Abstract: Light from an object moving through an imaging system is collected, dispersed, and imaged onto a time delay integration (TDI) detector that is inclined relative to an axis of motion of the object, producing a pixilated output signal. In one embodiment, the movement of the image object over the TDI detector is asynchronous with the movement of the output signal producing an output signal that is a composite of the image of the object at varying focal point along the focal plane. In another embodiment, light from the object is periodically incident on the inclined TDI detector, producing a plurality of spaced apart images and corresponding output signals that propagate across the TDI detector. The inclined plane enables images of FISH probes or other components within an object to be produced at different focal points, so that the 3D spatial relationship between the FISH probes or components can be resolved.

Abstract: An illumination system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is defined by spaced-apart, opposed first and second surfaces disposed on opposite sides of a central volume. Preferably the first reflecting surface forms an acute angle with the second reflecting surface. A beam of light is directed into the reflection cavity so that light is reflected back and forth between the first and second surfaces a plurality of times, illuminating a different portion of the central volume with each pass until, having ranged over the central volume, the light exits the reflection cavity. The “recycling” of the light beam in this manner substantially improves the signal to noise ratio of a detection system used in conjunction with the reflection cavity by increasing an average illumination intensity in the central volume.

Abstract: Combinatorially-synthesized deoxyribonucleic acid (DNA) oligonucleotides attached to encoded beads that are hybridized to amplified and labeled genomic DNA or ribonucleic acid (RNA) are analyzed using a flow imaging system. Oligonucleotides and corresponding reporters are bound to the surfaces of a plurality of small beads such that different beads bear different oligo sequences. Each bead bears a unique optical signature comprising a predefined number of unique reporters, where each reporter comprises a predefined combination of different fluorochromes. The composite spectral signature in turn identifies the unique nucleotide sequence of its attached oligo chains. This optical signature is rapidly decoded using an imaging system to discriminate the different reporters attached to each bead in a flow in regard to color and spatial position on the bead.

Abstract: When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI/flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.

Abstract: A pair of optical gratings are used to modulate light from an object, and the modulated light from either optical is used to determine the velocity of the object. Each optical grating is offset from a reference focal point by the same distance, one grating being offset in a positive direction, the other in a negative direction. Signals produced in response to the modulated light can be processed to determine a direction in which a primary collection lens should be moved in order to improve a focus of the imaging system on the object. The lens is moved incrementally in the direction so determined, and the process is repeated until an optimal focus is achieved. In a preferred embodiment, the signals are weighted, so that the optical grating disposed closest to the optimal focus position contributes the most to velocity detection.

Abstract: When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI/flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.

Abstract: A flow imaging system is used to implement surface plasmon resonance (SPR) detection to study bio-molecular interactions. The flow imaging system is used to capture SPR absorption spectra of large numbers of objects, where each object includes both a metal film capable of exhibiting SPR, and detecting molecules. Analyte molecules are added to a solution of such objects, and the result is introduced into the flow imaging system which collects full SPR spectral data from individual objects. The objects can be nanoparticles or larger particles that support metal island films. The SPR spectral data can be used to determine specificity, kinetics, affinity, and concentration with respect to the interactions between the detecting molecules and the analyte molecules.

Abstract: A low pulsatility syringe pump including a duplex bearing set rotatingly supporting a lead screw, and a transmission having a first drive train configured to increase a number of motor rotations required for a single rotation of the lead screw, and a second drive train configured to reduce the number of motor rotations required for a single rotation of the lead screw as compared to the first drive train. Another embodiment also includes a motor configured to rotate the syringe about its own axis, independent of the motion of the lead screw. In this other embodiment, the fluid in the syringe barrel includes objects (such as cells, latex beads, etc.) entrained in the fluid. The rate of rotation (e.g., about three revolutions per second) is chosen such that each object traces a substantially circular pathway in the syringe barrel and remains in suspension.

Abstract: A pair of optical gratings are used to modulate light from an object, and the modulated light from either optical is used to determine the velocity of the object. Each optical grating is offset from a reference focal point by the same distance, one grating being offset in a positive direction, the other in a negative direction. Signals produced in response to the modulated light can be processed to determine a direction in which a primary collection lens should be moved in order to improve a focus of the imaging system on the object. The lens is moved incrementally in the direction so determined, and the process is repeated until an optimal focus is achieved. In a preferred embodiment, the signals are weighted, so that the optical grating disposed closest to the optimal focus position contributes the most to velocity detection.

Abstract: When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI/flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.

Abstract: Light from an object moving through an imaging system is collected, dispersed, and imaged onto a time delay integration (TDI) detector that is inclined relative to an axis of motion of the object, producing a pixilated output signal. In one embodiment, the movement of the image object over the TDI detector is asynchronous with the movement of the output signal producing an output signal that is a composite of the image of the object at varying focal point along the focal plane. In another embodiment, light from the object is periodically incident on the inclined TDI detector, producing a plurality of spaced apart images and corresponding output signals that propagate across the TDI detector. The inclined plane enables images of FISH probes or other components within an object to be produced at different focal points, so that the 3D spatial relationship between the FISH probes or components can be resolved.

