Abstract: The present invention uses the small temperature changes from reactions and utilizes them in high throughput screening methods. Briefly, a thermal block containing a series of thermally isolated wells is used so that a reaction can take place in each well without affecting the temperature of any other well. A chemical or biological reaction, such as a binding reaction, is allowed to occur in each well or chamber and the optical properties of the all of the wells are monitored using optical, preferably Kromoscopic, measurements. A determination of temperature in each of the wells from those Kromoscopic measurements can be used to determine if reaction occurred.

Abstract: The present invention relates to a method and apparatus of that utilizes a reflective enclosure to simulate optical homogeneity in an otherwise inhomogeneous sample. The illumination sources and sample are placed within the reflective enclosure, thus providing a method for examining a sample that is different from transmission, reflection or transflection. This apparatus and method are particularly well adapted to in vivo non-invasive testing for constituents of blood.

Abstract: The present invention relates to a method and apparatus of that utilizes a reflective enclosure to simulate optical homogeneity in an otherwise inhomogeneous sample. The illumination sources and sample are placed within the reflective enclosure, thus providing a method for examining a sample that is different from transmission, reflection or transflection. This apparatus and method are particularly well adapted to in vivo non-invasive testing for constituents of blood.

Abstract: An improved method and apparatus for use in optical testing of concentration in samples has been developed. The apparatus restricts the solid angle of illumination and the solid angle of detection to eliminate a high proportion of the scattered radiation while allowing the ballistic radiation and the snake-like radiation to be transmitted. In samples which contain multiple scattering centers, this allows less correction for variations in effective pathlength and allows easier calibration of the apparatus. The use of polarized radiation as a means of minimizing scattered radiation in the sample is also disclosed.

Abstract: The invention relates to the enhancement of the signal-to-background ratio of a non-invasive measurement of the concentration of a blood constituent at a measurement site by applying an external pressure at a location near the measurement site. In one embodiment, sufficient pressure is applied proximate to a measurement site to stop blood flow. The pressure is then suddenly relased, thereby generating a blood bolus passing through the site. By illuminating the measurement site before and during the passage of the blood bolus and observing the interaction of the input radiation with the measurement site, the concentration of a blood constituent can be measured. In another embodiment, the venous pulse is occluded by applying a pressure midway between systolic and diastolic pressure. By illuminating the measurement site in the absence of a venous pulse, the signal-to-background ration can be enhanced and the concentration of a blood constituent can be measured.

Abstract: An improved method and apparatus for use in optical testing of concentration in samples has been developed. The apparatus restricts the solid angle of illumination and the solid angle of detection to eliminate a high proportion of the scattered radiation while allowing the ballistic radiation and the snake-like radiation to be transmitted. In samples which contain multiple scattering centers, this allows less correction for variations in effective pathlength and allows easier calibration of the apparatus. The use of polarized radiation as a means of minimizing scattered radiation in the sample is also disclosed.

Abstract: The present invention provides a generally applicable apparatus and method for achieving measurements of a constituent in a sample. This is achieved by employing a detection means having a plurality of detectors responsive to radiation in a selected region of the spectrum, e.g., the infrared. In most embodiments, at least two of the detectors provide broad wavelength bandpass. If narrow bandpass sources or detectors are used, the information generated is processed in a manner similar to broadband information. The broad bandpass response of the detectors can be contrasted with the approach of classical spectrophotometry, in which the spectral response of the detectors is designed to be as narrow as feasible, and substantially narrower than the spectral features of the constituent or constituents of interest. The data is processed such that the contributions of known background constituents and scattering is eliminated prior to further processing, thereby yielding a better result in high background situations.

