Towards improved artificial lungs through biocatalysis

Abstract

Inefficient CO 2 removal due to limited diffusion represents a significant barrier in the development of artificial lungs and respiratory assist devices, which use hollow fiber membranes as the blood-gas interface and can require large blood-contacting membrane area. To offset the underlying diffusional challenge, "bioactive" hollow fiber membranes that facilitate CO 2 diffusion were prepared via covalent immobilization of carbonic anhydrase, an enzyme which catalyzes the conversion of bicarbonate in blood to CO 2 , onto the surface of plasma-modified conventional hollow fiber membranes. This study examines the impact of enzyme attachment on the diffusional properties and the rate of CO 2 removal of the bioactive membranes. Plasma deposition of surface reactive hydroxyls, to which carbonic anhydrase could be attached, did not change gas permeance of the hollow fiber membranes or generate membrane defects, as determined by scanning electron microscopy, when low plasma discharge power and short exposure times were employed. Cyanogen bromide activation of the surface hydroxyls and subsequent modification with carbonic anhydrase resulted in near monolayer enzyme coverage (88 %) on the membrane. The effect of increased plasma discharge power and exposure time on enzyme loading was negligible while gas permeance studies showed enzyme attachment did not impede CO 2 or O 2 diffusion. Furthermore, when employed in a model respiratory assist device, the bioactive membranes improved CO 2 removal rates by as much as 75 % from physiological bicarbonate solutions with no enzyme leaching. These results demonstrate the potential of bioactive hollow fiber membranes with immobilized carbonic anhydrase to enhance CO 2 exchange in respiratory devices.

A Mathematical Model to Predict CO2 Removal in Hollow Fiber Membrane Oxygenators

“…Another application of the model may be to investigate increasing the facilitated diffusivity by chemically binding carbonic anhydrase to the hollow fiber membranes. 15,18,21 The facilitated diffusivity could be adjusted in the model to estimate the enhanced CO 2 removal depending on the amount of enzyme that can be successfully added to the fibers.…”

A novel technique for the precise measurement of CO2 production rate in small aquatic organisms as validated on Aeshnid dragonfly nymphs

“…S5) arranged in parallel and fitted into a 1/8 inch acrylic tube, similar to previous designs (Kaar et al, 2007;Arazawa et al, 2012). The volume surrounding the fibres (0.6 ml) was perfused with water coming from the measuring chamber that was circulated in a closed loop by a peristaltic pump (Gilson MINIPULS 3, Middleton, WI, USA).…”

“…Water was circulated in a closed loop indicated by the blue arrows, and CO 2 -free purge-gas is represented by the dashed arrows. The interface between water and air was a hollow fibre membrane (HFM) gas exchanger, in which water was circulated on the outside of a bundle of gas permeable fibres and CO 2 -free purge-gas was circulated through the lumen of the fibres in a counter-current fashion, similar to previous designs (Kaar et al, 2007;Arazawa et al, 2012). See Materials and methods, Experimental setup for specifications of system components.…”

Extracorporeal Carbon Dioxide Removal: The Future of Lung Support Lies in the History

“…Among these, attempts to generate active mixing in the catheter include placement of an intra-aortic balloon pump in the vicinity of hollow fibers or rotation of the fiber bundle (dynamic intravascular lung assist devices) or positioning impellers to generate mixing [60,61]. In addition, biocatalysis achieved by immobilization of carbonic anhydrase on the surface of the fibers increases CO 2 liberation from bicarbonate and consequently may further promote increased CO 2 elimination by as much as 75% [62]. …”