Intact cell MALDI mass spectrometry biotyping for "at-line" monitoring of apoptosis progression in CHO cell cultures

Background Mammalian cell cultures, especially Chinese Hamster Ovary (CHO), are the predominant host for the production of biologics. Despite considerable progress in industry and academia alike (also enforced e.g. by the Process Analytical Technology Initiative of the FDA), particularly in the field of process monitoring there is still a need for innovative methods enabling improvement of process monitoring. For optimized process control it would be imperative to know as early as possible “when a cell needs what”, when it is stressed, running into substrate limitations etc., at best in an online or robust at line format. Intact cell MALDI mass spectrometry (ICM-MS) biotyping, a method used successfully in the field of clinical and environmental microbiology, is getting more attention in the context of mammalian cell cultivation. Here we report preliminary results of an assessment of a fast and high throughput at line capable ICM MS method for cell culture monitoring. As a first example, we choose apoptosis monitoring. The identification of specific mass spectrometric signatures related to early stages of apoptosis using ICMMS biotyping as reported here could be a promising tool for CHO culture.