RAMOS® for the Bioprocess Optimisation

The Advantages

  • More information on your microbiological processes
  • Differentiation of process-based and biological effects
  • Replaces expensive tests in a fermenter
  • Culture conditions identical to standard shake flask
  • Virtual non-stop operation thanks to short set-up times and simple handling
  • Ensures optimal screening conditions
  • Fast and specific media optimisation
  • Reduction of the effective test duration
  • Shortened "time to market"

RAMOS® supplies the required information for

  • Bioprocess development
  • Production strain screening
  • Process optimisation
  • Media optimisation
  • Fermentation validation
  • Scale-up


By default, investigations to determine the breathing activity in stirred tank reactors are carried out by separate exhaust gas analysis. Statistically reliable results, however, demand many parallel tests which considerably increase the amount of experimental effort required. By using RAMOS® eight tests may be carried out during the same period in parallel and recorded online, thus making the amount of time and costs only a fraction of that of conventional methods.

Media optimisation is a typical screening application with a correspondingly high number of experiments. Due to the considerable experimental effort in general complete or complex media (e.g. LB medium for E. coli) are used for the cultivation. The heterogeneous composition of complex media often leads to limitations in growth of product formation, as one or more substances are stoichiometrically or simply insufficiently available. Using the combination of RAMOS® with statistical experimental technique (DOE - Design Of Experiments), the influence of each substance on growth and product formation can be determined in a very short time.

Basic biological phenomena can be easily detected with the aid of the measurement curves, examples being:

  • Substrate/oxygen limitation
  • Product inhibition
  • Diauxia
  • Fermentation
  • Overflow metabolism

Key insights were obtained in this way during a number of tested processes, thus giving decisive impetus for many years of development work.

Areas of Application

  • Continuous monitoring of the growth of prokaryotic and eukaryotic
  • cultures including that of mammalian cells
  • Eightfold parallel online measurement of breathing activity under sterile conditions
  • Easy determination of typical characteristics (OTR, CTR, RQ, μ max )
  • Bioprocess optimisation through the early recognition of oxygen and substrate limitation or product inhibition
  • Bioassays (toxicity test, proliferation assay)
  • Determination of suitable operating parameters for primary and secondary screening (media, test duration, operating conditions)
  • Reduction of the development times for media and process optimisation
  • Process balancing and quantification
  • Quality control

Measurement of Oxygen Transfer Rate

The oxygen transfer rate (OTR) is the most suitable and most universally measured variable for the characterization and quantification of the physiological condition and the activity of a culture of aerobic micro-organisms, because almost every metabolic activity is coupled to oxygen consumption.

The online-measurement of the OTR in stirred bioreactors is nowadays state-of-the-art technology but is technically rather ­complex.

The determination of the OTR has, on the other hand, not been possible until now under sterile conditions in shaken bioreactors (shake flasks). RAMOS® fills this gap and combines the advantages of a shake flask (low space requirement, inexpensive, can be parallelized etc.) with those of the stirred bioreactor (online-measurement technology).

Measurement of Carbon Dioxide Transfer Rate

In addition to the OTR, the carbon dioxide transfer rate (CTR) and respiration quotient (RQ) are important sources of information for micro-biologists and cell-biologists.

The CTR (in the case of RAMOS® the "gas development rate") enables the additional use in many cases of RAMOS® for anaerobic and micro­ aerophilic organisms.

Using the RQ permits us to detect, among other things, which type of nutrient source of the microorganisms should be assimilated, for example

  • RQ(Glucose) = 1
  • RQ(triglycerides/lipids) = 0,65

The RAMOS® shake flask system was developed in cooperation with the Faculty for Bioprocess Engineering at the RWTH Aachen. The demand for equivalent culture conditions for microorganisms in regular shake flasks and in RAMOS® flasks was the top priority in the development of the system. For this reason, the volumetric flask was designed in such a way that in the lower liquid-filled section it matches a standard stirred flask in terms of gas and hydrodynamics.

Furthermore, a method was developed which makes it possible to determine the oxygen transfer rate solely from the change in the oxygen partial pressure in the gas section of the volumetric flask (no invasive electrodes). The system is protected by patent.

The gas composition above the culture liquid in the measuring system flasks is set identically to that of a normal flask in order to ensure equivalent culture conditions.

The handling of the system is simple and can be quickly learnt. After only a short time, like numerous users before you, you will not be able to imagine working without RAMOS®.

