CV8000 High-Throughput System

Through the combination of proprietary Yokogawa high speed Confocal Scanner Technology, water immersion lenses, up to four high field-of-vision cameras, a microscopic stage with cell cultivation environment, and an integrated robotic pipetter, the unit provides high throughput, high-resolution imaging and phenotypic screening, making it the ideal choice for a variety of applications. Though known as a live-cell friendly total HCA system, the intuitive CellPathfinder software makes the CV8000 user friendly as well. Researchers can choose from a variety of templates and flexible protocol editing capabilities, use the CE bright field and machine-learning functionalities to do label-free analysis, and the new Deep Learning option largely improves cell recognition accuracy.

•    Spinning Disk Technology result in higher scanning speeds and higher quality images
•    Real time Confocal, label-free imaging for Live and Kinetic experiments
•    High throughput increases efficiency
•    Reliable, proven technology

Introduction

Valley of death

Within the drug development market, demands on High Content Analysis systems for drug efficacy evaluation are increasing in accordance with the needs for cell-based assay and phenotypic screening. In order to increase screening efficiency, devices with higher speeds (higher throughput) are required.
On the other hand, in order to bridge the “valley of death” of the drug development process, the quality of screening hits must be increased.
This requires the construction of more complex evaluation systems that utilize multifaceted parameters via 3D cultivation systems, live-cell imaging and higher detail image analysis.
In current drug development research, determining how to implement throughput screening and complex evaluation system screening in parallel is an important issue.

Solution

The CellVoyager CV8000 is a high-end, High Content Analysis system that solves this contradictory screening challenge. Through the combination of a proprietary Yokogawa High Speed Confocal Scanner, water immersion lens, up to four high field-of-vision cameras, a microscopic stage with cell cultivation environment, and an integrated robotic pipetter, we have realized not only high throughput, high-resolution imaging, but also phenotypic screening via a more complex evaluation system. In addition, our specialized analysis software, CellPathfinder, uses deep leaning and machine learning to recognize target objects with high accuracy, supporting you from image analysis to results display using graphs.

The Yokogawa advantage

  • Confocal scanner unit
  • Live/kinetic experiment compatible
  • High throughput
  • Reliable, proven technology

Voyage to Unknown Worlds

Real time confocal, label-free imaging

Long-term liv e c ell imaging

Long-term livecell imaging

Stage incubator included as standard. Realization of non-stop, long-duration observation (3 days +) via humidity, temperature and CO2 control.

Left:Before incubation Right:After 68 hours incubation

Kinetic assay

Kinetic assay

Drug addition during imaging is made possible by an integrated robotic pipetter with disposable tips.
Ideal for kinetic experiments involving the observation of high speed phenomena.

Left:Before incubation Right:After stimulation

Organoid / Spheroid

Organoid / Spheroid

Yokogawa’ s spinning disk confocal technology excels in imaging of samples with depth, such as 3D culture samples where clear and quick imaging is difficult, allowing for evaluation close to in-vivo quality.

Left:Original image Right:Recognition image

Label-free analysis

Label-free analysis

Recognition and analysis can be performed by taking bright field images from several Z positions and creating a CE bright field image using the included CellPathfinder analysis software. Analysis accuracy is further enhanced via the new Deep Learning option.

Left:CE Bright Field Right:Cell Recognition image

Details

State-of-the-art technology that enables you to do what you want

Observe cells as they are -Dual spinning disk confocal system-

Dual spinning disk confocal system

A Yokogawa proprietary multi-scan method utilizing approximately 1,000 laser beams on the observation region and tandem disks rotating at high speed. The disks comprise a pinhole array disk with approximately 20,000 pinholes arranged in an equal pitch spiral pattern, and a microlens array disk that focuses the excitation light laser into individual pinholes. Not only does this allow high speed imaging, but it also largely prevents phototoxicity and fluorescence photobleaching.

Deeper, clearer observation -Pinhole disk exchanger-

Pinhole disk exchanger
 
Pinhole disk exchanger

Two different types of pinhole disks (25/50μm) can be used, according to the sample. For thick samples, reducing the pinhole diameter allows for higher confocality, shaper images. For dark samples, increasing the pinhole diameter allows for brighter images.

Organoid imaging example Upper:25μm pinhole Lower:50μm pinhole

Higher throughput screening -Optical configuration-

Optical configuration

The optical system configuration can be selected according to the purpose. A single 96-well plate can be imaged in four colors in one minute by attaching four high- sensitivity wide -field sCMOS cameras. The system is also compatible with FRET and CellPainting assay.

