High Content Analysis Systems

High Content Analysis Systems

A selection of powerful High Content Analysis Systems combined with intuitive user software to provide flexible research applications.

Yokogawa’s High Content Analysis Systems (HCA), also known as High Content Screening Systems (HCS), lead the microscopy industry in higher product quality, personalized process control, and streamlined user interfaces. With over 25 years of experience and a track record of proven success, we are ready to help you exceed your goals.

Details

What is High Content Analysis (HCA)?

High-content analysis is a principle methodology for so-called phenotypic screening in drug discovery and development process. Assessing a vast number of compounds is time consuming, therefore, acquiring a large number of high resolution cellular images with fast scanning speed is critically important for drug screening. Yokogawa high-content analysis imagers have balanced these generally conflicting requirements at a high level of performance. The core technology, the microlens-enhanced dual Nipkow disk in Yokogawa Confocal Scanner or Confocal Spinning disc Unit (CSU), makes it possible to capture high quality images with remarkably short acquisition time.

In addition to the image acquisition unit, a precisely controlled fast moving automated stage chamber is also an essential component of our imaging systems. Monolayer fixed cell samples have been commonly used in drug screening. However, cellular environments in such fixed 2D samples are quite different from those of actual live systems, and the divergence often causes a significant discrepancy between experimental results and what is observed in real organisms.

These days, using 3D samples such as spheroids and organoids, and live cell samples to mimic realistic cellular environments are becoming more and more popular due to cell culture technology development. Yokogawa CSU is renowned in the microscopy field not only for the high image quality and fast capturing speed, but also for the live cell friendliness. Our high-content confocal imaging systems based on the CSU are the ideal solution for drug screening using elaborated 3D and live cell assay systems as well as 2D fixed samples. User friendly high content analysis software CellPathfinder, with its versatile functionalities, powerfully supports the analysis of various phenotype changes and target reactions. It also has state-of-the-art machine learning and deep learning function for complex sample analysis. All the technologies are packed into the Yokogawa high-content analysis system.

High Content Analysis vs Traditional Methods

Traditional Methods High Content Analysis (HCA)
High-Throughput Screening (HTS) Flow Cytometry (FCM) Microscopy

Strength:

  • High-speed handling of a large number of samples

Weakness:

  • Calculates only averages for wells

Strength:

  • Acquires numeric data on individual cells

Weakness:

  • Adherent cells must be removed

Strength:

  • Detailed observation of cellular events

Weakness:

  • Slow

Strengths:

  • Rapidly analyzers a large number of samples
  • Detailed observation of cellular events
  • Temporal analysis of live cells
  • Acquires numeric data on individual cells
  • Automated high-speed imaging and analysis
  • Adherent cells can be observed as is

Confocal Imagers with Powerful Analysis Software

Our high content analysis (HCA) systems are the best solutions for a range of research applications from basic science to drug discovery screening.

Resources

Overview:

Visualizing the cell behavioral basis of epithelial morphogenesis and epithelial cancer progression

Overview:

PhenoVista Biosciences is the leading provider of custom, imaging-based, phenotypic assay services. With a collaborative and scientifically driven project design and management approach, PhenoVista has a proven track record of delivering high-quality data from robust and scalable assays. PhenoVista’s key advantage lies in the ability of their industry-trained scientists to combine world-class understanding of diverse biological systems with cutting-edge quantitative imaging to deliver clear, actionable output data.

Overview:

Spinning Disk Confocal Microscopy for Quantitative Imaging and Multi-Point Fluorescence Fluctuation Spectroscopy.

Overview:

Fluorescent ubiquitination-based cell cycle indicator (Fucci) is a set of fluorescent probes which enables the visualization of cell cycle progression in living cells.

Industries:
Application Note
Application Note
Overview:

Cell stage categorized using FucciTime lapse imaging of Fucci-added Hela cells was conducted over 48 hrs at 1 hr intervals. Gating was performed based on the mean intensities of 488 nm and 561 nm for each cell. They were categorized into four stages, and the cell count for each was calculated.

