Abstract: An apparatus including an LED excitation source and module useful for full plate imaging fluorescence instruments as well as methods for calibrating such instruments. The apparatus may include a light source operative to provide simultaneous illumination of a first wavelength selected to a plurality of samples to excite the fluorescent emission of light of a second wavelength by said plurality of samples wherein the light source is an LED array; and an optical sensor, responsive to light at said second wavelength.

Abstract: A reflective light imaging system for use in high-throughput screening of samples disposed in multiple-well plates. The system can include a set of mirrors and lenses. The first mirror has a central aperture through which light from the object passes. The first mirror has a concave reflective surface that faces the image plane. The next element is a second mirror with a convex reflective surface. The system can include an aberration corrective system positioned between the second mirror and the image plane, and an optical sensor near the image plane. Light from an object passes through the central aperture of the first mirror and is reflected off the convex surface of the second mirror. The light then strikes the reflective surface of the first mirror. The light from the first mirror is then collected by the aberration correction system and transmitted toward the image plane.

Abstract: Broad-range light-detection systems, including components and methods of use thereof. These systems may include apparatus and methods for detecting light with increased speed and/or detection efficiency, particularly in applications involving repeated analysis of the same sample and/or successive analysis of different samples, and particularly when the sample or samples have a wide range of light intensities. These systems also may include apparatus and methods for detecting light with increased accuracy over a broad range of intensities. These systems also may include vapparatus and methods for automatically scaling detection range to improve detection based on the intensity of the detected light.

Abstract: Apparatus and methods for optical illumination and/or detection with improved flexibility and/or read speed. The apparatus and methods may include mechanisms for selecting and switching between multiple excitation wavelengths and/or simultaneously reading from a plurality of sample sites. The apparatus and methods may be used with microplates, PCR plates, cell culture plates, biochips, chromatography plates, microscope slides, and other substrates for high-throughput screening, genomics, SNPs analysis, pharmaceutical research and development, life sciences research, and other applications.

Abstract: Broad-range light-detection systems, including components and methods of use thereof. These systems may include apparatus and methods for detecting light with increased speed and/or detection efficiency, particularly in applications involving repeated analysis of the same sample and/or successive analysis of different samples, and particularly when the sample or samples have a wide range of light intensities. These systems also may include apparatus and methods for detecting light with increased accuracy over a broad range of intensities. These systems also may include vapparatus and methods for automatically scaling detection range to improve detection based on the intensity of the detected light.

Abstract: Apparatus and methods for combining multiple modes and methods of optical detection, postprocessing, and/or feedback loops in bioanalytical measurements. The methods may include (1) positioning a composition at an examination site in a multi-mode instrument; (2) detecting light transmitted form the composition using the multi-mode instrument in a first optical measurement mode; (3) detecting light transmitted from the composition using the multi-mode instrument in a second optical measurement mode, the second mode being different than the first mode; and (4) computing a quantity related to a property of the composition using the light detected in at least one of the optical measurement modes. These steps may be performed on one or more samples, simultaneously and/or sequentially. The quantity may relate to photoluminescence, chemiluminescence, absorption, and/or scattering, among others.

Abstract: A reflective light imaging system for use in high-throughput screening of samples disposed in multiple-well plates. The system can include a set of mirrors and lenses. The first mirror has a central aperture through which light from the object passes. The first mirror has a concave reflective surface that faces the image plane. The next element is a second mirror with a convex reflective surface. The system can include an aberration corrective system positioned between the second mirror and the image plane, and an optical sensor near the image plane. Light from an object passes through the central aperture of the first mirror and is reflected off the convex surface of the second mirror. The light then strikes the reflective surface of the first mirror. The light from the first mirror is then collected by the aberration correction system and transmitted toward the image plane.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) contacting a sample polynucleotide with a reference polynucleotide at an assay site, where at least one of the polynucleotides is capable of emitting luminescence, (2) illuminating the assay site with light capable of stimulating such luminescence, (3) detecting light transmitted from the assay site, and (4) deriving information relating to the extent of hybridization between the sample and reference polynucleotides based on the detected light. The methods may further include (1) illuminating with and/or detecting polarized light, (2) deriving information relating to the sequence of the sample polynucleotide from the extent of hybridization, and (3) converting the light to a signal and distinguishing between a portion of the signal attributable to luminescence and a portion attributable to background.

