APPLICATIONS

Monitor culture media conditions in upstream processing

Detect changing media conditions that may affect protein expression, production yield and culture metabolic balance

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Inconsistent upstream conditions can contribute to bioreactor underperformance, batch loss and increased manufacturing risk.

CLADE™ analytical tools support at-line monitoring of culture media components, helping teams identify nutrient depletion and metabolite accumulation during upstream bioprocessing.

At-line monitoring of culture media conditions

CLADE™ advanced mid-IR spectroscopy and chemometric data processing deliver rapid end-point information on sample composition. This supports monitoring of nutrients such as glucose, metabolites such as lactate and other media components over time with minimal user effort.

Culture media control

Detect depletion of media components or accumulation of undesired metabolites over time.

At-line monitoring, with results in 4 minutes

Obtain upstream process sample results in minutes using the CLADE™ MIRA Analyzer.

Multi-attribute data from a single measurement

Monitor protein concentration, nutrients and metabolites in one go.

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Proprietary algorithms for rapid and easy data evaluation

For media monitoring where the API or target protein is not present, CLADE’s Data-Driven algorithm can reduce calibration effort by using digital twins of individual substances stored in the spectral database SpecHub™.

For upstream samples that include the expressed protein, QA Scan can be used given a calibration has been performed. In the current workflow, it requires a single calibration procedure with two reference samples.

Use CLADE™ data-driven insights to reduce manual evaluation effort and help identify process risks earlier.

Use case: Monitor protein expression and culture media after induction

Suboptimal or inconsistent upstream conditions can affect protein expression and metabolic balance, resulting in lower production yield.

In this example, culture samples taken before induction (T0) and after induction of protein expression (T1-T3) were run on the CLADE™ MIRA Analyzer. The resulting spectra show how the chemical fingerprint changes as concentrations of protein, glucose, lactate, amino acids and other components change during culture growth.

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Upstream Processing Figure 1

Figure 1. Overlaid spectra of culture samples analysed at four time points using the CLADE™ MIRA Analyzer.

In this example, the protein signal is highest at T3, visible as increased absorbance in the Amide I/II region (1450-1700 cm⁻¹).

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Seamless evaluation of spectral data with QA Scan

CLADE™ QA Scan runs in CLADE™ Sphere and transforms mid-IR FTIR spectra from the MIRA Analyzer into end-point results for selected quality attributes, once an appropriate method or model has been configured.

The QA Scan output presents predicted values for selected components and attributes in a table format.

In Figure 2, the QA Scan output reports selected media components from an induced culture sampled before and after induction of protein expression.

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AttributeT_0T_1T_2T_3
Protein Concentration [mg/ml]0Gene
expression
induced
0222
Glucose [mg/ml]5.70.10.20.4
Lactate [mg/ml]0.0100.030.02
Asparagine [mg/ml]00.50.81.4
Isoleucing [mg/ml]00.10.50.9
Glutamine [mg/ml]0.20.50.71
Citric Acid [mg/ml]1.81.70.81.3
Ammonia [mg/ml]1.21.41.21.4
Phosphoric Acid [mg/ml]10851

Figure 2. CLADE™ QA Scan end-point output table presenting predicted values for the sample components and attributes tested.

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