USRE46559E1 - Enhancing flow cytometry discrimination with geometric transformation - Google Patents

Enhancing flow cytometry discrimination with geometric transformation Download PDF

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USRE46559E1
USRE46559E1 US15/438,423 US200515438423A USRE46559E US RE46559 E1 USRE46559 E1 US RE46559E1 US 200515438423 A US200515438423 A US 200515438423A US RE46559 E USRE46559 E US RE46559E
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dimensional
processor
population
data
computer readable
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George C. Malachowski
Paul Barclay Purcell
Edward Allan Stanton
Kenneth Michael Evans
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Beckman Coulter Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1429—Signal processing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1429—Signal processing
    • G01N15/1433—Signal processing using image recognition
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1434—Optical arrangements
    • G01N15/1436—Optical arrangements the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
    • G01N15/1475—
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/149—Optical investigation techniques, e.g. flow cytometry specially adapted for sorting particles, e.g. by their size or optical properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology

Definitions

  • the present invention includes in embodiments apparatus and methods for real-time discrimination of particles while being sorted by flow cytometry.
  • embodiments of the invention may include application of various mathematical operations to manipulate data in real-time resulting in enhanced discrimination between populations of particles.
  • sperm may not express surface antigens that are indicators of the presence of X or Y chromosomes.
  • X bearing sperm may have a larger mass of genetic material.
  • a dye such as Hoechst, may have the property of binding to DNA.
  • light emitted by X bearing sperm when ignited by ultra-violet laser, may be slightly brighter and this can be used as a discrimination to sort and separate the sperm.
  • Subtle differences can also be due to flow cytometer geometries as well.
  • mammalian sperm are generally paddle shaped and when they pass through a flow cytometer they can have a random orientation. This orientation may obscure the differential light coming from the X and Y bearing cells. Consequently, a cytometer may have a specialized orienting nozzle that can use a hydrodynamic effect to orientate the cells to a reasonable degree.
  • a bivariate histogram may be collected, the parameters may be a forward and side angle fluorescence.
  • a population may show the effect of orientation.
  • a slight separation of two populations may make a drawing of a closed contour around each population difficult.
  • a contour may be needed to establish a region that can be exclusively sorted.
  • An object of the present invention may include applying mathematical operations to data to allow enhanced discrimination between populations.
  • Another object of the invention in embodiments may include performing a geometric perhaps 2-dimensional transformation of flow cytometry data so that particles can be sorted.
  • FIG. 1 is an illustration of a sort overview in accordance with some embodiments of the present invention.
  • FIG. 2 illustrates forward and side light detection systems in accordance with some embodiments of the present invention.
  • FIG. 3 is an example of a histogram of sperm sorting data prior to rotation.
  • FIG. 4 is an example of a histogram of sperm sorting data after scaling.
  • FIG. 5 is an example of a histogram of sperm sorting data after rotation.
  • FIG. 6 is an example of a histogram of sperm sorting data after scaling and rotation.
  • FIG. 7 is a conceptual depiction of a system for analyzing detected signal data in one embodiment.
  • the present invention includes a variety of aspects, which may be combined in different ways.
  • the following descriptions are provided to list elements and describe some of the embodiments of the present invention. These elements are listed with initial embodiments, however it should be understood that they may be combined in any manner and in any number to create additional embodiments.
  • the variously described examples and preferred embodiments should not be construed to limit the present invention to only the explicitly described systems, techniques, and applications. Further, this description should be understood to support and encompass descriptions and claims of all the various embodiments, systems, techniques, methods, devices, and applications with any number of the disclosed elements, with each element alone, and also with any and all various permutations and combinations of all elements in this or any subsequent application.
  • Embodiments of the invention may include various methods, apparatus, systems and the like to distinguish particles during flow cytometry.
  • a fluid stream ( 1 ) may be established in a flow cytometer in which particles ( 2 ) may be entrained.
  • particles may be sperm; however other kinds of particles are certainly possible and all are meant to be included in this disclosure.
  • Particles may be coupled with a light emitting element, for example one embodiment may include a Hoechst dye. Each individual particle may emit a first signal and perhaps even at least one additional signal.
  • a detector ( 42 ) may be placed so as to detect signals from the particles as can be understood from FIGS. 1 and 2 .
  • a first signal detector may detect a first signal affiliated with an individual particle and perhaps even at least one additional signal detector may detect at least one additional signal affiliated with an individual particle. This may include any kind of signal that may be in association, perhaps even close association with an individual particle such as but not limited to fluorescence, radiance, and the like.
  • FIGS. 1 and 2 represent a flow cytometry sort overview.
  • a nozzle ( 32 ) may allow particles ( 2 ) entrained in a fluid stream ( 1 ) to move through a laser beam ( 34 ) at an interrogation point ( 33 ).
  • a signal detector ( 42 ) such as a forward scatter detector ( 30 ) and perhaps even a side scatter collection objective ( 31 ) may be placed appropriately to collect signals affiliated to a particle. It may also be desirable to provide primary laser focusing optics ( 43 ).
  • signals may include fluorescence emitted from a light emitting particle coupled with individual particles after passing through a laser beam.
  • Signals emitted from a particle may be passed through optics and perhaps even a pinhole strip ( 44 ) to assist in collection of data.
  • a signal detector may be connected to a system, as discussed hereafter, in which signal data indicative of the signals may be processed and analyzed in order to determine a sort decision.
  • Computers, computer programming, hardware, software and the like may assist in a sort decision. While a sort decision is being determined, particles may pass through a drop delay ( 35 ). This time frame may be very short. After a sort decision may have been made, a pulse of charge ( 37 ) may be applied to a droplet ( 23 ) containing a particle. Droplets may pass through charged deflection plates ( 38 ) in order to sort particles into a desired sort receptacle ( 40 ) having containers.
  • a waste collection tube ( 39 ) may be included in embodiments.
  • signal data may be analyzed.
  • Embodiments may include converting signals (e.g. a first signal and at least one additional signal) affiliated with each individual particle into n-dimensional parameter data. This may be done with a signal processor responsive to the signals.
  • a signal processor may provide a conversion of a first signal and at least one additional signal into n-dimensional parameter data.
  • N-dimensional parameter data may include one-dimensional or perhaps even multi-dimensional (2-D, 3-D, 4-D, etc.) data which can be associated with each signal detected.
  • Signal data may be converted to relate each signal with a coordinate, such as an intensity of a color, and the like and may even be plotted in a Cartesian coordinate system.
  • Signals may be plotted on a graph ( 13 ). Since differences between particles may vary slightly, signals affiliated with the particles may also vary slightly. This slight difference may be so small that when plotted, the n-dimensional parameter data corresponding to the signals, may place data points very close together. These may be so close that it may be difficult to categorize the data points into a population. Conventional technologies may have disregarded these points that are so close together and may have decided to throw out that particle because it could not have been distinguished. It may be desirable in embodiments to reconfigure data to enhance separation between data points.
  • Embodiments may include distinguishing at least two populations ( 8 ) of n-dimensional parameter data.
  • a population differentiation element may include a geometric transformation and may allow n-dimensional parameter data to be categorized into one of at least two populations. For example, a sperm may be categorized into a X-bearing sperm population and a Y-bearing population.
  • a geometric two-dimensional transformation may be performed on flow cytometry data such that particles or even cells may be sorted into separate vials based on an appropriate property. In the sperm example, one vial containing cells for male and one vial containing cells for female.
  • a transformation may include a matrix dot product of various translation, scale, and perhaps even rotation operations for discriminating male determining from female determining cells and may even maintain proper cell type identification during signal drift over time.
  • the transformations may be combined into a single transformation matrix so that the calculations can be performed within the available signal processing time such as with a Digital Signal Processor.
  • the present invention may include real-time classifying n-dimensional parameter data of each of the individual particles into one of at least two populations.
  • a real-time classification element may include classifying signal data into a population, making a sort decision, and sorting a particle all within the small amount of time it takes for the particle to move through a flow cytometer. Accordingly, the present invention may provide in embodiments, sorting individual particles based upon a real-time classification.
  • the present invention may provide in embodiments, visually distinguishing at least two populations of n-dimensional parameter data. This may assist a user to ensure that a sorting may be running properly. This may also allow for user input to assist in discrimination between populations.
  • Embodiments may include graphically placing n-dimensional parameter data for each of the individual particles in relation to at least two populations. For example, it may be desirable to plot n-parameter data in a Cartesian coordinate system. A first signal may be plotted on one axis ( 14 ) and at least one additional signal may be plotted on at least one additional axis ( 15 ), as can be seen in FIG. 3 .
  • a histogram ( 17 ) of the n-dimensional parameter data may be provided.
  • Certain particles or cells may exhibit signals that can show enhanced differences by translation or scaling effects.
  • a male determining and female determining sperm cell may not be discriminated from each other using a typical unaltered light signal detected by a flow cytometer.
