New oxygen-sensitive luminescent materials were obtained by physically immobilizing luminescent ruthenium(11) diimine complexes in silicone rubber. The dyes were made silicone-soluble by converting them into the respective ion pairs with organic anions. Acetic acid-releasing one-component RTV silicones were found to provide the best matrix for sensor membranes. The dyed silicone prepolymers were spread onto planar solid supports, cured, and characterized in terms of quenching by oxygen, response time, interferences, storage stability, and photostability. Strong evidence is presented from quenching experiments that the luminescent ion pairs are present in both a monomolecular and an aggregated form, the respective quenching constants being highly different. This results in nonlinear Stern-Volmer graphs. The new oxygen-sensitive materials are considered to present a major improvement over existing sensor materials in terms of response time, luminescence intensity, and long-term stability. They not only may be applied as planar films but also as very thin coatings on various kinds of waveguides. We also describe several novel materials for use as light-tight optical isolations. They are spread onto the oxygen-sensitive films in order to minimize interferences by (a) ambient light and (b) potentially interfering sample properties such as color, turbidity, fluorescence, and varying refractive index.

Oxygen-Sensitive Luminescent Materials Based on Silicone-Soluble Ruthenium Diimine Complexes

FIBER-OPTIC PHYSIOLOGICAL PROBES Abstract Fiber-optic sensors suitable for monitoring physiological analyte concentration. An analyte-permeable matrix is disposed in the light path definedby the axial core at one end of an optical fiber segment. The matrix contains anindicator molecule covalently linked to a polymer, preferably methyl methacrylate/methacrylamidopropyltrimethylammonium chloride, N-vinyl-pyrrolidone/p-aminostyrene, methyl methacrylate/hydroxymethyl methacrylate, methyl methacrylate/N-vinylpyrrolidone, or methyl methacrylate/acrylic acid. In representative embodiments, the polymer is approximately 94:6 mole/mole percent of either methyl methacrylate/methacrylamidopropyltrimethylammonium chloride or N-vinylpyrrolidone/p-aminostyrene copolymer. Drift-free performance is obtained with such sensors having analyte-permeable matrices of significantly less than about 70 microns in thickness. The indicator molecule may be covalently linked to the polymer through an aminoarylalkylamine, such as 4-(aminophenyl)-ethylamine or 4-(aminophenyl)-propylamine. The indicator molecule may be an absorptive molecule, such as phenol red or carboxynaphthophthalein (hydrogen ion analyte), in which case the indicator molecule may be covalently linked to the polymer through either an azo-amide or an amidyl-amide linkage. The indicator molecule may be a luminescent molecule, such as carboxynaphthofluorescein (hydrogen ion analyte) or an oxygen-quenchableporphyrin derivative. The sensor may have a reflector disposed in the light pathdistal with respect to the optical fiber segment to the analyte-permeable matrix. Suitable reflectors include gold foil or films of titanium dioxide, zinc oxide, or barium sulfate. A pCO2 sensor is configured with a gas-permeable but ion-impermeable membrane encapsulating an analyte-permeable matrix that includes a base having a pKa ranging from about 6.0 to about 7.8. The outer membrane may be a silicone, polycarbonate, or urethane. The base may be an inorganic salt, such as bicarbonate, in which case the analyte-permeable matrix should include an antioxidant. Alternatively, the base may be a polymeric base containing, e.g., 2-vinylpyridine, 4-vinylpyridine, histamine, 1-vinylimidazole, or 4-vinylimadazole. Gas-permeability is afforded to the matrix by a minor component of hydrophilic polymer such as polyethylene glycol. A plurality of thepH, pO2, and PCO2 sensors may be disposed together in substantially coterminal array to make a multi-variable probe, which may also include a thermocouple wire.

Fiber-optic physiological probes

This is the first comprehensive review on methods and materials for use in optical sensing of pH values and on applications of such sensors. The Review starts with an introduction that contains subsections on the definition of the pH value, a brief look back on optical methods for sensing of pH, on the effects of ionic strength on pH values and pKa values, on the selectivity, sensitivity, precision, dynamic ranges, and temperature dependence of such sensors. Commonly used optical sensing schemes are covered in a next main chapter, with subsections on methods based on absorptiometry, reflectometry, luminescence, refractive index, surface plasmon resonance, photonic crystals, turbidity, mechanical displacement, interferometry, and solvatochromism. This is followed by sections on absorptiometric and luminescent molecular probes for use pH in sensors. Further large sections cover polymeric hosts and supports, and methods for immobilization of indicator dyes. Further and more specific sections summarize the state of the art in materials with dual functionality (indicator and host), nanomaterials, sensors based on upconversion and 2-photon absorption, multiparameter sensors, imaging, and sensors for extreme pH values. A chapter on the many sensing formats has subsections on planar, fiber optic, evanescent wave, refractive index, surface plasmon resonance and holography based sensor designs, and on distributed sensing. Another section summarizes selected applications in areas, such as medicine, biology, oceanography, bioprocess monitoring, corrosion studies, on the use of pH sensors as transducers in biosensors and chemical sensors, and their integration into flow-injection analyzers, microfluidic devices, and lab-on-a-chip systems. An extra section is devoted to current challenges, with subsections on challenges of general nature and those of specific nature. A concluding section gives an outlook on potential future trends and perspectives.

Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications

A parameter of blood is sensed in vivo with a system which includes a catheter and a probe. The catheter has a lumen extending therethrough, a proximal end, a distal end and a distal opening at the distal end. The probe includes one or more sensors at its distal end. A saline solution is introduced into the lumen so that there is an interface adjacent the distal opening of the catheter between the blood and saline solution. The probe is received within the catheter and affixed thereto. The interface is moved back and forth in the lumen to expose the sensors to blood so that they can sense the blood parameters of interest.

Intravascular blood parameter measurement system

A fiber optic sensor suitable for measuring and monitoring fluid parameters, e.g. blood parameters such as carbon dioxide and oxygen partial pressure and hydrogen ion concentration ( pH ). Analyte sensitive chemistry in such probes includes molecules sensitive to responding to an analyte change in an optically detectable system. Methods of making analyte measuring chemistries including disposing an indicator complex in the path of light and casting over it films of permeable / semi- permeable polymer membranes capable of diffusion of gases and other analytes. A liquid control validation solution ) acts as a simulating standard for blood gas analysis. Liquid calibration solutions which mimic fluids such as blood to validate and test sensors for long term stability.

Fiber-optic probe for the measurement of fluid parameters

Optical fluorescence has an extensive history of application in the laboratory to the measurement of ionic concentrations and the partial pressures of oxygen and carbon dioxide. The use of optical fluorescence based sensors to fulfill a recognized need for continuous invasive monitoring of arterial blood gases offers a number of inherent advantages. However, the requirements placed upon a blood gas probe and supporting instrumentation appropriate for use in the clinical environment result in significant design challenges in selection of suitable fluorescent dyes, maintenance of mechanical integrity while obtaining required miniaturization of sensors, and in the transmission, acquisition, and processing of low level light signals. An optical fluorescence based intravascular blood gas monitoring system has been developed which is particularly suited for the critical care and surgical settings and which has a sensor probe that can be introduced into the patient via a radial artery catheter. This system has shown an excellent agreement of measured with true values of pH, pCO2, and P02 in both in vitro and animal studies. Linear regression analysis of typical in vitro data, where true levels were established via tonometry and standardization to a high accuracy laboratory pH measuring instrument, shows slope/intercept values very close to 1.0/0.0 and correlation coefficients of greater than 0.99 for all three parameters.

Optical Fluorescence and Its Application to an Intravascular Blood Gas Monitoring System

In vitro and in vivo animal studies have shown accurate measurements of arterial blood pH (pHa), carbon dioxide tension (PaCO2), and oxygen tension (PaO2) with small intravascular fluorescent probes. Initial human clinical studies showed unexplained intermittent large drops in sensor oxygen tension (PiO2). Normal volunteers were studied to elucidate this problem. In the first part of this study, the probe and cannula were manipulated and the probe configuration and its position within the cannula were varied. The decreases in PiO2 were judged to be primarily due to the sensor touching the arterial wall. Retraction of the sensor tip within the cannula eliminated the problem. In the second part of this study, the accuracy of the retracted probe was evaluated in 4 subjects who breathed varying fractions of inspired oxygen and carbon dioxide. The arterial ranges achieved were 7.20 to 7.59 for pH, 22 to 70 mm Hg for PaCO2, and 46 to 633 mm Hg for PaO2. Linear regression of 48 paired sensor (i) versus arterial values showed pHi = 0.896 pHa + 0.773 (r = 0.98, SEE = 0.017); PiCO2 = 1.05 PaCO2-1.33 (r = 0.98, SEE = 2.4 mm Hg); and PiO2 = 1.09 PaO2-20.6 (r = 0.99, SEE = 21.2 mm Hg). Bias (defined as the mean differences between sensor and arterial values) and precision (SD of differences) were, respectively, -0.003 and 0.02 tor pHi, 0.77 and 2.44 mm Hg for PiCO2, and -2.9 and 25.4 mm Hg for PiO2. The mean in vivo 90% response times for step changes in inspired gas were 2.64, 3.88, and 2.60 minutes, respectively, for pHi, PiCO2, and PiO2.

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Progress in the development of a fluorescent intravascular blood gas system in man

Continuous In Vivo Monitoring of Blood Gases

Blood pH measurements present unique challenges due to the lack of a method to determine accuracy. Therefore an operational pH scale has been defined with the use of accepted pH standard buffer solutions in order to achieve precision and consistency. Historically, blood pH has been measured electrochemically with the glass electrode, in-vitro. The glass electrode is subject to drifts and to extraneous potentials that adds uncertainties to the measured values and must rely on frequent recalibrations to provide precision and consistency. A recent commercial entry, the fiber optic fluorescent pH sensor avoids these problems. The result is a stable sensor capable of continuous in-vivo monitoring of blood pH in spite of the intricacies introduced by the use of the operationally defined pH.

Optical pH Measurements In Blood

A system for determining the value of a compositional parameter of blood, including a sensor for producing a signal related to the value of the compositional parameter. A computer analyzes the signal and produces an output representing the value of the compositional parameter of blood. There is a delayed response in the system such that the signal has a time-varying waveform that varies from an initial value to an equilibrated value. The equilibrated value is predicted by detecting the occurrence of an inflection point and then computing an estimate of the equilibrated value based upon the assumption that the waveform varies exponentially from the inflection point to the equilibrated value.

William W. Miller

Papers

Optical Fluorescence and Its Application to an Intravascular Blood Gas Monitoring System

Progress in the development of a fluorescent intravascular blood gas system in man

Continuous In Vivo Monitoring of Blood Gases

Optical pH Measurements In Blood

System and method for predicting the value of a compositional parameter of blood