Capturing finer structures -Original water immersion lens-

water immersion lens

Water immersion lenses excel in capturing high-resolution images of cells within a liquid. The CV8000 can be equipped wit h a 40x or 60x water immersion objective lens. Our 40x lens is a particularly unique lens capable of highly advanced spherical aberration correction, allowing for the capture of bright high-resolution images over a full wide -field. The lens water supply is also completely automated. This equipment makes high throughput screening via water submersion lens possible.

Capturing live cell movement -High-precision incubator and robot pipetter-

robot pipetter

The stage incubator features an airtight construction, managing humidity, temperature and CO2 levels. The integrated robotic pipetter conducts the following process fully automatically: tip pickup → reagent collection from the reagent plate → reagent addition to the sample plate → tip disposal. Not only can images be rapidly obtained before and after reagent instillation, but it’s also possible to add reagents to single wells multiple times, and adjust the addition speed etc., broadening the range of dynamics observation via reagent instillation.

A more live cell-friendly total HCA system

Making long-duration live-cell imaging possible -Featuring a s table built -in stage incubator-

HeLa cells were seeded in a 96 well plate at a density of 500 cells per well, and cultured for 24 hours. The well plate was then placed in the internal stage incubator and cell culturing was conducted for 72 hour s, and the total area (hereinafter Total Area) occupied by cells was analyzed. As a result, minimal unevenness in cell multiplication was observed across the 96-wells (excluding the four corner wells) when compared to a regular CO2 incubator.

Cell multiplication comparison with regular CO<sub>2</sub> incubator after 72hr incubation

Cell multiplication comparison with regular CO2 incubator after 72hr incubation(n=3)

  • 96 well average: 90
  • Average of outermost 36 wells: 81
  • Average of 60 wells (excl. outermost): 96

The values represent the following: CV8000 Total Area after 72hrs / Total Area at 0hrs (hereinafter Total Area ratio) / CO2 incubator Total Area ratio x 100.
(Numbers near to 100 me an that cell multiplication was approximately equal for the CV8000 and CO2 incubator.)
Cell multiplication near to that of the CO2 incubator was verified, excluding the four corner wells.

Cell multiplication curves for each well of a 96-well plate

Cell multiplication curves for each well of a 96-well plate

  • Vertical axis: Total Area
  • Horizontal axis: Time (0-72 hours)

Cell multiplication was low in the four corner wells; however, it continued in the other wells.。

Total Area ratio after cultivation start

Total Area ratio after cultivation start (24, 48 and 72 hours) (n=3)

Excluding the four corner wells, even after 72 hours, there were no large differences in cell multiplication.
The low variation in cell multiplication speed across the wells can 24 hours 48 hours 72 hours be seen.

More info Evaluation of cell-culture condition in CV8000’s internal stage incubator

System Integration

Centralized process management, from the cultivation environment, to transfer, imaging, analysis and data management.
We offer optimum systems in response to our customers’ needs.

System Integration

High Content Analysis Software CellPathfinder

The software analyzes image data captured with the CV8000, creates graphs and exports various data. Beginner and expert users alike can take full advantage of the software, thanks to an abundance of templates and flexible protocol editing capability. CE bright field and machine-learning functionalities make label-free analysis possible. The new Deep Learning option has also been added, largely improving cell recognition accuracy.

More info High Content Analysis Software CellPathfinder

Just click the menu item for analysis

Just click the menu item for analysis

Simply follow the flow displayed at the top of the screen. The analysis menu has easy-to-understand icons. Simply click the desired menu item and the protocol will load.

Fast results for immediate verification and study

Fast results for immediate verification and study

Computed numeric data can be displayed in a variety of ways. Graph plots and cell images are linked, making for easy result verification and inquiry.

Unbiased phenotype evaluation via AI

Unbiased phenotype evaluation via AI

Machine-learning also provides bias-free digitization of visually-evaluated experiments. Automatic recognition is made possible simply by clicking the shape you want the software to learn.

Label-free phenotype analysis

Label-free phenotype analysis

Eliminates the time, cost and influence on cells associated with cell labelling. Even higher precision classification is made possible through combination with deep learning.

