS combines high resolution imaging with advanced software tools to help create robust phenotypic fingerprints of the subtle differences at the core of successful phenotypic assays.

Specifications

21 CFR Part 11 Compatible No
Automation Compatible Yes
Detection Method Transmission, Fluorescence
Height 45.0 cm
Imaging Modality High Content
Interface Ethernet
Length 98.0 cm
Light Source LED
Portable No
Product Brand Name Operetta CLS
Warranty Yes
Width 66.0 cm
Resources, Events & More
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Application Note

Analyzing ERK Signal Transduction in Live Cells Using a FRET-Based Biosensor

Extracellular signal-regulated kinase (ERK) is a key component in the regulation of embryogenesis, cell differentiation, cell proliferation, and cell death. The ERK signaling pathway is altered in various cancer types and is frequently investigated as a target for therapeutic intervention. This application note describes how a live cell FRET assay to study ERK signaling was performed on the Operetta CLS™ high-content analysis system. The optimized design of the FRET-based biosensor, the high-quality imaging of the Operetta CLS system and the easy-to-use image analysis tools of the Harmony® software contribute to the robustness of the high-content assay.

PDF 1 MB
Automated Single Cell Tracking using the Operetta System: Analyzing Chemokinesis of Cancer Cells

In this application note, we describe a high-content screening application for analyzing the migration of non-small cell lung cancer cells in a live cell assay. Using the Operetta® high-content imaging system and digital phase contrast imaging, we tracked migrating cancer cells using automated single cell tracking in the Harmony® high-content imaging and analysis software.

PDF 1 MB
Cell Painting for Phenotypic Screening

Cell Painting is a powerful high-content screening method which combines cell and computational biology to unravel cells’ responses and gain a deeper understanding of the effects of chemical and genetic perturbagens.

However, implementation of cell painting is not without its challenges - from choosing a cell model and labeling reagents, to optimizing instrumentation and making sense of the thousands of features that are extracted during data analysis.

Download our application note to learn how to:

  • Set up optimal imaging parameters and see the effect of different acquisition modes on compound clustering
  • Easily perform the assay using the dyes provided in the PhenoVue Cell Painting kit
  • Extract and analyze more than 5700 cellular features
  • Visualize multidimensional data using the Signals Screening analysis platform

PDF 1 MB
Distinguishing Cell Types by Phenotypic Profiling of the Nucleus

The promise of high-content screening is the acceleration of discovery by extracting as much relevant information as possible from cells. Nevertheless, a large percentage of high-content screens analyze only a small number of image-based properties. As a result, valuable information from precious cells and disease models is not utilized. As nearly all screening approaches require a nuclear counterstain such as Hoechst to facilitate segmentation, phenotypic profiling of the nuclei can offer new and additional perspectives on assays at no extra cost.

PDF 1 MB
Multi-Parametric Assessment of EGF Treatment Effects on Signaling Pathways, Growth and Proliferation Using AlphaLISA SureFire Ultra and Cellular Imaging

In this application note, we demonstrate an efficient cell-based workflow for the assessment of EGF treatment effects in a cellular model of human skin cancer.

Treatment effects on several intracellular signaling pathways were examined using PerkinElmer’s homogeneous, no-wash AlphaLISA® SureFire® Ultra assays. To determine concurrent time-dependent effects of different EGF concentrations on cellular health and proliferation, ATP concentrations were assessed with ATPlite™ 1step luminescence assay and cultures were fluorescently labeled, imaged and analyzed using the Operetta CLS™ high-content analysis system.

PDF 6 MB
Phenotypic Analysis of Hypertrophy in Human iPSC-Derived Cardiomyocytes

Learn how a phenotypic screening assay to study time-dependent effects of endothelin-1-induced hypertrophy was set up using human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Learn how: The Opera Phenix system has been applied in the field of neurodegenerative diseases. In this assay, the Opera Phenix system is 4 times faster than the previous Opera® system. Primary neuron morphology is analyzed in a straightforward approach using Harmony software. Careful assay optimization can increase throughput, and minimize the data burden, without compromising assay performance.

PDF 1 MB

Article

5 Top Tips for a Successful High-content Screening Assay with a 3D Cell Model System

Whether you’re familiar with high-content screening and are looking to exploit the increased physiological relevance of complex 3D cell models, or you want to take your analysis of 3D cell models to the next level, migrating from simple plate-reader assays to a high-content approach, you’ll need the right tools and strategies to overcome the challenges these models present.

PDF 1 MB
Artemisinins Target GABAA Receptor Signaling and Impair α Cell Identity

Recent progress toward regenerating pancreatic ß cells lays the foundation for continued advancement in diabetes research. Find out more about how enhanced GABAA signaling induces loss of a cell identity and encourages a cells to convert into insulin-producing ß-like cells.