  • a digitized signal may have 12 bits of resolution
  • a sorting electronics may have 8 bits of resolution possibly discarding the lower 4 bits.
  • a detected light from male determining and female determining sperm cells may be so similar that the lower 4 bits may be required to discriminate between them.
  • the cells may not effectively be discriminated in histogram data analysis of the detected parameters possibly because histograms may also degrade resolution.
  • Particles or sperm cells may occupy a small area of a histogram ( 17 ).
  • the variation of detected signals of cells or particles, perhaps such as male determining sperm cells with respect to female determining sperm cells may be small; as may be the variation within cell or particles of the same type.
  • the total range of variation for both types of cells or particles may span less than half the total available range. Therefore, the lower bits of resolution may be important for discriminating between the cells or particles and perhaps even the upper bits may not be necessary to identify both types of cells or particles.
  • the invention may exploit this characteristic, in embodiments, by translating a center of the total range of signal variation for both types of cells or particles to an origin of a Cartesian coordinate system, scaling the data about the origin effectively increasing the variance between types, then translating back to its original location.
  • histogram data may show sufficient variation for discriminating between two types of cells or particles while even preserving enough information to identify both types from instrument noise, dead or destroyed cells, other foreign particles, and the like. This has particular applicability for sperm cell sex discrimination.
  • N-dimensional parameter data may be combined, in embodiments, to mathematically achieve numerical results representative of an alteration.
  • An alteration calculation may include any kind of manipulation of data.
  • embodiments may provide manipulating n-dimensional parameter data mathematically to achieve a desired result. This may include a rotational alteration perhaps with a rotational alteration calculation applied to n-dimensional parameter data.
  • Other embodiments may include a translation alteration perhaps with a translational alteration calculation.
  • n-dimensional parameter data may be combined to mathematically achieve numerical results representative of a scaling operation perhaps with a scaled alteration calculation.
  • Other kinds of alterations and calculations may be used and any alteration may be applied as a single operation or perhaps even in combination with others. Classification of a particle may be based upon numerical results representative of an alteration.
  • a signal ( 45 ) associated with a particle may be detected by at least one detector ( 46 ) in which signal data may be sent to a signal processor ( 47 ).
  • signal data may be converted into n-dimensional parameter data to which at least one alteration ( 48 ) (e.g. rotational alteration, translation operation, scaling operation, any combination of these and the like) may be applied to the n-dimensional parameter data.
  • alteration e.g. rotational alteration, translation operation, scaling operation, any combination of these and the like
  • n-dimensional parameter data may be classified into one of at least two populations providing a real-time classification ( 49 ).
  • a particle differentiation decision ( 50 ) may be made based upon a real-time classification of the n-dimensional parameter data to which directions may be sent to a flow cytometer ( 51 ) in order to charge and sort the particles.
  • Certain particles or cells may exhibit signals that can show enhanced differences by a rotational alteration of the data.
  • the invention may involve rotating data to increase a separation of data from male determining cells to female determining cells. Two sources of light may be detected for each cell. The range of light intensity from one source from male determining cells may overlap the same light source range from female determining cells. Employing a scale factor, as described above, may increase the separation of the mean distribution of the signal range but may not completely eliminate an overlap.
  • the invention may consider a shape of the signal distribution in two-dimensional analysis where signals from perhaps both light sources may be correlated in a two-dimensional Cartesian coordinate system.
  • each of the populations such as cell types may have an elliptical shaped population ( 18 ) with similar non-orthogonal angles of inclination of a major axis and may even have a similar length of a minor axis.
  • the difference in Y-intercept of the ellipse major axis for one cell type to the other type may be greater than the length of the minor axis. Since the major axes may be nearly parallel, it may be desirable to orient the elliptical shaped populations orthogonal to at least one axis.
  • a rotation about a mid-point between the two major axes may orient each ellipse orthogonal to the Y-axis possibly effectively eliminating the Y-axis overlap.
  • Signals such as perhaps light intensity may vary with time, which may preclude the setting of fixed regions by which sort decisions may be based.
  • populations may drift due to physical changes to the detectors, absorption or degradation of dye, and even other uncontrollable conditions. Consequently, sort regions may need to be monitored and adjusted during the sort. This may be tedious, labor intensive and even prone to error.
  • One embodiment of the present invention may hold a population in its original location by employing a scale operation in the transformation matrix.
  • One possible scale factor could be a ratio of an initial mean value of the signal range with respect to the current mean; which may effectively scale the signal up or down proportionately to the amount of drift from the initial mean.
  • a flow cytometer may be used to generate a stream into which the cells or other particulates may be injected.
  • a detection point may be established which may cause a source of laser light to strike the cells perhaps causing a dye that is carried on genomic material to fluoresce.
  • sperm may be orientated by the hydrodynamics of the injection device, and perhaps the fluorescence level could be proportional to the amount of genomic mass.
  • Fluorescence may be detected by sensors established forward of the detection point and possibly even to an angle, such as 90 degrees, of this point as may be understood in FIGS. 1 and 2 .
  • a sensory system can pass a pulse of light to an electrical device which may convert a pulse level into binary numbers suitable for manipulation by a Digital Signal Processor (“DSP”).
  • DSP Digital Signal Processor
  • a signal processor for example a Digital Signal Processor may contain highly optimized algorithms that can perform a specialization transformation of at least two signal values. This transformation may cause a resulting population of signal to adopt a form, such as where a separation of X and Y bearing sperm may be delineated. Clarity of delineation may allow each population to be selected more accurately than in any other separation system.
  • the selection of which population is to be sorted can be made by an electronic system such as by controlling a droplet break-off of a standard flow cytometer. There may be a delay between a detection of a fluorescence and a particle falling into a last breaking drop ( 36 ). This time may be known. Thus an electronic system can apply an electric charge to the drop containing the particle of interest. High voltage plates below the breaking drops may cause the drop to move and be placed into a collection vial. In this fashion, a high level of selected particles, perhaps such as pure sperm cells can be collected as may be understood in FIG. 1 .
  • a Digital Signal Processor may control the position of the populations.
  • Flow cytometers may have variability in the pointing accuracy of a laser beam which can cause an intensity of fluorescence from each cell to shift.
  • a DSP may act as a sensory device to monitor a shifting of light intensity and may even perform a correcting scale to ensure that the populations residing in the fluorescence bivariate remain in the same position. This may ensure that the correct sperm are sorted.
  • the process of transformation, zooming and perhaps even control may be imbedded in one geometric transform. Multiple transformation and zoom could be incorporated perhaps even with non-linear, logarithmic, table look up, or even discretely unique data portion transformations. Transformation may uniquely supply the accuracy required to provide highly pure particle separation.
  • One method of gaining spatially separated data may be to use compensation algorithms as those skilled in the art could appreciate.
  • Rotation of the data may be a more accurate mechanism to do this.
  • Rotated data can be used as a parameter in sort decisions and perhaps even in any other histograms. If data has been properly rotated, a univariate histogram of the parameter of interest can contain gaps in the populations.
  • a rotation function may be utilized to set the X and Y populations on a bivariate to be horizontal.
  • the populations of interest may typically be close together, it may be desirable—either alone or in combination with other aspects—to zoom in on a region in order to exaggerate a distinction between the populations. This may be another mechanism to allow separation of the populations.
  • the long sorts typical of sperm sorting or the like may cause data to shift over time. Shifts may be fixed by setting a tracking region and using this region in a newly computed parameter. In embodiments, an automatic region setting algorithm may be implemented. In other embodiments, regions may be set according to a desired purity level.
  • a rotation could be done using hardware that can access the data in an acquisition rack and may have a capability to modify an event frame prior to a sort decision being made. Rather than design new hardware, it may be desirable to implement this in a DSP perhaps by using a rotation algorithm. This may include an ability to do compensation on data when rotating it. In addition to rotation, a user can specify a region to zoom in on.
  • the present invention may provide specification of a center point of a rotation. This may allow a finer control of the rotation in order to achieve maximum separation.
  • N-dimensional space alteration functions may be combined with a vector having data points so as to alter the n-dimensional parameter data.
  • a combination of a function and data points may include, but is not limited to: calculating a first 1st-dimensional alteration value times a 1st-dimensional data point summed with a second 1st-dimensional alteration value times a 2nd-dimensional data point summed with a third 1st-dimensional alteration value times a 3rd-dimensional data point to thereby create a first dimensional altered data point; and calculating a first 2nd-dimensional alteration value times a 1st-dimensional data point summed with a second 2nd-dimensional rotational value times a 2nd-dimensional data point summed with a third 2nd-dimensional alteration value times a 3rd-dimensional data point to thereby create a second dimensional altered data point.
  • a n-dimensional space alteration function may include a first 3rd-dimensional alteration value, a second 3rd-dimensional alteration value and a third 3rd-dimensional alteration value.
  • a combination of data may include calculating a first 3rd-dimensional alteration value times a 1st-dimensional data point summed with a second 3rd-dimensional rotational value times a 2nd-dimensional data point summed with a third 3rd-dimensional alteration value times a 3rd-dimensional data point to thereby create a third dimensional altered data point.
