Many recent advances in remote optical sensors of O₂, pH, and pCO₂ have been based on luminescence species as the reporter molecule. Both organic probes and, more recently, transition metal complexes are being used on inorganic or organic polymer supports. Polymer supported systems are highly microheterogeneous. However, heterogeneity has an enormous effect on luminescence, quenching, and photochemistry, which has led to considerable difficulty in properly interpreting and correcting sensor behavior. An intimate understanding of the detailed interactions between the complexes and their environment is necessary before the rational design of new high performance sensors and probes can be achieved. Key to such understanding is developing reliable models for the nature of this heterogeneity and its consequences in sensor performance. While several different models for heterogeneity have evolved, it is not widely appreciated that these models are not unique and that proof of such models is extraordinarily difficult. We outline some different models, demonstrate their effect on sensor response, spell out the magnitude of the uniqueness problem, and indicate what types of measurement are necessary to differentiate between models.

A high performance, miniature, dual-channel spectrometer has been design ed for use in spectrocolorimeters. It contains an aberration corrected holographic grating at f/1.6 and two custom photodiode linear arrays (128 channels each) covering the visible spectrum (380 nm to 720 nm). The spectrometer is interfaced with optical fibers and is calibrated separately from the instrument. A wavelength calibration method based on several spectral lines was developed for the spectrometer. The method calculates the bandpass function, the centroid location and the bandwidth at the calibration wavelengths. The dispersion curve is fitted with a parabolic correction for the residuals. The wavelength scale precision and accuracy were measured.

Vibrational optical activity has evolved to a sophisticated level over the past twenty years. For infrared vibrational circular dichroism (VCD), instrumental techniques involving dispersive and Fourier transform spectrometers became well established before the development of satisfactory theoretical methods. In Raman optical activity (ROA), there has been a revolution recently in instrumental techniques and a broadening of the theoretical basis for describing ROA intensities. In this paper we will describe the instrumental basis for the measurement of VCD and ROA and discuss the potential of vibrational optical activity for applications in process analysis.

Recent advances in both imaging spectrometers and CCD based multichannel detection systems have made possible optical process monitoring and control of several sites simultaneously using a single system. Developments in optical monitoring leading to the present state of technology are reviewed. The benefits of these new multisite systems are discussed both in terms of advances in process control they make possible and the cost reduction they represent.

Fiber Optics are a medium for transmitting light. Think of having a garden hose five hundred meters long. When looking through it you are able to see 50% of the light. Now you understand the power of fiber optics. The wide variety of fiber optics presently available has advanced its use for sensing, process control and laser delivery applications. However, there is a strong need to understand fiber optics at the basic level. The focus of this paper will discuss the basics of fiber optics for step-index fibers.

A new HPLC absorbance detector, the Waters Model 996 is described. It covers the spectral range 190 to 800 nm with a nominal resolution of 1.2 nm, equivalent to one diode element. It is based on a deuterium arc source, a 512 element, self-scanned, photodiode array detector and a flat-field, aberration-corrected, concave holographic grating. A design approach is described which establishes the best cell geometry to minimize the concentration limit of detection through fully exploiting the performance potential of the key components. Sensitivity to flow stream artifacts, such as refractive index changes during gradient elution and pump- induced compositional ripple or thermal pulsations, are minimized in the optical design through the use of a 'reversed taper beam'. Source output is stabilized using a separate photodetector. After outlining the original objectives and the restrictions which they place on the design, we describe the optical system. Next we explain the logic behind the design, and end with representative performance data.

Dispersive instruments for the observation of infrared circular dichroism were designed and constructed. Equations governing infrared CD are summarized, and the principles and details of the measurement of this effect are discussed. Results obtained from aqueous solutions of biological molecules are presented, and the conformational sensitivity of the technique is demonstrated.

This paper treats some of the general requirements of optoelectronic instrumentation systems for fiber optic chemical sensors and points out how non-imaging optical elements can be used to meet those requirements. Passive fiber optic chemical sensors, specifically remote spectroscopic absorbance, fluorescence, and Raman systems, are discussed. The operation of non-imaging optics (NIOs) is explained, as are applications of these optical elements in fiber illumination, sample light collection, and filtering subsystems. Optical design detection methodologies are also presented. The above topics are treated in an introductory or 'tutorial' fashion.

