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Artificial lung (AL) systems provide respiratory support to patients with severe lung disease, but none can adapt to the changing respiratory needs of the patients. Precisely, none can automatically adjust carbon dioxide (CO2) removal from the blood in response to changes in patient activity or disease status. Because of this, all current systems limit patient comfort, activity level, and rehabilitation. A portable servoregulation controller that automatically modulates CO2 removal in ALs to meet the real-time metabolic demands of the patient is described. The controller is based on a proportional-integral-derivative (PID) based closed-loop feedback control system that modulates sweep gas (air) flow through the AL to maintain a target exhaust gas CO2 partial pressure (target EGCO2 or tEGCO2). The presented work advances previous research by (1) using gas-side sensing that avoids complications and clotting associated with blood-based sensors, (2) incorporating all components into a portable, battery-powered package, and (3) integrating smart moisture removal from the AL to enable long term operation. The performance of the controller was tested in vitro for ∼12 h with anti-coagulated bovine blood and 5 days with distilled water. In tests with blood, the sweep gas flow was automatically adjusted by the controller rapidly (CO2 level when confronted with changes in inlet blood partial pressure of CO2 (pCO2) levels at various AL blood flows. Overall, the CO2 removal from the AL showed a strong correlation with blood flow rate and blood pCO2 levels. The controller successfully operated continuously for 5 days when tested with water. This study demonstrates an important step toward ambulatory AL systems that automatically modulate CO2 removal as required by lung disease patients, thereby allowing for physiotherapy, comfort, and activity.