  • a rotational alteration may include alteration values based upon an angle of rotation allowing altered data points to increase discrimination of at least two populations of n-dimensional data.
  • a scaled alteration may include alteration values are based upon a zoom and tracking element allowing altered data points to increase discrimination of at least two populations of n-dimensional data.
  • a translation alteration may include alteration values which may translate n-parameter data with respect to a center point of rotation.
  • the following are examples of matrices that may be used in order to do rotation about a given center point and even zoom or tracking on a region and the like.
  • T( ⁇ RC x , ⁇ RC y ) may translate an event to an origin and then the opposite in order to translate it back to a proper coordinate system. This may be done with all listmode data in the first quadrant.
  • the data that is being zoomed may be centered in a histogram. This may be why that data could be translated to half (1 ⁇ 2) the resolution rather than back to a center point of a zoomed region.
  • translation alterations may be based upon an operation such as rotation in x-axis, rotation in y-axis, rotation in z-axis, translation, scale, perspective, higher order and the like operations.
  • Some examples include the following 3-D algorithms:
  • R Z ⁇ ( ⁇ ) ⁇ cos ⁇ ( ⁇ ) - sin ⁇ ( ⁇ ) 0 0 sin ⁇ ( ⁇ ) cos ⁇ ( ⁇ ) 0 0 0 0 1 0 0 0 0 1 ⁇
  • T ⁇ ( T X , T Y , T Z ) ⁇ 1 0 0 T X 0 1 0 T Y 0 0 1 T Z 0 0 0 1 ⁇
  • Programs may solve the particular equation used and may download the result to the DSP.
  • a DSP code may perform a simple matrix multiplication using the matrices supplied by computer programs.
  • a computer program may create zoom parameters such that a mean of the zoomed signals may remain fixed. The mean may remain at the same position within a tracking region.
  • Software may allow a user to designate regions bounds which a zoom function may utilize. Software may send a center of a zoom, zoom value and even tracking gain to a DSP.
  • zooming of a square region on a split of populations may be shown on a Forward-Fluorescence versus a Side-fluorescence bivariate histogram.
  • a zoom region may be a square or perhaps even non-square with a maximum size which may be equal to a size of a bivariate.
  • it may be desirable to use a gain set at 1 and offset at 0 on both parameters.
  • a zoom region can be set as a fraction in percentage of the bivariate range in linear units. As those skilled in the art would recognize, 1/16 may offer a digital advantage.
  • software gain (distinct from a zoom gain) can be altered. Because the DSP may be a fixed point processor, a highly optimized assembly code may be used to do the floating point math.
  • the present invention in embodiments may include simultaneously processing two or more alteration calculations. This may include simultaneously processing n-dimensional parameter data to mathematically achieve numerical results of both a rotational alteration and a scaled alteration. Other embodiments may include simultaneously processing n-dimensional parameter data to mathematically achieve numerical results of a rotational alteration, a scaled alteration and perhaps even a translation alteration. Of course, additional alterations may be simultaneously or perhaps even sequentially processed as well.
  • FIG. 3 may be an image of data prior to rotation.
  • FIG. 4 shows an image of data after scaling
  • FIG. 5 show an image of data after rotation
  • FIG. 6 shows an image of data after scaling and rotation.
  • These may include one type of illustrations of data that can be expected. It is also common to see these illustrations of data from sperm sorting data. While rotating may allow a user to gain spatially separated data, it may distort the relative values of intensity and in embodiments, may not be used for any reason other than gaining the space between distinct populations. It may be possible to remove the values on the axis of the rotated data in order to assure that users have a visual way of recognizing this.
  • the basic concepts of the present invention may be embodied in a variety of ways. It involves both transformation techniques as well as devices to accomplish the appropriate transformation.
  • the transformation techniques are disclosed as part of the results shown to be achieved by the various devices described and as steps which are inherent to utilization. They are simply the natural result of utilizing the devices as intended and described.
  • some devices are disclosed, it should be understood that these not only accomplish certain methods but also can be varied in a number of ways. Importantly, as to all of the foregoing, all of these facets should be understood to be encompassed by this disclosure.
  • each of the various elements of the invention and claims may also be achieved in a variety of manners.
  • an element is to be understood as encompassing individual as well as plural structures that may or may not be physically connected.
  • This disclosure should be understood to encompass each such variation, be it a variation of an embodiment of any apparatus embodiment, a method or process embodiment, or even merely a variation of any element of these.
  • the words for each element may be expressed by equivalent apparatus terms or method terms—even if only the function or result is the same. Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action.
  • JP4126081 (A) 04/27/92 SAKAMOTO KAZUCHIKA et al. JP61139747 (A) 06/27/86 ITO YUJI JP61159135 (A) 07/18/86 ITO YUJI SU1056008 11/23/83 TRETYAKOV ALEKSANDR et al. SU1260778-A1 09/30/86 YAGUNOV ALEKSEJ et al WO96/12172 A1 04/25/1996 Van Den Engh WO 99/44037 02/26/1999 Malachowski WO01/28700 A1 04/26/2001 Ellison, et al.
  • each of the transformation devices as herein disclosed and described ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative designs which accomplish each of the functions shown as are disclosed and described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, ix) each system, method, and element shown or described as now applied to any specific field or devices mentioned, x) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, xi) the various combinations and permutations of each of the elements disclosed, xii) each potentially dependent claim or concept as a dependency on each and every one of the
  • any claims set forth at any time are hereby incorporated by reference as part of this description of the invention, and the applicant expressly reserves the right to use all of or a portion of such incorporated content of such claims as additional description to support any of or all of the claims or any element or component thereof, and the applicant further expressly reserves the right to move any portion of or all of the incorporated content of such claims or any element or component thereof from the description into the claims or vice-versa as necessary to define the matter for which protection is sought by this application or by any subsequent continuation, division, or continuation-in-part application thereof, or to obtain any benefit of, reduction in fees pursuant to, or to comply with the patent laws, rules, or regulations of any country or treaty, and such content incorporated by reference shall survive during the entire pendency of this application including any subsequent continuation, division, or continuation-in-part application thereof or any reissue or extension thereon.

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11119030B2 (en) 2014-02-13 2021-09-14 Sony Corporation Particle sorting device, particle sorting method, program, and particle sorting system
US11193874B2 (en) 2012-03-30 2021-12-07 Sony Corporation Micro-particle sorting apparatus and method of determining a trajectory of an ejected stream carrying micro-particles
US11204309B2 (en) * 2015-10-19 2021-12-21 Sony Corporation Image processing device, fine particle sorting device, and image processing method
US11313784B2 (en) 2013-01-28 2022-04-26 Sony Corporation Microparticle sorting device, and method and program for sorting microparticles
US11408813B2 (en) 2004-07-27 2022-08-09 Beckman Coulter, Inc. Enhancing flow cytometry discrimination with geometric transformation