PDF 1016 KB
Developing a Phenotypic In Vitro Model for Progression of Liver Steatosis

Hepatic steatosis, a reversible state of metabolic dysregulation, is the first step in the progression of nonalcoholic fatty liver disease (NAFLD). It is characterized by excessive intracellular lipid accumulation and can progress to nonalcoholic steatohepatitis (NASH) and hepatocellular injury. Currently, there are no FDA-approved medicines to treat NAFLD or NASH, and the complex molecular and genetic mechanisms are not completely understood. To address this, Siobhan Malany, from the Conrad Prebys Center for Chemical Genomics in Florida, US, and colleagues developed a model of hepatic steatosis in functional human induced pluripotent stem cell-derived hepatocytes (hiPSC-Hep).

PDF 1 MB
Inhibiting Interleukin 11 Signaling Reduces and Reverses Many Dangerous Effects of NAFLD/NASH in Mouse Models

Accumulation of fat in liver cells, a process called steatosis, is a common health problem that has many possible causes. Nonalcoholic fatty liver disease (NAFLD) is a group of conditions caused by the buildup of fat in the liver, with some sources estimating that one in four people develop it in their lifetime. NAFLD, if left untreated, may progress to nonalcoholic steatohepatitis (NASH). Dr. Anissa A. Widjaja and colleagues recently examined the connection between interleukin 11 (IL-11) signaling and the development of liver disease.

PDF 748 KB
Tackling Biofilm Formation

Microbial biofilm formation has important implications for human health and disease. Biofilms on indwelling devices such as implants, blood and urinary catheters, heart valves and endotracheal tubes represent a persistent source of pathogenic microbes that can invade the human body and cause serious illness. This article provides an overview of novel approaches to improve our understanding of biofilms and enhance the diagnosis and treatment of bacterial implant infections.

PDF 2 MB
The Why and How of Live-Cell Imaging for Research and Drug Discovery

Live-cell imaging, the study of living cells using microscopy, has become a requisite technology in many fields of biomedical research, such as cell biology, developmental biology and cancer research. Also, in drug discovery, researchers adopt live-cell imaging as they look for a more detailed understanding of cellular behavior.

In our article, learn about:

  • The 3 different categories of live-cell assays
  • 5 key benefits of live-cell imaging assays
  • Examples of key live-cell assays, e.g. calcium flux, immune-cell killing, single-cell tracking

PDF 1 MB

Brochure

3D Cell Culture Solutions Brochure

Download our brochure to learn how our solutions help you to grow, detect, and analyze 3D cells.

PDF 4 MB

Case Study

High-Content Analysis of Drug-Induced Oligodendrocyte Differentiation Promoting Remyelination in Multiple Sclerosis

One of the greatest challenges in multiple sclerosis (MS) therapy is the halting or reversal of the failure of remyelination in the brain in order to reverse disabilities in MS patients. This case study highlights the recent work of Dr. Paul Tesar and colleagues at the Case Western Reserve University School of Medicine, which could potentially lead to such novel treatments, as it aims to control the function of stem cells in the body and thereby to help the body repair itself.

PDF 3 MB
Improving the Throughput of a Neuroprotection Assay Using the Opera Phenix High-Content Screening System

This case study shows how a previously-described neuroprotection assay was easily and directly transferred to the Opera Phenix® high-content screening system, with a 4-fold decrease in acquisition time. In the assay, primary rat neurons are co-cultured on top of rat-derived astrocytes. To induce axon degeneration experimentally, NGF is withdrawn, leading to neuronal cell death, while astrocytes remain healthy. This can be captured by two readouts: the total axon area and the total number of nuclei. Neuroprotective drug candidates lead to an increase in the total axon area while keeping the number of nuclei (astrocytes) constant. Decreasing nuclei counts indicate a cytotoxic effect.

Download the case study to learn how:

  • Primary neuron morphology is analyzed in a straightforward approach using Harmony® software
  • Careful assay optimization can increase throughput, and minimize the data burden, without compromising assay performance

PDF 4 MB
Re-Tooling Anti-Microbial Research for the 21st Century

Antimicrobial resistance (AMR) is one of today’s major global public health challenges. Recently, there has been renewed investment in the discovery of novel antimicrobials to urgently address the growing number of drug-resistant infections. This case study describes how Professor Gordon Dougan and his team at the Cambridge Biomedical Research Centre are using high-content analysis to phenotype individual bacteria within a population to investigate adaptive mechanisms of antimicrobial resistance, and to screen for novel alternatives to existing antimicrobials.

