The Perkin-elmer Corporation

August Ninth Analyses, Inc.

Perkinelmer Instruments LLC

Perkin-elmer Corp., Applied Biosystems Division

Perkinelmer Las, Inc.

Alan M Ganz

David H Tracy

Yongdong Wang

Paul G Saviano

David A Huppler

Robert Alan Hoult

Jerry E Cahill

Henry C Weber

Linda G Lee

Timothy M Woudenberg

John S Shigeura

Kevin S Bodner

Charles R Connell

Lincoln J McBride

Eugene F Young

Koichi Nishikida

Gitesh Kumar

Juan C Ivaldi

John P Coates

Christopher B Hanna

A method for determining characteristics of a material includes illuminating the material with coherent light so as to produce scattered light; autocorrelating the scattered light; preprocessing a signal representative of the scattered light to produce a processed signal; and associating the analyzed data with particular characteristics of the material. At least one of a cumulant analysis and a cluster analysis may be performed to provide analyzed data. The determined characteristics may be used for real time control or termination a process used to alter the characteristics of the material. Specifically, monitoring of a process for changes in particle size as a function of time or to determine various physical and/or chemical characteristics of the particles or a mixture containing same, including homogeneity, may be achieved. An apparatus operating generally in accordance with the method is also disclosed.

Method and apparatus for determining particle size and composition of mixtures

Method and apparatus for evaluating one or more materials in accordance with size of particles. The method includes evaluating a spectrum of light reflected from a first group of particles; evaluating a spectrum of light reflected from a second group of particle; comparing results of said evaluating of said first group with results of said evaluating of said second group; and providing an indication of a state of said material when said comparing produces a predetermined comparison result. Distance between a first light conductor for conducting light to the particles and a second light conductor for conducting light from said particles for said evaluations may be varied. Monitoring of a process for changes in particle size as a function of time or to determine various physical and/or chemical characteristics of the particles or a mixture containing same, including homogeneity, may be achieved.

Constituents such as oxy- and deoxy-hemoglobin are monitored non-invasively in an animal organ such as a brain with a spectrometric instrument by passing radiation through the organ. Concentrations are computed from the spectral intensities and from a statistical correlation model. To predetermine the correlation model, the procedures are effected for a plurality of organs of a same type with each organ having established concentrations of the selected constituents, and the correlation model is statistically determined from the concentrations and corresponding intensities. For more accuracy computations are normalized to path length which may be determined by utilizing several discrete wavelengths with RF modulations.

Monitoring constituents of an animal organ using statistical correlation

For conversion of spectral information of an FTIR spectrometric instrument for comparison with that of a dispersion instrument, a first standard function is selected for spectral line shape for the first instrument, and a second standard function for line shape is selected for the second instrument. A conversion factor is computed for converting the first standard function to the second standard function. In ordinary operations, first spectral information is obtained with the first instrument for a first sample, and second spectral information is obtained with the second instrument for a second sample. The conversion factor is applied to the first spectral information to effect converted information, and the converted information is compared with the second spectral information. Such conversion also is applied between chromatographic instruments.

Standardizing between analytical instruments

Standardization is achieved for FTIR spectrometric instruments that effect an intrinsic distortion in spectral information, the distortion being associated with an aperture size. An idealized function of spectral line shape is specified. With a small calibration aperture, spectral data is obtained for a basic sample having known 'true' spectral data, and standard spectral data also is obtained for a standard sample. With a larger, normal sized aperture, standard spectral data is obtained again for the calibration sample. A transformation factor, that is a function of this data and the standardized function, is applied to spectral data for test samples to effect standardized information. In another embodiment, the standard sample has known true spectral data, and the basic sample is omitted. In either case, the transformation factor is applied to the sample data in logarithm form, the antilogarithm of the result effects the standardized information.