Abstract: Apparatus and methods for measuring light transmitted from a sample. The apparatus may include a stage, a light source, and a detector. The stage may be configured to hold a microplate having a plurality of sample wells. The apparatus may be configured to take frequency-domain time-resolved measurements of one or more of luminescence lifetimes and reorientational correlation times of a luminescent analyte in the sample.

Abstract: Frequency-domain light detection systems and components and uses thereof for performing time-resolved luminescence assays. The systems may include methods for identifying and/or correcting for background and/or quenching, among others. The systems also may include apparatus for increasing duty cycle and/or sensitivity, among others.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) allele-specific hybridization, using luminescence detection, (2) allele-specific oligonucleotide ligation, using dye-labeled oligonucleotide ligation with luminescence resonance energy transfer (FRET) detection, and (3) allele-specific nucleotide incorporation, using primer extension with luminescence polarization (FP) detection. More specifically, the methods may include (1) locating a sample containing a nucleic acid material at an examination site, (2) illuminating the sample, (3) detecting light transmitted from the sample, and (4) determining the presence, absence, and/or identity of a nucleic acid target in the sample using the light transmitted from the sample.

Abstract: Apparatus and methods for determining temporal properties of photoluminescent samples using frequency-domain photoluminescence measurements, where the measurements may include photon counting and/or the separation of measured luminescence into potentially overlapping time bins.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) contacting a sample polynucleotide with a reference polynucleotide at an assay site, where at least one of the polynucleotides is capable of emitting luminescence, (2) illuminating the assay site with light capable of stimulating such luminescence, (3) detecting light transmitted from the assay site, and (4) deriving information relating to the extent of hybridization between the sample and reference polynucleotides based on the detected light. The methods may further include (1) illuminating with and/or detecting polarized light, (2) deriving information relating to the sequence of the sample polynucleotide from the extent of hybridization, and (3) converting the light to a signal and distinguishing between a portion of the signal attributable to luminescence and a portion attributable to background.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) allele-specific hybridization, using luminescence detection, (2) allele-specific oligonucleotide ligation, using dye-labeled oligonucleotide ligation with luminescence resonance energy transfer (FRET) detection, and (3) allele-specific nucleotide incorporation, using primer extension with luminescence polarization (FP) detection. More specifically, the methods may include (1) locating a sample containing a nucleic acid material at an examination site, (2) illuminating the sample, (3) detecting light transmitted from the sample, and (4) determining the presence, absence, and/or identity of a nucleic acid target in the sample using the light transmitted from the sample.

Abstract: Apparatus and methods for determining temporal properties of photoluminescent samples using frequency-domain photoluminescence measurements, where the measurements may include photon counting and/or the separation of measured luminescence into potentially overlapping time bins.

Abstract: Apparatus and methods for identifying and correcting for quenching in luminescence assays using luminescence lifetimes and/or luminescence intensities. One aspect of the invention involves identifying quenching using combinations of luminescence lifetimes and/or intensities. Another aspect of the invention involves correcting for quenching by eliminating false positives or false negatives due to quenching in luminescence assays.

Abstract: Apparatus and methods for measuring light transmitted from a sample. The apparatus may include a stage, a light source, and a detector. The stage may be configured to hold a microplate having a plurality of sample wells. The apparatus may be configured to take frequency-domain time-resolved measurements of one or more of luminescence lifetimes and reorientational correlation times of a luminescent analyte in the sample.