Currently, the production of Advanced Therapy Medicinal Products is highly sensitive to any contamination sources and therefore takes place in clean and sterile environments. Several days are required for each production, making these products extremely expensive. Throughout the process, numerous quality controls must be performed. This is especially true during the expansion phase in order to monitor cell growth and to detect any contamination. Bioreactor's content must periodically be sampled to perform these controls. Two major drawbacks can be identified: a delayed knowledge of the quality control result and an additional risk of new contaminations due to sampling. In this work, we present optical spectroscopy methods which can be used to drastically reduce the risk of contamination. They provide a real time control of what happens in the bioreactor in a closed system manner. Cell concentrations are measured with an accuracy below 5% and contamination can be detected about 3 hours after it occurred. The real time operation leads to several tens of thousand dollars' savings because it allows stopping the production as soon as a problem arises. Consequently, the price of these products should be greatly reduced and they may be proposed to more patients.

Resonant biosensors are known for their high accuracy and high level of miniaturization. However, their fabrication costs prevent them from being used as disposable sensors and their effective commercial success will depend on their ability to be reused repeatedly. Accordingly, all the parts of the sensor in contact with the fluid need to tolerate the regenerative process which uses different chemicals (H3PO4, H2SO4 based baths) without degrading the characteristics of the sensor. In this paper, we propose a fluidic interface that can meet these requirements, and control the liquid flow uniformity at the surface of the vibrating area. We study different inlet and outlet channel configurations, estimating their performance using numerical simulations based on finite element method (FEM). The interfaces were fabricated using wet chemical etching on Si, which has all the desirable characteristics for a reusable biosensor circuit. Using a glass cover, we could observe the circulation of liquid near the active surface, and by using micro-particle image velocimetry (μPIV) on large surface area we could verify experimentally the effectiveness of the different designs and compare with simulation results.

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