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CellCelector

The world's most versatile automated single cell and colony picking system

The ALS CellCelector™ platform is a unique and fully automated cell imaging and picking system developed for detection, selection and isolation of single cells, clusters, spheroids and organoids as well as single cell clones and adherent colonies. It is widely used in a multitude of research areas (e.g. circulating tumor cell/CTC screening, stem cell research as well as cell line development and antibody discovery).

Technology

The CellCelectorcombines an automated inverted fluorescence microscope with a high-speed scanning stage, a high-precision microfluidic cell picking robot and a PC workstation running powerful image processing software typing all system components together. As such the ALS CellCelector is a unique combination of a high-content imaging system and a fully automated micro-manipulation robot. The unique versatility of the CellCelector™ is achieved by three exchangeable picking modules utilizing either high-precision glass capillaries, reusable (autoclavable) stainless steel scraping tips or disposable plastic tips. Further versatility is added through compatibility with a huge range of source (microtiter plates, petri dishes, slides, CellCelector Nanowell arrays or custom plates) and destination labware formats (microplates, petri dishes, slides, PCR tubes/plates etc.).


CellCelector single cell and colony picker: Before and after picking image documentation
Example of automatically acquired before and after picking images during single cell picking (bright field, 10 x, PC3 cell line)
The operation principle of the ALS CellCelector™ can be summarized as following:

  • Image the source plates
  • Detect/Select cells, clusters or colonies of interest
  • Pick target cells and transfer them into destination plates

The whole workflow is fully automated and documented by providing a live image during picking, cell tracking data from source plate to destination plate as well as before and after picking images.

Depending on the application and user requirements the cells to be picked can be detected, identified and selected fully automatically either label-free based on the target cell size and morphology or through positive/negative fluorescence markers. As an alternative semi-automated or manual on-screen selection by the operator is possible.

Multiple benefits


  • Open platform allowing the development of your own imaging, detection and picking protocols
  • Versatility: single cell picking, isolation of clusters, spheroids, organoids, adherent colonies, single cell clones from a variety of liquid and semi-solid medias
  • Up to 100 % picking/transfer efficiency (depending on application)
  • Extremely gentle cell transfer resulting in high cell integrity and outgrowth rates after the cell transfer (including up to 95 % viability in single cell cloning applications)
  • Isolation of living or fixed cells
  • Fully automated or interactive picking modes with live on-screen visualization of the picking process
  • High scanning and picking throughput resulting in fast retrieval of cells - the ALS CellCelector™ is therefore compatible with Single Cell RNA analysis applications or for the isolation of living cells
  • Optionally deck tray with cooled destination positions available to prevent degradation of RNA of picked cells
  • Automated adjustment of picking position and height
  • Validated protocols for detection and isolation of single cells in suspension, adherent cells or colonies, 3D clones in liquid or semi-solid media etc. for downstream molecular analysis or cloning (e.g. for cell line development)
  • Compatibility with standard and custom cell culture labware
  • Complete documentation and traceability from source plate to destination including cell tracking data as well as before and after picking images
  • The high-content imaging subsystem can also be used for imaging applications without picking
  • Easy to operate, doesn’t require highly skilled operator
  • No routine maintenance necessary

Key specifications and features


  • Bright field, phase contrast and fluorescence imaging in up to 7 channels
  • Magnifications from 1.25 x to 60 x for optimal imaging resolution and speed
  • Automated image analysis, cell/colony segmentation and gating based on cell morphology and/or the presence or absence of fluorescent markers
  • Various image gallery modes of detected cells allow for an easy and fast pick list review
  • Picking capillaries/tips ranging from 20 µm to 1.2 mm inner diameter covering the whole spectrum of application scenarios
  • User adjustable picking protocols allow for fine tuning of different aplications (e.g. aspiration volumes and speeds etc.)
  • Various application-specific picking modes: single cell recovery, cell pooling, replica plate generation, cell deposition onto microscope stage, serial picking modes for enrichment/purification scenarios, interactive picking and deposit modes
  • Can be installed within a standard biological safety cabinet / cell culture hood or in our ALS Incubator FlowBox combining a sterile laminar air flow with temperature, CO2 and humidity control for handling of sensitive cells and running long term experiments (see below).

CellCelector™ software

The CellCelector™ is controlled by powerful yet easy-to-use software guiding the operator through all steps of the workflow including the plate scanning, image analysis, target cell detection and review as well as picking and documentation. Many smart and unique features allow for robust and straightforward operation.
CellCelector software

User-exchangeable picking modules


The CellCelector platform is the world’s most flexible cell picking system allowing switching from rare single cell picking for liquid biopsies to clone picking from methylcellulose for antibody discovery within minutes.