PDF 1 MB

Ebook

Adding Depth: 3-D Cell Culture

Download this booklet from The Scientist and PerkinElmer to learn about how the third dimension affects cell behavior, the similarities and differences between 2-D and 3-D culture, common 3-D culture models, and how to image and analyze 3-D culture models.

PDF 5 MB
Cellular Analysis in 3D

While 3D cell culture provides unprecedented opportunities for both increased physiological relevance and analysis using a high-content approach, it is also more complex than traditional 2D cell culture. This booklet, from Biocompare and PerkinElmer, will unravel some of the complexities often encountered when using 3D cell models for drug discovery and provide insights and solutions that will streamline workflows and facilitate the development of effective therapeutics. Topics covered include: Reagents and instruments for growing, detecting, and analyzing 3D cell models; 3D culture methodologies; the value of high-content screening with 3D cell models and how to improve image acquisition and image analysis with high-content assays.

PDF 2 MB
High-Content Analysis: Advancing Your Knowledge to Help Combat Infectious Disease

Infectious diseases remain a major burden to human health. The increased globalization of modern society that facilitates the spread of infectious diseases, and phenomena such as anti-microbial resistance, underscore the importance of the development of new preventative and therapeutic approaches.

Download this booklet to learn how high-content imaging and analysis enable high-throughput functional and phenotypic assays that can be adapted to a wide range of pathogens; read a series of Featured Publication Notes describing the contribution of high-content analysis in the study of diseases such as ebola, zika, tuberculosis, listeria and malaria and find examples of studies in which a high-content approach has been used in parasitic, viral and bacterial disease research.

Please download the pdf and view in Adobe Reader or Acrobat for optimum performance.

PDF 3 MB
Live-cell Imaging eBook

Live-cell imaging has evolved from allowing observation of large-scale changes to capturing subtle changes in dynamic cellular processes. Today, live-cell imaging coupled with high-content analysis enables researchers to extract quantitative data in real-time, facilitating new insights in basic life science research and drug discovery. Modern live-cell imaging systems can capture rapid cellular events, track cell movement, monitor protein signaling, screen cell health, and much more.

Download the eBook from The Scientist and PerkinElmer to discover:

  • Early attempts at live-cell imaging
  • Key challenges and considerations for live-cell imaging
  • A guide for choosing the appropriate imaging system and optimizing cell health
  • Advances in live-cell imaging technology

PDF 2 MB

Featured Publication Note

Manual

Five Top Tips for a Successful High-Content Screening Assay with a 3D Cell Model System

Whether you’re familiar with high-content screening, or a newcomer, you’ll need the right tools and strategies to overcome the challenges of using complex 3D cell models in such an assay. For example, growing consistent, reproducible 3D cultures can be problematic and imaging large, thick cell samples can be challenging, while managing the huge volumes of data generated is perhaps the most demanding aspect of all. In this article, we provide our top tips for running a successful high-content screening assay using a 3D cell model. Learn how you can: Generate uniform 3D cell models, Get the best quality images, Minimize imaging time and volume of data, Get deeper insights from your 3D cell model and Avoid unnecessary data transfer steps.

PDF 1 MB

Technical Note

3D Volumetric Analysis of Luminal Spaces Inside Cysts or Organoids

High-content assays using 3D objects such as cysts or organoids can be challenging from the perspectives of both image acquisition and image analysis. In this technical note we describe how to image and analyze epithelial Madin-Darby canine kidney (MDCK) cysts in 3D on the Operetta CLS high-content analysis system.

We address:

  • How to reduce the loss of image resolution as you image deeper into the sample
  • How to enable 3D segmentation and analysis for your 3D high-content assays
  • How to increase throughput for 3D imaging through shorter exposure times
  • How to eliminate long and tedious data transfer steps

PDF 1 MB
3D Volumetric and Zonal Analysis of Solid Spheroids

Multicellular 3D “oids” (tumoroids, spheroids, organoids) have the potential to better predict the effects of drug candidates during preclinical screening. However, compared to 2D cell monolayers, assays using 3D model systems are more challenging.

In this technical note we describe how to image and analyze solid spheroids in 3D using the Opera Phenixand OperettaCLS high-content screening systems and Harmony® 4.8 imaging and analysis software.

We address:

  • How to reduce image acquisition time and data volume
  • How to analyse fully and partially imaged spheroids in 3D
  • How to define zones and quantify spatial differences within spheroids
  • PDF 1 MB
    Clearing Strategies for 3D Spheroids

    In drug discovery programs, multicellular spheroids have emerged as powerful tools to bridge the gap between in vitro cell culture models and in vivo tissues. However, one of the greatest challenges in higher throughput 3D imaging is the acquisition of images of solid spheroids, owing to the reduced light penetration.

