Hollow Fiber Microreactor Combined with Digital Twin to Optimize the Antimicrobial Evaluation Process

Abstract

In order to reproduce pharmacokinetics (PK) profiles seen in vivo, the Hollow Fiber Infection Model (HFIM) is a useful in vitro module in the evaluation of antimicrobial resistance. In order to reduce the consumption of culture medium and drugs, we developed a hollow fiber microreactor applicable to the HFIM by integrating the HFIM function. Next, we constructed a novel control method by using the “digital twin” of the microreactor to achieve precise concentration control. By integrating functions of the HFIM, the extra-capillary space volume was reduced to less than 1/10 of conventional HFIM. The control method with the digital twin can keep drug concentration in the extra-capillary space within an error of 10% under simulated drug destruction. The control method with the digital twin can also stabilize the drug concentration both in the intra-capillary space and the extra-capillary space within 15 min.