Abstract: An illuminiation system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is disposed between spaced-apart, opposed first and second surfaces disposed on opposite sides of a moving stream of objects. A light collection system is disposed substantially orthogonal to a plane passing through the surfaces and the stream so as to collect light that is scattered from or emitted by the objects as they pass through a field of view disposed between the first and second surfaces. A beam of light from a laser source is directed through the stream of moving objects in a direction nearly orthogonal to the stream (but slightly inclined) and lying in the plane that extends through the surfaces and the stream. Due to the reflection angle and the distance between the stream and the first surface, the point at which the light reflected from the first surface intersects the stream on a second pass is displaced from where it passed though the stream on its initial pass.

Abstract: An illumination system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is disposed between spaced-apart, opposed first and second surfaces disposed on opposite sides of a moving stream of objects. A light collection system is disposed substantially orthogonal to a plane passing through the surfaces and the stream so as to collect light that is scattered from or emitted by the objects as they pass through a field of view disposed between the first and second surfaces. A beam of light from a laser source is directed through the stream of moving objects in a direction nearly orthogonal to the stream (but slightly inclined) and lying in the plane that extends through the surfaces and the stream. Due to the reflection angle and the distance between the stream and the first surface, the point at which the light reflected from the first surface intersects the stream on a second pass is displaced from where it passed though the stream on its initial pass.

Abstract: Light from an object such as a cell moving through an imaging system is collected and dispersed so that it is imaged onto a plurality of separate detectors. The light is spectrally dispersed by a plurality of spaced-apart dichroic reflectors, each detector receiving light from a different one of the dichroic reflectors. Each dichroic filter reflects light of a different predefined color, passing light of other colors. The output signal from each detector is indicative of a different characteristic of the object. In one configuration, each detector is provided with a separate imaging lens. In another configuration, the detectors are spaced at varying distances from the corresponding dichroic reflectors, so that separate imaging lenses are not required.

Abstract: Light from an object such as a cell moving through an imaging system is collected and dispersed so that it can be imaged onto a time delay and integration (TDI) detector. The light can be emitted from a luminous object or can be light from a light source that has been scattered or not absorbed by the object or can include a light emission by one or more probes within or on the object. Multiple objects passing through the imaging system can be imaged, producing both scatter images and dispersed images at different locations on one or more TDI detectors.

Abstract: In an instrument generating images from the fluorescent emissions of a plurality of fluorescent dyes carried by objects in a flow stream, spectral dispersion is used to expand the images of the objects along one axis of a two-dimensional photosensor array according to emission wavelength. The dispersion is unable to completely separate the emissions of a plurality of dyes because the emission spectra of the dyes overlap in wavelength. The method of the present invention accomplishes accurate estimation of the intensity of the light received from each of a plurality of dyes by decomposing the two dimensional spectrally dispersed images into a set of characteristic parameters using either an iterative curve fitting optimization method or a linear algebraic method.

Abstract: Light from an object such as a cell moving through an imaging system is collected, and imaged onto a time delay integration (TDI) detector, producing a pixelated output signal in response to the image of the object. The light can be emitted from a luminous object, from a source and scattered by the object, or can be a fluorescent emission by one or more object probes. Light absorbed or reflected by the object can also produce images for determining specific characteristics of the object. In one set of embodiments, the movement of the object is synchronized with that of the pixelated output signal, which is controlled by the readout rate of the TDI detector. Alternatively, the readout rate of the pixelated output signal is not synchronized with the movement of the object, thereby permitting multiple signals to be produced for each of a plurality of objects over time.

Abstract: Light from an object such as a cell moving through an imaging system is collected and dispersed so that it is imaged onto a plurality of separate detectors. The light is spectrally dispersed by a plurality of spaced-apart dichroic reflectors, each detector receiving light from a different one of the dichroic reflectors. Each dichroic filter reflects light of a different predefined color, passing light of other colors. The output signal from each detector is indicative of a different characteristic of the object. In one configuration, each detector is provided with a separate imaging lens. In another configuration, the detectors are spaced at varying distances from the corresponding dichroic reflectors, so that separate imaging lenses are not required.

Abstract: When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI/flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.

Abstract: An illumination system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is disposed between spaced-apart, opposed first and second surfaces disposed on opposite sides of a moving stream of objects. A light collection system is disposed substantially orthogonal to a plane passing through the surfaces and the stream so as to collect light that is scattered from or emitted by the objects as they pass through a field of view disposed between the first and second surfaces. A beam of light from a laser source is directed through the stream of moving objects in a direction nearly orthogonal to the stream (but slightly inclined) and lying in the plane that extends through the surfaces and the stream. Due to the reflection angle and the distance between the stream and the first surface, the point at which the light reflected from the first surface intersects the stream on a second pass is displaced from where it passed though the stream on its initial pass.