title: Micro sequential injection system as the interfacing device for process analytical applications.
abstract: It is an important and desirable capability to be able to control the quality and quantity of biological product by maintaining and adjusting bioreactor performance throughout its production duration. Amino acids are the building blocks of proteins. Scientists will need to ensure sufficient supply of amino acids as the substrates in the bioreactors as well as to control the excess level of undesirable free amino acid byproducts to maintain an optimum growth environment for cell culture. We have developed a compact and robust sample preparation platform capable of interfacing with analytical instruments to achieve bioreactor amino acids monitoring. We demonstrated the feasibility of this concept by incorporating an automatic amino acid sample preparation protocol to a micro sequential injection (μSI) system connected to an ultra-performance liquid chromatography system for real-time, at-line amino acid separation, and quantitation. The μSI system was configured into a "platform-like" sample preparation system that is able to accommodate future wet chemistry-type sample preparations. Its real-time amino acid results can be readily available to bioprocess scientists for quick decision making and design of their next experiment. Potential automatic feedback control mechanisms can be established through trigger events based on predetermined analytical signal thresholds so the system can communicate with facility infrastructure to control bioreactors in near real-time fashion. The proposed μSI system described in this paper can be widely used as an automatic sample preparation system connected to the front-end of analytical instruments to enable process analytical technology applications.
authors: Analytical Core Services, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320.
authors: Chao-Hsiang Richard
authors: CH
authors: Wu
authors: Siowfong
authors: S
authors: Wee
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design; D005246:Feedback; D055616:Microtechnology / Q000295:instrumentation*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D011994:Recombinant Proteins
keywords: amino acids; at-line real-time monitoring; bioreactor monitoring; mammalian cell culture; micro sequential injection; therapeutic antibodies