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2264427B1 (en) 1997-01-31 2017-05-03 Xy, Llc Optical apparatus with focussing reflector for converging radiation onto a flow of particles, and related method of analysis
US6149867A (en) 1997-12-31 2000-11-21 Xy, Inc. Sheath fluids and collection systems for sex-specific cytometer sorting of sperm
US7208265B1 (en) 1999-11-24 2007-04-24 Xy, Inc. Method of cryopreserving selected sperm cells
BRPI0115792B1 (pt) 2000-11-29 2020-05-05 Colorado State Univ sistema para separação de espermatozóides congelados/descongelados em populações portadoras de cromossomo-x e portadoras de cromossomo-y
US7713687B2 (en) 2000-11-29 2010-05-11 Xy, Inc. System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations
JP4595067B2 (ja) 2002-08-01 2010-12-08 エックスワイ，エルエルシー 低圧精子細胞分離システム
US8486618B2 (en) 2002-08-01 2013-07-16 Xy, Llc Heterogeneous inseminate system
CA2534394C (en) 2002-08-15 2013-01-08 Xy, Inc. High resolution flow cytometer
US7169548B2 (en) 2002-09-13 2007-01-30 Xy, Inc. Sperm cell processing and preservation systems
ES2918578T3 (es) 2003-03-28 2022-07-19 Inguran Llc Aparato y métodos para proporcionar esperma animal clasificado por sexo
NZ544103A (en) 2003-05-15 2010-10-29 Xy Llc Efficient haploid cell sorting for flow cytometer systems
CA2561519C (en) 2004-03-29 2017-08-22 Monsanto Technology Llc Sperm dispersions for use in insemination
CA2574499C (en) 2004-07-22 2016-11-29 Monsanto Technology Llc Process for enriching a population of sperm cells
US8214157B2 (en) * 2006-03-31 2012-07-03 Nodality, Inc. Method and apparatus for representing multidimensional data
US20090269800A1 (en) * 2008-04-29 2009-10-29 Todd Covey Device and method for processing cell samples
US20100042351A1 (en) * 2008-07-10 2010-02-18 Covey Todd M Methods and apparatus related to management of experiments
US9183237B2 (en) 2008-07-10 2015-11-10 Nodality, Inc. Methods and apparatus related to gate boundaries within a data space
US20100014741A1 (en) * 2008-07-10 2010-01-21 Banville Steven C Methods and apparatus related to gate boundaries within a data space
US20100030719A1 (en) * 2008-07-10 2010-02-04 Covey Todd M Methods and apparatus related to bioinformatics data analysis
FR2935802B1 (fr) * 2008-09-05 2012-12-28 Horiba Abx Sas Procede et dispositif de classification, de visualisation et d'exploration de donnees biologiques
US9034257B2 (en) 2008-10-27 2015-05-19 Nodality, Inc. High throughput flow cytometry system and method
US20100204973A1 (en) * 2009-01-15 2010-08-12 Nodality, Inc., A Delaware Corporation Methods For Diagnosis, Prognosis And Treatment
WO2013096137A1 (en) * 2011-12-20 2013-06-27 Becton, Dickinson And Company System and method to improve yield of sorted particles
JP5994337B2 (ja) 2012-03-30 2016-09-21 ソニー株式会社 微小粒子分取装置及びディレイタイム決定方法
JP2016515211A (ja) * 2013-03-15 2016-05-26 ベックマン コールター， インコーポレイテッド フローサイトメーター用の光学系
US10466158B2 (en) * 2017-04-11 2019-11-05 Sony Corporation Microparticle sorting apparatus and delay time determination method
US10593082B2 (en) 2017-07-18 2020-03-17 Becton, Dickinson And Company Dynamic display of multi-parameter quantitative biological data
CN110770571B (zh) 2017-07-18 2022-09-20 贝克顿·迪金森公司 多参数定量生物学数据的动态交互显示
US10636182B2 (en) 2017-07-18 2020-04-28 Becton, Dickinson And Company Dynamic interactive display of multi-parameter quantitative biological data
JP2022516233A (ja) 2018-12-28 2022-02-25 ベクトン・ディキンソン・アンド・カンパニー サンプルの蛍光物質をスペクトル的に分解する方法及びシステム
CN111521549B (zh) * 2020-05-13 2021-01-01 洹仪科技(上海)有限公司 一种颗粒分选装置及方法
CN115867971A (zh) * 2020-05-18 2023-03-28 贝克顿·迪金森公司 用于检测数据中的异质性的分辨率指数及其使用方法
WO2021257553A1 (en) * 2020-06-17 2021-12-23 Idexx Laboratories Inc. Flow cytometer and laser optics assembly thereof
CA3200930A1 (en) * 2020-12-23 2022-06-30 Lakshmi Krishnan Particle classification and sorting systems and methods

Citations (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3299354A (en) 1962-07-05 1967-01-17 Coulter Electronics Aperture tube structure for particle study apparatus
US3661460A (en) 1970-08-28 1972-05-09 Technicon Instr Method and apparatus for optical analysis of the contents of a sheathed stream
US3710933A (en) 1971-12-23 1973-01-16 Atomic Energy Commission Multisensor particle sorter
US3761941A (en) 1972-10-13 1973-09-25 Mead Corp Phase control for a drop generating and charging system
US3810010A (en) 1968-11-02 1974-05-07 Telefunken Patent Particle analysis method and apparatus wherein liquid containing particles is sucked into a constricted flow path
US3826364A (en) 1972-05-22 1974-07-30 Univ Leland Stanford Junior Particle sorting method and apparatus
US3833796A (en) 1971-10-13 1974-09-03 Georgia Tech Res Inst Method and apparatus for chromosome digitizing
US3960449A (en) 1975-06-05 1976-06-01 The Board Of Trustees Of Leland Stanford Junior University Measurement of angular dependence of scattered light in a flowing stream
US3963606A (en) 1974-06-03 1976-06-15 Coulter Electronics, Inc. Semi-automatic adjusting delay for an electronic particle separator
US3973196A (en) 1974-05-24 1976-08-03 Coulter Electronics, Inc. Method and apparatus for ejecting a metered amount of particulate sample
US4014611A (en) 1975-04-30 1977-03-29 Coulter Electronics, Inc. Aperture module for use in particle testing apparatus
US4070617A (en) 1974-05-08 1978-01-24 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Device for controlling the particle flow in an apparatus for measuring the properties of particles suspended in liquid
US4074809A (en) 1976-07-19 1978-02-21 Coors Container Company Apparatus and methods for inspection of can bodies by use of light
US4162282A (en) 1976-04-22 1979-07-24 Coulter Electronics, Inc. Method for producing uniform particles
US4230558A (en) 1978-10-02 1980-10-28 Coulter Electronics, Inc. Single drop separator
EP0025296A2 (en) 1979-08-20 1981-03-18 Ortho Diagnostic Systems Inc. Apparatus and method for positioning the point of droplet formation in the jetting fluid of an electrostatic sorting device
US4302166A (en) 1976-04-22 1981-11-24 Coulter Electronics, Inc. Droplet forming apparatus for use in producing uniform particles
US4317520A (en) 1979-08-20 1982-03-02 Ortho Diagnostics, Inc. Servo system to control the spatial position of droplet formation of a fluid jet in a cell sorting apparatus
US4318483A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Automatic relative droplet charging time delay system for an electrostatic particle sorting system using a relatively moveable stream surface sensing system
US4318481A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Method for automatically setting the correct phase of the charge pulses in an electrostatic flow sorter
US4318482A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Method for measuring the velocity of a perturbed jetting fluid in an electrostatic particle sorting system
US4325483A (en) 1979-08-20 1982-04-20 Ortho Diagnostics, Inc. Method for detecting and controlling flow rates of the droplet forming stream of an electrostatic particle sorting apparatus
US4325706A (en) * 1980-08-15 1982-04-20 Ortho Diagnostic Systems Inc. Automated detection of platelets and reticulocytes in whole blood
US4341471A (en) 1979-01-02 1982-07-27 Coulter Electronics, Inc. Apparatus and method for measuring the distribution of radiant energy produced in particle investigating systems
US4350410A (en) 1980-10-08 1982-09-21 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Multiprism collimator
US4361400A (en) 1980-11-26 1982-11-30 The United States Of America As Represented By The United States Department Of Energy Fluidic assembly for an ultra-high-speed chromosome flow sorter
US4395676A (en) 1980-11-24 1983-07-26 Coulter Electronics, Inc. Focused aperture module
US4400764A (en) 1980-02-05 1983-08-23 The Boeing Company Low backscatter illumination system
SU1056008A1 (ru) 1982-01-25 1983-11-23 Предприятие П/Я Р-6681 Проточный цитофлуориметр
US4487320A (en) 1980-11-03 1984-12-11 Coulter Corporation Method of and apparatus for detecting change in the breakoff point in a droplet generation system
US4498766A (en) 1982-03-25 1985-02-12 Becton, Dickinson And Company Light beam focal spot elongation in flow cytometry devices
US4501336A (en) 1982-06-03 1985-02-26 Kemp Billy W Method and apparatus of a self-aligning sleeve for the correction of the direction of deviated boreholes
