Different analytical processes can be used to reach the same conclusions during design, manufacturing, or quality control procedures. However, some methods far outweigh the others in terms of labour, cost, and time savings. Online, inline, offline, and at-line analytical processes each have their own advantages and disadvantages, but compact mass spectrometry kits are revolutionising the way results can be achieved.

Ref: https://metrohm.blog/on-in-at-offline/


Online measurements are conducted via a bypass from the main source of the substance. Measuring devices such as Raman interfaces or compact mass spectrometers like the Microsaic 4500 MiD  or MiD ProteinID are used in the bypass, enabling analysis of the sample outside of the (potentially disruptive) conditions of the main source. Depending on the application, the sample can then be re-introduced, or disposed of appropriately.

      • Ability to analyse samples in isolated conditions
      • Continuous monitoring
      • Observation of short-lived reaction intermediates
      • Cheaper than offline laboratory analysis
      • Logistically simple
      • Can be automated
      • Reduced risk of contamination
      • Set-up potentially complex
      • More time consuming than inline analysis

Unlike offline and at-line processes, online measurement can take place as near to the source as possible, enabling rapid analysis and improved quality control.


Inline, or in-situ, measurements are taken directly in the main source. For example, a measuring device placed directly into a water-carrying pipe or Bioreactor. Analysis is performed in real-time, allowing changes to be observed instantly. Near-infrared (NIR) or UV systems work well inline.

      • Instant analysis
      • Continuous monitoring
      • Cheaper than laboratory analysis
      • Logistically simple
      • Possibility of automation
      • High risk of contamination
      • Disruptive conditions can damage measuring devices
      • Limited information provided by suitable detectors

What inline analysis may introduce a higher risk of contamination but, it makes up for in speed and convenience. Even with the right equipment there are limitations to the amount of information that can be obtained from an inline detector.


Offline measurements typically take place in an external laboratory away from the location of the main source of sample. Testing water for contaminants as well as the monitoring of bioreactors is typically achieved in this format, however miniaturised mass spectrometers can now deliver real-time analysis and monitoring, as seen in Microsaic’s partnership with EcoWaterOS and the introduction of the MiD ProteinID.

      • Increased range of equipment available
      • Useful for measuring accuracy of online or inline measuring devices
      • Time-consuming
      • Logistically complex
      • Often costly
      • Continual monitoring not possible
      • Requires sterile transportation of samples
      • Incorrect handling of samples can reduce analysis accuracy.

Unlike any other analytical process, offline measurement is entirely separate from the source. Other common use cases are in manufacturing or food production, when substances from suppliers are analysed for compliance to ISO and FSA standards.


At-line is similar to offline analysis, although sample analysis generally takes place using a detector close to the main source, rather than being transported to one further away. While it doesn’t offer the same automation as inline and online analysis, this can be a much better alternative to offline methods.

      • Less time delay than offline analysis
      • Ability to analyse samples in isolated conditions
      • Cheaper and easier to use solutions available
      • Less automated than online or inline analysis
      • Labour intensive
      • Increased risk of contamination

While the convenience of working on-site cannot be ignored, introducing compact PAT instrumentation can reduce labour and laboratory costs, and improve productivity.

Increasing convenience and reducing costs in all sectors

Real or near-time analysis is vital for online and inline applications, but with advances in mini mass spectrometry, instantaneous results can be achieved no matter what setup is used. As the costs, size, and accessibility of mass spectrometry improves, so too will design, manufacturing, and quality control processes.

To learn more about our point-of-need technology for PAT in Bioprocessing please join us at IFPAC in Washington DC from 11th-15th June. We will be presenting our recent work on the continuous monitoring of cell cultures CQAs and CPPs.

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