NOVELTY - The method comprises positioning an electrochemical cell in biological system comprising oxygen. The electrochemical cell comprises a substrate comprising a roughened, first face and a roughened, second face, an anode (102) disposed on the first face of the substrate, and a cathode (104) disposed on the second face of the substrate. The anode comprises a crosslinked anode enzyme and a crosslinked mediator. The anode enzyme includes a glucose-responsive enzyme. The glucose-responsive enzyme comprises an enzyme cofactor. The cathode comprises a cathode enzyme.    USE - The method is useful for manufacturing a fuel cell that is useful for operating an electrical device such as pacemaker, nerve growth stimulator, nerve stimulator for relief of chronic pain, stimulator for regrowth of bone or other tissue, drug-release valve or microvalve and fluid-flow control valve including a valve in a duct or in the urinary tract implanted in a plant or an animal.    ADVANTAGE - The method is capable of manufacturing the fuel cell with high output power density and increased resistance to fouling.    DETAILED DESCRIPTION - The method comprises positioning an electrochemical cell in biological system comprising oxygen. The electrochemical cell comprises a substrate comprising a roughened, first face and a roughened, second face, an anode (102) disposed on the first face of the substrate, and a cathode (104) disposed on the second face of the substrate. The anode comprises a crosslinked anode enzyme and a crosslinked mediator. The anode enzyme includes a glucose-responsive enzyme. The glucose-responsive enzyme comprises an enzyme cofactor. The cathode comprises a cathode enzyme. A portion of the electrochemical cell is configured to be subcutaneously positioned in a subject. The electrochemical cell further comprises a mass transport limiting membrane disposed over the anode and cathode. The mass transport limiting membrane is configured to limit contact of macromolecules of greater than or equal to 5000 daltons with the anode and cathode. The mass transport limiting membrane includes a hydrogel. The hydrogel comprises 20 wt.% of fluid when in equilibrium with analyte-containing fluid.    DESCRIPTION OF DRAWING(S) - The figure shows a schematic cross sectional view of a fuel cell.    Anode (102)    Cathode (104)    Anode electrolysis layer (106)    Cathode electrolysis layer (108)    Non-fouling coating. (109)