Spectroscopic techniques play a key role in the everyday work of the pharmaceutical analyst. In addition to the normal use of the various spectroscopies for simple, routine analyses, a pharmaceutical analytical chemist might use spectroscopy to perform a host of additional functions. These might include, for example, the characterization of a polymorphic substance by either X-ray diffraction or nuclear magnetic resonance spectroscopy, the identification of a foreign material in a tablet dosage form by infrared microspectroscopy, or the selection of a wavelength for liquid chromatographic analysis by photodiode array ultraviolet-visible spectroscopy. The following presentation is meant to acquaint the non-pharmaceutical chemist with some of the ways spectroscopy is utilized in the pharmaceutical analysis research and development laboratory.

The choice of fluorescence as an analytical tool is often based on its intrinsic sensitivity. Compounds can be identified on the basis of their steady-state excitation and emission spectra. Resolution and information can be enhanced by the parameters obtained from time-resolved fluorescence. This includes both the intensity decay (lifetimes) and anisotropy decay parameters. For example, often substances have overlapping steady-state excitation and emission spectra. Thus, they can be difficult to resolve. However, these same compounds will often have different fluorescence lifetimes. This allows resolution by excited-state decay kinetics. By testing various associations of the intensity decay parameters with the excitation and emission parameters, as well as with other experimental variables such as pH, temperature, pressure, viscosity, or interaction with other solutes (such as collisional quenchers), one can obtain substantial information about the physical and chemical nature of the sample. In this way, one may 'finger print' complex mixtures, assess compound purity, and characterize a fluorescent compound.

A colorimeter in general is composed of two parts: (1) A device which records the optical data, and (2) a means of interpreting the acquired optical signal. The most basic (and one of the best) colorimeter is the eye-brain combination; however, the results depend on the observer. In 1931 the Commission Internationale de l'Eclairage (CIE) laid down the color matching properties of a standard observer. These properties enable an unbiased classification of an arbitrary spectral distribution and have become the basis of applied colorimetry since 1931. The colorimeter described herein consists of a spectrograph with a solid state array detector for collecting the data and a computer with software for controlling the detector and interpreting the acquired signal using the CIE standard colorimetric observer.

A new infrared phase modulated ellipsometer (IRPME) is presented here. The polarization phase modulation technique takes advantage of the high frequency modulation (37 kHz) provided by a ZnSe photoelastic modulator. In order to increase the signal to noise ratio, the conventional globar source was superseded by a cascade arc, which emitted intensity corresponds to that of a blackbody at a temperature > 10,000 K. Ellipsometric measurements can be recorded from 700 up to 4000 cm^-1 combining photovoltaic InSb and MCT detectors. A monochromator is used to record spectra, with a 2 - 5 cm^-1 spectral resolution, depending on the wavelength domain. The signal acquisition and data processing is based on the use of a numerical electronic system. The improvements of both optical and electronic parts of the ellipsometer result in increased performances by more than one order of magnitude. The precision on (Psi) and (Delta) is now approximately equals 0.01 deg., achieving a submonolayer sensitivity.

Holographic Optical Components including the Holographic Notch and SuperNotch^TM Filter, Holographic Bandpass Filter and the Holographic Transmission Grating have been developed to meet the needs of Raman spectroscopy applications. Combined as an integrated assembly, these holographic components in conjunction with a laser diode, CCD array or discrete detector and suitable collection and imaging optics form the basis of a new type of compact, robust and cost effective Holographic Raman Sensor suitable for process monitoring and control applications.

Diode laser spectroscopy provides exceptional sensitivity and selectivity for real-time characterization of reacting systems and gas streams. High frequency wavelength modulation techniques achieve species detection limits that are routinely in the ppm range and can reach sub-ppb levels under favorable conditions. Narrow laser linewidths guarantee selective detection of key species even in the presence of myriad other components. Diode laser spectroscopy is also relatively immune from interference by black body radiation or chemiluminescence. Prototype diode-laser based systems have been demonstrated successfully for trace gas detection in turbulent, high temperature particle-laden streams, for oxygen quantitation in flames, for free radical characterization in a plasma etching reactor and for greenhouse gas flux measurements in air. We also discuss the availability of laser wavelengths, compatibility with fiber optics, cost safety and expectations for new laser development.

Recent developments in Raman instrumentation have produced sensitive compact rugged systems capable of monitoring industrial processes in-situ using fiber optic probes. Raman spectroscopy's ability to give definitive molecular information in aqueous and organic matrices makes it exceedingly powerful in monitoring and troubleshooting chemical processing.

