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              Membranes, Synthetic, Applications                                                          341

              in Fig. 52. The enzyme glucose oxidase is immobilized  fuses into the membrane, where it is converted gluconic
              within a crosslinked polymer containing amine functional  acid. Dissociation of the acid protonates the tertiary amine
              groups. The polymer is normally impermeable to insulin  groups on the polymer network, and causes it to swell
              (M.W. = 6000) but permeable to the much smaller glu-  and become more permeable to insulin, which is released
              cose molecules (M.W. = 180). Glucose from the body dif-  into the bloodstream. When the glucose level drops, the
                                                                enzymatic reaction subsides, and the membrane network
                                                                contracts to stop passage of insulin. In this case the syn-
                                                                thetic membrane closely mimics the complex functional
                                                                response of a biological membrane. The implications of
                                                                this development go beyond the obvious application to the
                                                                treatment of diabetes. The same principle of using bio-
                                                                chemical signals to modulate membrane permeability can
                                                                be applied to the design of other self-regulating sensors
                                                                and control systems.


                                                                VIII. MEMBRANE SENSORS

                                                                Two attributes of synthetic membranes are often applied to
                                                                the design of analytical devices: as a selective barrier, and
                                                                as a substrate in which chemical or biochemical reactions
                                                                are performed. In many cases, the membrane helps trans-
                                                                late the activity of specific analytes into easily measurable
                                                                quantitiessuchaselectricalpotentialsorspectrophotomet-
                                                                ric absorption.
                                                                  Membrane-based analytical devices that generate elec-
                                                                trical responses (current or potential) are referred to as
                                                                membrane electrodes. The most common membrane elec-
                                                                trodes are the ion-selective electrodes (ISE) used for mea-
                                                                suring the activity of ions in solution. A typical ISE con-
                                                                sists of a reference electrode surrounded by a standard
                                                                electrolyte solution; an ion-specific membrane separates
                                                                this “internal solution” from the solution to be analyzed.
                                                                Only ions to which the membrane is permeable can reach
                                                                the internal solution to alter the electrochemical balance
                                                                to generate a signal. The pH electrode is an ISE in which
                                                                the membrane is a proton-permeable glass. To measure
                                                                other ions, various membrane materials are designed to
                                                                provide permeation pathways for the analyte ions. These
                                                                include single crystals of insoluble inorganic salts, ion-
                                                                exchange resins dispersed in inert matrices, polymeric
                                                                ion-exchange membranes, homogeneous polymer films
                                                                (sometimesswollenwithasolvent),andliquidmembranes
                                                                containing carriers or complexing agents. All of these de-
                                                                vices make use of the membrane as a selective barrier, and
                                                                are referred to as primary electrodes.
                                                                  A sensitized electrode is a composite device that com-
                                                                bines a membrane reactor and a primary electrode. The
              FIGURE 52 A glucose-sensitive membrane with controllable per-  membrane reactor converts a specific analyte into prod-
              meability to insulin. (Key: GluOx, glucose oxidase; I, insulin; G,  ucts that are measurable by the primary electrode. Mem-
              glucose;—COOH, gluconic acid; and —NR 2 , tertiary amine func-
              tional group in the membrane matrix.) [From Horbett et al. (1984).  brane reactors containing immobilized enzymes, cells, or
              In “Recent Advances in Drug Delivery Systems” (J. M. Anderson  neutral carriers are capable of very selective conversion
              and S. W. Kim, eds.), Plenum, New York.]          of sugars, amino acids, organic acids, and alcohols, and
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