Abstract: Disclosed is a method of assaying, in assay apparatus, for at least the ligand intended to be used to assay analyte in a sample, with which analyte the ligand will specifically bind. The method provides a product in which a ligand is labeled with a detectable tag and is immobilized on an appropriate substrate. An assay is made to measure the immobilized, labeled ligand by detecting the tag labeling the latter. The product can then be used to assay for the analyte by contacting the latter so as to form a complex. The extent and rate of specific binding of the analyte in the complex is identifiable, either by competition assay or sandwich assay as a rate of change, so the relative proportions of analyte and ligand are readily determinable.

Abstract: The invention provides non-invasive methods and apparati for measurement of the concentration of a selected constituent of a subject's blood. The invention cools a segment of the subject's tympanic membrane and employs the thermal radiation that the subject's inner ear emits and is transmitted through this cold segment to directly obtain absorption information related to the concentration of various constituents of blood flowing through the membrane. In particular the invention utilizes optical devices inserted into the external ear cavity to direct a portion of the transmitted radiation onto an infrared detection and analysis device. The signal from the detection device is analyzed to obtain the concentration of the constituent of interest. The invention can employ both traditional spectrophotometric techniques and also non-spectrophotometric techniques to derive the concentration of a particular constituent.

Abstract: Improvement methods and apparatus for determination of optical properties of objects have been developed. The apparatus and methods of the invention provide an analog of color perception of human vision, preferably in the near infrared region, replacing spectrophotometers and narrow band sources used in other non-invasive near infrared detection methods. A plurality of detector units are used, each covering a broad and overlapping region of the detected spectrum, paralleling color perception and colorimetry. The improvements are primarily concerned with improving the signal-to-background (or noise) ratio such that the data stream is improved. These improvements use congruent sampling, comparison of different data streams from different sample portions or filter sets, using an interrogation system with sufficient speed to allow testing of arterial blood, and using a filter with a spectral structure. In some circumstances, a neural net is used for analysis, allowing the system to learn.

Abstract: The present invention provides a generally applicable apparatus and method for achieving measurements of a constituent in a sample. This is achieved by employing a detection means having a plurality of detectors responsive to radiation in a selected region of the spectrum, e.g., the infrared. In most embodiments, at least two of the detectors provide broad wavelength bandpass. If narrow bandpass sources or detectors are used, the information generated is processed in a manner similar to broadband information. The broad bandpass response of the detectors can be contrasted with the approach of classical spectrophotometry, in which the spectral response of the detectors is designed to be as narrow as feasible, and substantially narrower than the spectral features of the constituent or constituents of interest. The data is processed such that the contributions of known background constituents and scattering is eliminated prior to further processing, thereby yielding a better result in high background situations.

Abstract: Disclosed is a method of assaying and apparatus for assaying, in assay apparatus, for an analyte in a sample by specifically binding the analyte to a binding molecule having a detectable tag to form a complex, the presence of which can be determined quantitatively by measuring the amount of tag. In one embodiment, the sample is contacted in that apparatus with a complex of binding molecules so as to effect the specific binding. The complex has at least two differently tagged different binding molecules in a predetermined ratio, at least a first of which tagged binding molecules being that which will specifically bind to the analyte. The second tagged binding molecule is one which will not specifically bind to the analyte or to other moieties in the sample. The relative non-specific binding characteristics of those binding molecules with respect to said apparatus are in a known or predetermined relationship.

Abstract: An improved method and apparatus for use in optical testing of concentration in samples has been developed. The apparatus restricts the solid angle of illumination and the solid angle of detection to eliminate a high proportion of the scattered radiation while allowing the ballistic radiation and the snake-like radiation to be transmitted. In samples which contain multiple scattering centers, this allows less correction for variations in effective pathlength and allows easier calibration of the apparatus. The use of polarized radiation as a means of minimizing scattered radiation in the sample is also disclosed.