Colorimetric performance parameters (repeatability and reproducibility) of a new spectrophotometer/colorimeter manufactured by BYK-Gardner, Inc. are reported. The color- view^TM spectrophotometer (CVS) uses forty-five degree illumination and zero degree viewing geometry relative to the plane of the test specimen. The CVS is designed for the measurement of diffuse reflectance factor. It is designed to conform to national and international recommendations for Spectrophotometry and Colorimetry. Colorimetric performance was evaluated by measuring colored tiles manufactured by the British Ceramic Research Association (BCRA). Instrument repeatability was recorded after an hour, eight hours, and thirty days. Routine performance of the CVS shows that color difference repeatability over short and medium time periods is within 0.15 CIELAB color difference unit. The long term repeatability is within 0.4 unit. Reproducibility was evaluated by making color measurements on BCRA tiles with 54 instruments. Measurements made on CVS instruments indicate that its reproducibility is better than the reproducibility of product standards. Reproducibility is well within the requirement for industrial applications. Actually, the repeatability and reproducibility is comparable to that of reference instruments in national standardizing laboratories.

A compact and high-speed ellipsometer system with a new ellipsometric analyzer has been developed. Its size is 130 X 65 X 25 mm, and the weight 400 g including a light source and analyzers with no moving part. With an automatic x-(theta) stage, it takes only 20 seconds to obtain an area distribution map of a thin film-thickness on a 8-inch wafer at 2 mm pitch of 6,000 points. Its compactness and high-speed might make it widely applicable to various processes.

Product appearance can be a critical component in the determination of final quality assessment. Basic optical measurements are made to determine whether the product color, or gloss attributes meet specified standards. Comparison of product to standard usually occurs at the end of the process. The objective of this paper is to show how and when appearance- measuring devices, used to measure appearance in the steps of a process, can keep process variables in check.

Although color measurement is widely used in quality control, it is not routinely automated. Most color measurement centers on reflectance rather than transmission measurement. To automate color measurement of liquids meant that we had to design a flow-through cell which would give equivalent results to a manual cell. The flowcell shows comparable results to the manual cell regardless of the angle of the observer.

A survey of the industrial process control applications using array spectrometers. Includes discussion of desirable features of an industrial spectrometer system.

Recent advances in the development of calcium-sensitive fluorescent dyes and spectrofluorometry have greatly increased their use in assessing transient changes in free cytosolic calcium during contraction of single isolated cardiac myocytes. The same fluorescent images used for this purpose can be captured using a video frame-grabber for subsequent analysis of the distribution of free calcium within each myocyte, and also provide excellent contrast for edge-detection systems used to track changes in myocyte length during contraction. We have applied these techniques to the study of differences in free calcium concentration and contraction in normal ventricular myocytes and in myocytes obtained from hypertrophied failing hearts. In the process, we have sought to optimize our equipment and procedures to meet specific needs. Progress with cell imaging, signal averaging, and data acquisition and processing is described in the context of our experimental objectives.

An analytical method based on fiber optic near infrared spectroscopy (NIR) and partial least squares data analysis (PLS) was developed to monitor a reaction in which a methyl ester is transesterified with polyethylene glycol 300 (PEG 300) to give the corresponding PEG 300 ester and methanol. A series of multivariant modeling techniques which predict the transesterification reaction end point by monitoring the PEG 300 content were evaluated. The models were developed by making a series of transesterification reactions, collecting grab samples, analyzing them by using the NIR spectrophotometer and liquid chromatography (HPLC) to construct a training and validation set consisting of 50 data points. The models were evaluated in the laboratory setting and the PLS model was used in a pilot plant to predict the reaction end point. Use of the NIR modeling system in the pilot plant led to reduced reaction times and a concomitant rise in product quality. A purged NEMA enclosure was manufactured and was used to house the NIR instrumentation in the pilot plant setting.

Quantitation of benzene in gasoline is becoming important due to new federal and state regulations. To meet these regulations an on-line analysis method for benzene in gasoline is needed. It has been shown that NIR is an ideal instrument for on-line analytical measurements. We report in this paper an analysis of benzene in synthetic gasoline with a standard error of prediction of 0.22 wt%. Both principal component analysis and partial least squares chemometric calibration methods were used. Both methods gave the same results for the prediction of the validation sample set.

Remote spectroscopic sensing in the infrared places tight constraints on measurement system stability and analog signal integrity. The stability of each component of the system needs to be considered, including detectors, electronics, fiber cables, spectrometer, optical components and light sources. A full discussion of the signal-to-noise limit of a fiber remote systems is given. The parameters affecting the ability of the system to be used for long term process sensing are reviewed. Environmental data is presented on the optical throughput stability of infrared fiber optics, fiber-optic cables and sensors with changing temperature. The effect of water and vibration on bare and protected infrared fibers is discussed. The measurement stability of each component of a FT-IR remote fiber-optic system is related to the final measurement stability of the complete system. It is shown that, within certain environmental limits, the signal-to-noise limit of the measurement may be realized with careful system configuration and calibration.

