Optical Sensors for Blood Analytes (2001)

membrane (such as PVC) that separates an aqueous sample containing the primary ion from an aqueous-based internal electrolyte. The membrane contains an ionophore that acts as a selective ion transporter or carrier and a lipophilic salt that acts as a charge exchanger. Changes in activity (concentration) of the primary ion in the sample solution result in, ideally, Nernstian changes in the potential at the surface of the membrane. Advantages of ISE’s over other sensors include high selectivity which is imparted by the ionophore and the other membrane components and, since the response to the primary ion is a change in surface potential, very rapid response. However, fabrication of ISE’s is problematic due to the need for compatibility between ionophore, membrane and the other components and in the final application, e.g., diagnostic instruments for blood analysis, ISE’s require continual calibration and utilize expensive electronics. There is now a concerted industry effort to develop instrumentation, particularly for clinical applications, that is based on bulk optical sensors or bulk optodes. 2 In these systems, an ionophore and a chromophore are deposited in a bulk polymer membrane and the interaction between these two components provides an optical signal upon complexation. Sensing relies on diffusion of the ion through the bulk polymer to the ionophore followed by chromophore response to complexation. While bulk optodes suffer from slower response times due to diffusion, their use can decrease both the chemical complexity of the sensor and the electronic complexity of the final sensing instrument. Also, unlike ISE’s, bulk optodes are not limited to a single physical configuration or shape, but rather can be tailored for specific applications or instrument designs. Arguably, the most important component of either ISE’s or bulk optodes is the ionophore or ion complexation site, since it is this structure that to a large degree imparts the sensitivity and selectivity to the eventual sensor. In bulk optode sensors an additional component is required (the chromophore) to provide the optical signal for ion complexation. For the detection of cationic analytes, a wide variety of neutral or charged ionophores coupled with charged or neutral chromophores have been investigated. The operation of these systems depends on maintaining bulk neutrality or balance of charge in the bulk and this is usually achieved by the migration of protons into and out of the membrane in response to the movement of the primary ion. It is this protonation/deprotonation equilibrium that also often provides the optical response for ion complexation. For example, extraction of a cation from solution into the ionophoric site in the membrane will result in deprotonation of a chromophore in the membrane and in the process change its absorption, fluorescence or some other optical characteristic. One drawback of such a mechanism, however, is that sensors fabricated from such systems are obviously sensitive to pH in addition to the primary ion and measurements must be adjusted for changes in pH from sample to sample. Another approach is the incorporation