Industries:
Overview:

List of Selected Publications : CQ1

Application Note
Application Note
Application Note
Overview:

List of Selected Publications : CV8000, CV7000, CV6000

Application Note
Overview:

The CV8000 nuclear translocation analysis software enables the analysis of changes in the localization of signal molecules that transfer between cytoplasm and nuclei, such as proteins. The following is an example of the translocation analysis of NFκB, a transcription factor.

Application Note
Overview:

The CQ1 confocal image acquisition mechanism with the distinctive CSU® unit has a function to sequentially acquire fine cell images along the Z-axis and capture information from the entire thickness of
cells which include heterogenic populations of various cell cycle stages. In addition, saved digital images can be useful for precise observation and analysis of spatial distribution of intracellular molecules.
The CQ1 capability to seamlessly analyze images and obtain data for things such as cell population statistics to individual cell morphology will provide benefits for both basic research and drug discovery
targetingM-cell cycle phase.

Overview:

Applications: Colony Formation, Scratch Wound, Cytotoxicity, Neurite Outgrowth, Co-culture Analysis, Cell Tracking

Industries:
Yokogawa Technical Report
1.2 MB
Yokogawa Technical Report
2.2 MB
Overview:

In this tutorial, we will learn how to perform cell tracking with CellPathfinder through the analysis of test images.

Overview:

In this tutorial, using images of zebrafish whose blood vessels are labeled with EGFP, tiling of the images and recognition of blood vessels within an arbitrary region will be explained.

Overview:

In this tutorial, a method for analyzing ramified structure, using CellPathfinder, for the analysis of the vascular endothelial cell angiogenesis function will be explained.

Overview:

In this tutorial, we will learn how to perform time-lapse analysis of objects with little movement using CellPathfinder, through calcium imaging of iPS cell-derived cardiomyocytes.

Overview:

In this tutorial, we will observe the change in number and length of neurites due to nerve growth factor (NGF) stimulation in PC12 cells.

Overview:

In this tutorial, image analysis of collapsing stress fibers will be performed, and concentration-dependence curves will be drawn for quantitative evaluation.

Overview:

In this tutorial, we will identify the cell cycles G1-phase, G2/M-phase, etc. using the intranuclear DNA content.

Overview:

In this tutorial, intranuclear and intracytoplasmic NFκB will be measured and their ratios calculated, and a dose-response curve will be created.

Overview:

In this tutorial, spheroid diameter and cell (nuclei) count within the spheroid will be analyzed.

Overview:

In this tutorial, a method for analyzing ramified structure, using CellPathfinder, for the analysis of the vascular endothelial cell angiogenesis function will be explained.

Downloads

Videos

Product Overview
Overview:

The CV8000 features a cell incubator with an improved airtight design that facilitates the observation of cell behavior over long periods of time. In addition, the CV8000 comes with CellPathfinder, a new program that can analyze images of unlabeled cells and 3D images of samples. With these features, the CV8000 improves the efficiency of drug discovery research and biomedical research on leading-edge subjects such as iPS and ES cells.

Overview:

Yokogawa's CQ1 open platform integrates seamlessly with Advanced Solutions BioAssemblyBot® 400. With laboratory automation becoming a standard in research, Yokogawa's high content confocal system's ability to work with robots like Advanced Solutions' BioAssemblyBot® 400 is essential to advancing laboratory automation.

Overview:

Visualizing the complex spatiotemporal dynamics of human stem cells as they proliferate and make cell fate decisions is key to improving our understanding of how to robustly engineer differentiated tissues for therapeutic applications.

In this webinar, Dr. Rafael Carazo Salas will describe multicolor, multiday high-content microscopy pipelines that his group has recently developed to visualize the dynamical cell fate changes of human Pluripotent Stem Cells (hPSCs).