Fiber-optic-based, on-line photometric/spectrophotometric analytic methods are becoming increasingly more important in the process control industries because of unique benefits such as: safety, real-time data capture, immunity to EMI/RFI, and simplicity of installation. End- users employing fiber-optic methods are experiencing increased production yields, less waster, and greater product consistency all because the process can be controlled more efficiently. Extractive and in-situ flow cells have proven to be valuable means of 'looking' at the process stream. These techniques are currently being offered by several manufacturers of on-line fiber-optic photometric/spectrophotometric instruments. Custom Sensors & Technology has developed practical techniques for optical energy transmission in the 250 - 2000 nm wavelength range. In addition to discussing extractive and in-situ methods of sampling, various design considerations are addressed which relate to the efficiency of coupling light energy into and out of extractive flow cells and in-situ probes. In-situ probes can be of the transmission, turbidity, attenuated total reflection, or diffuse reflection types; and can be installed in a sanitary or threaded pipe fitting.

Direct insertion of fiber optic probes into production streams to monitor chemical composition is an attractive concept from a cost and sampling standpoint. Goals including closed loop process control, raw material identification, and waster stream reduction cannot be realized if the fiber optic interface leaks or its signal output deteriorates. A successful long term probe interface must be a rugged and reliable as a conventional process transducer, yet allow normal maintenance activity. The wide variety of materials and environments encountered in production areas forces the designer to integrate technology from diverse fields and to capitalize on combinations which generate reliable results. Viable approaches include spring energized seals and adjustable pathlength in-line transmission cells. Although certain designs may operate effectively for limited periods of time, long term success demands identification and correction of failure modes in prototypes and utilization of construction materials compatible with the temperature, pressure, flow, and corrosion extremes at the sample point. The designs discussed herein can be scaled and modified at minimal additional cost to suit the current application.

Quality control of dyes by traditional means is a time-consuming process not suited for a chemical manufacturing street. Using the spectrometrical data of a liquid dye in conjunction with a trained neural network, the task can be solved on-line and continuously. The basis of the system is explained and discussed.

An important requirement in many industries is the ability to perform on-line monitoring and control of harsh, multi-phase process streams. During the last ten years, significant progress has occurred in the hardware and applications for Fourier Transform Infrared (FT-IR) spectroscopy. Instrumentation is now available which can perform, in harsh environments, continuous unattended and simultaneous measurements of absorbed (or reflected) and emitted radiation. The applications of FT-IR include: (1) concentrations of multiple species and phases (gases, liquid, particles, surfaces) as low as ppb; (2) temperatures of multiple species and phases (gases, liquid, particles, surfaces) with accuracies as good as +/- 1 degree(s)C at any elevated temperature; (3) measurement of particle sizes; (4) measurement of film thickness; (5) in-situ line-of-sight data; (6) in-situ spatially resolved data using tomography; (7) data on extracted samples; and (8) data on time scales as short as a few milliseconds.

The role of on-line chemical analyzers is vital to process monitoring and control and product quality. Although traditional optical filter methods such as UV-VIS, NIR, and IR have enjoyed considerable success when applied on-line, they often require inconvenient and complex sampling schemes. These restrictions can be largely eliminated by fiber optic probes as evidenced by their growing popularity. Fiber optic technology also allows remote location of full spectrum analyzers which in turn facilitates multicomponent analysis. Recently, we have developed a Raman spectrograph which utilizes fiber optic probes and a CCD detector. We have been most successful with this system when it is applied to processes in a short term, investigative role. Examples of reaction intermediates and products, contaminant identification, and process optimization will be given.

Newly commercialized Fourier transform Raman spectroscopic instrumentation provides a simpler alternative for vibrational spectroscopic analysis. Instrument vendors currently design for laboratory use, but there are many potential process applications of these stable, easy to use instruments. Raman spectroscopy is highly suited to analysis of aqueous samples. Near infrared excitation minimized fluorescence interference and allows for remote operation via fiber optic probes. The Department of Energy has funded research at the Measurement and Control Center to establish the utility of this method for on-line composition analysis in distillation columns. Laboratory evaluation and instrument employs an air-cooled laser and a thermoelectrically cooled detector. The device is mounted on a three by three foot cart for convenient location in control rooms. Current fiber optic extension cables allow for analysis in a cell thirty five meters from the instrument. Application of the device to an acid recovery column at Tennessee Eastman Corporation in Kingsport, Tennessee will be discussed. Sensor placement is critical to optimal application of any on-line device. Potential energy savings and product throughput increase will be detailed.