US4515274A (en) 1981-12-02 1985-05-07 Coulter Corporation Particle analyzing and sorting apparatus
US4523809A (en) 1983-08-04 1985-06-18 The United States Of America As Represented By The Secretary Of The Air Force Method and apparatus for generating a structured light beam array
US4538733A (en) 1983-10-14 1985-09-03 Becton, Dickinson And Company Particle sorter with neutralized collection wells and method of using same
EP0160201A2 (en) 1984-05-03 1985-11-06 Becton Dickinson and Company Improved optical features of flow cytometry apparatus
JPS61139747A (ja) 1984-12-12 1986-06-27 Canon Inc 粒子解析装置
US4598408A (en) 1984-10-22 1986-07-01 Trw Inc. High extraction efficiency cylindrical ring resonator
US4600302A (en) 1984-03-26 1986-07-15 Becton, Dickinson And Company Flow cytometry apparatus with uniform incoherent light excitation
JPS61159135A (ja) 1984-12-31 1986-07-18 Canon Inc 粒子解析装置
SU1260778A1 (ru) 1985-01-31 1986-09-30 Центральный научно-исследовательский рентгено-радиологический институт Устройство дл флуоресцентного анализа отдельных микрочастиц в потоке
US4631483A (en) 1984-02-01 1986-12-23 Coulter Electronics, Inc. Particle analyzing apparatus and method of moving particles in suspension through such apparatus
US4673288A (en) 1981-05-15 1987-06-16 Ratcom, Inc. Flow cytometry
US4691829A (en) 1980-11-03 1987-09-08 Coulter Corporation Method of and apparatus for detecting change in the breakoff point in a droplet generation system
US4702598A (en) 1985-02-25 1987-10-27 Research Corporation Flow cytometer
US4744090A (en) 1985-07-08 1988-05-10 Trw Inc. High-extraction efficiency annular resonator
US4758729A (en) 1987-08-28 1988-07-19 Spectra-Physics, Inc. Apparatus and method for measuring the included angle of a reflective cone
US4794086A (en) 1985-11-25 1988-12-27 Liquid Air Corporation Method for measurement of impurities in liquids
US4818103A (en) 1981-05-15 1989-04-04 Ratcom Flow cytometry
US4831385A (en) 1987-10-14 1989-05-16 Burlington Industries, Inc. Vacuum tray fluid-jet start-up system
US4845025A (en) 1987-11-10 1989-07-04 Coulter Corporation Biological sample mixing apparatus and method
US4877965A (en) 1985-07-01 1989-10-31 Diatron Corporation Fluorometer
JPH0224535A (ja) 1988-07-12 1990-01-26 Canon Inc 粒子解析装置
US4942305A (en) 1989-05-12 1990-07-17 Pacific Scientific Company Integrating sphere aerosol particle detector
US4981580A (en) 1989-05-01 1991-01-01 Coulter Corporation Coincidence arbitration in a flow cytomery sorting system
US4983038A (en) 1987-04-08 1991-01-08 Hitachi, Ltd. Sheath flow type flow-cell device
US4987539A (en) 1987-08-05 1991-01-22 Stanford University Apparatus and method for multidimensional characterization of objects in real time
US5005981A (en) 1989-09-08 1991-04-09 Becton, Dickinson And Company Apparatus for method for causing vortices in a test tube
US5007732A (en) 1987-04-20 1991-04-16 Hitachi, Ltd. Flow-cell device
US5030002A (en) 1989-08-11 1991-07-09 Becton, Dickinson And Company Method and apparatus for sorting particles with a moving catcher tube
US5034613A (en) 1989-11-14 1991-07-23 Cornell Research Foundation, Inc. Two-photon laser microscopy
US5079959A (en) 1988-09-19 1992-01-14 Hitachi, Ltd. Analyzing system using sheath flow of sample
EP0468100A1 (en) 1990-07-24 1992-01-29 Toa Medical Electronics Co., Ltd. Automatic focal-point adjustment method in flow imaging cytometer
US5098657A (en) 1989-08-07 1992-03-24 Tsi Incorporated Apparatus for measuring impurity concentrations in a liquid
US5101978A (en) 1989-11-27 1992-04-07 The United States Of America As Represented By The Secretary Of The Army Fluidic sorting device for two or more materials suspended in a fluid
JPH04126081A (ja) 1990-06-20 1992-04-27 P C C Technol:Kk 細胞融合及び融合細胞選別システム
JPH04126066A (ja) 1990-06-20 1992-04-27 P C C Technol:Kk プロトプラスト攪拌装置並びにそれを含む細胞融合装置及びフローサイトメーター装置
JPH04126064A (ja) 1990-09-14 1992-04-27 Nitto Shokai:Kk 二重包餡食品の製造法
US5127729A (en) 1983-12-24 1992-07-07 Inotech Ag Method and apparatus for guiding and collecting light in photometry or the like
US5135759A (en) 1989-05-10 1992-08-04 The United States Of America As Represented By The Secretary Of Agriculture Method to preselect the sex of offspring
US5144224A (en) 1991-04-01 1992-09-01 Larsen Lawrence E Millimeter wave flow cytometer
US5150313A (en) 1990-04-12 1992-09-22 Regents Of The University Of California Parallel pulse processing and data acquisition for high speed, low error flow cytometry
US5159397A (en) 1991-02-27 1992-10-27 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5159403A (en) 1990-11-22 1992-10-27 Toa Medical Electronics Co., Ltd. Flow cell mechanism in flow imaging cytometer
US5167926A (en) 1989-09-13 1992-12-01 Kabushiki Kaisha Tiyoda Seisakusho Apparatus for pretreating cells for flow cytometry
US5180065A (en) 1989-10-11 1993-01-19 Canon Kabushiki Kaisha Apparatus for and method of fractionating particle in particle-suspended liquid in conformity with the properties thereof
US5182617A (en) 1989-07-20 1993-01-26 Canon Kabushiki Kaisha Sample supply device and sample inspection apparatus using the device
US5199576A (en) 1991-04-05 1993-04-06 University Of Rochester System for flexibly sorting particles
US5215376A (en) 1989-09-08 1993-06-01 Becton, Dickinson And Company Method for causing vortices in a test tube
US5224058A (en) * 1990-05-01 1993-06-29 Becton, Dickinson And Company Method for data transformation
US5247339A (en) 1991-02-27 1993-09-21 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5259593A (en) 1990-08-30 1993-11-09 University Of Southern California Apparatus for droplet stream manufacturing
US5260764A (en) 1990-02-08 1993-11-09 Toa Medical Electronics Co., Ltd. Optical particle analyzing apparatus having two types of light source
US5298967A (en) 1992-06-02 1994-03-29 Pacific Scientific Company Measurement of concentrations of dissolved solvent
FR2699678A1 (fr) 1992-12-23 1994-06-24 Unceia Procédé cytométrique de séparation de spermatozoïdes X et Y en fonction de leur contenu en ADN.
US5359907A (en) 1992-11-12 1994-11-01 Horiba Instruments, Inc. Method and apparatus for dry particle analysis
US5367474A (en) 1993-02-08 1994-11-22 Coulter Corporation Flow cytometer
US5370842A (en) 1991-11-29 1994-12-06 Canon Kabushiki Kaisha Sample measuring device and sample measuring system
US5412466A (en) 1991-07-26 1995-05-02 Toa Medical Electronics Co., Ltd. Apparatus for forming flattened sample flow for analyzing particles
US5452054A (en) 1993-03-01 1995-09-19 General Signal Corporation Variable annular illuminator for photolithographic projection imager
US5467189A (en) 1993-01-22 1995-11-14 Venturedyne, Ltd. Improved particle sensor and method for assaying a particle
US5466572A (en) 1992-09-03 1995-11-14 Systemix, Inc. High speed flow cytometric separation of viable cells
US5471294A (en) 1991-10-24 1995-11-28 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5483469A (en) 1993-08-02 1996-01-09 The Regents Of The University Of California Multiple sort flow cytometer
US5503994A (en) 1993-10-08 1996-04-02 The Board Of Trustees Of The Leland Stanford Junior University System for sample detection with compensation for difference in sensitivity to detection of components moving at different velocities
WO1996012172A1 (en) 1994-10-14 1996-04-25 University Of Washington Flow cytometer jet monitor system
US5523573A (en) 1994-01-26 1996-06-04 Haenninen; Pekka Method for the excitation of dyes
US5558998A (en) 1992-02-25 1996-09-24 The Regents Of The Univ. Of California DNA fragment sizing and sorting by laser-induced fluorescence
US5596401A (en) 1993-09-16 1997-01-21 Toa Medical Electronics Co., Ltd. Particle analyzing apparatus using a coherence lowering device
US5601235A (en) 1993-12-04 1997-02-11 United Kingdom Atomic Energy Authority Aerosol generator
US5602349A (en) 1994-10-14 1997-02-11 The University Of Washington Sample introduction system for a flow cytometer
DE19549015C1 (de) 1995-12-28 1997-04-03 Siemens Ag Verfahren und Anordnung zur Überwachung eines abreißenden Flüssigkeitstrahls
US5641457A (en) 1995-04-25 1997-06-24 Systemix Sterile flow cytometer and sorter with mechanical isolation between flow chamber and sterile enclosure
US5643796A (en) 1994-10-14 1997-07-01 University Of Washington System for sensing droplet formation time delay in a flow cytometer
