Karen S. Bronk

Simultaneous monitoring of pH, CO2 and O2 using an optical imaging fiber

The interdependence of pH, CO2 and O2 during chemical and biochemical processes has driven the need to monitor them simultaneously, continuously and in situ, in order to exert better control over such reactions. We present the fabrication and performance of a multi-analyte imaging fiber sensor that allows pH, CO2 and O2 to be monitored simultaneously with rapid response. Sensing elements are fabricated by covalently immobilizing fluorescent indicators within polymer matrices via photopolymerization, resulting in the formation of distinct regions of analyte-sensitive polymer at the fibers distal end. The multianalyte sensors working range is 0%–100% for O2 and 0%–10% for CO2 in the pH range 5.5–7.5. The sensor was used to monitor the pH, CO2 and O2 changes during a beer fermentation.

API Quality by Design Example from the Torcetrapib Manufacturing Process

The concept and application of quality by design (QbD) principles has been and will undoubtedly continue to be an evolving topic in the pharmaceutical industry. However, there are few and limited examples that demonstrate the actual practice of incorporating QbD assessments, especially for active pharmaceutical ingredients (API) manufacturing processes described in regulatory submissions. We recognize there are some inherent and fundamental differences in developing QbD approaches for drug substance (or API) vs drug product manufacturing processes. In particular, the development of relevant process understanding for API manufacturing is somewhat challenging relative to criteria outlined in ICH Q8 (http://www.ich.org/cache/compo/276–254–1.html) guidelines, which are primarily oriented toward application of QbD for drug product manufacturing. This position paper provides a perspective of QbD application for API manufacture using an example from the torcetrapib API manufacturing process. The work includes a risk assessment, examples of multivariate design, and a proposed criticality assessment, all of which coalesce into an example of design space. Torcetrapib was a project in phase III development as a potent and selective inhibitor of cholesteryl ester transfer protein before being terminated in late 2006. The intent of Pfizer was to submit torcetrapib under the QbD paradigm (route selection, robustness, and reagent/solvent selection during phases I to III are significantly important in establishing a manufacturing process that would have the most flexibility in the final design space. For more information on this development phase for torcetrapib see Damon et al., Org Process Res Dev, 10(3):464–71, 2006, Org Process Res Dev, 10(3):472–80, 2006).

Concurrent imaging and sensing using a single optical imaging fiber

A sensor capable of simultaneous imaging and pH measurements has been prepared by coating the distal tip of a single imaging fiber with a pH sensitive material. The coated fiber is fabricated using photochemical polymerization with a spin coating technique and results in a fairly uniform coating of polyHEMA/fluorescein on the order of 5 micrometers thick. Performance data and imaging capabilities, as well as instrumentation requirements and deposition chemistry, will be discussed. Progress towards the fabrication of enzyme based biosensors utilizing this technique will also be presented.

Spatially resolved photopolymerized image-ready single-fiber sensor for blood gas analysis

Multiparameter sensors are fabricated by combining the optical pathways of imaging fibers with the spatial discrimination of CCD video cameras. Distinct sensing regions are placed on the distal face of an imaging fiber through site selective illumination of discrete regions of the fiber. Photopolymerization and detection systems are described.

Optical microsensor arrays

Fiber optic imaging bundles are comprised of thousands of individual fibers melted and drawn together in a coherent manner. Sensor arrays are fabricated by combining the optical pathways of imaging fibers with the spatial discrimination of CCD video cameras.

Simultaneous imaging and pH measurments with a single fiber optic imaging bundle

The distal tip of a 350-micrometers imaging fiber comprised of thousands of 4- to 6-micrometers fibers is coated with a thin layer of pH sensitive material. Polymerization is initiated photochemically and is combined with spin coating techniques to yield a uniform coating of polyHEMA/fluorescein on the order of 10 micrometers thick. Performance data for this fiber demonstrates it is capable of simultaneous pH measurements and near-field imaging.

Development of sensor arrays using fiber optic imaging bundles

A sensor capable of simultaneous imaging and pH measurements has been prepared by coating the distal tip of a single imaging fiber with a pH sensitive material. The coated fiber is fabricated using photochemical polymerization with a spin coating technique, and results in a fairly uniform coating of polyHEMA/fluorescein on the order of 10 micrometers thick. Performance data, and imaging capabilities, as well as instrumentation requirements and deposition chemistry, are discussed.

Simultaneous imaging and pH measurement with a single 250-micron-diameter optical fiber

The distal tip of a 200 micrometers imaging fiber comprised of thousands of 2 micrometers fibers is coated with a thin layer of pH sensitive material. Polymerization is initiated thermally, and results in a uniform coating of polyHEMA/fluorescein on the order of 10 micrometers thick. Performance data for this fiber demonstrates it is capable of simultaneous pH measurements and near field imaging.

Microfabrication of optical sensor array

Arrays of selective sensing regions are photopolymerized on the distal tip of a single imaging fiber. Important considerations for preparing sensors include surface modification for polymer adhesion, monomer preparation, micropositioning, polymerization kinetics, and instrument response. Using the technique described in this paper, we have prepared optical sensor arrays of upwards of eight discrete sensors all disposed on a single optical fiber.