Abstract: Improvements in non-invasive detection methods for glucose and other constituents of interest in a sample have been developed. The apparatus and methods of the invention provide an analog of color perception of human vision, preferably in the near infrared region, replacing spectrophotometers and narrow band sources used in other non-invasive near infrared detection methods. A plurality of detector units are used, each covering a broad and overlapping region of the detected spectrum, paralleling color perception and colorimetry. The improvements are primarily concerned with improving the signal-to-background (or noise) ratio such that the data stream is improved. These improvements use congruent sampling, comparison of different data streams from different sample portions or filter sets, using an interrogation system with sufficient speed to allow testing of arterial blood, and using a filter with a spectral structure. In some circumstances, a neural net is used for analysis, allowing the system to learn.

Abstract: A new non-invasive non-spectrophotometric method for measuring the blood concentration of analytes such as glucose has been developed. The apparatus and methods of the invention exploit analogies with colorimetry and color perception to extract concentration measurements from the global structure of the intensity versus wavelength absorbance or transmission profile. A plurality of broad spectrum filters transmit distinguishably coded beams of radiation in overlapping portions of the spectrum to the sample. Radiation reflected or transmitted by the sample is detected and decoded. LED's may be used instead of the broad spectrum radiation generating device and the filters. Further, a scanning interferometer can be used as the illuminating and coding device. In a preferred mode, congruent illumination is utilized. The coded signals are analyzed by analogy to colorimetry and visual processing and can be converted into concentration measurements.

Abstract: A new non-invasive detection method for glucose and other constituents of interest in a sample has been developed. The apparatus and methods of the invention provide an analog of color perception of human vision, preferably in the near infrared region, replacing spectrophotometers and narrow band sources used in other noninvasive near infrared detection methods. A plurality of detector units are used, each covering a broad and overlapping region of the detected spectrum, paralleling color perception and colorimetry. In some circumstances, a neural net is used for analysis, allowing the system to learn. A novel method for background discrimination is also described.

Abstract: An assay apparatus employing total internal reflection of excitation radiation at the interface between a replaceable optically conductive rod or fiber and a surrounding liquid phase of lower index of refraction. Immobilized on the surface of the fiber is a component of a complex formed in an immunological-type specific reaction. A fluorophore that can be excited into fluorescence by the excitation radiation is attached to another component of the complex. The rod is coaxially mounted within a tube that is sized with respect to said rod so that a fluid sample may be introduced into said tube.The rod and tubing are supported in a mounting assembly that is attachable to an optical assembly for transmitting excitation radiation into the proximal end of the rod and receiving fluorescent radiation emitted from the proximal end of the rod. Included in the apparatus is a mounting assembly for centering the rod within tube and for biasing the rod in a first direction against an annular seat.

Abstract: An assay method and apparatus employing total internal reflection of excitation radiation at an activated region on the surface of an optically conductive rod or fiber surrounded by a liquid phase of lower index of refraction, so as to excite into fluorescence fluorophores in the liquid present in a thin layer around the rod surface. The induced fluorescence is then gathered and measured. Excitation occurs while flowing a sample of the liquid phase through an enclosure of fixed dimensions bounded in part by the activated region.

Abstract: A method and apparatus for fluorescent immunoassay utilizes total internal reflection at the interface between a solid phase and a liquid phase of lower index of refraction to produce an evanescent wave in the liquid phase. The solid phase is arranged and illuminated so as to provide multiple total internal reflections at the interface. In a preferred embodiment, the solid phase is in the form of an optical fiber to which is immobilized a component of the complex formed in the immunochemical reaction. A fluorophore is attached to another component of the complex. The fluorescent labelled component may be either the complement to or an analog of the immobilized component, depending on whether competitive or sandwich assays are to be performed. In the case of competitive assays, the labelled component is preferably pre-loaded to the immobilized component in a controlled concentration. The fiber (and the attached constituent of the assay) is immersed in the liquid phase sample.

Abstract: An assay apparatus and methods employing total internal fluorescence to define a thin observed volume of a multi-phase suspension from which the suspended phase, because of its size and shape, is substantially excluded. Observations of the fluorescence of a known quantity of fluorescent material introduced into a known volume of the sample containing the observed volume permits quantitation of the volumes of the suspended and suspending phases.