Key Topics:

  • Visualizing how human Pluripotent Stem Cells (hPSCs) proliferate and undergo early differentiation in vitro, by high content microscopy
  • Learning about experimental and computational pipelines that enable monitoring single-cell fate dynamics
  • Learning about novel “live” reporters of hPSC cell fate

Speaker
Rafael Carazo Salas, PhD
Professor, School of Cellular and Molecular Medicine
University of Bristol

Overview:

Physiologically relevant 3D cell models are being adopted for disease modeling, drug discovery and preclinical research due to their functional and architectural similarity to their tissue/sample of origin, especially for oncology research. Multifunctional profiling and assays using 3D cell models such as tumoroids tend to be manual and tedious. Further, high-content imaging of biomarkers in 3D cell models can be difficult.
In this two-part webinar present to you streamlined technologies which can bring consistent timesaving, ease-of-use, and high-quality data to your 3D cell-based workflows:

(A)  The Pu·MA System is a microfluidics-based benchtop automated device for performing “hands-off” 3D cell-based assays. In this webinar, application scientist Dr. Katya Nikolov will present data from optimized assays using tumoroids followed by Yokogawa’s high-content imaging systems for biomarker detection.

(B) Yokogawa’s high-content imaging systems such as CellVoyager CQ1 provide superior confocal imaging using the Nipkow Spinning Disk Confocal Technology. Here, application scientist, Dan Collins will present details of the high-content imaging capabilities, easy to use and intuitive image acquisition software, especially for increasing productivity and a streamlined workflow.

Learn How:

  • The open platform, Pu·MA System can be used to automate your 3D cell-based assays
  • To perform automated IF staining for biomarkers using tumoroid models without perturbing your precious samples
  • Image acquisition from 3D cell models using Yokogawa’s high-content imaging platforms
  • Image analysis from cells, complex spheroids, colonies, or tissues using the CellPathfinder high content analysis software
Overview:

Director of Laboratory Automation, Duane Currier covers the integration of a high-content imager into a modern laboratory automation system and workflows built to utilize the Yokogawa CV8000. The session describes the integration topology used in the High Throughput Bioscience Center at St. Jude and discusses some of the technical challenges that were faced, with special attention given to data handling and analysis. Using examples of experiment workflows from recent projects, the session will address the variety of ways we have used our high-content imager in the context of a high throughput screening center.

Key Topics:

  • Key considerations for integrating a high-content imager into a laboratory robot system
  • Methods for interfacing between robots and the imager
  • Important considerations for imaging data management and analysis
  • How the St. Jude High Throughput Bioscience Center supports the diverse imaging needs of its projects
Overview:

Physiologically relevant 3D cell models are essential for drug discovery and preclinical research due to their functional and architectural similarity to solid tumors. One of the challenges faced by researchers is that many of the assays using these precious samples tend to be manual and tedious.

Using proprietary microfluidics technology, Protein Fluidics has created the Pu·MA System for automated complex 3D cell-based assays. In this webinar, application scientist Dr. Katya Nikolov will present her work on combining this novel automation technology with Yokogawa’s high-content imaging systems for biomarker detection in 3D cell models. Nikolov will demonstrate the utility of an automated immunofluorescence staining workflow followed by confocal imaging within the Pu·MA System flowchips. This automated workflow enables quantitative assessment of biomarkers which provides valuable data for further understanding disease mechanisms, preclinical drug efficacy studies, and in personalized medicine.

This webinar will explore:

  • The Pu·MA System and novel technology for automated 3D cell-based assays
  • How to perform automated immunofluorescence staining for biomarkers with a “hands-off” assay workflow
  • How to visualize biomarkers after the assay with high-content imaging within the flowchip
Overview:

Human pluripotent stem cells are proven efficient models for drug screening campaigns. They provide access to unlimited starting material amenable to high throughput small molecule compound screening. Due to their capacity to generate mode complex cellular models, they also offer the potential to perform high content screening in tissue-specific organoids for further human target validation.

Dr. Alejandro Hidalgo-Gonzalez at MCRI(Murdoch Children's Research Institute) in Australia is a user of our HCA system CellVoyager CV8000 and he has established a pipeline for assay development and automated unbiased phenotypic drug screening using human pluripotent stem cell-derived cells and organoids. This is a recording of his presentation at an educational webinar organized by A*STAR in Singapore.