US5650847A (en) 1995-06-14 1997-07-22 Erkki Soini Method and device for determination of parameters of individual microparticles
US5672880A (en) 1994-12-08 1997-09-30 Molecular Dynamics, Inc. Fluoresecence imaging system
US5675401A (en) 1994-06-17 1997-10-07 Carl-Zeiss-Stiftung Illuminating arrangement including a zoom objective incorporating two axicons
US5700692A (en) 1994-09-27 1997-12-23 Becton Dickinson And Company Flow sorter with video-regulated droplet spacing
US5707808A (en) 1996-04-15 1998-01-13 The Regents Of The University Of California Optical selection and collection of DNA fragments
US5759767A (en) 1996-10-11 1998-06-02 Joseph R. Lakowicz Two-photon and multi-photon measurement of analytes in animal and human tissues and fluids
US5777732A (en) 1994-04-28 1998-07-07 Hanninen; Pekka Luminescence-scanning microscopy process and a luminescence scanning microscope utilizing picosecond or greater pulse lasers
US5786560A (en) 1995-03-31 1998-07-28 Panasonic Technologies, Inc. 3-dimensional micromachining with femtosecond laser pulses
US5796112A (en) 1993-06-03 1998-08-18 Hamamatsu Photonics K.K. Laser scanning optical system and laser scanning optical apparatus
US5815262A (en) 1995-09-07 1998-09-29 Basf Aktiengesellschaft Apparatus for parallelized two-photon fluorescence correlation spectroscopy (TPA-FCS), and the use thereof for screening active compounds
US5824269A (en) 1994-12-26 1998-10-20 Toa Medical Electronics Co., Ltd. Flow cytometer
US5835262A (en) 1994-12-28 1998-11-10 Research Development Corporation Of Japan Multi-wavelength optical microscope
US5880457A (en) 1996-06-14 1999-03-09 Hamamatsu Photonics K.K. Voltage division circuit for a photomultiplier tube
US5885840A (en) 1997-02-10 1999-03-23 Compucyte Corp. Multiple assays of cell specimens
US5912257A (en) 1995-09-06 1999-06-15 The Research Foundation Of State University Of New York Two-photon upconverting dyes and applications
WO1999044037A1 (en) 1998-02-27 1999-09-02 Cytomation, Inc. Method and apparatus for flow cytometry
WO2000032542A1 (en) 1998-11-30 2000-06-08 The University Of Queensland Carriers for combinatorial compound libraries
WO2001028700A1 (en) 1999-10-21 2001-04-26 Cytomation, Inc. Transiently dynamic flow cytometer analysis system
US20030184730A1 (en) 2002-01-23 2003-10-02 The Regents Of The University Of California Fast 3D cytometry for information in tissue engineering
US6630990B2 (en) 2001-06-05 2003-10-07 Abbott Laboratories Optical method and apparatus for red blood cell differentiation on a cell-by-cell basis, and simultaneous analysis of white blood cell differentiation
US6662117B2 (en) 2000-07-24 2003-12-09 Sysmex Corporation Particle analyzer and particle classifying method
US20040062685A1 (en) * 2002-09-27 2004-04-01 Norton Pierce O Fixed mounted sorting cuvette with user replaceable nozzle
US6763149B2 (en) 2001-04-25 2004-07-13 Amnis Corporation Method and apparatus for correcting crosstalk and spatial resolution for multichannel imaging
US20050112541A1 (en) * 2003-03-28 2005-05-26 Monsanto Technology Llc Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm
US6944338B2 (en) 2000-05-11 2005-09-13 Becton Dickinson And Company System for identifying clusters in scatter plots using smoothed polygons with optimal boundaries
JP4126064B2 (ja) 2003-11-27 2008-07-30 本田技研工業株式会社 移動体の制御装置
US9625367B2 (en) * 2004-07-27 2017-04-18 Beckman Coulter, Inc. Enhancing flow cytometry discrimination with geometric transformation

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3229354A (en) * 1961-04-24 1966-01-18 Gen Electric Method of assembling a mercury button switch
JPH0738838Y2 (ja) 1990-09-28 1995-09-06 東亜医用電子株式会社 粒子分析装置及び該装置に用いるフローセル
WO1992007245A1 (en) 1990-10-10 1992-04-30 The University Of Maryland Method and apparatus for performing phase fluorescence lifetime measurements in flow cytometry
CA2235069C (en) 1995-10-19 2010-12-14 Advanced Reproduction Technologies, Inc. Methods and compositions to improve germ cell and embryo survival and function
US5985216A (en) 1997-07-24 1999-11-16 The United States Of America, As Represented By The Secretary Of Agriculture Flow cytometry nozzle for high efficiency cell sorting
US6149867A (en) 1997-12-31 2000-11-21 Xy, Inc. Sheath fluids and collection systems for sex-specific cytometer sorting of sperm
US6071689A (en) 1997-12-31 2000-06-06 Xy, Inc. System for improving yield of sexed embryos in mammals
US8131053B2 (en) * 1999-01-25 2012-03-06 Amnis Corporation Detection of circulating tumor cells using imaging flow cytometry
US7208265B1 (en) 1999-11-24 2007-04-24 Xy, Inc. Method of cryopreserving selected sperm cells
CA2408939C (en) 2000-05-09 2011-11-08 Xy, Inc. High purity x-chromosome bearing and y-chromosome bearing populations of spermatozoa
US7713687B2 (en) 2000-11-29 2010-05-11 Xy, Inc. System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations
US7043500B2 (en) 2001-04-25 2006-05-09 Board Of Regents, The University Of Texas Syxtem Subtractive clustering for use in analysis of data
NZ544103A (en) 2003-05-15 2010-10-29 Xy Llc Efficient haploid cell sorting for flow cytometer systems
US8541227B2 (en) 2005-02-25 2013-09-24 Dako Denmark A/S Cell counting
US7113266B1 (en) * 2005-03-30 2006-09-26 Beckman Coulter, Inc. Flow cytometer for differentiating small particles in suspension

Patent Citations (140)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3299354A (en) 1962-07-05 1967-01-17 Coulter Electronics Aperture tube structure for particle study apparatus
US3810010A (en) 1968-11-02 1974-05-07 Telefunken Patent Particle analysis method and apparatus wherein liquid containing particles is sucked into a constricted flow path
US3661460A (en) 1970-08-28 1972-05-09 Technicon Instr Method and apparatus for optical analysis of the contents of a sheathed stream
US3833796A (en) 1971-10-13 1974-09-03 Georgia Tech Res Inst Method and apparatus for chromosome digitizing
US3710933A (en) 1971-12-23 1973-01-16 Atomic Energy Commission Multisensor particle sorter
US3826364A (en) 1972-05-22 1974-07-30 Univ Leland Stanford Junior Particle sorting method and apparatus
US3826364B1 (da) 1972-05-22 1984-09-25
US3761941A (en) 1972-10-13 1973-09-25 Mead Corp Phase control for a drop generating and charging system
US4070617A (en) 1974-05-08 1978-01-24 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Device for controlling the particle flow in an apparatus for measuring the properties of particles suspended in liquid
US3973196A (en) 1974-05-24 1976-08-03 Coulter Electronics, Inc. Method and apparatus for ejecting a metered amount of particulate sample
US3963606A (en) 1974-06-03 1976-06-15 Coulter Electronics, Inc. Semi-automatic adjusting delay for an electronic particle separator
US4014611A (en) 1975-04-30 1977-03-29 Coulter Electronics, Inc. Aperture module for use in particle testing apparatus
US3960449A (en) 1975-06-05 1976-06-01 The Board Of Trustees Of Leland Stanford Junior University Measurement of angular dependence of scattered light in a flowing stream
US4162282A (en) 1976-04-22 1979-07-24 Coulter Electronics, Inc. Method for producing uniform particles
US4302166A (en) 1976-04-22 1981-11-24 Coulter Electronics, Inc. Droplet forming apparatus for use in producing uniform particles
US4074809A (en) 1976-07-19 1978-02-21 Coors Container Company Apparatus and methods for inspection of can bodies by use of light
US4230558A (en) 1978-10-02 1980-10-28 Coulter Electronics, Inc. Single drop separator
US4341471A (en) 1979-01-02 1982-07-27 Coulter Electronics, Inc. Apparatus and method for measuring the distribution of radiant energy produced in particle investigating systems
US4317520A (en) 1979-08-20 1982-03-02 Ortho Diagnostics, Inc. Servo system to control the spatial position of droplet formation of a fluid jet in a cell sorting apparatus
US4318483A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Automatic relative droplet charging time delay system for an electrostatic particle sorting system using a relatively moveable stream surface sensing system
US4318481A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Method for automatically setting the correct phase of the charge pulses in an electrostatic flow sorter
US4318480A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Method and apparatus for positioning the point of droplet formation in the jetting fluid of an electrostatic sorting device