Standardizing a spectrometric instrument

A spectrometric instrument includes a detector with detecting subarrays on small portions of the surface. Spectral data are acquired for selected subarrays at a first time for a drift standard, and compared to a zero position to obtain first offset data. Data are acquired similarly at a second time to obtain second offset data. The offset data are utilized to obtain a spectral shift for any subarray position at any selected time. The shift is applied to a matrix model used for converting test data to compositional information. Archive data for the model is obtained in the foregoing manner, using slit scanning in the instrument to achieve sub-increments smaller than the detector pixel size, with a procedure to assure that there is an integral number of scanning steps across one pixel. The drift standard may be chemical analytes, or an optical interference element producing fringes related to spectral positions in each subarray. A procedure is used to identify the fringe peaks to spectral position, with temperature correction.

Analyzing spectrometric data

A system is provided for carrying out real time fluorescence-based measurements of nucleic acid amplification products. In a preferred embodiment of the invention, an excitation beam is focused into a reaction mixture through a surface, the reaction mixture containing (i) a first fluorescent indicator capable of generating a first fluorescent signal whose intensity is proportional to the amount of an amplification product in the volume of the reaction mixture illuminated by the excitation beam and (ii) a second fluorescent indicator homogeneously distributed throughout the reaction mixture capable of generating a second fluorescent signal proportional to the volume of reaction mixture illuminated by the excitation beam. Preferably, the excitation beam is focused into the reaction mixture by a lens through a portion of a wall of a closed reaction chamber containing the reaction mixture. The same lens is used to collect the first and second fluorescent signals generated by the first and second fluorescent indicators, respectively, in response to the excitation beam. The ratio of the fluorescent intensities of the first and second fluorescent signals provides a stable quantitative indicator of the amount of amplification product synthesized in the course of the amplification reaction.

System for real time detection of nucleic acid amplification products

A method and apparatus are provided for correction of spectra for stray radiation in a spectrometric instrument, involving a sequence of steps as follows. Spectral patterns are obtained with the instrument initially for monochromatic radiation at a plurality of selected calibration wavelengths. By computer program, the peak profile at the calibration wavelength in each pattern is replaced with a substitute based on the remaining pattern. The resulting data are interpolated to effect values denoted 'stray proportions' for the ordered wavelengths of the instrument. Spectral data at each ordered wavelength are obtained with the instrument for a sample, and multiplied in the computer program by stray proportions for corresponding wavelengths to effect further sets of values denoted 'stray portions' that are identified to the ordered wavelengths. Each set is identified to one of the wavelength increments of the instrument across the spectral range. In each set, the stray portions for the ordered wavelengths are summed. The total for each wavelength increment is subtracted from the original sample data for the increment to effect spectral data corrected for stray.

Correction of spectra for stray radiation

A spectrometric instrument which exhibits an intrinsic profile for a sharp spectral line produces profile data for narrow spectral lines. The spectral lines are effected with a high finesse etalon of gold coated polymer. A transformation filter is computed for transforming the profile data to a gaussian profile. A wavelength calibration is combined with the filter to effect a correction matrix which is applied to sample data to generate calibrated standardized data. Iteratively a correction matrix is applied to calibration data to generate standardized calibration data which is utilized for the wavelength calibration. Calibration is effected with an optical standard, an interference etalon and a fringe formula. Etalon effective thickness is first estimated and then precisely determined so that fringe peaks calibrate wavelength.

Standardizing and calibrating a spectrometric instrument

To calibrate a photodetector, a rotating disk with a slot is disposed in a light beam with decreasing speed from a defined maximum rotational speed to a defined minimum speed, while magnitudes and times of signals are read out and stored. Vernier pairs of signals occur in adjacent readout intervals, and non-vernier signals exclude the verniers. Readout times for verniers are used to estimate a preliminary function of rotations versus time. From the function are estimated an occurrence time for each pair and period of disk rotation at the time. Vernier fraction is the ratio of one signal in the pair to the sum of the pair. A time offset is the product of vernier fraction, slot fraction of the disk and the estimated period. Occurrence times corrected with the time offset are utilized to fit a corrected function of disk rotations versus time. Points of time for the non-vernier signals are determined from the corrected function, each point corresponding to disk rotations to a corresponding non-vernier signal. These points of time are employed with corresponding signals for linearly calibrating the photodetector.

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Trumbull, CT, United States of America

Alan M Ganz