    One solution is to use optical clearing techniques, which can enhance the imaging depth in spheroids by removing lipid and protein molecules.

    In this technical note, we compare different optical clearing strategies for 3D spheroids and quantify the clearing effectiveness and alterations in spheroid morphology, and demonstrate how to increase imaging depth in 3D spheroids by a factor of four.

    PDF 1 MB
    How to Perform Successful Long Term Live Cell Imaging in a High-Content Analysis System

    Live cell imaging has gained importance within drug discovery over recent times, as researchers look for more meaningful insights into cellular behavior and function. However, setting up live cell experiments can be challenging, as temperature, CO2 and evaporation need to be controlled to ensure optimal cell growth conditions. In this technical note, we demonstrate:

  • Successful five day live cell imaging on Operetta CLS and Opera Phenix high-content systems
  • Avoidance of phototoxicity with gentle digital phase contrast imaging
  • Analysis of cell growth and morphology on a single cell level without any fluorescence staining
  • PDF 3 MB
    How to Perform Successful Long Term Live Cell Imaging in a High-Content Analysis System

    Download our technical note to find out how you can overcome some of the challenges associated with long-term live cell imaging. Learn how you can perform successful five-day live cell imaging on Operetta CLS™ and Opera Phenix™ high-content systems, avoid phototoxicity with gentle digital phase contrast imaging, and analyze cell growth and morphology on a single cell level without fluorescence staining.

    PDF 3 MB
    Improved High-Content Imaging of Tissue Sections

    Automated image acquisition and analysis of tissue sections can be challenging owing to the inherent height variations throughout each specimen, and this can hinder their use in screening applications.

    In this technical note we show how PreciScan intelligent image acquisition enables generation of accurate high-resolution images, overcoming issues caused by factors such as height variations in the specimen or varying positions of the tissue sections on the slides, while also significantly reducing the data volume and acquisition time.

    PDF 2 MB
    Opera Phenix High-Content Screening System: Improved 3D Imaging

    Spinning disk confocal microscopy is a common tool for live cell microscopy and reduces background fluorescence from out of focus planes. However, for 3D imaging, confocal image quality can be limited by a phenomenon known as ‘pinhole crosstalk’ which can lead to blurred images in conventional spinning disk systems. The confocal scanning unit of the Opera Phenix High-Content Screening System provides an increased distance between pinholes to reduce the pinhole crosstalk, leading to improved 3D image quality. Learn more in our Technical Note.

    PDF 1 MB
    The Benefits of Water Immersion Lenses for High-Content Screening

    The key parameters in high-content imaging - speed, sensitivity (or intensity) and resolution - cannot be optimized independently as altering one of them influences the others. For example, increasing the resolution by choosing a higher magnification requires imaging of more fields to maintain the same cell number – at the expense of speed; or increasing the fluorescence intensity can be achieved by increasing the exposure time – again at the expense of speed. Nevertheless, there is a way to overcome some of these obstacles and here, in this Technical Note, we explain why the choice of the objective lens is critical.

    PDF 1 MB

    White Paper

    Artificial Intelligence, Machine Learning and Deep Learning: Applications in Cellular Imaging for Improved Drug Discovery Productivity

    There has been a lot of buzz around artificial intelligence, machine learning and deep learning. Is the reality living up to the hype?

    In the world of cellular imaging and its application to drug discovery, there is evidence of real progress against some of the critical challenges facing scientists using these technologies.

    In this white paper, you will learn about:

    • Challenges in cellular imaging and drug discovery that Artificial Intelligence (AI), Machine Learning (ML) and Deep Learning (DL) are helping to overcome
    • How these technologies are used by leading cellular imaging scientists
    • An outlook to how AI, ML and DL in cellular imaging have the potential to further advance drug discovery and improve productivity in the future

    PDF 1 MB
    High Content Screening in Three Dimensions

    Researchers are increasingly looking to 3D cell cultures, microtissues, and organoids to bridge the gap between 2D cell cultures and in vivo animal models. This whitepaper documents a streamlined procedure for getting the most information, as quickly as possible, using solutions from PerkinElmer.

    PDF 1 MB
    Phenotypic Drug Discovery with High Content Screening

    Today's drug discovery strategies require candidate compounds to fail early and cheaply in the discovery stage, rather than late and expensively in the clinical phase. Testing compounds early in physiologically relevant model systems and leveraging rich information from image-based screens are ways of focusing on those compounds that give rise to the right phenotypic changes without undesirable effects on the system.

    Learn:

    1. Why you should consider phenotypic vs. target based drug discovery strategies
    2. Challenges you should be aware of for phenotypic assays
    3. How to maximize the return on your phenotypic assays

    PDF 1010 KB