Specifications

High-throughput Cytological Discovery System

Model CV8000
Sample format Multiple well plate (6, 12, 24, 48, 96, 384, 1536 wells), glass slide
Image mode Confocal mode: max. 4 color simultaneous recording
Bright field/phase contrast (10x, 20x for 6, 12, 24 well plates), digital phase contrast (10x, 20x)
Output data format Image data: 16bit TIFF, PNG
umerical data: CSV, original format
Excitation wavelength 405/445/488/561/640 nm, all solid laser, max. 5 lasers 
【Option】365 nm LED
White light illumination LED
Autofocus Laser-based mode, image-based mode
Objectives Max. 6 lenses are available, automatically switchable
Dry: 2x, 4x, 10x, 20x, 40x Water immersion: 20x, 40x, 60x
hase contrast: 10x, 20x Long working distance: 20x
Confocal unit Microlens-enhanced wide-view dual Nipkow disk confocal scanner, 50 μm pinhole
【Option】 25 μm pinhole disk and auto pinhole disk exchanger
Camera sCMOS (effective pixels: 2000X2000 pixel size: 6.5 μm), max. 4 cameras
Stage incubator Temperature for incubation : 35-40℃ CO2 supply box (CO2: 5%, forced humidification)

Robot pipetter

【Option】 Disposable tip type (96tip or 384tip type)
Bar code reader 【Option】 1 or 2 dimension
Workstations Dual-monitor work station for system control, dual-monitor work station for data analysis
Analysis software High Content Analysis Software CellPathfinder
Granularity, Neurite, Nuclear morphology, Nuclear translocation, Plasma membrane translocation, Machine learning, Label-free analysis, 3D analysis, Deep Learning, etc.
Operating environment 15~30℃ 30~70%RH (no condensation)
Power supply Measurement unit:AC100-240V, 50/60Hz, 2KVA max
Workstation for system control:AC100-240V, 50/60Hz, 1.3KVA max
Workstation for data analysis:AC100-240V, 50/60Hz, 950VA max
Dimensions Measurement unit: W1,280×D895×H1,450 mm
Weight Measurement unit: 510Kg

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CV8000 Partner

North America, Europe

WAKO Automation USA, Inc.

WAKO Automation USA, Inc.
Recommended vendor for High Content Screening integration and automation solutions.

 

Asia

Shanghai Genesci Medical technology

Shanghai Genesci Medical technology Co.,Ltd.
People's Republic of China (excluding Hong Kong, Taiwan, Macao)


Oceania

TrendBio

TrendBio
Australia, New Zealand

  • CellPathfinder

    Cell imaging software supports label-free samples and provides multiple graphing options with a streamlined, easy-to-use interface.

    See More

Resources

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:

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.

Application Note
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:
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
Application Note
Application Note
Application Note
Application Note
Overview:

List of Selected Publications : CV8000, CV7000, CV6000

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:
Yokogawa Technical Report
Overview:

We have been developing a prototype of a genomic drug test support system using our CSU confocal scanner. This system administers chemical compounds that serve as potential drug candidates into living cells, which are the most basic components of all living organisms, records the changes in the amount and localization of target molecules inside cells with the CSU confocal scanner and a highly sensitive CCD camera, and processes and quantifies the captured high-resolution image data.

Yokogawa Technical Report
1.2 MB
Yokogawa Technical Report
2.2 MB
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, 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, spheroid diameter and cell (nuclei) count within the spheroid will be analyzed.

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 identify the cell cycles G1-phase, G2/M-phase, etc. using the intranuclear DNA content.

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 observe the change in number and length of neurites due to nerve growth factor (NGF) stimulation in PC12 cells.

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, 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.

The numerical apertures of the CV8000 objectives are 2X 0.08NA 4X 0.16NA 10X 0.40NA 10X PH 0.30NA 20X 0.75NA 20X LWD 0.45NA 20X PH 0.45NA 20XWI 1.0NA 40X 0.95NA 40X WI 1.0NA 60X WI 1.2NA To learn more, click here. ...
The wavelengths for the emission filters that come with the CV8000 are listed below. Additionally, you may custom order additional emission filters for specific needs. To learn more, click here. 445/45 525/50 600/37 676/29 488/568 (Dual Band F...

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:

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:

In this webinar, Professor Jonny Sexton discusses a pipeline, developed in the Sexton lab, for the quantitative high-throughput image-based screening of SARS-CoV-2 infection to identify potential antiviral mechanisms and allow selection of appropriate drug combinations to treat COVID-19. This webinar presents evidence that morphological profiling can robustly identify new potential therapeutics against SARS-CoV-2 infection as well as drugs that potentially worsen COVID-19 outcomes.

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:

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:

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:

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:

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.

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