The speed and specificity of Fourier Transform Infrared Spectroscopy (FTIR) affords great advantages in the study of chemical reactions. Reactants, intermediates, and products can be monitored in-situ and in real time, under reaction conditions.

Spectroscopy, in particular mid-infrared spectroscopy, has only recently begun to realize its full potential as a means of monitoring manufacturing processes. Its progress is not only a result of technological improvements, but also a result of the development and application of advanced methods of data processing. Chemometrics, the combination of chemistry and mathematical and statistical techniques, has made it possible to solve problems that would have been considered impossible several years ago. As the field has developed the emphasis has been on the mathematics and statistics, sometimes at the expense of chemistry. The discussion focuses on two topics where an understanding of the problem and the chemistry involved can lead to better, more robust quantitative method. The first is calibration design where several two and three component systems are used as examples to evaluate alternative designs. The second is the choice of quantitative algorithm. Several examples are used to assess the effect of component interactions and the presence of unidentified components on the performance of common quantitative approaches.

We have developed an FT-IR method, using a Spectra-Tech Monit-IR 400 systems, to monitor off-line the completion of a reaction in real-time. The reaction is moisture-sensitive and analysis by more conventional methods (normal-phase HPLC) is difficult to reproduce. The FT-IR method is based on the shift of a diazo band when a conjugated beta-diketone is transformed into a silyl enol ether during the reaction. The reaction mixture is examined directly by IR and does not require sample workup. Data acquisition time is less than one minute. The method has been validated for specificity, precision and accuracy. The results obtained by the FT-IR method for known mixtures and in-process samples compare favorably with those from a normal-phase HPLC method.

The infrared microprobe is a powerful analytical technology for problem-solving in the pharmaceutical industry, providing the problem-solver with a tool for analyzing organic and many inorganic materials at the microscopic level. While the most obvious application of the infrared microprobe is the analysis of contaminants and product defects, SIRM also provides a way of monitoring solid-state forms, states of hydration or solvation, identities of inclusions in crystals, polymorphism, and quantitative analysis of materials. Analyzing and monitoring packaging materials (which are often multi-layered polymer materials) is another major area of SIRM application. The instrumentation and applications for SIRM are presented.

Fourier transform infrared microscopy offers many unique advantages in studying pharmaceutical packaging materials and formulations because of its sensitivity and variety of measurement modes with precise control of the area to the analyzed. This report discusses the application of FTIR microscopy in studying commonly encountered pharmaceutical packaging components such as multi-layer laminate films, disposable syringes and rubber stoppers. The use of the instrument to study pharmaceutical formulation parameters such as polymorphism and component identification is also presented.

An on-line infrared analyzer is being developed for monitoring cephamycin C loading on ion exchange resin. Accurate measurement of product loading offers productivity improvements with direct savings from product loss avoidance, minimized raw material cost, and reduced off-line laboratory testing. Ultrafiltered fermentation broth is fed onto ion exchange columns under conditions which adsorb the product, cephamycin C, to the resin while allowing impurities to pass unretained. Product loading is stopped when the on-line analyzer determines that resin capacity for adsorbing product is nearly exhausted. Infrared spectroscopy has been shown capable of quantifying cephamycin C in the process matrix at concentrations that support process control decisions. Process-to-analyzer interface challenges have been resolved, including sample conditioning requirements. Analyzer requirements have been defined. The sample conditioning station is under design.

In-situ FTIR has been used to monitor reactions occurring in an automated laboratory calorimeter. The study successfully acquired both Arrhenius parameters and heats of reaction from a single experiment. The combination of enhanced control and measurement sensitivity affords an efficient method of reaction monitoring and process development. In addition to providing composition monitoring, the FTIR-based analysis system revealed reaction pathway information. The highly controllable automated laboratory calorimeter accurately and precisely regulated and recorded reaction conditions leading to the estimation of model parameters with high confidence.

Fourier transform infrared spectroscopy (FTIR) is being applied successfully in process development and optimization of bulk chemicals in the pharmaceutical industry. The speed and specificity of FTIR affords great advantages in the study of these chemical processes. Reactants, intermediates, and products can be monitored in-situ and in real time, under reaction conditions.

Near Infrared technology has emerged as a useful tool for in-line polymeric measurements. Anhydrous optical fibers, industrially hardened optical benches, rapid data acquisition systems, chemometrics, and improved sampling hardware have enabled process NIR measurements in real time.