White Light Spectroscopy for Sampling-Free Bacterial Contamination Detection During CAR T-Cells Production: Towards...

Advanced therapy medicinal products (ATMPs), especially effective against cancer, remain costly due to their reliance on genetically modified T cells. Contamination during production is a major concern, as traditional quality control methods involve samplings, which can themselves introduce contaminants. It is therefore necessary to develop methods for detecting contamination without sampling and, if possible, in real time. In this article, we present a white light spectroscopy method that makes this possible. It is based on shape analysis of the absorption spectrum, which evolves from an approximately Gaussian shape to a shape modified by the 1/λ component of bacterial absorption spectra when contamination develops. A warning value based on this shape descriptor is proposed. It is demonstrated that a few hours are sufficient to detect contamination and trigger an alarm to quickly stop the production. This time-saving should reduce the cost of these new drugs, making them accessible to as many people as possible. This method can be used regardless of the type of contaminants, provided that the shape of their absorption spectrum is sufficiently different from that of pure T cells so that the shape descriptor is efficient.