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.

numera_lab4 numera_lab2

NUMERA®

Key Features
  • 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

NUMERA®

Key Benefits
  • 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®

Main Devices

 

Numera® is a modular PAT system. Each installation includes a Control Module, a Routing Module, and at least one Multiplexer Module. The Dilution and Filtration Modules for sample preparation are optional modules.
Control Module
• Touch screen
• Configurations settings for system preparation, cleaning, and settings
• Various communication ports
• Compressed air distribution
  control module - Numera

 

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

Multiplexer module Numera

 

 

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

 

 

Dilution Module
• Dilution from 1:2 to 1:20
• Reagent addition, mixing, and incubation
• Precise and reproducible sample processing
  Dilution Module Numera

 

 

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

 

 

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
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 50 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:

• Single-use 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 single-use 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)
  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.

Analyzer integration Numera - Sampling system

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

 

"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.

“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

Numera_lab5 numera_lab2

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