US4318482A (en) 1979-08-20 1982-03-09 Ortho Diagnostics, Inc. Method for measuring the velocity of a perturbed jetting fluid in an electrostatic particle sorting system
US4325483A (en) 1979-08-20 1982-04-20 Ortho Diagnostics, Inc. Method for detecting and controlling flow rates of the droplet forming stream of an electrostatic particle sorting apparatus
EP0025296A2 (en) 1979-08-20 1981-03-18 Ortho Diagnostic Systems Inc. Apparatus and method for positioning the point of droplet formation in the jetting fluid of an electrostatic sorting device
US4400764A (en) 1980-02-05 1983-08-23 The Boeing Company Low backscatter illumination system
US4325706A (en) * 1980-08-15 1982-04-20 Ortho Diagnostic Systems Inc. Automated detection of platelets and reticulocytes in whole blood
US4350410A (en) 1980-10-08 1982-09-21 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Multiprism collimator
US4487320A (en) 1980-11-03 1984-12-11 Coulter Corporation Method of and apparatus for detecting change in the breakoff point in a droplet generation system
US4691829A (en) 1980-11-03 1987-09-08 Coulter Corporation Method of and apparatus for detecting change in the breakoff point in a droplet generation system
US4395676A (en) 1980-11-24 1983-07-26 Coulter Electronics, Inc. Focused aperture module
US4361400A (en) 1980-11-26 1982-11-30 The United States Of America As Represented By The United States Department Of Energy Fluidic assembly for an ultra-high-speed chromosome flow sorter
US4673288A (en) 1981-05-15 1987-06-16 Ratcom, Inc. Flow cytometry
US4818103A (en) 1981-05-15 1989-04-04 Ratcom Flow cytometry
US4515274A (en) 1981-12-02 1985-05-07 Coulter Corporation Particle analyzing and sorting apparatus
SU1056008A1 (ru) 1982-01-25 1983-11-23 Предприятие П/Я Р-6681 Проточный цитофлуориметр
US4498766A (en) 1982-03-25 1985-02-12 Becton, Dickinson And Company Light beam focal spot elongation in flow cytometry devices
US4501336A (en) 1982-06-03 1985-02-26 Kemp Billy W Method and apparatus of a self-aligning sleeve for the correction of the direction of deviated boreholes
US4523809A (en) 1983-08-04 1985-06-18 The United States Of America As Represented By The Secretary Of The Air Force Method and apparatus for generating a structured light beam array
US4538733A (en) 1983-10-14 1985-09-03 Becton, Dickinson And Company Particle sorter with neutralized collection wells and method of using same
US5127729A (en) 1983-12-24 1992-07-07 Inotech Ag Method and apparatus for guiding and collecting light in photometry or the like
US4631483A (en) 1984-02-01 1986-12-23 Coulter Electronics, Inc. Particle analyzing apparatus and method of moving particles in suspension through such apparatus
US4600302A (en) 1984-03-26 1986-07-15 Becton, Dickinson And Company Flow cytometry apparatus with uniform incoherent light excitation
EP0160201A2 (en) 1984-05-03 1985-11-06 Becton Dickinson and Company Improved optical features of flow cytometry apparatus
US4598408A (en) 1984-10-22 1986-07-01 Trw Inc. High extraction efficiency cylindrical ring resonator
JPS61139747A (ja) 1984-12-12 1986-06-27 Canon Inc 粒子解析装置
JPS61159135A (ja) 1984-12-31 1986-07-18 Canon Inc 粒子解析装置
SU1260778A1 (ru) 1985-01-31 1986-09-30 Центральный научно-исследовательский рентгено-радиологический институт Устройство дл флуоресцентного анализа отдельных микрочастиц в потоке
US4702598A (en) 1985-02-25 1987-10-27 Research Corporation Flow cytometer
US4877965A (en) 1985-07-01 1989-10-31 Diatron Corporation Fluorometer
US4744090A (en) 1985-07-08 1988-05-10 Trw Inc. High-extraction efficiency annular resonator
US4794086A (en) 1985-11-25 1988-12-27 Liquid Air Corporation Method for measurement of impurities in liquids
US4983038A (en) 1987-04-08 1991-01-08 Hitachi, Ltd. Sheath flow type flow-cell device
US5007732A (en) 1987-04-20 1991-04-16 Hitachi, Ltd. Flow-cell device
US4987539A (en) 1987-08-05 1991-01-22 Stanford University Apparatus and method for multidimensional characterization of objects in real time
US4758729A (en) 1987-08-28 1988-07-19 Spectra-Physics, Inc. Apparatus and method for measuring the included angle of a reflective cone
US4831385A (en) 1987-10-14 1989-05-16 Burlington Industries, Inc. Vacuum tray fluid-jet start-up system
US4845025A (en) 1987-11-10 1989-07-04 Coulter Corporation Biological sample mixing apparatus and method
JPH0224535A (ja) 1988-07-12 1990-01-26 Canon Inc 粒子解析装置
US5079959A (en) 1988-09-19 1992-01-14 Hitachi, Ltd. Analyzing system using sheath flow of sample
US4981580A (en) 1989-05-01 1991-01-01 Coulter Corporation Coincidence arbitration in a flow cytomery sorting system
US5135759A (en) 1989-05-10 1992-08-04 The United States Of America As Represented By The Secretary Of Agriculture Method to preselect the sex of offspring
US4942305A (en) 1989-05-12 1990-07-17 Pacific Scientific Company Integrating sphere aerosol particle detector
US5182617A (en) 1989-07-20 1993-01-26 Canon Kabushiki Kaisha Sample supply device and sample inspection apparatus using the device
US5098657A (en) 1989-08-07 1992-03-24 Tsi Incorporated Apparatus for measuring impurity concentrations in a liquid
US5030002A (en) 1989-08-11 1991-07-09 Becton, Dickinson And Company Method and apparatus for sorting particles with a moving catcher tube
US5215376A (en) 1989-09-08 1993-06-01 Becton, Dickinson And Company Method for causing vortices in a test tube
US5005981A (en) 1989-09-08 1991-04-09 Becton, Dickinson And Company Apparatus for method for causing vortices in a test tube
US5167926A (en) 1989-09-13 1992-12-01 Kabushiki Kaisha Tiyoda Seisakusho Apparatus for pretreating cells for flow cytometry
US5180065A (en) 1989-10-11 1993-01-19 Canon Kabushiki Kaisha Apparatus for and method of fractionating particle in particle-suspended liquid in conformity with the properties thereof
US5034613A (en) 1989-11-14 1991-07-23 Cornell Research Foundation, Inc. Two-photon laser microscopy
US5101978A (en) 1989-11-27 1992-04-07 The United States Of America As Represented By The Secretary Of The Army Fluidic sorting device for two or more materials suspended in a fluid
US5260764A (en) 1990-02-08 1993-11-09 Toa Medical Electronics Co., Ltd. Optical particle analyzing apparatus having two types of light source
US5150313A (en) 1990-04-12 1992-09-22 Regents Of The University Of California Parallel pulse processing and data acquisition for high speed, low error flow cytometry
US5224058A (en) * 1990-05-01 1993-06-29 Becton, Dickinson And Company Method for data transformation
JPH04126066A (ja) 1990-06-20 1992-04-27 P C C Technol:Kk プロトプラスト攪拌装置並びにそれを含む細胞融合装置及びフローサイトメーター装置
JPH04126081A (ja) 1990-06-20 1992-04-27 P C C Technol:Kk 細胞融合及び融合細胞選別システム
EP0468100A1 (en) 1990-07-24 1992-01-29 Toa Medical Electronics Co., Ltd. Automatic focal-point adjustment method in flow imaging cytometer
US5259593A (en) 1990-08-30 1993-11-09 University Of Southern California Apparatus for droplet stream manufacturing
JPH04126064A (ja) 1990-09-14 1992-04-27 Nitto Shokai:Kk 二重包餡食品の製造法
US5159403A (en) 1990-11-22 1992-10-27 Toa Medical Electronics Co., Ltd. Flow cell mechanism in flow imaging cytometer
US5159397A (en) 1991-02-27 1992-10-27 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5247339A (en) 1991-02-27 1993-09-21 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5144224A (en) 1991-04-01 1992-09-01 Larsen Lawrence E Millimeter wave flow cytometer
US5199576A (en) 1991-04-05 1993-04-06 University Of Rochester System for flexibly sorting particles
US5412466A (en) 1991-07-26 1995-05-02 Toa Medical Electronics Co., Ltd. Apparatus for forming flattened sample flow for analyzing particles
US5471294A (en) 1991-10-24 1995-11-28 Toa Medical Electronics Co., Ltd. Flow imaging cytometer
US5370842A (en) 1991-11-29 1994-12-06 Canon Kabushiki Kaisha Sample measuring device and sample measuring system
US5558998A (en) 1992-02-25 1996-09-24 The Regents Of The Univ. Of California DNA fragment sizing and sorting by laser-induced fluorescence
US5298967A (en) 1992-06-02 1994-03-29 Pacific Scientific Company Measurement of concentrations of dissolved solvent
US5466572A (en) 1992-09-03 1995-11-14 Systemix, Inc. High speed flow cytometric separation of viable cells
US5359907A (en) 1992-11-12 1994-11-01 Horiba Instruments, Inc. Method and apparatus for dry particle analysis
FR2699678A1 (fr) 1992-12-23 1994-06-24 Unceia Procédé cytométrique de séparation de spermatozoïdes X et Y en fonction de leur contenu en ADN.