Overview:

Dr. Sexton discusses high content screening for phenotypic-based drug discovery and development using Yokogawa technologies. This webinar presents the methodology behind acquiring good images that are able to leverage the three-dimensionality of different cell systems. His assays include 3D models such as organoids and spheroids.

In this webinar, you will discover:

  • How to identify when 2D or 3D methods are required to achieve desired results.
  • How to leverage your High Content Imaging Systems to get optimal signals and backgrounds.
  • Techniques that are used to improve cell observation yield and statistical distributions of morphological features.
Overview:

In the last few decades, the pharmaceutical industry has transformed people’s lives. However, the development of new drugs is becoming increasingly difficult and a paradigm shift in the drug discovery workflow is required to reduce attrition and transform conventional drug screening assays into translatable analytical techniques for the analysis of drugs in complex environments, both in-vitro and ex-vivo. The ability to visualize unlabelled compounds inside the cell at physiological dosages can offer valuable insight into the compound behavior both on and off-target.

SiLC-MS is a semi-automated methodology that allows the collection of intracellular contents using a modified CQ1 imaging system developed by Yokowaga. The instrument is equipped with a confocal microscope that allows bright field imaging as well as fluorescence imaging with 4 lasers (405, 488, 561, and 640 nm). Sampling is performed using the tips developed by Professor Masujima (1-4).

In this study, we show the applicability of the SiLC-MS technology to drug discovery, as it is crucial to identify compound and its metabolites when incubated in a mammalian cell at a therapeutic dose. We report on the validation studies performed using the SiLC-MS platform, in these validation studies we assess the ability to distinguish different cell types based on their metabolomic fingerprint, furthermore, we have also evaluated if this assay was sensitive enough to detect drugs intracellularly.

Presenter: Carla Newman, Scientific Leader (Celluar Imaging and Dynamics), GSK

Overview:

3D imaging experts from Yokogawa and Insphero have come together to provide helpful tips and tricks on acquiring the best 3D spheroid and organoid imaging. This webinar focuses on sample preparation, imaging, and analysis for both fixed and live cells in High Content Screening assays. The experts also discuss automated tools that can help researchers understand the large volume of data in these High Content Imaging Analysis Systems.

Overview:

This webinar highlights Yokogawa’s High Content Solutions, the benchtop confocal CellVoyager CQ1, and CellVoyager CV8000. Utilizing Yokogawa’s dual-wide microlens spinning disk confocal technology, these automated HCA systems provide remarkable image quality while increasing your output. This frees up time to complete other research activities. Also, recent additions to the CSU-W1 confocal upgrade is discussed. The SoRa, a super-resolution solution, and the Uniformizer, an image flattening device. Both of which can be added to the lightpath of your CSU-W1-enhanced microscope.

Agenda:
Introduction to Yokogawa
SoRa for CSU-W1 super-resolution with confocal
Two high content instruments from Yokogawa: The CQ1 and the CV8000

Presenter:
Dan J. Collins, Applications Scientist, Yokogawa Life Science

Overview:

Generating translatable high-content imaging data from physiologically-relevant cell models, including 2D and 3D structures, is extremely valuable for drug discovery and pre-clinical research. In this webinar, James Evans, CEO of PhenoVista Biosciences presents case studies on how Yokogawa’s Benchtop CQ1 Confocal System can improve throughput and standardize processes for complex 3D cell-based phenotypic assays.

Key learning objectives:

  • Strategies for designing and implementing high-content screening assays
  • Approaches for deciding between 2D and 3D model systems
Overview:

Image-based phenotypic screening relies on the extraction of multivariate information from cells cultured in a large number of screened conditions. In this webinar, we explored the application of complex and biologically relevant model systems for drug screening, such as small intestinal organoids.

Key topics include:

  • Learn how to upscale, streamline, and automate intestinal organoid handling
  • Learn how to image in complex three-dimensional (3D) model systems and how to approach large imaging datasets
  • Understand the basics of multivariate analysis on image-inferred features

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