The RAMOS® system fits on a standard benchtop. It is supplied fully assembled with a shaker, incubator, control PC, USV and software. 

Successful examinations carried out using RAMOS® include those with the following organisms

  • Bacillus sp.
  • Botrytis cinerea
  • Catharanthus roseus
  • CHO Zellen
  • Corynebacterium glutamicum
  • Escherichia coli
  • Nicotiana tabacum
  • Pichia pastoris
  • Pichia stipitis
  • Pseudoalteromonas haloplanctis
  • Pseudomonas fluorescens
  • Pseudomonas putida
  • Saccharomyces cerevisiae
  • Hybridoma Zellen
  • Streptomyces lividans
  • Vibrio natregiens
  • Xanthomonas campestris
  • Arthrospira platensis
  • Wolffia australiana
  • Gluconobacter oxydans
  • Hansenula polymorpha
Incubator dimensions
(D x W x H)
750 x 690 x 490 mm
Weight approx. 66 kg (device without cooling system)
Size of the tray (W x D) 420 x 420 mm
Standard sized volumetric flasks 8 volumetric flasks (250 ml), bracket for 6 additional standard shake flasks (250 ml) for sample taking (reference flasks) or 8 shake flasks (500 ml).
Electrical connections 230 V AC, 3 A, other voltages on request
Gas connections None, air intake from ambient air, optional upstream gas mixer
Resolution Oxygen transfer rate ≤ 0.001 mol/l/h (20 ml culture volume, 10 min measurement time), better resolution at greater volumes and longer measurement time
Error OTR < 5 %
Temperature control A water cooling system is necessary for temperatures under +30 °C (optional) and a cooling unit for under +20 °C
Temperature range Without cooling RT +30 °C to +50 °C, with a water cooling system RT -5 °C to +50 °C on request +4 to +50 °C
Uncertainty T-control ± 0.2 °C
Product code Description
VA-RAMOSOTR RAMOS®-system for OTR measurement with 8 volumetric flasks, without incubator shaker and control PC
VA-RAMOSINKSHA RAMOS® incubator shaker, up to 300 rpm
CG-RAMOSABK OS for the controlling of a RAMOS® system (for equipment cf. CG-ABK2)
VA-RAMOSRPM Increase in the shaker rotation speed up to a max. of 400 rpm including balancing
VA-RAMOSCTR RAMOS® system extension CTR/RQ measurement for 8 volumetric flasks
VA-RAMOSTKSE RAMOS® cooler, P max = 1 bar, T min cooling medium = 2 °C (1, 2)
VA-RAMOSTKSDM Pressure regulator for RAMOS® cooler down to 5 °C below the ambient temperature (with cooling water at 1...5 bar)
VA-RAMOSTKSKA Cooling unit for RAMOS® cooler down to 10 °C below ambient temperature (2)
VA-RAMOST500 Modified tray for 8 x 500 ml volumetric flasks
VA-RAMOSMK250 RAMOS® replacement volumetric flasks 250 ml (without fittings and filters)
VA-RAMOSMKX RAMOS® volumetric flasks, customized production
VA-RAMOSFI1 Replacement sterile diaphragm filters for the O 2 sensors, 8 pcs
VA-RAMOSMTP4 Extension for microtiter plates, special tray with 4 measuring chambers

Please note:

The cooler VA-RAMOSTKSE can be used as follows:
1. For the compensation of an elevated laboratory temperature which is less than 5 degrees below the required incubator temperature. Here it is sufficient to use tap or cooling water as a cooling medium in conjunction with the pressure regulator VA-RAMOSTKSDM. A VA-RAMOSTKSKA cooling thermostat is required if the system is intended to work independently from a water supply system.

2. A cooling thermostat is required for the achievement of incubator temperatures which are up to 10 degrees under the laboratory temperature.

RAMOS®-fb Fed-Batch Extension

The RAMOS® system Fed-Batch Extension enables fully automated fed-batch fermentation in shake flasks or stirred vessels.

More about RAMOS®-fb Fed-Batch System

RAMOS®-cl Light Exposure Expansion

Light energy is a necessary condition for the cultivation of plant cells or general phototrophic organisms (reactions to light and darkness). For this purpose a light module was developed for the RAMOS® which enables an individual light exposure for  each flask.

More about RAMOS®-cl Light Exposure Expansion