US5467189A (en) 1993-01-22 1995-11-14 Venturedyne, Ltd. Improved particle sensor and method for assaying a particle
US5367474A (en) 1993-02-08 1994-11-22 Coulter Corporation Flow cytometer
US5452054A (en) 1993-03-01 1995-09-19 General Signal Corporation Variable annular illuminator for photolithographic projection imager
US5796112A (en) 1993-06-03 1998-08-18 Hamamatsu Photonics K.K. Laser scanning optical system and laser scanning optical apparatus
US5483469A (en) 1993-08-02 1996-01-09 The Regents Of The University Of California Multiple sort flow cytometer
US5596401A (en) 1993-09-16 1997-01-21 Toa Medical Electronics Co., Ltd. Particle analyzing apparatus using a coherence lowering device
US5503994A (en) 1993-10-08 1996-04-02 The Board Of Trustees Of The Leland Stanford Junior University System for sample detection with compensation for difference in sensitivity to detection of components moving at different velocities
US5601235A (en) 1993-12-04 1997-02-11 United Kingdom Atomic Energy Authority Aerosol generator
US5523573A (en) 1994-01-26 1996-06-04 Haenninen; Pekka Method for the excitation of dyes
US5777732A (en) 1994-04-28 1998-07-07 Hanninen; Pekka Luminescence-scanning microscopy process and a luminescence scanning microscope utilizing picosecond or greater pulse lasers
US5675401A (en) 1994-06-17 1997-10-07 Carl-Zeiss-Stiftung Illuminating arrangement including a zoom objective incorporating two axicons
US5700692A (en) 1994-09-27 1997-12-23 Becton Dickinson And Company Flow sorter with video-regulated droplet spacing
WO1996012172A1 (en) 1994-10-14 1996-04-25 University Of Washington Flow cytometer jet monitor system
US5602039A (en) 1994-10-14 1997-02-11 The University Of Washington Flow cytometer jet monitor system
US5602349A (en) 1994-10-14 1997-02-11 The University Of Washington Sample introduction system for a flow cytometer
EP0786079B1 (en) 1994-10-14 2003-05-21 University of Washington Flow cytometer jet monitor system
US5643796A (en) 1994-10-14 1997-07-01 University Of Washington System for sensing droplet formation time delay in a flow cytometer
US5726364A (en) 1994-10-14 1998-03-10 The University Of Washington Sample introduction apparatus for a flow cytometer
US5672880A (en) 1994-12-08 1997-09-30 Molecular Dynamics, Inc. Fluoresecence imaging system
US5824269A (en) 1994-12-26 1998-10-20 Toa Medical Electronics Co., Ltd. Flow cytometer
US5835262A (en) 1994-12-28 1998-11-10 Research Development Corporation Of Japan Multi-wavelength optical microscope
US5786560A (en) 1995-03-31 1998-07-28 Panasonic Technologies, Inc. 3-dimensional micromachining with femtosecond laser pulses
US5641457A (en) 1995-04-25 1997-06-24 Systemix Sterile flow cytometer and sorter with mechanical isolation between flow chamber and sterile enclosure
US5650847A (en) 1995-06-14 1997-07-22 Erkki Soini Method and device for determination of parameters of individual microparticles
US5912257A (en) 1995-09-06 1999-06-15 The Research Foundation Of State University Of New York Two-photon upconverting dyes and applications
US5815262A (en) 1995-09-07 1998-09-29 Basf Aktiengesellschaft Apparatus for parallelized two-photon fluorescence correlation spectroscopy (TPA-FCS), and the use thereof for screening active compounds
US5916449A (en) 1995-12-28 1999-06-29 Siemens Aktiengesellschaft Method and arrangement for monitoring a separating liquid stream
DE19549015C1 (de) 1995-12-28 1997-04-03 Siemens Ag Verfahren und Anordnung zur Überwachung eines abreißenden Flüssigkeitstrahls
EP0781985A2 (de) 1995-12-28 1997-07-02 Siemens Aktiengesellschaft Verfahren und Anordnung zur Überwachung eines abreissenden Flüssigkeitsstrahls
US5707808A (en) 1996-04-15 1998-01-13 The Regents Of The University Of California Optical selection and collection of DNA fragments
US5880457A (en) 1996-06-14 1999-03-09 Hamamatsu Photonics K.K. Voltage division circuit for a photomultiplier tube
US5759767A (en) 1996-10-11 1998-06-02 Joseph R. Lakowicz Two-photon and multi-photon measurement of analytes in animal and human tissues and fluids
US5885840A (en) 1997-02-10 1999-03-23 Compucyte Corp. Multiple assays of cell specimens
WO1999044037A1 (en) 1998-02-27 1999-09-02 Cytomation, Inc. Method and apparatus for flow cytometry
US6589792B1 (en) 1998-02-27 2003-07-08 Dakocytomation Denmark A/S Method and apparatus for flow cytometry
US6248590B1 (en) 1998-02-27 2001-06-19 Cytomation, Inc. Method and apparatus for flow cytometry
WO2000032542A1 (en) 1998-11-30 2000-06-08 The University Of Queensland Carriers for combinatorial compound libraries
WO2001028700A1 (en) 1999-10-21 2001-04-26 Cytomation, Inc. Transiently dynamic flow cytometer analysis system
US6944338B2 (en) 2000-05-11 2005-09-13 Becton Dickinson And Company System for identifying clusters in scatter plots using smoothed polygons with optimal boundaries
US6662117B2 (en) 2000-07-24 2003-12-09 Sysmex Corporation Particle analyzer and particle classifying method
US6763149B2 (en) 2001-04-25 2004-07-13 Amnis Corporation Method and apparatus for correcting crosstalk and spatial resolution for multichannel imaging
US6630990B2 (en) 2001-06-05 2003-10-07 Abbott Laboratories Optical method and apparatus for red blood cell differentiation on a cell-by-cell basis, and simultaneous analysis of white blood cell differentiation
US20030184730A1 (en) 2002-01-23 2003-10-02 The Regents Of The University Of California Fast 3D cytometry for information in tissue engineering
US20040062685A1 (en) * 2002-09-27 2004-04-01 Norton Pierce O Fixed mounted sorting cuvette with user replaceable nozzle
US20050112541A1 (en) * 2003-03-28 2005-05-26 Monsanto Technology Llc Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm
JP4126064B2 (ja) 2003-11-27 2008-07-30 本田技研工業株式会社 移動体の制御装置
US9625367B2 (en) * 2004-07-27 2017-04-18 Beckman Coulter, Inc. Enhancing flow cytometry discrimination with geometric transformation

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
Denk, W., et al (1995). Two-photon molecular excitation in laser scanning microscopy. Handbook of Biological Conical Microscopy. J. B. Pawley, ed., Plenum Press, New York, pp. 444-458.
Garner, D. L. et al; Quantification of the X- and Y- Chromosome-Bearing Spermatozoa of Domestic Animals by Flow Cytometry.sup.1, Biology of Reproduction 28, pp. 312-321, (1983).
Goppert-Mayer, M. 1931,. Uber Elementarakte mit zwei Quantensprungen nnalen der Physik, pp. 273-294.
Johnson, Lawrence A. Sex Preselection by Flow Cytometric Separation of X and Y Chromosome-bearing Sperm based on NA Difference: a Review, Reprod. Fertil. Dev., 1995, 7, pp. 893-903.
Mann et al, "The Use of Projections for Dimensionality Reduction of Flow Cytometric Data," Cytometry, 5:304-307, (1984). *
Manni, Jeff; (1996). Two-Photon Excitation Expands the Capabilities of Laser-Scanning Microscopy, Biophotonics International, pp. 44-52.
McLeod, J., Eastman Kodak Company, Hawk-Eye Works, Rochester, NY, Journal of the Optical Society of America; vol. 44, No. 8, Sep. 1953, pp. 592-597.
Melamed et al, An Historical Review of the Development of Flow Cytometers and Sorters,, 1979, pp. 3-9.
Pinkel, D., "Flow Chambers and Sample Handling," Flow Cytometry: Instrumentation and Data Analysis, pp. 77-128 (1985).
Piston, D. W., et al. (1995). Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in-situ cornea with two-photon excitation laser scanning microscopy. J of Microscopy 178: 20-27.
Piston. D. W., et al (1994). Two-photon-excitation fluorescence imaging of three-dimensional calcium ion activity. Applied Optics 33: 662-669.
Skogen-Hagenson, M. J. et al; "A High Efficiency Flow Cytometer," The Journal of Histochemistry and Cytochemistry, vol. 25, No. 7, pp. 784-789, 1977, USA.
Van Dilla et al. (Eds.)Flow Cytometry: Instrumentation and Data Analysis,, "Overview of Flow Cytometry: Instrumentation and Data Analysis" by Martin Van Dilla, 1985, pp. 1-8.
Williams, R. M. et al. (1944). Two photon molecular excitation provides intrinsic 3-dimensional resolution for laser-based microscopy and microphotochemistry. FASEB J. 8: 804-813.

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11408813B2 (en) 2004-07-27 2022-08-09 Beckman Coulter, Inc. Enhancing flow cytometry discrimination with geometric transformation
US11193874B2 (en) 2012-03-30 2021-12-07 Sony Corporation Micro-particle sorting apparatus and method of determining a trajectory of an ejected stream carrying micro-particles
US11313784B2 (en) 2013-01-28 2022-04-26 Sony Corporation Microparticle sorting device, and method and program for sorting microparticles
US11119030B2 (en) 2014-02-13 2021-09-14 Sony Corporation Particle sorting device, particle sorting method, program, and particle sorting system
US11204309B2 (en) * 2015-10-19 2021-12-21 Sony Corporation Image processing device, fine particle sorting device, and image processing method

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