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

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.