Menu Close Menu
    numera_article_e3848ffd39

    Numera®

    Advanced Bioprocess Sampling Solution

    Numera® is a fully automated sampling system that never sleeps, integrating and improving every process analytical technology with reliable real-time results 24/7. Combined with Lucullus® software, Numera® is a seamless all-in-one sampling solution.

     

    Sampling from up to 16 vessels

    2 to 3 ml sampling volume

    Sampling time ~8 minutes

    Sample storage and cooling

    Sample transfer to up to 4 analyzers

    Unique filtration technology for cell removal

    Automated sampling 24/7
     
    High frequency and low volume sampling
     
    Individual sample preparation including consistent cell removal.
    On-line measurements with common analyzers
     
    Automated data import from analyzers and advanced feedback control loops with Lucullus®

    About Numera®

     

    Numera® is a modular PAT system. Each installation includes a Control Module, a Routing Module, and at least one Multiplexer Module, while the Dilution and Filtration Modules for sample preparation are optional.

    The Autosampler/Sample Collector stores retained samples at  4°C  for further processing. 

    Numera® can be used in many applications – from single-use, bench-top reactors, up to production.

    The modular design of Numera® allows configurations for single reactor sampling and storage up to multiple reactor sampling including dilution, filtration, and integration of various on-line analyzers.

     

    luculluas_numera_ac8e435fb0

    Numera® Modules

    • Numera - Control Unit (CPU)

      Control Module

      • Touch screen
      • Configuration settings for system preparation, cleaning, and settings
      • Various communication ports
      • Compressed air distribution
    • Numera - Multiplexer Unit

      Multiplexer Module

      • Multiplexing of up to 4 bioreactors per module
      • Up to 4 modules per Numera® system
      • Pinch valve sterility barrier with ethanol rinsing
      • Sterile air blow back mechanism to prevent cross-contamination and preserve low volume sampling
    • Numera - Routing Unit (SRU)

      Routing Module

      • Individual sample distribution within one process
      • Direct transfer to maximum 4 analyzers (biochemistry analyzers or cell counters)
    • Numera - Dilution Unit (SDU)

      Dilution Module

      • Dilution from 1:2 to 1:20
      • Reagent addition, mixing, and incubation
      • Precise and reproducible sample processing
    • Numera - Filtration Unit (TFU)

      Filtration Module

      • Unique cross-flow filtration technology
      • Low protein binding PES membrane
      • Up to 700 filtrations per coil
      • Membrane pore sizes: 0.22 μm, 0.45 μm, 0.65 μm, and 1.2 μm
      • Fresh membrane section for every filtration cycle avoiding cross-contamination and clogging 

    Setup and Configuration

    Autosampler / Sample Collector

    Storage of retained samples or intermediate storage of samples for further processing is achieved with the Autosampler. In addition, manually taken samples can be stored for processing with the Numera® and/or for transfer to analyzers. Cooling is guaranteed in a range of 4 to 20 °C. There are two different sizes of Autosampler available. Both are equipped with a syringe pump and a rinse station.

    The Autosampler can be equipped with 2 well plates per Peltier rack module. Securecell offers well plates for 1.5 ml and 4.0 ml glass vials. Standard deep-well plates with 2, 5, or 10 ml can also be used.

    ASX7200

    • 2 Peltier Rack Modules (storage at 4 to 20°C)
    • 4 well plate positions
    • Optional: 1 HPLC injection valve
    ASX7400-1
    ASX7400
    • 4 Peltier Rack Modules (storage at 4 to 20 °C)
    • 8 well plate positions
    • Optional: 1 or 2 HPLC injection valve(s)

    ACCESSORIES

    Well plates
    • 40 x 1.5 ml vials
    • 24 x 4.0 ml vials
    • Standard deep-well plates with 2, 5, or 10 ml

    HPLC/UHPLC Injection Valves
    • Variants from 5,000 to 20,000 psi
    • Vertical port injector
    • Sample loop (ID 0.14 mm) from 5 to 20 μl

    Product Configuration

    The modular design of Numera® allows configurations for single reactor sampling and storage up to multiple reactor sampling including dilution, filtration, and integration of various on-line analyzers.
     
    Reactor configuration 1
    A maximum length of 10 m between the Numera® and the reactors is recommended.
     
    Reactor configuration 2

    Up to 4 Multiplexer Modules can be stacked on a central system. This allows to connect up to 16 bioreactors.

     

    Reactor configuration 3Multiplexer Modules can be decentralized, depending on the available space and laboratory organization.

     

    Reactor configuration 4The Autosampler should be put close to the system. The distance to connected analyzers is limited to 10 m.