At the core of such flexibility are several user-exchangeable picking modules the ALS CellCelector can be equipped with. This enables a fast and smooth transition between different applications. The system automatically recognizes the installed module and loads the corresponding application parameters. Due it its flexibility the CellCelector system can be easily shared by several research groups and represents an ideal tool for shared resources or core facility settings.
Single cell picking module

Single cell picking module

The single cell picking module uses liquid buffered single-use glass capillaries for gentle high-precision low-volume aspiration of cells and liquids. This module is therefore ideal for the isolation of individual single cells and any other kind of multi-cellular objects (clusters, single cell clones, spheroids, organoids, embryoid bodies, neuro-spheres etc.) from a mixed culture in liquid or semi-solid media.
Adherent colony picking module

Adherent colony picking module (aka scrape module)

The scrape module utilizes reusable and autoclavable stainless steel ScrapeTips allowing for cross contamination free adherent colony picking. This module is perfectly suited for clonal picking of stem cell colonies (iPSC, mESC, hESC, hASC and others) in liquid media both from feeder cells and feeder-free cultures, the creation of replica plates and any other adherent colony or tissue applications.
Semi-solid media picking module

Semi-solid media picking module

The semi-solid media picking module utilizes disposable plastic PrecisionTips effectively preventing any cross-contamination and offering minimal routine maintenance. This module is ideal for picking of clones, colonies, spheroids, large organoids and other 3D objects from semi-solid media like methylcellulose, Matrigel®, agarose and others.

Accessories

The ALS CellCelector can be easily customized using a wide range of adapters designed to handle your current labware: source plates (installed on the microscope stage) and destination plates (placed on the robot deck tray). Therefore the CellCelector can be operated without need for expensive custom consumables or reagents. You can continue to use the labware used to establish your application - the CellCelector™ will simply automate it.  
Adapters for microscope stage

Applications

The CellCelector is an open modular platform which can be used in many different research areas. If necessary it can be easily shared by several research groups switching between different applications, e.g.

  • Rare single cell detection and isolation / single cell sorting (e.g. recovery of circulating tumor cells (CTCs), fetal cells (for cell-based non-invasive prenatal testing (cbNIPT)) and others)
  • Single cell PCR analysis and next-generation sequencing
  • Single cell RNA-Seq
  • Cluster/spheroid isolation with cell heterogeneity analysis on single cell level
  • Single cell cloning with integrated monoclonality proof (eliminating the need for sub-cloning rounds) in pharmaceutical cell line development
  • High-throughput single plasma B-Cell and Hybridoma clone screening for antibody discovery
  • Semi-solid media cloning (e.g. Hybridoma clones for antibody discovery)
  • Stem cell colony picking (e.g. clonal picking of iPSC, hESC and others, gentle passaging of newly derived iPS cell lines) from feeder cells and feeder free cultures
  • Single stem cell cloning from gene-edited cell pools (after CRISPR/Cas9 etc.)
  • Picking of embryoid bodies, neuro-spheres, RPE cultures and other differentiated cells
  • Cell and gene therapy applications through hematopoietic stem cells
  • Regenerative medicine applications         

CellCelector Housing Options

Often the handling of cells requires a sterile working environment. The ALS CellCelector is offered with several different housing options ranging from a simple PCR hood for operator safety to our most sophisticated option - the ALS Incubator Flowbox providing both sterility and a controlled cell culture environment for your sensitive cells and long term experiments. Of course the CellCelectorcan be also installed within a biosafety cabinet or cell culture hood that you have already available in your lab (please contact us for details).

CellCelector PCR hood

CellCelector PCR hood

This ALS-designed benchtop PCR hood protects the system from dust while ensuring operator safety. This is sufficient when no re-cultivation of the picked cells is necessary (e.g. cells are picked exclusively for downstream molecular analysis applications like single cell DNA, RNA or Next-Gen sequencing of the picked single cells).

Customized biosafety cabinet

Customized biosafety cabinet

The NuAire Class II biosafety laminar flow cabinet has been customized for the CellCelector. It provides sterile working conditions necessary for live cell isolation and cloning applications.

Incubator FlowBox

Incubator FlowBox

The ALS Incubator Flowbox represents a unique combination of a laminar air flow for sterile work and physiological cell culture conditions including precise temperature, CO2 and humidity control.
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