In-line acoustic particle manipulation enhances PAT in bioprocesses

Process analytical technology (PAT) is central to modern bioprocess control, but many in-line measurements struggle when key analytes are present in complex media, which can be heterogeneous and thus obstruct precise analysis by e.g. high turbidity (e.g., cells, debris, gas bubbles). This can reduce sensitivity, increase drift, and force reliance on at-/off-line sampling, limiting real-time decision-making. A generic, gentle, and sterile-compatible way to condition the sample directly in the flow would strengthen inline analytics across upstream and downstream operations.
We present an in-line concept based on acoustic particle manipulation, where an externally driven ultrasonic field selectively translates and concentrates suspended constituents via acoustic radiation forces. By shaping the local particle distribution—enriching targets, clearing the optical path, or stabilizing the measurement volume—acoustics acts as a “front-end” to enhance existing PAT sensors such as optical spectroscopy, scattering and microscopy. This enables improved signal-to-noise and selectivity e.g. the in-line determination of intracellularly enriched products (PHB in cyanobacteria) [1].
Furthermore, the acoustic add-ons can be used to facilitate clean surfaces throughout the process, enhancing the robustness of in-line measurements and ensuring precise data streams from challenging
Overall, in-line acoustic manipulation provides a versatile physical preconditioning step that broadens the operating window of PAT and supports more reliable, real-time monitoring and control in bioprocesses.

Literature:
[1] Doppler, P. et al. Bioengineering 2021, 8 (9), 129.