     

    Reactor Connection and Sterility

    Reactor Connections

    Numera® can be used in many applications – from single use, bench-top reactors, up to production. The appropriate connection options are available for all purposes. The modular concept includes:

    • Autoclavable sampling sets
    • Sample lines 1 – 10m
    Single Use Bioreactors
    Single-Use Bioreactors

    + Sample lines

    BENCHTOP REACTORS
    Benchtop Reactors
    + Sample lines
    + Dip tube
    + Adapters
    STAINLESS STEEL REACTORS
    Stainless Steel Reactors
    + Sample lines
    + Sampling port
    single-use sampling
    Single-Use Sampling Sets

    At the Multiplexer, autoclavable sampling sets including all tubings for sterile sampling, ethanol cleaning and flush back with sterile air, are installed for each sample vessel.

    Sample lines
    Sample Lines

    From 1 to 10 meters are used to attach the sampling set at the Multiplexer to the corresponding bioreactor interface with Luer-Lock screw connections.

    dip tubes
    Dip Tubes

    Stainless steel dip tubes with a Luer-Lock connector are used in combination with a suitable reactor adapter to sample from bench-top (glass) bioreactors.

    Adapter
    Adapters

    Adapters from 10 – 19 mm and PG13.5 are available to mount the dip tubes to any common head-plate port.

    Aseptic Sampling Port
    Aseptic Sampling Port

    The Aseptic Sampling Port enables sampling from stainless steel bioreactors using the 25 mm side port. The connection to the Numera® System is made with a Septum Piercing Needle with side entry. The needle comes with a holder that fits to the Aseptic Sampling Port and with a Luer-Lock connector.

    Sampling & Sterility Concept

    • Minimal sample loss
    • No sample dilution
    • Guaranteed sterility
    • No cross contamination
     
    Sample lines and sampling sets are autoclaved in bags before use and protected with sterile air filters and clamps to maintain sterility during installation.

    The clamps are removed after mounting the tubes on the pinch valves. The tubes are subsequently connected to the Multiplexer Module input and to the bioreactor/vessel interface. Luer-Lock screws ensure the connection between sampling set, sample line and bioreactor interface.

    After completion of the sampling procedure, the remaining sample in the sampling line is pushed back into the bioreactor with sterile air. An ethanol rinsing procedure cleans the sampling sets at the Multiplexer Module to remove sample residues and prevent contamination. A rinsing procedure guarantees complete removal of ethanol.
     
    Proof of sterility in a technical run
    graph
    Figure: values for pH (red line), pO2 (blue line) and O2 inflow (black line) over process time. The steady values indicate a sterile process over 15 days. Samples were drawn every 2 h.
     
    You can find the full article here 

    Analytics and Sample Management

    Analyzer Integration

    Numera® can be used in combination with various analyzers to perform on-line analytics:

    1. Cell counters (e.g., ViCELL XR®, Cedex® HiRes)
    2. Biochemistry Analyzers (e.g., Cedex® Bio HT, Bioprofile® FLEX2)
    3. HPLC Sytems (e.g., Agilent 1200 Series, Thermo Fisher Vanquish)


    For each analyzer integration, specific accessories and information are needed that are provided by Securecell.

    Numera and Analyzer integration for advanced sample management for bioprocessing

    HPLC Integration

    The Autosampler setup can include an injection valve for HPLC (up to 20,000 psi). Direct injection provides loss-free and fast analytics with HPLC system of various vendors.

    Sample Management with Lucullus Software

    The combination of the automated sampling system, Numera®, and the Process Information Management System, Lucullus®, enables the orchestration of the whole workflow covering sampling, measurement, process monitoring and control.

    • Sample planning (time- and event-based)
    • Analytical methods for all analyzers
    • Barcode and label printing
    • Automated event-based sample triggering during process
    • Sample preparation and sample storage
    • Automated on-line measurements
    • Centralized data management and process monitoring
    • Advanced process control and feedback loops

    Sample Management - Numera and Lucullus software

     

    “Securecell’s support goes beyond the simple supplier-customer relationship. With Securecell we chose a partner that is actively supporting us in our mission of automating and digitalizing our laboratory environment.”
    - Nick Wierckx

    Professor at Institute of Bio- and Geosciences Forschungszentrum Jülich

    "Whether on- or off-line, Numera delivers accurate HPLC data fast and with little effort."
    - DR. Ueli von Ah

    Biotechnology Research Group Leader, Agroscope

    "High-density, time-resolved data reduce the number of experiments!"
    - PROF. Christoph Herwig

    Professor for Biotchemical Engineering, TU Wien

    "Numera improved the automation of our Continuous Countercurrent Tangential Chromatography (CCTC) System."
    - Oleg Shinkazh

    CEO and Founder, ChromaTan Corp.

    Insights

    Unique, modular sampling system for bioprocesses

    Related Products and Technologies